CONIOSETIN, METHOD FOR THE PRODUCTION THEREOF AND ITS USE AS A MEDICAMENT

摘要

Farnesylthio-peptide compounds (I), designated coniosulfides, are new. Coniosulfides of formula (I) (including stereoisomers and stereoisomer mixtures) and their salts are new; [Image] R 1H; 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl or 6-10C aryl (all optionally substituted by one or more groups Q); or (6-10C) aryl-(1-4C) alkyl, NH 2, 1-6C alkylamino or 2-6C alkenylamino; Q : OH, =O, NH 2 or halo; or 1-6C alkoxy, 2-6C alkenyloxy, 6-10C aryl, 1-6C alkylamino or 2-6C alkenylamino (all optionally substituted by CN, amide or oxime functions); R 2H, 1-3C alkyl, n-butyl or isobutyl; R 3residue consisting of 1-10 aminoacids (optionally protected at the N-terminal); R 4H, 1-6C alkyl, -CO-(1-6C) alkyl; p : 0-2; Provided that the compounds (I; R 1, R 2, R 4 = H; R 3 = -COMe; p = 0 or 1) are excluded. Independent claims are also included for: (1) the preparation of (I); and (2) the use of the pyrrolidine-dione derivative coniosetin of formula (VI) for the production of a medicaments for the treatment and prophylaxis of degenerative neuropathy or Alzheimer's disease. [Image] ACTIVITY : Neuroprotective; Nootropic. MECHANISM OF ACTION : Amyloid Precursor Protein-FE 65 (APP-FE65) Interaction Inhibitor. Coniosulfide A (Ia) had IC 5 0 2.3 MicroM for inhibition of APP-FE 65 interaction.