Use of sulfonylguanidine derivatives, mostly new compounds, for treating e.g. pain and neurodegeneration, have affinity for the gabapentin binding site

摘要

Use of sulfonylguanidines (I), optionally as racemates, pure, or mixed stereoisomers (particularly enantiomers or diastereoisomers), and/or salts with acids or bases, and/or as solvates, especially hydrates, for treating a wide variety of disorders. The disorders are: pain (especially neuropathic, chronic or acute) epilepsy and/or migraine; hyperalgesia (thermal or mechanical), (cold) allodynia or inflammatory or post-operative pain; hot flushes, post-menopausal pain, amyotropic lateral sclerosis, reflex sympasthetic dystrophy, spastic paralysis, restless leg syndrome, inherited nystagmus, psychiatric or neuropathological conditions (bipolar disorders, anxiety, panic attacks, mood fluctuations, mania, depression, manic-depressive states, painful diabetic neuropathy, multiple sclerosis, Parkinson's , Alzheimer's or Huntington's diseases), gastrointestinal injury, erythromelalgic or post-poliomyelotic pain, trigeminal or post-herpetic neuralgia. (I) have formula R1-SO2-N=C(NH2)-NR2R3 and/or the tautomeric form R1-SO2-NH-C(=NH)-NH2, with the preferred tautomer depending on the status of aggregation or solvent used. R1 = 1-10C alkyl (linear or branched, saturated or unsaturated, optionally substituted one or more times), 3-8C cycloalkyl or bicyclic alkylene (saturated or unsaturated, optionally substituted one or more times), (hetero)aryl (both optionally substituted one or more times), or 3-9C cycloalkyl or (hetero)aryl, all optionally substituted one or more times, linked through 1-4C alkyl, linear or branched, saturated or unsaturated; R2 = R1 but not bicyclic alkylene, and the optionally substituted 3-9C cycloalkyl or (hetero)aryl may be linked through 1-3C alkyl (saturated or unsaturated), sulfonyl or NH or R2 = NR4R5 or SO2R6; R4 and R5 = R1, but not bicyclic alkylene, also hydrogen or 11-18C alkyl, or together form CH2CH2(O or NR7)CH2CH2; R6 and R7 = R5 but not hydrogen; R3 = hydrogen or R2, but not NR4R5 or SO2R6, or R2 and R3 together form (CH2)n or CH2CH2(O or NR8)CH2CH2; n = 4 or 5; R8 = R7 or bicyclic alkylene . An Independent claim is also included for (I) as new compounds where R1 = optionally substituted (hetero)aryl; R2 = optionally substituted (hetero)aryl attached through optionally unsaturated 1-3C alkyl, and R3 = hydrogen, except where R2 = benzyl and R1 = phenyl (optionally as part of fused ring system), optionally substituted by Me or amino.