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US 8,410,110 B2Granted
9-(piperazinylalkyl) carbazoles as Bax-modulators
AssigneeMerck Serono SA
InventorsSerge Halazy, Dennis Church, Bruno Antonsson, Agnes Bombrun, Patrick Gerber, Jean-Claude Martinou
Life of this patent
Estimating the term…
Abstract
Piperazine compounds for use as pharmaceutically active compounds and in pharmaceutical formulations that are useful for the treatment of disorders associated with apoptosis, including neurodegenerative disorders, diseases associated with polyglutamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders, renal hypoxia, hepatitis and AIDS, where the piperazine compounds are represented by formula (I) and the terms R0, R1, R2, R3, k, l, m, n, and X are defined herein:
Claims13
A process for the inhibition of Bax in a patient in need thereof, the process comprising:
- administering, in an amount sufficient to inhibit Bax in the patient, a compound of formula (I):
- as well as a pharmaceutically acceptable salt thereof, in racemic form or in an enantiomeric excess, wherein:
- R0 and R1 are selected independently from each other and are hydrogen;
- halogen;
- cyano;
- sulfonyl of formula —SO2—R, wherein R is hydrogen, aryl, heteroaryl, C1-6 alkyl, or C1-6 alkyl substituted with a halogen;
- sulfoxy;
- substituted or unsubstituted C1-C6-thio-alkoxy;
- nitro;
- primary, secondary or tertiary amine or sulfonamide;
- aminocarbonyl;
- amino-thiocarbonyl;
- hydroxy;
- substituted or unsubstituted C1-C6-alkoxy;
- aryloxy;
- heteroaryloxy;
- carboxylic amide;
- alkoxycarbonyl;
- carboxylic ester;
- carboxylic acid;
- substituted or unsubstituted C1-C6-alkyl carbonyl;
- substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl;
- substituted or unsubstituted saturated or unsaturated C3-C8-cycloalkylcarbonyl;
- substituted or unsubstituted C1-C6-alkyl;
- substituted or unsubstituted C2-C6-alkenyl;
- substituted or unsubstituted C2-C6-alkynyl;
- substituted or unsubstituted aryl or heteroaryl;
- or substituted or unsubstituted 3-8 membered saturated or unsaturated cyclic alkyl;
- R2 is hydrogen, substituted or unsubstituted C1-C6-alkyl, substituted or unsubstituted C2-C6-alkenyl, substituted or unsubstituted C2-C6-alkynyl, substituted or unsubstituted aryl or heteroaryl, substituted or unsubstituted 3-8 membered saturated and unsaturated cyclic alkyl, sulfoxy, sulfonyl of formula —SO2—R, sulfonamide, carboxylic amide, aminocarbonyl, alkoxycarbonyl, hydrazine acyl, substituted or unsubstituted carbonyl-C1-C6-alkyl, substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl, substituted or unsubstituted saturated or unsaturated C3-C8-cycloalkylcarbonyl, alkoxy, or C1-C6-thioalkoxy;
- R3 is hydrogen, halogen, substituted or unsubstituted C1-C6-alkyl, substituted or unsubstituted C2-C6-alkenyl, substituted or unsubstituted C2-C6-alkynyl, substituted or unsubstituted aryl or heteroaryl, substituted or un-substituted 3-8 membered saturated and unsaturated cyclic alkyl, alkoxycarbonyl, carboxylic amide, C1-C6-alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, hydroxy, substituted or unsubstituted C1-C6-alkyl carbonyl, substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl, substituted or unsubstituted saturated or unsaturated C4-C8-cycloalkylcarbonyl, or an oxo (═O) group;
- k and l are independently from each other an integer from 0 to 4;
- X is a group of the formula —(CR′R″)—, wherein R′ is halogen and R″ is hydrogen or halogen;
- m and n are independently from each other an integer from 1 to 3;
- and
- o is an integer from 0 to 8.
32 more elements
A process for the treatment of at least one of the following neurodegenerative disorders:
- epilepsy;
- Alzheimer's disease;
- Huntington's disease;
- Parkinson's disease;
- retinitis pigmentosa;
- Crohn's disease;
- amyotrophic lateral sclerosis;
- multiple sclerosis;
- spino-cerebellar ataxias, and dentatorubral-pallidoluysian atrophy in a patient in need thereof, the method comprising:
- administering, in an amount sufficient to treat the disorder in the patient, a compound of formula (I):
- as well as a pharmaceutically acceptable salt thereof, in racemic form or in an enantiomeric excess, wherein:
- R0 and R1 are selected independently from each other and are hydrogen;
- halogen;
- cyano;
- sulfonyl of formula —SO2—R, wherein R is hydrogen, aryl, heteroaryl, C1-6 alkyl, or C1-6 alkyl substituted with a halogen;
- sulfoxy;
- substituted or unsubstituted C1-C6-thio-alkoxy;
- nitro;
- primary, secondary or tertiary amine or sulfonamide;
- aminocarbonyl;
- amino-thiocarbonyl;
- hydroxy;
- substituted or unsubstituted C1-C6-alkoxy;
- aryloxy;
- heteroaryloxy;
- carboxylic amide;
- alkoxycarbonyl;
- carboxylic ester;
- carboxylic acid;
- substituted or unsubstituted C1-C6-alkyl carbonyl;
- substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl;
- substituted or unsubstituted saturated or unsaturated C3-C8-cycloalkylcarbonyl;
- substituted or unsubstituted C1-C6-alkyl;
- substituted or unsubstituted C2-C6-alkenyl;
- substituted or unsubstituted C2-C6-alkynyl;
- substituted or unsubstituted aryl or heteroaryl;
- or substituted or unsubstituted 3-8 membered saturated or unsaturated cyclic alkyl;
- R2 is hydrogen, substituted or unsubstituted C1-C6-alkyl, substituted or unsubstituted C2-C6-alkenyl, substituted or unsubstituted C2-C6-alkynyl, substituted or unsubstituted aryl or heteroaryl, substituted or unsubstituted 3-8 membered saturated and unsaturated cyclic alkyl, sulfoxy, sulfonyl of formula —SO2—R, sulfonamide, carboxylic amide, aminocarbonyl, alkoxycarbonyl, hydrazine acyl, substituted or unsubstituted carbonyl-C1-C6-alkyl, substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl, substituted or unsubstituted saturated or unsaturated C3-C8-cycloalkylcarbonyl, alkoxy, or C1-C6-thioalkoxy;
- R3 is hydrogen, halogen, substituted or unsubstituted C1-C6-alkyl, substituted or unsubstituted C2-C6-alkenyl, substituted or unsubstituted C2-C6-alkynyl, substituted or unsubstituted aryl or heteroaryl, substituted or un-substituted 3-8 membered saturated and unsaturated cyclic alkyl, alkoxycarbonyl, carboxylic amide, C1-C6-alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, hydroxy, substituted or unsubstituted C1-C6-alkyl carbonyl, substituted or unsubstituted arylcarbonyl or heteroarylcarbonyl, substituted or unsubstituted saturated or unsaturated C4-C8-cycloalkylcarbonyl, or an oxo (═O) group;
- k and l are independently from each other an integer from 0 to 4;
- X is a group of the formula —(CR′R″)—, wherein R′ is halogen and R″ is hydrogen or halogen;
- m and n are independently from each other an integer from 1 to 3;
- and
- o is an integer from 0 to 8.
41 more elements
Dependencies are inferred from the claim text.