IP Library › Granted Patent US 7,745,435

Granted Patent B2

US 7,745,435 · App. 12/176,123 · Granted Jun 29, 2010

Triheterocyclic compounds and compositions thereof

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Quick Facts

Patent No.: US 7,745,435
App. No.: 12/176,123
Granted: Jun 29, 2010
Kind: B2

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Abstract

The present invention relates to novel Triheterocyclic Compounds, compositions comprising a Triheterocyclic Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Triheterocyclic Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, treating or preventing a viral infection, or inhibiting the replication and/or infectivity of a virus.

Claims (288)

1. A compound of the Formula

or a pharmaceutically acceptable salt thereof wherein

Q 1 is —N(R 1 )—;

Q 2 is —C(R 3 )—;

Q 3 is —C(R 5 )—;

Q 4 is —C(R 9 )—;

R 1 is —Y m (R a ), wherein —R a is —H, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 )OR 14 , —C(O)R 14 , —C(O)(CH 2 ) n —R 14 , —O—C(O)OR 14 , —O—C(O)NHR 14 , —O—C(O)N(R 14 ) 2 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 2 is —H, —C 1 -C 8 alkyl or —OH;

R 3 is —C 1 -C 8 alkyl;

R 4 is —Y m (R b ), wherein R b is —H, halogen, —NH 2 , —CN, —NO 2 , —SH, —N 3 , —C 1 -C 8 alkyl, —O—(C 1 -C 8 alkyl), —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 ,—O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 5 is —C 1 -C 8 alkyl;

R 6 is —H;

R 7 is —Y m —(R c ), wherein —R c is —C 1 -C 8 alkyl, —O—(C 1 -C 8 alkyl), —O-benzyl, —NH 2 , —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —CN, —NO 2 , —N 3 , —C 2 -C 8 alkynyl, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 , —O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 8 is —Y m (R d ), wherein —R d is —H, —OH, halogen, amino, —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —CN, —NO 2 , —N 3 , —C 1 -C 8 alkyl, —(C 1 -C 8 alkyl)-OH, —O—(C 1 -C 8 alkyl), —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ), —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 , —O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 9 is —Y m (R e ), wherein —R e is —H, —NH 2 , C 1 -C 8 alkyl, —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —C(O)N(C 1 -C 5 alkyl) 2 , —NHC(O)(C 1 -C 5 alkyl), —NHC(═NH 2 + )NH 2 , —CN, —NO 2 , N 3 , -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 , —C(O)N(R 14 ) 2 , —C(O)NHR 14 , -S-R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , —NR 14 C(S)N(R 14 ) 2 ;

R 10 , R 11 , R 12 , and R 13 are independently —Y m (R e ), wherein —R e is —H, halogen, —NH 2 , C 1 -C 8 alkyl, —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —C(O)NH(C 1 -C 5 alkyl), —C(O)N(C 1 -C 5 alkyl) 2 , —NHC(O)(C 1 -C 5 alkyl), —NHC(═NH 2 + )NH 2 , —CN, —NO 2 , N 3 , -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 , —O—C(O)OR 14 , —O—C(O)NHR 14 , —O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , —NR 14 C(S)N(R 14 ) 2 , with the proviso that neither R 10 nor R 12 is —OH;

each R 14 is independently —H, —C 1 -C 8 alkyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —C 2 -C 8 alkenyl, or —C 2 -C 8 alkynyl;

each Y is independently —C 1 -C 8 alkylene-, —C 2 -C 8 alkenylene- or —C 2 -C 8 alkynylene-;

each m is independently 0 or 1; and

each n is independently an integer ranging from 0 to 6.

2. The compound of claim 1 where Q 1 is —NH.

3. The compound of claim 1 where Q 1 is —NH—, Q 4 is —CH—, and R 2 is —H.

4. The compound of claim 1 where Q 1 is —NH—, Q 4 is —CH—, and R 2 , R 4 , R 8 and R 10 -R 13 are —H.

5. The compound of claim 1 where Q 1 is —NH—, Q 2 is —C(C 1 -C 8 alkyl)-, Q 3 is —C(C 1 -C 8 alkyl)-, Q 4 is —CH—, R 7 is —O—(C 1 -C 8 alkyl)-, and R 2 , R 4 , R 8 and R 10 -R 13 are —H.

6. A composition comprising a pharmaceutically acceptable carrier or vehicle and an effective amount of a compound of the Formula

or a pharmaceutically acceptable salt thereof wherein

Q 1 is —N(R 1 )—;

Q 2 is —C(R 3 )—;

Q 3 is —C(R 5 )—;

Q 4 is —C(R 9 )—;

R 1 is —Y m (R a ), wherein —R a is —H, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 , —O—C(O)N(R 14 ) 2 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 2 is —H, —C 1 -C 8 alkyl or —OH;

R 3 is —C 1 -C 8 alkyl;

R 5 is —C 1 -C 8 alkyl;

R 6 is —H;

R 7 is —Y m —(R c ), wherein —R c is —C 1 -C 8 alkyl, —O—(C 1 -C 8 alkyl), —O-benzyl, —NH 2 , —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —CN, —NO 2 , —N 3 , —C 2 -C 8 alkynyl, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 ,—O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , or —NR 14 C(S)N(R 14 ) 2 ;

R 9 is —Y m (R e ), wherein —R e is —H, —NH 2 , C 1 -C 8 alkyl, —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —C(O)N(C 1 -C 5 alkyl) 2 , —NHC(O)(C 1 -C 5 alkyl), —NHC(═NH 2 + )NH 2 , —CN, —NO 2 , N 3 , -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 ,—O—C(O)OR 14 , —O—C(O)NHR 14 , —C(O)N(R 14 ) 2 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , —NR 14 C(S)N(R 14 ) 2 ;

R 10 , R 11 , R 12 , and R 13 are independently —Y m (R e ), wherein —R e is —H, halogen, —NH 2 , C 1 -C 8 alkyl, —NH(C 1 -C 5 alkyl), —N(C 1 -C 5 alkyl) 2 , —NH(phenyl), —N(phenyl) 2 , —NH(naphthyl), —N(naphthyl) 2 , —C(O)NH(C 1 -C 5 alkyl), —C(O)N(C 1 -C 5 alkyl) 2 , —NHC(O)(C 1 -C 5 alkyl), —NHC(═NH 2 + )NH 2 , —CN, —NO 2 , N 3 , -3- to 9-membered heterocycle, —OR 14 , —O(CH 2 ) n OR 14 , —C(O)R 14 , —O—C(O)R 14 , —C(O)(CH 2 ) n —R 14 , —O—C(O)OR 14 , —O—C(O)NHR 14 ,—O—C(O)N(R 14 ) 2 , —C(O)N(R 14 ) 2 , —C(O)OR 14 , —C(O)NHR 14 , —S—R 14 , —SOR 14 , —S(O) 2 R 14 , —NHC(O)R 14 , —NHSR 14 , —NHSOR 14 , —NHS(O) 2 R 14 , O—C(S)R 14 , O—C(S)OR 14 , O—C(S)NHR 14 , O—C(S)N(R 14 ) 2 , —C(S)OR 14 , —C(S)NHR 14 , —C(S)N(R 14 ) 2 , —NHC(S)R 14 , —NR 14 C(S)R 14 , —NHC(S)NHR 14 , —NHC(S)N(R 14 ) 2 , —NR 14 C(S)NHR 14 , —NR 14 C(S)N(R 14 ) 2 , with the proviso that neither R 10 nor R 12 is —OH;

each R 14 is independently —H, —C 1 -C 8 alkyl, —C 3 -C 12 cycloalkyl, -phenyl , -naphthyl, -3- to 9-membered heterocycle, —C 2 -C 8 alkenyl, or —C 2 -C 8 alkynyl;

each Y is independently —C 1 -C 8 alkylene-, —C 2 -C 8 alkenylene- or —C 2 -C 8 alkynylene-;

each m is independently 0 or 1; and

each n is independently an integer ranging from 0 to 6.

7. The compound of claim 1 where the pharmaceutically acceptable salt is tartrate salt or mesylate salt.

8. The compound of claim 1 where the compound of Formula (Ia) is:

2-[5-4-iodo-3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-5,6-dimethoxy-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene-4-methoxy-5H-pyrrol-2-yl]-3-morpholin-4-ylmethyl-1H-indole;

5-bromo-2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-3-(4-phenyl-piperazin-1-ylmethyl)-1H-indole;

2-({2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-3-hydroxymethyl-4-methoxy-5H-pyrrol-2-yl]-1H-indol-3-ylmethyl}-amino)-ethanol;

[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-2-(3-methylaminomethyl-1H-indol-2-yl)-5H-pyrrol-3-yl]-methanol;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-ethoxy-5H-pyrrol-2-yl]-3-(2-morpholin-4-yl-ethyl)-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-5-methoxy-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-3-(2-pyrrolidin-2-yl-ethyl)-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-ethoxy-5H-pyrrol-2-yl]-3-(2-pyrrolidin-2-yl-ethyl)-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-ethoxy-5H-pyrrol-2-yl]-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-1H-indole;

(2-{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-ethoxy-5H-pyrrol-2-yl]-1H-indol-3-yl}-ethyl)-dimethyl-amine;

2-[5,(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-3-(2-morpholin-4-yl-ethyl)-1H-indole;

(2-{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-1H-indol-3-yl}-ethyl)-dimethyl-amine;

1-{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indol-1-yl}-2-methyl-propan-1-one;

carbonic acid tert-butyl ester 2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-1H-indol-4-yl ester;

carbonic acid tert-butyl ester 2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-1H-indol-4-yl-ester;

3-{5-[5-(1H-indol-2-yl)-3-methoxy-pyrrol-2-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-propan-1-ol;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-5-fluoro-1H-indole;

{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indol-1-yl}-phenyl -methanone;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-6-fluoro-1H-indole;

6-chloro-2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-isopropoxy-5H-pyrrol-2-yl]-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-(3-methoxy-benzyloxy)-5H-pyrrol-2-yl]-1H-indole;

2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indole-1-carboxylic acid (4-dimethylamino-phenyl)-amide;

2-[5,(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indole-1-carboxylic acid (4-benzyloxy-phenyl)-amide;

(4-bromo-phenyl)-{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indol-1-yl}-methanone;

4-{2-[5-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-4-methoxy-5H-pyrrol-2-yl]-indol-1-ylmethyl}-phenol;

[2-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-5-(1H-indol-2-yl)-2H-pyrrol-3-yl]-(4-methoxy-phenyl)-amine;

3-{5-[5-(1H-indol-2-yl)-3-methoxy-pyrrol-2-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-propionic acid methyl ester; or

a pharmaceutically acceptable salt thereof.

9. The composition of claim 6 where Q 1 is —NH.

10. The composition of claim 6 where Q 1 is —NH—, Q 4 is —CH—, and R 2 is —H.

11. The composition of claim 6 where Q 1 is —NH—, Q 4 is —CH—, and R 2 , R 4 , R 8 and R 10 -R 13 are —H.

12. The composition of claim 6 where Q 1 is —NH—, Q 2 is —C(C 1 -C 8 alkyl)-, Q 3 is —C(C 1 -C 8 alkyl)-, Q 4 is —CH—, R 7 is —O—(C 1 -C 8 alkyl)-, and R 2 , R 4 , R 8 and R 10 -R 13 are —H.

13. The composition of claim 6 where the pharmaceutically acceptable salt is tartrate salt or mesylate salt.

14. The composition of claim 6 where the compound of Formula (Ia) is: