Anticonvulsant, anxiolytic and especially analgesic medicaments, comprising new or known beta-thio-alpha-aminoacid compounds having strong affinity for gabapentin binding site

摘要

The use of beta -thio- alpha -aminoacids (I) as anticonvulsants, analgesics or anxiolytics and in the treatment of a very wide range of specific disorders (mainly pain-related, psychiatric and neuropathological disorders) is new. Some compounds (I), i.e. (I'), are new. The use of beta -thio- alpha -aminoacids of formula (I) (in the form of racemates, enantiomers, diastereomers or enantiomer or diastereomer mixtures and as free aminoacids or acid or base addition salts) in: (A) the preparation of medicaments for treating: (i) pain (especially neuropathic, chronic or acute pain), epilepsy and/or migraine; (ii) hyperalgesia and allodynia (especially thermal hyperalgesia, mechanical hyperalgesia and allodynia and cold allodynia) or inflammatory or post-operative pain; or (iii) hot flushes, post-menopausal disorders, amyotropic lateral sclerosis, reflex sympathetic dystrophy, spastic paralysis, restless leg syndrome, acquired nystagmus, psychiatric or neuropathic disorders (e.g. bipolar disorders, anxiety, panic attacks, mood swings, manic or manic depressive behavior, depression, painful diabetic neuropathy, symptoms and pain caused by multiple sclerosis or Parkinson's disease or neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease or epilepsy), gastrointestinal damage, erythro-melalgic or post-poliomyelitic pain or trigeminal or post-herpetic neuralgia; or (B) as anticonvulsants, analgesics or anxiolytics. R1, R2 = H; or optionally unsaturated 1-10C alkyl, benzyl, aryl, 3-8C cycloalkyl or heteroaryl (all optionally mono- or polysubstituted); or R1 + R2 = (CH2)n (optionally- (i) unsaturated, (ii) branched, (iii) mono- or polysubstituted and/or (iv) having 1 or 2C replaced by S, O or NR4); n = 3-6; R3 = H, as R4, or -L-R'3; R'3 = 3-8C cycloalkyl, aryl or heteroaryl (all optionally mono- or polysubstituted); and R4 = optionally unsaturated 1-10C alkyl (optionally mono- or polysubstituted); and L = direct bond or optionally unsaturated 1-3C alkylene. Independent claims are also included for: (1) Thioaminoacid compounds of formula (I') (including enantiomers, salts etc) as new compounds; and (2) Preparation of (I'). One of R'1, R'2 = optionally unsaturated 1-6C alkyl (optionally mono- or polysubstituted); and the other is an optionally unsaturated 3-10C alkyl, phenyl, thiophenyl or 3-8C cycloalkyl (all optionally mono- or polysubstituted).