Thio-substituted biaryl-methanesulfinyl derivatives
View Patent ↗The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions that include substituted biaryl-methanesulfinyl acetamides of Formula (I): wherein Ar, Y, R 1 , R 2 , R 4 , R 5 , q and x are as defined herein; and their use in the treatment of diseases, including treatment of sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder; Parkinson's disease; Alzheimer's disease; attention deficit disorder; attention deficit hyperactivity disorder; depression; or fatigue associated with a neurological disease; as well as the promotion of wakefulness.
1. A compound of Formula (I):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or
5 to 14 membered heteroaryl group substituted by 0-5 R 3 , wherein said heteroaryl group is selected from phenoxathiinyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, imidazopyridinyl, triazolyl, purine and 2-benzo [1,4]dioxine;
Y is C 1 -C 6 alkylene substituted with 0-3 R 20A ;
R 1 is selected from H, C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(═O) 2 NR 12 R 13 , —(C 6 -C 10 aryl)-NR 12 R 13 wherein said aryl is substituted with 0-3 R 20 ; NR 21 C(═O)R 14 , C(═O)R 14 , C(═O)OR 11 , OC(═O)R 11 , and NR 21 S(═O) 2 R 11 ;
R 2 is selected from H, F, Cl, Br, I, OR 16 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , and S(═O) 2 R 16 ;
alternatively, two R 2 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 3 is selected from H, F, Cl, Br, I, OR 16 , OCF 3 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , CH 2 OR 16 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl, C 7 -C 10 arylalkyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NR 15 S(═O ) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 4 and R 5 at each occurrence are independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl;
alternatively, R 4 and R 5 , together with the carbon atom to which they are attached, form a 3-7 membered spirocyclic ring;
R 11 at each occurrence is independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 ; and C 6 -C 10 aryl substituted with 0-3 R 20 ;
R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 and C 6 -C 10 aryl substituted with 0-3 R 20 ;
alternatively, R 12 and R 13 , together with the nitrogen to which they are attached, form a 3-7 membered heterocyclic ring substituted with 0-3 R 20 , wherein said heterocyclic ring is selected from piperazinyl, piperidinyl and pyrrolidinyl;
R 14 at each occurrence is independently selected from C 1 -C 6 alkyl substituted with 0-3 R 20 ; C 6 -C 10 aryl substituted with 0-3 R 20 ; C 6 -C 10 and C 7 -C 10 arylalkyl substituted with 0-3 R 20 ;
R 15 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 16 at each occurrence is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 17 and R 18 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 20 at each occurrence is independently selected from F, Cl, Br, I, OH, OR 22 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl substituted by 0-1 R 26 ; C 7 -C 10 arylalkyl, ═O, C(═O)R 22 , C(═O)OR 22 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 ,NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , SR 22 , S(═O)R 22 , and S(═O) 2 R 22 ;
R 20A at each occurrence is independently selected from F, Cl, OH, C 1 -C 4 alkoxy, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkyl-OH, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, and C 3 -C 5 cycloalkyl;
R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 22 at each occurrence is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, and C 6 -C 10 aryl;
R 23 and R 24 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;
R 26 at each occurrence is independently selected from H, F, Cl, Br, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;
x is 0, 1, 2, 3, or 4; and
q is 1 or 2;
provided,
when Y is —CH 2 —, Ar is phenyl substituted by 0-5 R 3 , and —C(R 4 )(R 5 )— is —CH(C 1 -C 3 alkyl)—, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Y is —CH 2 —, R 1 is H, C(═O)OR 11 , or C(═O)NR 12 R 13 ; Ar is phenyl substituted by 0-2 R 3 , and R 3 is H, F, Cl, Br, I, CH 3 , OCH 3 , SCH 3 , CN, NO 2 , or methylenedioxyphenyl; then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is imidazopyridine substituted by 0-5 R 3 , Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is in the meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring and Ar is a heteroaryl group attached to the phenyl ring through a nitrogen atom, then Ar is pyrrolyl, indolyl, triazolyl, or 1,3-dihydroisoindolyl;
when Y is —CH 2 — and Ar is pyridyl substituted by a nitro, a methyl, a second methyl, and a C(═O)OC 3 H 7 group, then R 1 is not H;
when Y is —CH 2 — and Ar is a purine or imidazopyridine, substituted by 0-5 R 3 , then R 1 is not H;
when q is 1, Y is butylene and Ar is phenyl, substituted by 0-5 R 3 , in the para position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 1, Y is —CH 2 — or —CH 2 —CH 2 —, and Ar is pyrrolyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; then R 1 is not H;
when q is 1, R 2 is OH, and Ar is phenyl of cycloalkenyl; then R 1 is not H or C(═O)OR 11 ;
when q is 1, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 2, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when q is 2, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is 1, 2-(methylenedioxy)-phenyl, then Ar is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; and
when q is 2, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H.
2. A compound of claim 1 , wherein q is 1.
3. A compound of claim 1 , wherein R 1 is C(═O)NR 12 R 13 .
4. A compound of claim 1 , wherein Y is —CH 2 —.
5. A compound of claim 1 , wherein Ar is phenyl substituted by 0-5 R 3 .
6. A compound of claim 1 , wherein Ar is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
7. A compound of claim 1 of Formula (Ib):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof.
8. A compound of claim 1 of Formula (Ie):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or
5 to 14 membered heteroaryl group substituted by 0-5 R 3 wherein said heteroaryl group is selected from phenoxathiinyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, and 2-benzo [1,4]dioxine;
R 2 is selected from H, F, Cl, Br, I, OR 16 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NHC(═O)R 16 , NHCO 2 R 16 , OC(═O)NR 17 R 18 , NHC(═S)R 16 , and S(═O) 2 R 16 ;
alternatively, two R 2 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 3 is selected from H, F, Cl, Br, I, OR 16 , OCF 3 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , CH 2 OR 16 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl, C 7 -C 10 arylalkyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NHC(═O)R 16 , NHCO 2 R 16 , OC(═O)NR 17 R 18 , NHC(═S)R 16 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NHS(═O) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 20 at each occurrence is independently selected from F, Cl, Br, I, OH, OR 22 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl substituted by 0-1 R 26 ; C 7 -C 10 arylalkyl, ═O, C(═O)R 22 , C(═O)OR 22 , OC(═O)R 22 , C(═O)NR 23 R 24 , NHC(═O)R 22 , NHCO 2 R 22 , OC(═O)NR 23 R 24 , NHC(═S)R 22 , SR 22 , S(═O)R 22 , and S(═O) 2 R 22 ;
R 22 at each occurrence is independently selected from H, C 1 -C 4 alkyl, C 1 -C 4 alkyl-OH, and C 6 -C 10 aryl;
R 23 and R 24 at each occurrence are each independently selected from H, C 1 -C 4 alkyl, and C 6 -C 10 aryl; and
R 26 at each occurrence is independently selected from H, F, Cl, Br, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy; and
provided,
when Ar is phenyl substituted by 0-2 R 3 , and R 3 is H, F, Cl, Br, I, CH 3 , OCH 3 , SCH 3 , CN, NO 2 , or methylenedioxyphenyl; then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
9. A compound of claim 8 , wherein Ar is phenyl substituted by 0-5 R 3 , wherein said Ar group is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
10. A compound of claim 8 , wherein Ar is C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; wherein said Ar group is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
11. A compound of claim 8 , wherein Ar is a 5 to 14 membered heteroaryl group substituted by 0-5 R 3 , wherein said heteroaryl group comprises one, two, or three heteroatoms selected from N, O, S or Se; wherein said 5 to 14 membered heteroaryl group is selected from phenoxathiinyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, and 2-benzo[1,4]dioxine; wherein said Ar group is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
12. A compound of claim 8 of Formula (If):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof.
13. A compound of claim 8 of Formula (Ig):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof.
14. A compound of claim 8 of Formula (Ih):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof.
15. A compound of claim 8 , wherein Ar is phenyl substituted by 0-5 R 3 , wherein said Ar group is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring.
16. A compound of claim 1 of Formula (I):
and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt forms thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or a 5 to 10 membered heteroaryl group substituted by 0-5 R 3 , wherein said heteroaryl group comprises one, two, or three heteroatoms selected from N, O, or S; wherein said 5 to 10 membered heteroaryl group is selected from quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, and 2-benzo[1,4]dioxine;
Y is C 1 -C 3 , alkylene substituted with 0-1 R 20A ;
R 1 is selected from H, C(═O)NR 12 R 13 , and C(═O)OR 11 ;
R 2 is selected from H, F, Cl, Br, C 1 -C 4 alkoxy, CN, CF 3 , C 1 -C 4 alkyl;
alternatively, two R 2 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 3 is selected from H, F, Cl, Br, OR 16 , OCF 3 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , CH 2 OR 16 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl, C 7 -C 10 , arylalkyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NHC(═O)R 16 , NHCO 2 R 16 , OC(═O)NR 17 R 18 , NHC(═S)R 16 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NHS(═O) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 4 and R 5 at each occurrence are independently selected from H, methyl, and ethyl;
R 20 at each occurrence is independently selected from F, Cl, Br, OH, OR 22 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl substituted by 0-1 R 26 ; C 7 -C 10 arylalkyl, ═O, C(═O)R 22 , C(═O)OR 22 , OC(═O)R 22 , C(═O)NR 23 R 24 , NHC(═O)R 22 , NHCO 2 R 22 , OC(═O)NR 23 R 24 , NHC(═S)R 22 , SR 22 , S(═O)R 22 , and S(═O) 2 R 22 ;
R 20A at each occurrence is independently selected from F, Cl, OH, methoxy, ethoxy, methyl, and ethyl; and
R 26 at each occurrence is independently selected from H, F, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy.
17. A compound of claim 16 , wherein q is 1.
18. A compound of claim 16 , wherein q is 1; and Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —.
19. A compound of claim 16 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; and R 1 is C(═O)NR 12 R 13 .
20. A compound of claim 16 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; and R 1 is C(═O)NH 2 .
21. A compound of claim 16 , wherein:
the Ar group is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or a 5 to 10 membered heteroaryl group substituted by 0-5 R 3 , wherein said aryl, cycloalkenyl, or heteroaryl group is selected from phenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, naphthyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)- benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, or 2-benzo[1,4]dioxine;
R 1 is C(═O)NR 12 R 13 .
22. A compound of claim 21 , wherein q is 1.
23. A compound of claim 21 , wherein q is 1; and Ar is phenyl substituted by 0-5 R 3 .
24. A compound of claim 21 , wherein q is 1; Ar is phenyl substituted by 0-5 R 3 ; and Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —.
25. A compound of claim 21 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; and R 3 is selected from F, Cl, and Br.
26. A compound of claim 21 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; R 3 is selected from F, Cl, and Br; and R 1 is C(═O)NH 2 .
27. A compound of claim 16 , wherein:
the Ar group is in the meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or a
5 to 10 membered heteroaryl group substituted by 0-5 R 3 , wherein said aryl, cycloalkenyl, and heteroaryl group is selected from phenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, naphthyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, or 2-benzo[1,4]dioxine;
R 1 is H or C(═O)NR 12 R 13 .
28. A compound of claim 27 , wherein q is 1; and R 1 is C(═O)NR 12 R 13 .
29. A compound of claim 27 , wherein q is 1; Ar is phenyl substituted by 0-5 R 3 ; and R 1 is C(═O)NR 12 R 13 .
30. A compound of claim 27 , wherein q is 1; Ar is phenyl substituted by 0-5 R 3 ; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; and R 1 is C(═O)NR 12 R 13 .
31. A compound of claim 27 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; R 3 is selected from F, Cl, and Br; and R 1 is C(═O)NR 12 R 13 .
32. A compound of claim 27 , wherein q is 1; Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; R 3 is selected from F, Cl, and Br; and R 1 is C(═O)NH 2 .
33. A compound of claim 1 of Formula (I):
and stereoisomeric forms, mixtures stereoisomeric forms or pharmaceutically acceptable salt forms thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-3 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-3 R 3 ; or a
5 to 10 membered heteroaryl group substituted by 0-1 R 3 ; wherein said aryl, cycloalkenyl, or heteroaryl group is selected from phenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, naphthyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, and 2-benzo[1,4]dioxine;
Y is —CH 2 —, —CH(OCH 3 )—, or —CH 2 CH 2 —;
R 1 is selected from H, C(═O)NR 12 R 13 , and C(═O)OR 11 ;
R 2 is selected from H, Cl, F, methoxy, ethoxy, methyl, ethyl, and propyl;
alternatively, two R 2 groups may be combined to form a methylenedioxy group;
R 3 is selected from H, F, Cl, Br, CF 3 , cyano, OCF 3 , NO 2 , OH, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, CH 2 ═CH 2 , morpholinyl, OR 16 , NR 17 R 18 , CH 2 OR 16 , C(═O)R 16 , C(═O)OR 16 , C(═O)NR 17 R 18 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NHS(═O) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 4 is H;
R 5 is H;
R 11 at each occurrence is independently selected from H and C 1 -C 6 alkyl substituted with 0-3 R 20 ;
R 12 and R 13 at each occurrence are each independently selected from H, and C 1 -C 3 alkyl substituted with 0-1 R 20 ; wherein said alkyl is methyl, ethyl, n-propyl or i-propyl;
alternatively, R 12 and R 13 , together with the nitrogen to which they are attached, form a 3-7 membered heterocyclic ring substituted with 0-3 R 20 ; wherein said 3-7 membered heterocyclic ring is selected from piperazinyl, piperidinyl, and pyrrolidinyl;
R 16 at each occurrence is independently selected from H, methyl, ethyl, propyl, butyl, and phenyl;
R 17 and R 18 at each occurrence are each independently selected from H, methyl, and ethyl;
R 20 at each occurrence is independently selected from F, Cl, OH, CN, CF 3 , methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, CH 2 CH 2 OH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, OR 22 , NR 23 R 24 , C(═O)R 22 , C(═O)OR 22 , C(═O)NR 23 R 24 , and phenyl substituted by 0-1 R 26 ;
R 22 at each occurrence is independently selected from H, methyl, ethyl, propyl, butyl, and CH 2 CH 2 OH;
R 23 and R 24 at each occurrence are each independently selected from H, methyl, ethyl, propyl, butyl, and phenyl;
R 26 at each occurrence is independently selected from H, F, methyl, ethyl, propyl, methoxy, and ethoxy; and
x is 0, 1, or 2;
provided,
when Y is —CH 2 —, R 1 is H, C(═O)OR 11 , or C(═O)NR 12 R 13 ; Ar is phenyl substituted by 0-2R 3 , and R 3 is H, F, Cl, Br, I, CH 3 , OCH 3 , SCH 3 , CN, NO 2 , or methylenedioxyphenyl; then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )-substituent on the core phenyl ring.
34. A compound of claim 33 , wherein q is 1.
35. A compound of claim 33 , wherein:
the Ar group is in the ortho position to the —C(R 4 )(R 5 )-substituent on the core phenyl ring;
Ar is C 6 -C 10 aryl substituted by 0-3 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-3 R 3 ; or a
5 to 10 membered heteroaryl group substituted by 0-1 R 3 ; wherein said aryl, cycloalkenyl, or heteroaryl group is selected from phenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, naphthyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, and 2-benzo[1,4]dioxine;
R 1 is C(═O)NR 12 R 13 .
36. A compound of claim 35 , wherein q is 1.
37. A compound of claim 35 , wherein q is 1; and Ar is phenyl substituted by 0-3 R 3 .
38. A compound of claim 35 , wherein q is 1; Y is —CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; and R 3 is selected from F, Cl, and Br.
39. A compound of claim 33 , wherein:
the Ar group is in the meta position to the —C(R 4 )(R 5 )-substituent on the core phenyl ring;
Ar is C 6 -C 10 aryl substituted by 0-3 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-3 R 3 ; or a
5 to 10 membered heteroaryl group substituted by 0-1 R 3 ; wherein said aryl, cycloalkenyl, or heteroaryl group is selected from phenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, naphthyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, and 2-benzo[1,4]dioxine;
R 1 is H or C(═O)NR 12 R 13 .
40. A compound of claim 39 , wherein q is 1.
41. A compound of claim 39 , wherein q is 1; and Ar is phenyl substituted by 0-3 R 3 .
42. A compound of claim 39 , wherein q is 1; Y is —CH 2 —; Ar is phenyl substituted by 0-3 R 3 ; and R 3 is selected from F, Cl, and Br.
43. A compound selected-from the following Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 14A, 15, 15A 16, 16A, or 17:
TABLE 1
Ex.
Ar
No.
Ar
Position
q
R
1
3-thienyl
ortho
1
CH 2 CONH 2
2
3-thienyl
ortho
1
CH 2 CO—N-pyrrolidinyl
3
3-thienyl
ortho
1
CH 2 CON(CH 3 ) 2
4
3-thienyl
ortho
1
CH 2 CONHCH(CH 3 ) 2
5
3-thienyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
6
3-thienyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
7
3-thienyl
ortho
1
CH 2 CO-l-(4-hydroxy)-piperidinyl
8
3-thienyl
ortho
0
CH—(OCH3)CONH 2
9
3-thienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxamide)-piperazinyl
10
3-thienyl
ortho
1
CH 2 CO-1-(4-carboxamide)-piperazinyl
11
3-thienyl
ortho
1
CH 2 CO-1-(4-phenylcarboxamide)-piperazinyl
12
3-thienyl
ortho
1
CH 2 CO—N-piperazinyl
13
3-thienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
14
3-thienyl
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
15
3-thienyl
ortho
1
CH 2 COOH
16
3-thienyl
ortho
2
CH 2 CO-1-(4-acetyl)-piperazinyl
17
5-chloro-2-
ortho
1
CH 2 CONH 2
thienyl
18
4-methyl-3-
ortho
1
CH 2 CONH 2
thienyl
19
3-thienyl
meta
1
CH 2 CONH 2
20
3-thienyl
meta
1
CH 2 CO—N-pyrrolidinyl
21
3-thienyl
meta
1
CH 2 CON(CH 3 ) 2
22
3-thienyl
meta
1
CH 2 CONHCH(CH 3 ) 2
23
3-thienyl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
24
3-thienyl
meta
1
CH 2 CON(CH 2 ) 2 OH
25
3-thienyl
meta
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
26
3-thienyl
meta
1
CH 2 CO-1-(4-phenyl)-piperazinyl
27
3-thienyl
meta
1
CH 2 CO-1-(4-ethylcarbaxylate)-piperazinyl
28
3-thienyl
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
29
3-thienyl
meta
1
CH 2 CO—N-piperazinyl
30
3-thienyl
meta
1
CH 2 CO-1-(4-carboxamide-piperazinyl
31
3-thienyl
meta
1
CH 2 CO-1-(4-propylphenyl)-piperazinyl
32
3-thienyl
meta
1
CH 2 CO-1-(4-propyl)-piperazinyl
33
5-chloro-2-
meta
1
CH 2 CONH 2
thienyl
34
3-thienyl
para
1
CH 2 CO—N-pyrrolidinyl
35
3-thienyl
para
1
CH 2 CONH 2
36
3-thienyl
para
1
CH 2 CON(CH 3 ) 2
37
3-thienyl
para
1
CH 2 CONHCH(CH 3 ) 2
38
3-thienyl
para
1
CH 2 CONHCH 2 CN
39
3-thienyl
para
1
CH 2 CO-1-(4-acetyl)-piperazinyl
40
3-thienyl
para
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
41
3-thienyl
para
1
CH 2 CO-1-(4-methyl)-piperazinyl
42
3-thienyl
para
1
CH 2 CO-1-(4-cyclohexyl)-piperazinyl
43
3-thienyl
para
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
44
3-thienyl
para
1
CH 2 CO-1-(4-carboxamide)-piperazinyl
45
3-thienyl
para
1
CH 2 CO—N-piperazinyl
46
3-thienyl
para
1
CH 2 CO-1-(4-ethylcarboxamide)-piperazinyl
47
2-benzothienyl
ortho
1
CH 2 CONH 2
48
2-benzothienyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
49
2-benzothienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
50
2-bentothienyl
ortho
1
CH 2 CO—N-piperazinyl
51
2-benzothienyl
ortho
1
CH 2 CO-1-(4-carboxamide)-piperazinyl
52
2-benzothienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxamide)-piperazinyl
53
2-benzothienyl
ortho
1
CH 2 CO-1-(4-phenylcarboxamide)-piperazinyl
54
2-benzothienyl
ortho
0
CH 2 CONH 2
55
2-benzothienyl
ortho
1
(CH 2 ) 2 CONH 2
56
2-benzotbienyl
ortho
1
(CH 2 ) 2 CO-1-(4-methyl)-piperazinyl
57
2-benzothienyl
ortho
1
CH 2 COOH
58
2-benzothienyl
ortho
2
CH 2 CONH 2
59
2-(1,1-dioxo)-
ortho
2
CH 2 CONH 2
benzothienyl
60
2-benzothienyl
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
61
3-benzothienyl
ortho
1
CH 2 CONH 2
62
3-benzothienyl
ortho
0
CH 2 CONH 2
63
3-benzothienyl
ortho
1
(CH 2 ) 2 CO-1-(4-methyl)-piperazinyl
64
3-benzothienyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
65
3-benzothienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
66
3-benzothienyl
ortho
1
CH 2 CO-1-(4-hydroxyethyl)-piperazinyl
67
2-benzothienyl
meta
1
CH 2 CONH 2
68
2-benzotbienyl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
69
2-benzothienyl
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
70
2-benzothienyl
meta
1
CH 2 CONHCH(CH 3 ) 2
72
2-benzothienyl
meta
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
73
2-benzothienyl
meta
1
CH 2 CON(C 2 H 5 ) 2
74
2-benzothienyl
para
1
CH 2 CONH 2
75
2-benzothienyl
para
1
CH 2 CO-1-(4-acetyl)-piperazinyl
76
2-benzothienyl
meta
1
CH 2 CO-1-(4-hydroxyethyl)-piperazinyl
77
3-benzothienyl
meta
1
CH 2 CONH 2
78
3-benzothienyl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
79
3-benzothienyl
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
80
3-benzothienyl
meta
1
CH 2 CO-1-(4-hydroxyethyl)-piperazinyl
81
3-benzothienyl
meta
1
CH 2 CO-1-(4-ethylcarboxylate)-piperazinyl
82
2-benzothienyl
para
1
CH 2 CO-1-(4-methyl)-piperazinyl
83
2-benzothienyl
para
1
CH 2 CO-1-(4-hydroxyethyl)-piperazinyl
84
3-benzothienyl
para
1
CH 2 CONH 2
85
2-indolyl
ortho
1
CH 2 CONH 2
86
3-furyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
87
3-furyl
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
88
3-furyl
ortho
1
CH 2 CONH 2
TABLE 2
Ex.
Ar
No.
Ar
Position
N
q
R
89
3-pyridyl
ortho
1
1
CH 2 CONH(isopropyl)
90
3-pyridyl
ortho
1
1
CH 2 CONH(CH 2 ) 2 OH
91
3-pyridyl
ortho
1
1
CH 2 CONH 2
92
3-pyridyl
ortho
1
1
CH 2 CONH 2
93
3-pyridyl
meta
0
1
CH 2 CONH 2
94
3-pyridyl
meta
1
1
CH 2 CO-1-(4-acetyl)piperazinyl
95
3-pyridyl
meta
1
1
CH 2 CONH(CH 2 ) 2 OH
96
3-pyridyl
meta
2
1
CH 2 CO—N-piperazinyl
97
3-pyridyl
meta
0
1
CH 2 CONH 2
98
3-pyridyl
para
1
I
CH 2 CONH 2
99
3-pyridyl
para
1
1
CH 2 CO-1-(4-acetyl)piperazinyl
100
3-pyridyl
para
2
1
CH 2 CO—N-piperazinyl
101
3-pyridyl
para
1
1
CH 2 CONH(CH 2 ) 2 OH
102
3-pyridyl
para
0
1
CH 2 CONH 2
103
2-furyl
ortho
0
1
CH 2 CON(CH 3 ) 2
104
2-furyl
ortho
0
1
CH 2 CONHCH 2 CN
105
2-furyl
ortho
0
1
CH 2 CONH(isopropyl)
106
2-furyl
ortho
0
1
CH 2 CONH 2
107
2-furyl
ortho
0
1
CH(OCH 3 )CONH 2
108
2-furyl
ortho
0
1
CH 2 CONH(CH 2 ) 2 OH
109
2-furyl
ortho
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
110
2-furyl
ortho
0
1
CH 2 COOH
111
2-furyl
meta
0
1
CH 2 CO—N-pyrrolidinyl
112
2-furyl
meta
0
1
CH 2 CON(CH 3 ) 2
113
2-furyl
meta
0
1
CH 2 CONH(isopropyl)
114
2-furyl
meta
0
1
CH 2 CONHCH 2 CN
115
2-furyl
meta
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
116
2-furyl
meta
0
1
CH 2 CONH(CH 2 ) 2 OH
117
2-furyl
meta
0
1
CH 2 CO—N-(4-piperidinol)
118
2-furyl
meta
1
1
CH 2 CO—N-piperazinyl
119
2-furyl
meta
0
1
CH 2 CONH 2
120
2-furyl
meta
0
1
CH 2 CO-1-[4-(2-
methoxyphenyl)]-piperazinyl
121
2-furyl
meta
0
1
CH 2 CO-1-[4-(4-fluorophenyl)]-
piperazinyl
122
2-furyl
meta
0
1
CH 2 CO-1-(4-phenyl)piperazinyl
123
2-furyl
meta
0
1
CH 2 CONH 2
124
2-seleninyl
meta
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
125
2-hydroxy-
meta
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
phenyl
126
2-benzofuryl
meta
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
127
2-benzofuryl
meta
0
1
CH 2 CONH(CH 2 ) 2 OH
128
2-furyl
para
0
1
CH 2 CONH 2
129
2-furyl
para
0
1
CH 2 CONH(isopropyl)
130
2-furyl
para
0
1
CH 2 CONHCH 2 CN
131
2-furyl
para
0
1
CH 2 CON(CH 3 ) 2
132
2-furyl
para
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
133
2-furyl
para
0
1
CH 2 CONH(CH 2 ) 2 OH
134
2-furyl
para
1
1
CH 2 CO—N-piperazinyl
135
2-thienyl
ortho
0
1
CH 2 CO—N-pyrrolidinyl
136
2-(5-bromo)-
ortho
0
1
CH 2 CO—N-pyrrolidinyl
thienyl
137
2-thienyl
ortho
0
1
CH 2 CON(CH 3 ) 2
138
2-(5-bromo)-
ortho
0
1
CH 2 CON(CH 3 ) 2
thienyl
139
2-thienyl
ortho
0
1
CH 2 CONH 2
140
2-thienyl
ortho
0
1
CH 2 CONH(CH 2 ) 2 OH
141
2-thienyl
ortho
1
1
CH 2 CO—N-piperazinyl
142
2-thienyl
ortho
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
143
2-thienyl
ortho
0
1
CH 2 CONH(isopropyl)
144
2-thienyl
meta
0
1
CH 2 CO—N-pyrrolidinyl
145
2-thienyl
meta
0
1
CH 2 CON(CH 3 ) 2
146
2-thienyl
meta
0
1
CH 2 CONH 2
147
2-thienyl
meta
0
1
CH 2 CONH(CH 2 ) 2 OH
148
2-thienyl
meta
1
1
CH 2 CO—N-piperazinyl
149
2-thienyl
meta
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
150
2-thienyl
para
0
1
CH 2 CO—N-pyrrolidinyl
151
2-(5-bromo)-
para
0
1
CH 2 CO—N-pyrrolidinyl
thienyl
152
2-thienyl
para
0
1
CH 2 CON(CH 3 ) 2
153
2-(5-bromo)-
para
0
1
CH 2 CON(CH 3 ) 2
thienyl
154
2-thienyl
para
0
1
CH 2 CONH 2
155
2-thienyl
para
0
1
CH 2 CONHCH 2 CN
156
2-thienyl
para
0
1
CH 2 CONH(isopropyl)
157
2-thienyl
para
0
1
CH 2 CO-1-(4-acetyl)piperazinyl
158
2-thienyl
para
0
1
CH 2 CONH(CH 2 ) 2 OH
159
2-thienyl
para
1
1
CH 2 CO—N-piperazinyl
436
2-furyl
ortho
0
2
CH 2 CO-1-(4-acetyl)piperazinyl
TABLE 3
Ex.
Ar
No.
Ar
Position
q
R
160
1,3-Dihydro-isoindol-2-yl
ortho
1
CH 2 CO—N-
pyrrolidinyl
161
1,3-Dihydro-isoindol-2-yl
ortho
1
CH 2 CONMe 2
162
1,3-Dihydro-isoindol-2-yl
meta
1
CH 2 CO—N-
pyrrolidinyl
163
1,3-Dihydro-isoindol-2-yl
meta
1
CH 2 CONMe 2
164
1,3-Dihydro-isoindol-2-yl
meta
1
CH 2 CONHCHMe 2
165
1,3-Dihydro-isoindol-2-yl
meta
1
CH 2 CONHCH 2 CN
TABLE 4
Ex.
Ar
No.
Ar
Position
q
R
166
2-Benzofuryl
Ortho
1
CH 2 CO-1-piperazinyl
167
2-Benzofuryl
Ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
TABLE 5
Ex.
Ar
No.
Ar
Position
q
R
168
2-benzo[1,4]-
Ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
dioxine
169
2-benzo[1,4]-
Ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
dioxine
170
2-benzo[1,4]-
Ortho
1
CH 2 CONHCH(CH 3 ) 2
dioxine
TABLE 6
Ex.
Ar
No.
Ar
Position
q
R
171
Pyrrol-1-yl
meta
1
CH 2 CONH(CH 2 ) 2 OH
172
Pyrrol-1-yl
meta
1
CH 2 CO-1-(4-hydroxyl)-piperidinyl
173
Pyrrol-1-yl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
174
Pyrrol-1-yl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
175
Pyrrol-1-yl
ortho
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
176
Pyrrol-1-yl
ortho
1
CH 2 CONH(CH 2 ) 2 O(CH2) 2 OH
TABLE 7
Ex. No.
Ar
Ar Position
q
R
177
Pyrrol-1-yl
ortho
1
CH 2 CO—N-pyrrolidinyl
178
Pyrrol-1-yl
ortho
1
CH 2 CONMe 2
179
Pyrrol-1-yl
ortho
1
CH 2 CONHCHMe 2
180
Pyrrol-1-yl
ortho
1
CH 2 CO-1-(4-acetyl)-
piperazinyl
181
Pyrrol-1-yl
meta
1
CH 2 CONHCH 2 CN
182
Pyrrol-1-yl
meta
1
CH 2 CONHCHMe 2
183
Pyrrol-1-yl
meta
1
CH 2 CONMe 2
TABLE 8
Ex. No.
Ar
Ar Position
q
R
184
2-Benzofuryl
Ortho
1
CH 2 CON(CH 3 ) 2
185
2-Benzofuryl
Ortho
1
CH 2 CONHCH(CH 3 ) 2
TABLE 9
Ex. No.
Ar
Ar Position
q
R
186
Pyrrol-1-yl
ortho
1
CH 2 CONH 2
187
Pyrrol-1-yl
meta
1
CH 2 CONH 2
188
Pyrrol-1-yl
para
1
CH 2 CONH 2
TABLE 10
Ex. No.
Ar
Ar Position
q
R
189
2-benzo[1,4]dioxine
ortho
0
CH 2 CONH 2
190
2-benzo[1,4]dioxine
ortho
1
CH 2 CONH 2
TABLE 11
Ex. No.
Ar
Ar Position
q
R
191
2-Benzofuryl
Ortho
1
CH 2 CONH 2
TABLE 12
Ex. No.
Ar
Ar Position
q
R
192
1,3-Dihydro-isoindol-2-yl
ortho
1
CH 2 CONH 2
193
1,3-Dihydro-isoindol-2-yl
meta
1
CH 2 CONH 2
TABLE 13
Ex.
Biphenyl
No.
Isomer
q
R
194
ortho
1
CH 2 CON(CH 3 ) 2
195
ortho
1
CH 2 CONH 2
196
ortho
1
CH 2 CONHCH 3
197
ortho
1
CH 2 CON(C 2 H 5 ) 2
198
ortho
1
CH 2 CONH(CH 2 ) 2 OH
199
ortho
1
CH 2 CONHCH 2 -(3-pyridyl)
200
ortho
1
CH 2 CONH(cyclobutyl)
201
ortho
1
CH 2 CONH-(cyclopentyl)
202
ortho
1
CH 2 CO—N-pyrrolidinyl
203
ortho
1
CH 2 CO—N-(2-carboxamide)-pyrrolidinyl
205
ortho
1
CH 2 CO—N-piperazinyl
206
ortho
1
CH 2 CO—N-1-(4-t-butylcarboxylate)-piperazinyl
207
ortho
1
CH 2 CO NHCH 2 CN
208
ortho
1
CH 2 CO NHCH 2 CF 3
210
ortho
1
CH 2 CONHCH(CH 3 ) 2
211
para
1
CH 2 CO NH 2
212
para
1
CH 2 CO—N-pyrrolidinyl
213
para
1
CH 2 CO N(CH 3 ) 2
215
Para
1
CH 2 CO—N-piperidinyl
216
para
1
CH 2 CONH(CH 2 ) 2 -(2-pyridyl)
217
para
1
CH 2 CONHCH 2 -(3-pyridyl)
218
Para
1
CH 2 CONHCH(CH 3 ) 2
219
Meta
1
CH 2 CONH 2
220
Meta
1
CH 2 CON(CH 3 ) 2
221
Meta
1
CH 2 CO—N-pyrrolidinyl
222
Meta
1
CH 2 CONHCH(CH 3 ) 2
TABLE 14
Ex.
Substitution on
No.
q
Biphenyl Moiety
n
R
223
1
4′-COCH 3
1
H
224
1
4′-F
1
H
225
1
4′-CH 3
1
H
226
1
2′-CH 3
1
H
227
1
3′,5′-Difluoro
1
H
228
1
3′,5′-Dimethyl
1
H
229
1
3′-F
1
H
230
1
2′-F
1
H
231
1
2′-OEt
1
H
232
1
3′-F,4′-Ph
1
H
233
1
2′-OMe, 5′-F
1
H
234
1
4′-OMe
1
H
235
1
4′-OPh
1
H
236
1
3′-CN
1
H
237
1
3′CONH 2
1
H
238
1
3′,5′-Dichloro
1
H
239
1
3′-CF 3
1
H
240
1
3′-SCH 3
1
H
241
1
3′-SOMe
1
H
242
1
3′-OCF 3
1
H
243
1
3′-CONMe 2
1
H
244
1
4′-OCF 3
1
H
245
1
4′-CF 3
1
H
246
1
4′-SCH 3
1
H
247
1
4′-SOCH 3
1
H
248
1
2′-Cl
1
H
249
1
3′-Cl
1
H
250
1
4′-Cl
1
H
251
1
2′-OMe
1
H
252
1
3′-OMe
1
H
253
1
3′,4′-Dimethoxy
1
H
254
1
3′,4′-Methylenedioxy
1
H
255
1
3′,4′-Ethylenedioxy
1
H
256
1
3′,4′-Propylenedioxy
1
H
257
1
2′,6′-Dimethoxy
1
H
258
1
2′,5′-Dimethoxy
1
H
259
1
3′-NO 2
1
H
260
1
2′-OH
1
H
261
1
3′-OH
1
H
262
1
4′-OH
1
H
263
1
4′-CN
1
H
264
1
3′-Me
1
H
265
1
2′-OCF 3
1
H
266
1
3′-Me, 4′-F
1
H
267
1
2′-SMe
1
H
268
1
3-Cl, 4′-F
1
H
269
1
2′-OMe, 5′-Cl
1
H
270
1
2′-SOMe
1
H
271
1
4,5-(OMe) 2
1
H
272
1
4′-Br
1
H
273
1
2′-OMe, 4′-Cl
1
H
274
1
2′-Me, 4′-Cl
1
H
275
1
2′-Cl, 4′-Cl
1
H
276
1
2′-CF 3
1
H
277
1
2′-F, 4′-Br
1
H
278
2
4′-Cl
1
H
279
1
4′-CHMe 2
1
H
280
1
4′-CMe 3
1
H
281
2
4′-Me
1
H
282
2
4′-F
1
H
283
1
4′-Cl
1
(CH 2 ) 2 OH
284
1
3′-Br
1
H
285
1
2′-Br
1
H
286
1
4′-Cl
1
NHR is replaced by N-
pyrrolidinyl group
287
1
4′-NMe 2
1
H
288
1
4′-CH═CH 2
1
H
289
1
4′-Cl
1
NHR is replaced by 4-
acetylpiperazinyl group
290
1
4′-SO 2 Me
1
H
291
1
3′,4′-Cl 2
1
H
292
1
4′-Et
1
H
293
1
4′-CH 2 OMe
1
H
294
1
4′-CO—N-(4-
1
H
oxo)piperidinyl
295
1
4′-NHSO 2 Me
1
H
296
1
4′-CONMe 2
1
H
298
1
4′-Cyclohexyl
1
H
299
1
3′,4′-F 2
1
H
300
1
3′,4′,5′-OMe 3
1
H
302
1
4′-Cl
2
H
303
1
3′-NMe 2
1
H
304
1
4′-CH 2 CHMe 2
1
H
305
1
5-F, 4′-Cl
1
H
306
1
3′-F, 4′-Cl
1
H
307
1
5-F, 4′-Me
1
H
308
1
5-F, 4′-F
1
H
309
1
5-F, 4′-NMe 2
1
H
310
1
3′-OMe, 4′-Cl
1
H
311
1
3′,4′-F 2 , 5′-OMe
1
H
312
1
3′-CF 3 , 4′-Cl
1
H
313
1
4′-OCH 2 CHMe 2
1
H
314
1
4′-COOMe
1
H
315
1
4′-CH 2 OH
1
H
316
1
4′-COOtBu
1
H
317
1
3′,4′-Me 2
1
H
318
1
3′-CF 3 , 4′-F
1
H
319
1
3′-F, 4′-Me
1
H
320
1
3′-Cl, 4′-Me
1
H
321
1
3′-Me, 4′-Cl
1
H
322
1
4,5-O—CH 2 —O, 4′-Cl
1
H
323
1
4,5-OMe 2 , 4′-Cl
1
H
324
1
4,5-O—CH 2 —O, 4′-F
1
H
325
1
5-F, 3′,4′-F 2
1
H
326
1
4,5-O—CH 2 —O, 4′-Me
1
H
327
1
4,5-O—CH 2 —O,
1
H
3′,4′-F 2
328
1
4,5-OMe 2 , 4′-F
1
H
329
1
4,5-OMe 2 , 4′-Me
1
H
330
1
4,5-OMe 2 , 3′,4′-F 2
1
H
331
1
3′-Me, 4′-OMe
1
H
332
1
5-Cl, 4′-Cl
1
H
333
1
3′,5′-Me 2 , 4′-Cl
1
H
334
1
5-Cl, 4′-F
1
H
335
1
3′-CF 3 , 4′-Me
1
H
336
1
3′-NO 2 , 4′-Cl
1
H
337
1
4-F, 4′-Cl
1
H
338
1
5-Cl, 3′,4′-F 2
1
H
339
2
5-F, 4′-Cl
1
H
340
1
4′-F
2
H
341
1
4-F, 4′-F
1
H
342
1
4-F, 4′-Me
1
H
343
1
4-F, 3′,4′-F 2
1
H
344
2
3′,4′-F 2
1
H
345
1
5-Cl, 4′-Me
1
H
346
1
4-OMe, 4′-Cl
1
H
347
1
6-Me, 4′-Cl
1
H
348
1
6-Me, 3′,4′-Cl 2
1
H
349
1
4-OMe, 3′,4′-Cl 2
1
H
350
1
4-Cl, 4′-Cl
1
H
351
1
4-F, 3′,4′-Cl 2
1
H
352
1
6-Me, 3′-F, 4′-Cl
1
H
TABLE 14A
Ex. No.
Q
Ar
n
R
353
1
cyclohexen-1-yl
1
H
354
1
cyclopenten-1-yl
1
H
355
1
cyclohepten-1-yl
1
H
356
1
Naphth-2-yl
1
H
357
1
phenoxathiin-4-yl
1
H
358
1
Quinolin-3-yl
1
H
359
1
3,5-dimethyl-isoxazol-4-yl
1
H
TABLE 15
Ex. No.
q
Substitution
360
1
6-Me
361
1
2-Me
362
1
4-OMe
363
1
2′-Cl
364
1
3′-Cl
365
1
4′-Cl
366
1
3′,4′-(OMe) 2
367
1
2′-Me, 4′-Cl
368
1
2′-OMe, 4′-Cl
369
1
2′-CN
370
1
2′-Cl, 4′-Cl
371
1
3′-OMe
372
1
4′-OMe
373
1
2′-OMe
374
1
3′-CN
375
1
4′-CN
376
1
2′-Me
377
1
3′-Me
378
1
4′-Me
379
1
2′-F
380
1
3′-F
381
1
4′-F
382
1
3′,4′-Cl 2
383
1
3′,4′-Me 2
384
1
4′-NMe 2
385
1
3′-NMe 2
386
1
4′-Br
387
1
3′-CONH 2
389
1
3′,4′,5′-OMe 3
390
1
3′-CF 3
391
1
3′-NO 2
392
1
3′,4′-F 2
393
1
3′-Cl, 4′-OMe
394
1
4′-Et
395
1
4′-OCF 3
396
1
4′-OCHMe 2
397
1
3′-F, 4′-Cl
398
1
3′-OMe, 4′-Cl
399
1
3′,4′-F 2 , 5′-OMe
TABLE 15A
Ex. No.
q
Ar
400
1
naphtha-2-yl
401
1
3,5-dimethyl-isoxazol-4-yl
TABLE 16
Ex. No.
Q
Substitution
402
1
3-F
403
1
2′-Cl
404
1
3′-Cl
405
1
4′-OMe
406
1
3′,4′-Methylenedioxy
407
1
2′,6′-(OMe) 2
408
1
4′-Cl
409
1
3′,4′-(OMe) 2
410
1
3′-OMe
411
1
4′-CN
412
1
2′,5′-(OMe) 2
413
1
3′-NO 2
414
1
3′-Me
415
1
2′-OMe
416
1
2′-Me, 4′-Cl
417
1
2′-OMe, 4′-Cl
418
1
2′,4′-Cl 2
419
2
3′,4′-(OMe) 2
420
1
3′,4′-Cl 2
421
1
3-F, 4′-Cl
422
1
3-F, 4′-Me
423
1
4′-Br
424
1
3′-Cl, 4′-OMe
425
1
3′,4′,5′-(OMe) 3
426
1
3′,4′-F 2
427
1
3-F, 4′-F
428
2
3-F, 4′-F
429
1
3-F, 4′-Cl
TABLE 16A
Ex. No.
q
Ar
430
1
(3,5-dimethyl)-isoxazol-4-yl
TABLE 17
Ex. No.
Ar
Ar Position
q
R
431
2-benzothienyl
ortho
1
CH 3
432
3-thienyl
ortho
1
CH 3
433
2-furyl
para
1
CH 3
434
2-thienyl
para
1
CH 3
435
phenyl
ortho
1
CH 3
and pharmaceutically acceptable salt forms thereof.
44. A compound selected from 2-[2-(5-chloro-benzo[b]thiophen-2-yl)-phenylmethanesulfinyl]-acetamide, 2-(2-benzo[b]thiophen-5-yl-phenylmethanesulfinyl)-acetamide, 2-[2-(3-chloro-benzofuran-2-yl)-phenylmethanesulfinyl]-acetamide, or the following Table 18:
TABLE 18
Ex. No.
Ar
n
437
4′-fluoro-3-benzothienyl
0
438
4′-fluoro-2-furyl
0
439
4′-fluoro-3-furyl
0
440
4′-fluoro-3-pyridyl
1
441
4′-fluoro-5-chloro-2-thienyl
0
442
5′-chloro-3-pyridyl
1
443
4′-fluoro-3-thienyl
0
444
4′-fluoro-5-chloro-2-benzothienyl
0
and pharmaceutically acceptable salt forms thereof.
45. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable excipients.