Pharmaceutically active pyrrolidine derivatives as Bax inhibitors

US7018988B2 · kind B2 · utility

Assignee

• APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.

Inventors

• Serge Halazy · Wolfisheim, FR
• Anna Quattropani · Rolle, CH
• Agnes Bombrun · Paris, FR
• Mattias Schwarz · Aigle, CH
• Russel J. Thomas · Siena, IT
• Anthony David Baxter · Hertford, GB

Key dates

• Filing date: Mar 20, 2001
• Grant date: Mar 28, 2006
• Expiry date: Mar 20, 2021

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D417/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7>; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2—, —SO2NH—; —CH2—; B is either a group —(C═O)—NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S;…