IP Library Granted Patent US 7,247,641
Granted Patent B2
US 7,247,641 · App. 10/486,239 · Granted Jul 24, 2007

Compounds, derivatives, compositions, preparation and uses

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Quick Facts
Patent No.
US 7,247,641
App. No.
10/486,239
Granted
Jul 24, 2007
Kind
B2
Abstract

This invention relates to compounds, pharmaceutical compositions, and methods of using the disclosed compounds for inhibiting PARP.

Claims (27)

1. A compound of the following general formula (II):

or a pharmaceutically acceptable salt, hydrate, prodrug, or mixtures thereof, wherein:

m is 1 and L is —C(R 7 R 8 )—N(R 9 )— or —N(R 9 )—C(R 7 R 8 )— or m is 2, L is —(N(R 9 )) n , and n is 1;

R 2 is hydrogen, lower alkyl, hydroxy, halogen, nitro, amino, alkylamino, or carboxy;

R 7 and R 8 are independently any of an hydrogen, hydroxyl, halogen, or an optionally substituted amino, nitroso, sulfonamide, lower alkyl, lower alkenyl, C 1 -C 6 straight or branched alkanol, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, alkoxy, aryloxy, alkylamino, arylamino, CH 2 COOH, aralkyl;

R 9 is an hydrogen, hydroxyl, optionally substituted amino, nitroso, methyl or lower alkyl, sulfonamide, lower alkenyl, C 1 -C 6 straight or branched alkanol, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, alkoxy, aryloxy, alkylamino, arylamino, CH 2 COOH, aralkyl or —C(O)(C 1 -C 10 alkyl)N(R 5 R 6 ); and

R 5 and R 6 are independently hydrogen, optionally substituted lower alkyl, lower alkenyl, C 1 -C 6 straight or branched alkanol, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylhalo, alkoxy, aryloxy, alkylamino, arylamino, alkynyl, aryl, benzyl, arylalkyl, CH 2 COOH, or R 5 and R 6 taken together form a 4, 5, 6, 7, or 8 membered substituted or unsubstituted heterocycloalkyl or cycloalkyl ring containing 1, 2 or 3 heteroatoms selected from O, N, S and combinations thereof,

wherein alkyl groups are optionally substituted by mercapto, carboxy, hydroxyl, or phenyl, benzyl or phenylethyl,

wherein amino groups are optionally substituted by C 1 -C 10 alkyl,

wherein aryl and heteroaryl groups are optionally substituted in 1-5 positions with halo, haloalkyl, hydroxyl, nitro, trifluoromethyl, C 1 -C 10 straight or branched chain alkyl, C 2 -C 10 straight or branched chain alkenyl, C 1 -C 10 alkoxy, —C(O)—O—(C 1 -C 10 alkyl), carboxy, C 2 -C 10 alkenyloxy, phenoxy, benzyloxy, amino, thiocarbonyl, thioester, cyano, imino, alkylamino, aminoalkyl, sulfhydryl, and thioalkyl, and

wherein the heterocycloalkyl is a cycloalkyl containing at least 1, 2, 3, or 4 heteroatoms selected from O, N, or S substituted for a ring carbon atom, and may be substituted by or fused to at least one 5 or 6 membered aryl or heteroaryl and/or substituted by at least one of amino, C 1 -C 10 straight or branched chain alkyl, C 1 -C 10 alkanol, C 1 -C 10 straight or branched chain alkylamino, C 1 -C 10 alkoxy, or C 1 -C 10 alkenyl, or benzyl, or phenyl or phenylethyl.

2. A compound of claim 1 ;

where

m is 1;

L is —C(R 7 R 8 )—N(R 9 )— or —N(R 9 )—C(R 7 R 8 )—;

R 2 is hydrogen, lower alkyl, hydroxy, halogen, nitro, amino, alkylamino, or carboxy;

R 7 and R 8 are independently any of an optionally substituted hydrogen, hydroxyl, halogen, amino, nitroso, methyl sulfonamide, lower alkyl, lower alkenyl, C 1 -C 6 straight or branched alkanol, cycloalkyl, heterocycloalkyl, heteroaryl, aryl alkoxy, aryloxy, alkylamino, arylamino, CH 2 COOH, aralkyl;

R 9 is an optionally substituted hydrogen, hydroxyl, amino, nitroso, methyl, lower alkyl, sulfonamide, lower alkenyl, C 1 -C 6 straight or branched alkanol, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, alkoxy, aryloxy, alkylamino, arylamino, CH 2 COOH, aralkyl or —C(O)(C 1 -C 10 alkyl)N(R 5 R 6 ); and

R 5 and R 6 are independently hydrogen, lower alkyl, lower alkenyl, C 1 -C 6 straight or branched alkanol, heterocycloalkyl, heteroaryl, alkylhalo, alkoxy, aryloxy, alkylamino, arylamino, alkynyl, aryl, benzyl, arylalkyl, CH 2 COOH, or R 5 and R 6 taken together form a 4, 5, 6, 7, or 8 membered substituted or unsubstituted heterocycloalkyl or cycloalkyl ring containing 1, 2 or 3 heteroatoms selected from O, N, S and combinations thereof,

wherein the heterocycloalkyl is a cycloalkyl containing at least 1, 2, 3, or 4 heteroatoms selected from O, N, or S substituted for a ring carbon atom, and may be substituted by or fused to at least one 5 or 6 membered aryl or heteroaryl and/or substituted by at least one of amino, C 1 -C 10 straight or branched chain alkyl, C 1 -C 10 alkanol, C 1 -C 10 straight or branched chain alkylamino, C 1 -C 10 alkoxy, or C 1 -C 10 alkenyl, or benzyl, or phenyl or phenylethyl.

3. A compound selected from the group consisting of:

4. The compound of claim 1 wherein L is —(N(R 9 ))—C(R 7 R 8 )—.

5. The compound of claim 4 wherein R 9 is —C(O)(C 1 -C 10 alkyl)N(R 5 R 6 ).

6. The compound of claim 5 wherein R 7 is H.

7. The compound of claim 6 wherein R 8 is H.

8. A pharmaceutical composition which comprises: (i) a therapeutically effective amount of at least one compound according to claim 1 and (ii) a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 wherein the carrier is a sterile solution, suspension, emulsion, a capsule or tablet.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 15, 2010
From: EISAI CORPORATION OF NORTH AMERICA
To: EISAI INC.
Reel/Frame 023796/0776 →