Substituted heterocycle fused gamma-carbolines
The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R 1 , R 5 , R 6a , R 6b , R 7 , R 8 , R 9 , X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.
1. A method for treating a human suffering from sleep disorders associated with 5HT2A receptor modulation, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I):
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein:
b is a single bond;
X is —CHR 10 — or —C(═O)—;
R 1 is selected from
H,
C(═O)R 2 ,
C(═O)OR 2 ,
C 1-8 alkyl,
C 2-8 alkenyl,
C 2-8 alkynyl,
C 3-7 cycloalkyl,
C 1-6 alkyl substituted with Z,
C 2-6 alkenyl substituted with Z,
C 2-6 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-3 alkyl substituted with Y,
C 2-3 alkenyl substituted with Y,
C 2-3 alkynyl substituted with Y,
C 1-6 alkyl substituted with 0–2 R 2 ,
C 2-6 alkenyl substituted with 0–2 R 2 ,
C 2-6 alkynyl substituted with 0–2 R 2 ,
aryl substituted with 0–2 R 2 , and
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0–2 R 2 ;
Y is selected from
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 3-6 cycloalkyl substituted with —(C 1-3 alkyl)-Z,
aryl substituted with —(C 1-3 alkyl)-Z, and
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with —(C 1-3 alkyl)-Z;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—OC(O)R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
halo,
C 1-3 haloalkyl,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and
C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 5 is H or C 1-4 alkyl;
R 6a and R 6b , at each occurrence, are independently selected from
H, —OH, —NR 46 R 47 , —CF 3 , C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, and
aryl substituted with 0–3 R 44 ;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-0 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-14 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 2-4 alkenyl substituted with 0–2 R 11 ,
C 2-4 alkynyl substituted with 0–1 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10 is selected from H, —OH,
C 1-6 alkyl substituted with 0–1 R 10B ,
C 2-6 alkenyl substituted with 0–1 R 10B ,
C 2-6 alkynyl substituted with 0–1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
phenyl substituted with 0–3 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0–1 R 12a ,
C 2-4 alkenyl substituted with 0–1 R 12a ,
C 2-4 alkynyl substituted with 0–1 R 12a ,
C 3-6 cycloalkyl substituted with 0–3 R 33 ,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–3 R 16 ;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 15 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alknyl, C 1-4 haloalkyl,
C 1-3 haloalkyl-oxy-, and C 1-3 alkyloxy-;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-, C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—, C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O;
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SOR 45 , SR 45 , NR 46 SO 2 R 45 , NR 46 COR 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H, C 1-4 alkyl,
—C(═O)NH(C 1-14 alkyl), —SO 2 (C 1-4 alkyl),
—C(═O)O(C 1-4 alkyl), —C(═O)(C 1-4 alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
provided when m is 0 or 1 then k is 1 or 2;
provided when m is 2 then k is 1;
provided that when R 6 or R 6a is NH 2 , then X is not —CH(R 10 ); and
provided that when n=0, then R 6 or R 6a is not NH 2 or —OH.
2. The method as defined in claim 1 where in the compound administered:
X is —CHR 10 — or —C(═O)—;
R 1 is selected from
H,
C(—O)R 2 ,
C(═O)OR 2 ,
C 1-8 alkyl,
C 2-8 alkenyl,
C 2-8 alkynyl,
C 3-7 cycloalkyl,
C 1-6 alkyl substituted with 0–2 R 2 ,
C 2-6 alkenyl substituted with 0–2 R 2 ,
C 2-6 alkynyl substituted with 0–2 R 2 ,
aryl substituted with 0–2 R 2 , and
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0–2 R 2 ;
R 2 , at each occurrence, is independently selected from
F, Cl, CH 2 F, CHF 2 , CF 3 ,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and
aryl substituted with 0–3 R 44 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 2-4 alkenyl substituted with 0–2 R 11 ,
C 2-4 alkynyl substituted with 0–1 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10 is selected from H, —OH,
C 1-6 alkyl substituted with 0–1 R 10B ,
C 2-6 alkenyl substituted with 0–1 R 10B ,
C 2-6 alkynyl substituted with 0–1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
phenyl substituted with 0–3 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0–1 R 12a ,
C 2-4 alkenyl substituted with 0–1 R 12a ,
C 2-4 alkynyl substituted with 0–1 R 12a ,
C 3-6 cycloalkyl substituted with 0–3 R 33 ,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–3 R 16 ;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 15 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl,
C 1-3 haloalkyl-oxy-, and C 1-3 alkyloxy-;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-14 haloalkyl, C 1-14 haloalkyl-oxy-, C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—, C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN;
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H and C 1-4 alkyl;
k is 1 or 2;
m is 0, 1, or 2; and
n is 0, 1, 2, or 3.
3. The method as defined in claim 2 where in the compound administered:
X is —CHR 10 —;
R 1 is selected from
H,
C(═O)R 2 ,
C(═O)OR 2 ,
C 1-6 alkyl,
C 2-6 alkenyl,
C 2-6 alkynyl,
C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–2 R 2 ,
C 2-4 alkenyl substituted with 0–2 R 2 , and
C 2-4 alkynyl substituted with 0–2 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected independently from
H, —OH, —NR 46 R 47 , —CF 3 , C 1-3 alkyl, and C 1-3 alkoxy;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , and NR 14 S(O) 2 R 12 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 1 ,
C 2-4 alkenyl substituted with 0–2 R 11 ,
C 2-4 alkynyl substituted with 0–1 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10 is selected from H, —OH,
C 1-6 alkyl substituted with 0–1 R 10B ,
C 2-6 alkenyl substituted with 0–1 R 10B ,
C 2-6 alkynyl substituted with 0–1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
phenyl substituted with 0–3 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 , C 1-6 alkyl,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , and NR 14 S(O) 2 R 12 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0–1 R 12a ,
C 2-4 alkenyl substituted with 0–1 R 12a ,
C 2-4 alkynyl substituted with 0–1 R 12a ,
C 3-6 cycloalkyl substituted with 0–3 R 33 ,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–3 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 15 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, F, Cl, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-14 haloalkyl-oxy-, C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—, C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H and C 1-4 alkyl;
k is 1 or 2;
m is 0 or 1; and
n is 0, 1 or 2.
4. The method as defined in claim 2 where in the compound administered:
X is —CH 2 —;
R 1 is selected from
H,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-4 cycloalkyl,
C 1-3 alkyl substituted with 0–1 R 2 ,
C 2-3 alkenyl substituted with 0–1 R 2 , and
C 2-3 alkynyl substituted with 0–1 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 42 ;
C 3-6 carbocyclic group substituted with 0–3 R 41 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is H, methyl, ethyl, methoxy, —OH, or —CF 3 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 2-4 alkenyl substituted with 0–2 R 11 ,
C 2-4 alkynyl substituted with 0–1 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0–1 R 12a ,
C 2-4 alkenyl substituted with 0–1 R 12a ,
C 2-4 alkynyl substituted with 0–1 R 12a ,
C 3-6 cycloalkyl substituted with 0–3 R 33 ,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of one N, two N, three N, one N one O, and one N one S; wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–2 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 16 , at each occurrence, is independently selected from
H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-, C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—, C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, and C 1-3 alkyl;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 3-6 cycloalkyl, and C 1-3 alkyl;
R 43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 0, 1 or 2.
5. The method as defined in claim 2 where in the compound administered:
X is —CH 2 —;
R 1 is selected from
H,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-4 cycloalkyl,
C 1-3 alkyl substituted with 0–1 R 2 ,
C 2-3 alkenyl substituted with 0–1 R 2 , and
C 2-3 alkynyl substituted with 0–1 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 42 ;
C 3-6 carbocyclic group substituted with 0–3 R 41 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is H, methyl, ethyl, methoxy, —OH, or —CF 3 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, F, Cl, —CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ,
R 8 is selected from
H, F, Cl, Br, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 2-4 alkenyl substituted with 0–2 R 11 ,
C 2-4 alkynyl substituted with 0–1 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0–2 R 33 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0–1 R 12a ,
C 2-4 alkenyl substituted with 0–1 R 12a ,
C 2-4 alkynyl substituted with 0–1 R 12a ,
C 3-6 cycloalkyl substituted with 0–3 R 33 ,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of N, O, and S; wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl; wherein said bicyclic heterocyclic ring system is substituted with 0–1 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 16 , at each occurrence, is independently selected from
H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-, C 1-14 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—, C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, and C 1-3 alkyl;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 3-6 cycloalkyl, and C 1-3 alkyl;
R 43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 0, 1 or 2.
6. The method as defined in claim 2 where in the compound administered:
X is —CH 2 —;
R 1 is selected from H,
C 1-5 alkyl substituted with 0–1 R 2 ,
C 2-5 alkenyl substituted with 0–1 R 2 , and
C 2-3 alkynyl substituted with 0–1 R 2 ;
R 2 is C 3-6 cycloalkyl;
R 5 is H, methyl, ethyl, or propyl;
R 6a is H, methyl, or ethyl;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, F, Cl, —CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ,
R 8 is selected from
methyl substituted with R 11 ;
ethenyl substituted with R 11 ;
OR 12 , SR 12 , NR 12 R 13 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 11 is selected from
phenyl-substituted with 0–5 fluoro;
2-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
2-(H 3 CC(═O))-phenyl-substituted with R 33 ;
2-(HC(═O))-phenyl-substituted with R 33 ;
2-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
2-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
2-(HOCH 2 )-phenyl-substituted with R 33 ;
2-(HOCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 CCH(OMe))-phenyl-substituted with R 33 ;
2-(H 3 COC(═O))-phenyl-substituted with R 33 ;
2-(HOCH 2 CH═CH)-phenyl-substituted with R 33 ;
2-((MeOC═O)CH═CH)-phenyl-substituted with R 33 ;
2-(methyl)-phenyl-substituted with R 33 ;
2-(ethyl)-phenyl-substituted with R 33 ;
2-(i-propyl)-phenyl-substituted with R 33 ;
2-(F 3 C)-phenyl-substituted with R 33 ;
2-(NC)-phenyl-substituted with R 33 ;
2-(H 3 CO)-phenyl-substituted with R 33 ;
2-(fluoro)-phenyl-substituted with R 33 ;
2-(chloro)-phenyl-substituted with R 33 ;
3-(NC)-phenyl-substituted with R 33 ;
3-(H 3 CO)-phenyl-substituted with R 33 ;
3-(fluoro)-phenyl-substituted with R 33 ;
3-(chloro)-phenyl-substituted with R 33 ;
4-(NC)-phenyl-substituted with R 33 ;
4-(fluoro)-phenyl-substituted with R 33 ;
4-(chloro)-phenyl-substituted with R 33 ;
4-(H 3 CS)-phenyl-substituted with R 33 ;
4-(H 3 CO)-phenyl-substituted with R 33 ;
4-(ethoxy)-phenyl-substituted with R 33 ;
4-(i-propoxy)-phenyl-substituted with R 33 ;
4-(i-butoxy)-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 C(═O))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
4-(H 3 CC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 CH(OH))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHCH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
4-(cyclopropyloxy)-phenyl-substituted with R 33 ;
4-(cyclobutyloxy)-phenyl-substituted with R 33 ; and
4-(cyclopentyloxy)-phenyl-substituted with R 33 ;
R 12 is selected from
phenyl-substituted with 0–5 fluoro;
2-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
2-(H 3 CC(═O))-phenyl-substituted with R 33 ;
2-(HC(═O))-phenyl-substituted with R 33 ;
2-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
2-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
2-(HOCH 2 )-phenyl-substituted with R 33 ;
2-(HOCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 CCH(OMe))-phenyl-substituted with R 33 ;
2-(H 3 COC(═O))-phenyl-substituted with R 33 ;
2-(HOCH 2 CH═CH)-phenyl-substituted with R 33 ;
2-((MeOC═O)CH═CH)-phenyl-substituted with R 33 ;
2-(methyl)-phenyl-substituted with R 33 ;
2-(ethyl)-phenyl-substituted with R 33 ;
2-(i-propyl)-phenyl-substituted with R 33 ;
2-(F 3 C)-phenyl-substituted with R 33 ;
2-(NC)-phenyl-substituted with R 33 ;
2-(H 3 CO)-phenyl-substituted with R 33 ;
2-(fluoro)-phenyl-substituted with R 33 ;
2-(chloro)-phenyl-substituted with R 33 ;
3-(NC)-phenyl-substituted with R 33 ;
3-(H 3 CO)-phenyl-substituted with R 33 ;
3-(fluoro)-phenyl-substituted with R 33 ;
3-(chloro)-phenyl-substituted with R 33 ;
4-(NC)-phenyl-substituted with R 33 ;
4-(fluoro)-phenyl-substituted with R 33 ;
4-(chloro)-phenyl-substituted with R 33 ;
4-(H 3 CS)-phenyl-substituted with R 33 ;
4-(H 3 CO)-phenyl-substituted with R 33 ;
4-(ethoxy)-phenyl-substituted with R 33 ;
4-(i-propoxy)-phenyl-substituted with R 33 ;
4-(i-butoxy)-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 C(═O))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
4-(H 3 CC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 CH(OH))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHCH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
4-(cyclopropyloxy)-phenyl-substituted with R 33 ;
4-(cyclobutyloxy)-phenyl-substituted with R 33 ; and
4-(cyclopentyloxy)-phenyl-substituted with R 33 ;
R 13 is H, methyl, or ethyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring selected from pyrrolyl, pyrrolidinyl, imidazolyl, piperidinyl, piperizinyl, methylpiperizinyl, and morpholinyl;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–3 heteroatoms selected from the group consisting of N, O, and S; wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl; wherein said bicyclic heterocyclic ring system is substituted with 0–1 R 16 ;
R 15 is H, methyl, ethyl, propyl, or butyl;
R 16 , at each occurrence, is independently selected from
H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 33 , at each occurrence, is independently selected from
H, F, Cl, —CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ;
k is 1;
m is 1; and
n is 1 or 2.
7. The method as defined in claim 2 where the compound administered is a compound of Formula (I-a):
wherein:
b is a single bond;
X is —CH 2 —, —CH(OH)—, or ° C(═O)—;
R 1 is selected from
hydrogen, methyl, ethyl, n-propyl, n-butyl, s-butyl,
t-butyl, n-pentyl, n-hexyl, 2-propyl, 2-butyl, 2-pentyl, 2-hexyl, 2-methylpropyl, 2-methylbutyl, 2-methylpentyl, 2-ethylbutyl, 3-methylpentyl, 3-methylbutyl,
4-methylpentyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl,
2-propenyl, 2-methyl-2-propenyl, trans-2-butenyl,
3-methyl-butenyl, 3-butenyl, trans-2-pentenyl,
cis-2-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl,
3,3-dichloro-2-propenyl, trans-3-phenyl-2-propenyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl,
benzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2,5-dimethylbenzyl, 2,4-dimethylbenzyl, 3,5-dimethylbenzyl,
2,4,6-trimethyl-benzyl, 3-methoxy-benzyl, 3,5-dimethoxy-benzyl, pentafluorobenzyl, 2-phenylethyl, 1-phenyl-2-propyl, 4-phenylbutyl, 4-phenylbenzyl, 2-phenylbenzyl,
(2,3-dimethoxy-phenyl)C(═O)—, (2,5-dimethoxy-phenyl)C(═O)—, (3,4-dimethoxy-phenyl)C(═O)—,
(3,5-dimethoxy-phenyl)C(═O)—, cyclopropyl-C(═O)—,
isopropyl-C(═O)—, ethyl-CO 2 —, propyl-CO 2 —, t-butyl-CO 2 —,
2,6-dimethoxy-benzyl, 2,4-dimethoxy-benzyl,
2,4,6-trimethoxy-benzyl, 2,3-dimethoxy-benzyl,
2,4,5-trimethoxy-benzyl, 2,3,4-trimethoxy-benzyl,
3,4-dimethoxy-benzyl, 3,4,5-trimethoxy-benzyl,
(4-fluoro-phenyl)ethyl,
—CH═CH 2 , —CH 2 —CH═CH 2 , —CH═CH—CH 3 , —C—CH, —C≡C—CH 3 , and
—CH 2 —C≡CH;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenyl,
methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—, butylC(═O)—, phenylC(═O)—,
methylCO 2 —, ethylCO 2 —, propylCO 2 —, isopropylCO 2 —, butylCO 2 —, phenylCO 2 —,
dimethylamino-S(═O)—, diethylamino-S(═O)—,
dipropylamino-S(═O)—, di-isopropylamino-S(═O)—, dibutylamino-S(═O)—, diphenylamino-S(═O)—,
dimethylamino-SO 2 —, diethylamino-SO 2 —, dipropylamino-SO 2 —, di-isopropylamino-SO 2 —, dibutylamino-SO 2 —,
diphenylamino-SO 2 —,
dimethylamino-C(═O)—, diethylamino-C(═O)—, dipropylamino-C(═O)—, di-isopropylamino-C(═O)—, dibutylamino-C(═O)—, diphenylamino-C(═O)—,
2-chlorophenyl, 2-fluorophenyl, 2-bromophenyl, 2-cyanophenyl, 2-methylphenyl, 2-trifluoromethylphenyl,
2-methoxyphenyl, 2-trifluoromethoxyphenyl,
3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl,
3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl,
3-propylphenyl, 3-isopropylphenyl, 3-butylphenyl,
3-trifluoromethylphenyl, 3-methoxyphenyl,
3-isopropoxyphenyl, 3-trifluoromethoxyphenyl,
3-thiomethoxyphenyl,
4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl,
4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl,
4-propylphenyl, 4-isopropylphenyl, 4-butylphenyl,
4-trifluoromethylphenyl, 4-methoxyphenyl,
4-isopropoxyphenyl, 4-trifluoromethoxyphenyl,
4-thiomethoxyphenyl,
2,3-dichlorophenyl, 2,3-difluorophenyl, 2,3-dimethylphenyl,
2,3-ditrifluoromethylphenyl, 2,3-dimethoxyphenyl,
2,3-ditrifluoromethoxyphenyl,
2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dimethylphenyl,
2,4-ditrifluoromethylphenyl, 2,4-dimethoxyphenyl,
2,4-ditrifluoromethoxyphenyl,
2,5-dichlorophenyl, 2,5-difluorophenyl, 2,5-dimethylphenyl,
2,5-ditrifluoromethylphenyl, 2,5-dimethoxyphenyl,
2,5-ditrifluoromethoxyphenyl,
2,6-dichlorophenyl, 2,6-difluorophenyl, 2,6-dimethylphenyl,
2,6-ditrifluoromethylphenyl, 2,6-dimethoxyphenyl,
2,6-ditrifluoromethoxyphenyl,
3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl,
3,4-ditrifluoromethylphenyl, 3,4-dimethoxyphenyl,
3,4-ditrifluoromethoxyphenyl,
2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl,
2,4,6-trimethylphenyl, 2,4,6-tritrifluoromethylphenyl,
2,4,6-trimethoxyphenyl, 2,4,6-tritrifluoromethoxyphenyl,
2-chloro-4-CF 3 -phenyl, 2-fluoro-3-chloro-phenyl,
2-chloro-4-CF 3 -phenyl, 2-chloro-4-methoxy-phenyl,
2-methoxy-4-isopropyl-phenyl, 2-CF 3 -4-methoxy-phenyl,
2-methyl-4-methoxy-5-fluoro-phenyl,
2-methyl-4-methoxy-phenyl, 2-chloro-4-CF 3 O-phenyl,
2,4,5-trimethyl-phenyl, 2-methyl-4-chloro-phenyl,
methyl-C(═O)NH—, ethyl-C(═O)NH—, propyl-C(═O)NH—,
isopropyl-C(═O)NH—, butyl-C(═O)NH—, phenyl-C(═O)NH—,
4-acetylphenyl, 3-acetamidophenyl, 4-pyridyl, 2-furanyl,
2-thiophenyl, 2-naphthyl;
2-Me-5-F-phenyl, 2-F-5-Me-phenyl, 2-MeO-5-F-phenyl,
2-Me-3-Cl-phenyl, 3-NO 2 -phenyl, 2-NO 2 -phenyl,
2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl,
2-Cl-6-F-phenyl, 2-Cl-4-(CHF 2 )O-phenyl,
2,4-diMeO-6-F-phenyl, 2-CF 3 -6-F-phenyl,
2-MeS-phenyl, 2,6-diCl-4-MeO-phenyl,
2,3,4-triF-phenyl, 2,6-diF-4-Cl-phenyl,
2,3,4,6-tetraF-phenyl, 2,3,4,5,6-pentaF-phenyl,
2-CF 3 -4-EtO-phenyl, 2-CF 3 -4-iPrO-phenyl,
2-CF 3 -4-Cl-phenyl, 2-CF 3 -4-F-phenyl, 2-Cl-4-EtO-phenyl,
2-Cl-4-iPrO-phenyl, 2-Et-4-MeO-phenyl,
2-CHO-4-MeO-phenyl, 2-CH(OH)Me-4-MeO-phenyl,
2-CH(OMe)Me-4-MeO-phenyl, 2-C(═O)Me-4-MeO-phenyl,
2-CH 2 (OH)-4-MeO-phenyl, 2-CH 2 (OMe)-4-MeO-phenyl,
2-CH(OH)Et-4-MeO-phenyl, 2-C(═O)Et-4-MeO-phenyl,
(Z)-2-CH═CHCO 2 Me-4-MeO-phenyl,
2-CH 2 CH 2 CO 2 Me-4-MeO-phenyl,
(Z)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
(E)-2-CH═CHCO 2 Me-4-MeO-phenyl,
(E)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
2-CH 2 CH 2 OMe-4-MeO-phenyl,
2-F-4-MeO-phenyl, 2-Cl-4-F-phenyl,
(2-Cl-phenyl)-CH═CH—, (3-Cl-phenyl)-CH═CH—,
(2,6-diF-phenyl)-CH═CH—, —CH 2 CH═CH 2 ,
phenyl-CH═CH—, (2-Me-4-MeO-phenyl)-CH═CH—,
cyclohexyl, cyclopentyl, cyclohexylmethyl,
—CH 2 CH 2 CO 2 Et, —(CH 2 ) 3 CO 2 Et, —(CH 2 ) 4 CO 2 Et,
benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl,
3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl,
2-OH-benzyl, 2-CO 2 Me-3-MeO-phenyl,
2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF 3 -4-CN-phenyl,
3-CHO-phenyl, 3-CH 2 (OH)-phenyl, 3-CH 2 (OMe)-phenyl,
3-CH 2 (NMe 2 )-phenyl, 3-CN-4-F-phenyl,
3-CONH 2 -4-F-phenyl, 2-CH 2 (NH 2 )-4-MeO-phenyl-,
phenyl-NH—, (4-F-phenyl)-NH—, (2,4-diCl-phenyl)-NH—,
phenyl-C(═O)NH—, benzyl-NH—, (2-Me-4-MeO-phenyl)-NH—,
(2-F-4-MeO-phenyl)-NH—, (2-Me-4-F-phenyl)-NH—,
phenyl-S—, —NMe2,1-pyrrolidinyl, and
—N(tosylate) 2 ,
provided that two of R 7 , R 8 , and R 9 , are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
m is 1, and
n is 0, 1 or 2.
8. The method as defined in claim 7 where the compound administered is a compound of Formula (V):
wherein:
b is a single bond, wherein the bridge hydrogens are in a cis position;
R 1 is selected from
hydrogen, methyl, ethyl, n-propyl, n-butyl, s-butyl,
t-butyl, n-pentyl, n-hexyl, 2-propyl, 2-butyl, 2-pentyl, 2-hexyl, 2-methylpropyl, 2-methylbutyl, 2-methylpentyl, 2-ethylbutyl, 3-methylpentyl, 3-methylbutyl,
4-methylpentyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 2-propenyl, 2-methyl-2-propenyl, trans-2-butenyl, 3-methyl-butenyl, 3-butenyl,
trans-2-pentenyl, cis-2-pentenyl, 4-pentenyl,
4-methyl-3-pentenyl, 3,3-dichloro-2-propenyl,
trans-3-phenyl-2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl,
—CH═CH 2 , —CH 2 —CH═CH 2 , —CH═CH—CH 3 , —C≡CH, —C≡C—CH 3 ,
and —CH 2 —C≡CH;
R 7 and R 9 , at each occurrence, are independently selected from hydrogen, fluoro, methyl, trifluoromethyl, and methoxy;
R 8 is selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenyl,
methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—, butylC(═O)—, phenylC(═O)—,
methylCO 2 —, ethylCO 2 —, propylCO 2 —, isopropylCO 2 —, butylCO 2 —, phenylCO 2 —,
dimethylamino-S(═O)—, diethylamino-S(═O)—,
dipropylamino-S(═O)—, di-isopropylamino-S(═O)—, dibutylamino-S(═O)—, diphenylamino-S(═O)—,
dimethylamino-SO 2 —, diethylamino-SO 2 —, dipropylamino-SO 2 —, di-isopropylamino-SO 2 —, dibutylamino-SO 2 —,
diphenylamino-SO 2 —,
dimethylamino-C(—O)—, diethylamino-C(═O)—,
dipropylamino-C(═O)—, di-isopropylamino-C(═O)—, dibutylamino-C(═O)—, diphenylamino-C(═O)—,
2-chlorophenyl, 2-fluorophenyl, 2-bromophenyl, 2-cyanophenyl, 2-methylphenyl, 2-trifluoromethylphenyl,
2-methoxyphenyl, 2-trifluoromethoxyphenyl,
3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl,
3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl,
3-propylphenyl, 3-isopropylphenyl, 3-butylphenyl,
3-trifluoromethylphenyl, 3-methoxyphenyl,
3-isopropoxyphenyl, 3-trifluoromethoxyphenyl,
3-thiomethoxyphenyl,
4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl,
4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl,
4-propylphenyl, 4-isopropylphenyl, 4-butylphenyl,
4-trifluoromethylphenyl, 4-methoxyphenyl,
4-isopropoxyphenyl, 4-trifluoromethoxyphenyl,
4-thiomethoxyphenyl,
2,3-dichlorophenyl, 2,3-difluorophenyl, 2,3-dimethylphenyl,
2,3-ditrifluoromethylphenyl, 2,3-dimethoxyphenyl,
2,3-ditrifluoromethoxyphenyl,
2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dimethylphenyl,
2,4-ditrifluoromethylphenyl, 2,4-dimethoxyphenyl,
2,4-ditrifluoromethoxyphenyl,
2,5-dichlorophenyl, 2,5-difluorophenyl, 2,5-dimethylphenyl,
2,5-ditrifluoromethylphenyl, 2,5-dimethoxyphenyl,
2,5-ditrifluoromethoxyphenyl,
2,6-dichlorophenyl, 2,6-difluorophenyl, 2,6-dimethylphenyl,
2,6-ditrifluoromethylphenyl, 2,6-dimethoxyphenyl,
2,6-ditrifluoromethoxyphenyl,
3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl,
3,4-ditrifluoromethylphenyl, 3,4-dimethoxyphenyl,
3,4-ditrifluoromethoxyphenyl,
2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl,
2,4,6-trimethylphenyl, 2,4,6-tritrifluoromethylphenyl,
2,4,6-trimethoxyphenyl, 2,4,6-tritrifluoromethoxyphenyl,
2-chloro-4-CF 3 -phenyl, 2-fluoro-3-chloro-phenyl,
2-chloro-4-CF 3 -phenyl, 2-chloro-4-methoxy-phenyl,
2-methoxy-4-isopropyl-phenyl, 2-CF 3 -4-methoxy-phenyl,
2-methyl-4-methoxy-5-fluoro-phenyl,
2-methyl-4-methoxy-phenyl, 2-chloro-4-CF 3 O-phenyl,
2,4,5-trimethyl-phenyl, 2-methyl-4-chloro-phenyl,
methyl-C(═O)NH—, ethyl-C(═O)N-H—, propyl-C(═O)NH—,
isopropyl-C(═O)NH—, butyl-C(═O)NH—, phenyl-C(═O)NH—,
4-acetylphenyl, 3-acetamidophenyl, 4-pyridyl, 2-furanyl,
2-thiophenyl, 2-naphthyl;
2-Me-5-F-phenyl, 2-F-5-Me-phenyl, 2-MeO-5-F-phenyl,
2-Me-3-Cl-phenyl, 3-NO 2 -phenyl, 2-NO 2 -phenyl,
2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl,
2-Cl-6-F-phenyl, 2-C1–4-(CHF 2 )O-phenyl,
2,4-diMeO-6-F-phenyl, 2-CF 3 -6-F-phenyl,
2-MeS-phenyl, 2,6-diCl-4-MeO-phenyl,
2,3,4-triF-phenyl, 2,6-diF-4-Cl-phenyl,
2,3,4,6-tetraF-phenyl, 2,3,4,5,6-pentaF-phenyl,
2-CF 3 -4-EtO-phenyl, 2-CF 3 -4-iPrO-phenyl,
2-CF 3 -4-Cl-phenyl, 2-CF 3 -4-F-phenyl, 2-Cl-4-EtO-phenyl,
2-Cl-4-iPrO-phenyl, 2-Et-4-MeO-phenyl,
2-CHO-4-MeO-phenyl, 2-CH(OH)Me-4-MeO-phenyl,
2-CH(OMe)Me-4-MeO-phenyl, 2-C(═O)Me-4-MeO-phenyl,
2-CH 2 (OH)-4-MeO-phenyl, 2-CH 2 (OMe)-4-MeO-phenyl,
2-CH(OH)Et-4-MeO-phenyl, 2-C(═O)Et-4-MeO-phenyl,
(Z)-2-CH═CHCO 2 Me-4-MeO-phenyl,
2-CH 2 CH 2 CO 2 Me-4-MeO-phenyl,
(Z)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
(E)-2-CH═CHCO 2 Me-4-MeO-phenyl,
(E)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
2-CH 2 CH 2 OMe-4-MeO-phenyl,
2-F-4-MeO-phenyl, 2-Cl-4-F-phenyl,
(2-Cl-phenyl)-CH═CH—, (3-Cl-phenyl)-CH═CH—,
(2,6-diF-phenyl)-CH═CH—, —CH 2 CH═CH 2 ,
phenyl-CH═CH—, (2-Me-4-MeO-phenyl)-CH═CH—,
cyclohexyl, cyclopentyl, cyclohexylmethyl,
—CH 2 CH 2 CO 2 Et, —(CH 2 ) 3 CO 2 Et, —(CH 2 ) 4 CO 2 Et,
benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl,
3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl,
2-OH-benzyl, 2-CO 2 Me-3-MeO-phenyl,
2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF 3 -4-CN-phenyl,
3-CHO-phenyl, 3-CH 2 (OH)-phenyl, 3-CH 2 (OMe)-phenyl,
3-CH 2 (NMe2)-phenyl, 3-CN-4-F-phenyl,
3-CONH 2 -4-F-phenyl, 2-CH 2 (NH 2 )-4-MeO-phenyl-,
phenyl-NH—, (4-F-phenyl)-NH—, (2,4-diCl-phenyl)-NH—,
phenyl-C(═O)NH—, benzyl-NH—, (2-Me-4-MeO-phenyl)-NH—,
(2-F-4-MeO-phenyl)-NH—, (2-Me-4-F-phenyl)-NH—,
phenyl-S—, —NMe 2 , 1-pyrrolidinyl, and
—N(tosylate) 2 ; and
n is 0, 1 or 2.
9. The method as defined in claim 1 where in the compound administered:
X is —CHR 10 — or —C(═O)—;
R 1 is selected from
C 1-6 alkyl substituted with Z,
C 2-6 alkenyl substituted with Z,
C 2-6 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-6 alkyl substituted with 0–2 R 2 ,
C 2-6 alkenyl substituted with 0–2 R 2 ,
C 2-6 alkynyl substituted with 0–2 R 2 ,
aryl substituted with 0–2 R 2 , and
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0–2 R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—OC(O)R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and
C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, and
aryl substituted with 0–3 R 44 ;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 14 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10 is selected from H, —OH,
C 1-6 alkyl substituted with 0–1 R 10B ,
C 2-6 alkenyl substituted with 0–1 R 10B ,
C 2-6 alkynyl substituted with 0–1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
phenyl substituted with 0–3 R 33 , and
5–6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , and NR 14 S(O) 2 R 12 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C24 alknyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 ,
C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 3-5 cycloalkyl, C 1-3 haloalkyl, C 1-3 haloalkyl-oxy-, C 1-3 alkyloxy-, C 1-3 alkylthio-, C 1-3 alkyl-C(═O)—, and C 1-3 alkyl-C(═O)NH—;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alknyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H, C 1-4 alkyl,
—C(—O)NH(C 1-4 alkyl), —SO 2 (C 1-4 alkyl),
—SO 2 (phenyl), —C(═O)O(C 1-4 alkyl), —C(═O)(C 1-4 alkyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from H, C 1-4 alkyl,
—C(═O)NH(C 1-4 alkyl), —C(═O)O(C 1-4 alkyl),
—C(═O)(C 1-4 alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, or 2; and
n is 0, 1 or 2.
10. The method as defined in claim 9 where in the compound administered:
X is —CHR 10 — or —C(═O)—;
R 1 is selected from
C 2-5 alkyl substituted with Z,
C 2-5 alkenyl substituted with Z,
C 2-5 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-5 alkyl substituted with 0–2 R 2 ,
C 2-5 alkenyl substituted with 0–2 R 2 , and
C 2-5 alkynyl substituted with 0–2 R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—OC(O)R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and
C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H, methyl, or ethyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, and C 3-6 cycloalkyl;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 1-4 alkyl substituted with 0–2 R 11 ,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O) 2 NR 12 R 13 , NR 14 S(O) 2 R 12 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10 is selected from H, —OH, C 1-6 alkyl, C 1-4 alkoxy, and
C 1-2 alkyl substituted with 0–1 R 10B ;
R 10B is C 3-6 cycloalkyl or
phenyl substituted with 0–3 R 33 ;
R 11 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 carbocyclic group substituted with 0–3 R 33 ,
aryl substituted with 0–5 R 33 ,
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O) 2 NR 12 R 13 , and NR 14 S(O) 2 R 12 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0–5 R 33 ;
C 3-10 carbocyclic group substituted with 0–3 R 33 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , methyl, and ethyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , methyl, and ethyl;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-3 alkyl;
R 47 , at each occurrence, is independently selected from H, C 1-4 alkyl,
—C(═O)NH(C 1-4 alkyl), —SO 2 (C 1-4 alkyl),
—SO 2 (phenyl), —C(═O)O(C 1-4 alkyl), —C(═O)(C 1-4 alkyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from H, C 1-4 alkyl,
—C(═O)NH(C 1-4 alkyl), —C(═O)O(C 1-4 alkyl),
—C(═O)(C1A alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, 2; and
n is 0, 1 or 2.
11. The method as defined in claim 9 where in the compound administered:
X is —CH 2 —;
R 1 is selected from
C 2-4 alkyl substituted with Z,
C 2-4 alkenyl substituted with Z,
C 2-4 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5–6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 2-4 alkyl substituted with 0–2 R 2 , and
C 2-4 alkenyl substituted with 0–2 R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
phenyl substituted with 0–5 R 42 ;
C 3-10 carbocyclic group substituted with 0–3 R 41 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and
C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H;
R 6a is selected from H, —OH, —CF 3 , methyl, ethyl, propyl, butyl, methoxy, and, ethoxy;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-3 haloalkyl)oxy, and
C 1-4 alkyl substituted with 0–2 R 11 ;
R 11 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, and (C 1-3 haloalkyl)oxy;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , and methyl;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 42 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0–1 R 43 ,
aryl substituted with 0–3 R 44 , and
5–10 membered heterocyclic ring system containing from 1–4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–3 R 44 ;
R 43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, n-butyl,
i-butyl, —C(═O)NH(methyl), —C(═O)NH(ethyl),
—SO 2 (methyl), —SO 2 (ethyl), —SO 2 (phenyl),
—C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl),
—C(═O)(ethyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, —C(═O)NH(methyl), —C(═O)NH(ethyl), —C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl), —C(═O)(ethyl), and —C(═O)H:
k is 1;
m is 0, 1, or 2; and
n is 0, 1 or 2.
12. The method as defined in claim 9 where in the compound administered:
X is —CH 2 —;
R 1 is selected from
ethyl substituted with Z,
propyl substituted with Z,
butyl substituted with Z,
propenyl substituted with Z,
butenyl substituted with Z,
ethyl substituted with R 2 ,
propyl substituted with R 2 ,
butyl substituted with R 2 ,
propenyl substituted with R 2 , and
butenyl substituted with R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
phenyl substituted with 0–3 R 42 ;
naphthyl substituted with 0–3 R 42 ;
cyclopropyl substituted with 0–3 R 41 ;
cyclobutyl substituted with 0–3 R 41 ;
cyclopentyl substituted with 0–3 R 41 ;
cyclohexyl substituted with 0–3 R 41 ;
pyridyl substituted with 0–3 R 41 ;
indolyl substituted with 0–3 R 41 ;
indolinyl substituted with 0–3 R 41 ;
benzimidazolyl substituted with 0–3 R 41 ;
benzotriazolyl substituted with 0–3 R 41 ;
benzothienyl substituted with 0–3 R 41 ;
benzofuranyl substituted with 0–3 R 41 ;
phthalimid-1-yl substituted with 0–3 R 41 ;
inden-2-yl substituted with 0–3 R 41 ;
2,3-dihydro-1H-inden-2-yl substituted with 0–3 R 41 ;
indazolyl substituted with 0–3 R 41 ;
tetrahydroquinolinyl substituted with 0–3 R 41 ; and
tetrahydro-isoquinolinyl substituted with 0–3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, methyl, and ethyl;
R 5 is H;
R 6a is selected from H, —OH, methyl, and methoxy;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from H, F, Cl, methyl, ethyl, methoxy, —CF 3 ,
and —OCF 3 ;
R 41 , at each occurrence, is independently selected from
H, F, Cl, Br, OH, CF 3 , NO 2 , CN, ═O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R 42 , at each occurrence, is independently selected from
H, F, Cl, Br, OH, CF 3 , SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, ═O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, n-butyl,
i-butyl, —C(═O)NH(methyl), —C(═O)NH(ethyl),
—SO 2 (methyl), —SO 2 (ethyl), —SO 2 (phenyl),
—C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl),
—C(═O)(ethyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, —C(═O)NH(methyl), —C(═O)NH(ethyl), —C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl), —C(—O)(ethyl), and —C(═O)H;
k is 1;
m is 0, 1, or 2; and
n is 0, 1 or 2.
13. The method as defined in claim 9 where the compound administered is a compound of Formula (I-a):
wherein:
b is a single bond;
X is —CH 2 —, CH(OH)—, or —C(═O)—
R 1 is selected from
—(CH 2 ) 3 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-bromo-phenyl),
—(CH 2 ) 3 C(═O)(4-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-methoxy-phenyl),
—(CH 2 ) 3 C(═O)(4-(3,4-dichloro-phenyl)phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 C(═O)(phenyl),
—(CH 2 ) 3 C(═O)(4-chloro-phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-t-butyl-phenyl),
—(CH 2 ) 3 C(═O)(3,4-difluoro-phenyl),
—(CH 2 ) 3 C(═O)(2-methoxy-5-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-fluoro-1-naphthyl),
—(CH 2 ) 3 C(═O)(benzyl),
—(CH 2 ) 3 C(═O)(4-pyridyl),
—(CH 2 ) 3 C(═O)(3-pyridyl),
—(CH 2 ) 3 CH(OH)(4-fluoro-phenyl),
—(CH 2 ) 3 CH(OH)(4-pyridyl),
—(CH 2 ) 3 CH(OH)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 S(3-fluoro-phenyl),
—(CH 2 ) 3 S(4-fluoro-phenyl),
—(CH 2 ) 3 S(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (3-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (4-fluoro-phenyl),
—(CH 2 ) 3 O(4-fluoro-phenyl),
—(CH 2 ) 3 O(phenyl),
—(CH 2 ) 3 O(3-pyridyl),
—(CH 2 ) 3 O(4-pyridyl),
—(CH 2 ) 3 O(2-NH 2 -phenyl),
—(CH 2 ) 3 O(2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-OH-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 O(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 O(2-NHC(═O)Me-phenyl),
—(CH 2 ) 3 NH(4-fluoro-phenyl),
—(CH 2 ) 3 N(methyl)(4-fluoro-phenyl),
—(CH 2 ) 3 CO 2 (ethyl),
—(CH 2 ) 3 C(═O)N(methyl)(methoxy),
—(CH 2 ) 3 C(═O)NH(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(phenyl),
—(CH 2 ) 2 NMeC(═O)(phenyl),
—(CH 2 ) 2 NHC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(2,4-difluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2,4-difluoro-phenyl),
—(CH 2 ) 3 (3-indolyl),
—(CH 2 ) 3 (1-methyl-3-indolyl),
—(CH 2 ) 3 (1-indolyl),
—(CH 2 ) 3 (1-indolinyl),
—(CH 2 ) 3 (1-benzimidazolyl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 3 (3,4 dihydro-1(2H)-quinolinyl),
—(CH 2 ) 2 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 C(═O)NH(4-fluoro-phenyl),
—CH 2 CH 2 (3-indolyl),
—CH 2 CH 2 (1-phthalimidyl),
—(CH 2 ) 4 C(═O)N(methyl)(methoxy),
—(CH 2 ) 4 CO 2 (ethyl),
—(CH 2 ) 4 C(═O)(Phenyl),
—(CH 2 ) 4 (cyclohexyl),
—(CH 2 ) 3 CH(phenyl) 2 ,
—CH 2 CH 2 CH═C(phenyl) 2 ,
—CH 2 CH 2 CH═CMe(4-F-phenyl),
—(CH 2 ) 3 CH(4-fluoro-phenyl) 2 ,
—CH 2 CH 2 CH═C(4-fluoro-phenyl) 2 ,
—(CH 2 ) 2 (2,3-dihydro-1H-inden-2-yl),
—(CH 2 ) 3 C(═O)(2-NH 2 -phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 ,C(═O)(2-NH 2 -4-OH-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 (1H-indazol-3-yl),
—(CH 2 ) 3 (5-F-1H-indazol-3-yl),
—(CH 2 ) 3 (7-F-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Cl-1-H-indazol-3-yl),
—(CH 2 ) 3 (6-Br-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHMe-phenyl),
—(CH 2 ) 3 (1-benzothien-3-yl),
—(CH 2 ) 3 (6-F-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (9H-purin-9-yl),
—(CH 2 ) 3 (7H-purin-7-yl),
—(CH 2 ) 3 (6-F-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-phenyl),
(CH 2 ) 3 C(═O)(2-NHCO 2 Et-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)NHEt-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHCHO-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-OH-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-MeS-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)CO 2 Me,
—(CH 2 ) 2 C(Me)CH(OH)(4-F-phenyl) 2 ,
—(CH 2 ) 2 C(Me)CH(OH)(4-Cl-phenyl) 2 ,
—(CH 2 ) 2 C(Me)C(═O)(4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-MeO-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(3-Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-Me-phenyl),
—(CH 2 ) 2 C(Me)C(═O)phenyl,
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenyl, benzyl,
HC(═O)—, methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—, n-butylC(═O)—, isobutylC(═O)—, secbutylC(═O)—, tertbutylC(═O)—, phenylC(═O)—,
methylC(═O)NH—, ethylC(═O)NH—, propylC(═O)NH—, isopropylC(═O)NH—, n-butylC(═O)NH—, isobutylC(═O)NH—, secbutylC(═O)NH—, tertbutylC(═O)NH—, phenylC(═O)NH—,
methylamino-, ethylamino-, propylamino-, isopropylamino-, n-butylamino-, isobutylamino-, secbutylamino-, tertbutylamino-, phenylamino-,
provided that two of substituents R 7 , R 8 , and R 9 , are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
k is 1 or 2;
m is 1 or 2; and
n is 0, 1 or 2.
14. The method as defined in claim 13 where the compound administered is a compound of Formula (V-a):
wherein:
b is a single bond, wherein the bridge hydrogens are in a cis position;
R 1 is selected from
—(CH 2 ) 3 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-bromo-phenyl),
—(CH 2 ) 3 C(═O)(4-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-methoxy-phenyl),
—(CH 2 ) 3 C(═O)(4-(3,4-dichloro-phenyl)phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 C(═O)(phenyl),
—(CH 2 ) 3 C(═O)(4-chloro-phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-t-butyl-phenyl),
—(CH 2 ) 3 C(═O)(3,4-difluoro-phenyl),
—(CH 2 ) 3 C(═O)(2-methoxy-5-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-fluoro-1-naphthyl),
—(CH 2 ) 3 C(═O)(benzyl),
—(CH 2 ) 3 C(═O)(4-pyridyl),
—(CH 2 ) 3 C(═O)(3-pyridyl),
—(CH 2 ) 3 CH(OH)(4-fluoro-phenyl),
—(CH 2 ) 3 CH(OH)(4-pyridyl),
—(CH 2 ) 3 CH(OH)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 S(3-fluoro-phenyl),
—(CH 2 ) 3 S(4-fluoro-phenyl),
—(CH 2 ) 3 S(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (3-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (4-fluoro-phenyl),
—(CH 2 ) 3 O(4-fluoro-phenyl),
—(CH 2 ) 3 O(phenyl),
—(CH 2 ) 3 NH(4-fluoro-phenyl),
—(CH 2 ) 3 N(methyl)(4-fluoro-phenyl),
—(CH 2 ) 3 CO 2 (ethyl),
—(CH 2 ) 3 C(═O)N(methyl)(methoxy),
—(CH 2 ) 3 C(═O)NH(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(phenyl),
—(CH 2 ) 2 NMeC(═O)(phenyl),
—(CH 2 ) 2 NHC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(2,4-difluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2,4-difluoro-phenyl),
—(CH 2 ) 3 (3-indolyl),
—(CH 2 ) 3 (1-methyl-3-indolyl),
—(CH 2 ) 3 (1-indolyl),
—(CH 2 ) 3 (1-indolinyl),
—(CH 2 ) 3 (1-benzimidazolyl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 3 (3,4 dihydro-1(2H)-quinolinyl),
—(CH 2 ) 2 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 C(═O)NH(4-fluoro-phenyl),
—CH 2 CH 2 (3-indolyl),
—CH 2 CH 2 (1-phthalimidyl),
—(CH 2 ) 4 C(═O)N(methyl)(methoxy),
—(CH 2 ) 4 CO 2 (ethyl),
—(CH 2 ) 4 C(═O)(phenyl),
—(CH 2 ) 4 (cyclohexyl),
—(CH 2 ) 3 CH(phenyl) 2 ,
—CH 2 CH 2 CH═C(Phenyl) 2 ,
—CH 2 CH 2 CH═CMe(4-F-phenyl),
—(CH 2 ) 3 CH(4-fluoro-phenyl) 2 ,
—CH 2 CH 2 CH═C(4-fluoro-phenyl) 2 ,
—(CH 2 ) 2 (2,3-dihydro-1H-inden-2-yl),
—(CH 2 ) 3 C(═O)(2-NH 2 -phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 24 -OH-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 (1H-indazol-3-yl),
—(CH 2 ) 3 (5-F-1H-indazol-3-yl),
—(CH 2 ) 3 (7-F-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Cl-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Br-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHMe-phenyl),
—(CH 2 ) 3 (1-benzothien-3-yl),
—(CH 2 ) 3 (6-F-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (9H-purin-9-yl),
—(CH 2 ) 3 (7H-purin-7-yl),
—(CH 2 ) 3 (6-F-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHCO 2 Et-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)NHEt-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHCHO-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-OH-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-MeS-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)CO 2 Me,
—(CH 2 ) 2 C(Me)CH(OH)(4-F-phenyl) 2 ,
—(CH 2 ) 2 C(Me)CH(OH)(4-Cl-phenyl) 2 ,
—(CH 2 ) 2 C(Me)C(═O)(4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-MeO-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(3-Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-Me-phenyl),
—(CH 2 ) 2 C(Me)C(═O)phenyl,
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—, methylC(═O)NH—, ethylC(═O)NH—, propylC(═O)NH—, isopropylC(═O)NH, methylamino-, ethylamino-, propylamino-, and isopropylamino-,
provided that two of substituents R 7 , R 8 , and R 9 , are independently selected from hydrogen, fluoro, chloro, methyl, trifluoromethyl, methoxy, and trifluoromethoxy;
m is 1 or 2; and
n is 0, 1 or 2.
15. The method as defined in claim 1 where the compound administered is selected from the group:
(±)-cis-9-(cyclopropylcarbonyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-9-isobutyryl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(±)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(3,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(2,3-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(5-isopropyl-2-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(3-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl(±)-cis-2-(2,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH7)-carboxylate;
(±)-cis-2-(2-chlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(2,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(3,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(2,3-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(4-isopropyl-2-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(3-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±)-cis-2-(2,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(±)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl(±)-cis-2-bromo-5,6,8,9,11,11a-hexahydro-4H-pyrido [3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl(±)-cis-2-(2,3-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl(±)-cis-2-(3,4-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl(±)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
(±)-cis-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(±)-cis-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(±)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
4-((±)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,11a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]qionolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±)-cis-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
(6aS,10aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-phenyl-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-phenyl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl(6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]-2-yl]-5-methoxybenzaldehyde;
(6aS,10aR)-2-(2,6-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
N-[4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenyl]-N-methylamine;
4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenylamine;
1-(2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-5-methoxyphenyl)ethanol;
tert-butyl(±)-cis-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
tert-butyl(8aS,12aR)-2-bromo-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
(8aS,12aR)-2-(2,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,3-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,6-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(4-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(±)-cis-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,3-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,4-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3-fluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(4-methoxy-2-methylphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2,4-bis(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-(trifluoromethyl)aniline;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-N-methyl-3-(trifluoromethyl)aniline;
2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]benzaldehyde;
{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]phenyl}methanol;
2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxybenzaldehyde;
{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}methanol;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-methylbenzonitrile;
1-{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}ethanol;
tert-butyl(7aS,11aR)-2-bromo-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
(7aS,11aR)-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(4-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-difluorophenyl)-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,4-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3-fluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2-chloro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2-fluoro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,111aR)-2-(4-methoxy-2-methylphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)phenol;
(7aS,11aR)-2-[2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2,4-bis(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)aniline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-N-methyl-3-(trifluoromethyl)aniline;
4-[(7aS,1 aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-methylbenzonitrile;
2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]benzaldehyde;
{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]phenyl}methanol;
2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxybenzaldehyde;
{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxyphenyl}methanol;
(8aS,12aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;
(7aS,11aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(8aS,12aR)-2-[3-chloro-2-methylphenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;
(7aS,11aR)-2-[3-chloro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[5-fluoro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(±)-cis-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(±)-cis-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(cyclobutylmethyl)-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-ethyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(2-fluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(2,2-difluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(cyclobutylmethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7ah)-yl)-1-(2-aminophenyl)-1-butanone;
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-aminophenyl)-1-butanone;
(±)-cis-3-(5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)propyl 4-fluorophenyl ether;
4-((±)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-pyridinyl)-1-butanone;
(±)-cis-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline;
(±)-cis-4-(4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((8aS,12aR)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((8aR,12aS)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±)4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone;
4-((±)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone;
4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone; and
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone.
16. The method as defined in claim 1 where the compound administered is selected from the group:
4-[(±)-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′,5′:4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(4-fluorophenyl)-1-butanone;
4-[(±)-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′,5′:4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;
4-[(±)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b:3,2,1-hi]indol-11-yl]-1-(4-fluorophenyl)-1-butanone;
4-[(±)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b:3,2,1-hi]indol-11-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;
tert-butyl(±)-cis-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate;
tert-butyl(±)-cis-2-bromo-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate; and
(±)-cis-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline.
17. The method as defined in claim 1 where the compound administered is selected from the group:
tert-butyl(±)-cis-2-bromo-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
tert-butyl(±)-cis-2-(2,4-dichlorophenyl)-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
(±)-cis-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aS,12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aR,12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aS,12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol; and
(8aR,12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol.