| 摘要 |
<p>#CMT# #/CMT# N-[(1,5-Diphenyl-1H-pyrazol-3-yl)methyl]sulfonamide derivatives (I) are new. #CMT# : #/CMT# N-[(1,5-Diphenyl-1H-pyrazol-3-yl)methyl]sulfonamide derivatives of formula (I) and their base or acid addition salts, hydrates or solvates are new. R 1 = 3-7C cycloalkyl (optionally substituted by one or more Alk), 3-7C cycloalkylmethyl (optionally substituted by one or more carbocycle or Alk), phenyl (optionally substituted by one or more halo, Alk, OAlk, CN, CF 3, OCF 3, S(O) nAlk, 1-4C alkylcarbonyl or phenyl), benzyl (optionally substituted by one or more halo, Alk, OAlk or OCF 3), thienyl, furyl, oxazolyl, thiazolyl, imidazolyl (all optionally substituted by one or more halo, Alk or OCF 3), naphthyl (optionally substituted by one or more Alk or di-Alk-amino), 2,3-dihydrobenzofuranyl (optionally substituted by one or more Alk) or 1-7C alkyl; R 2 = H or Alk; R 3 = OH, CN, OAlk, cyanomethyl, hydroxymethyl, 1-4C alkoxymethyl, fluoromethyl, tetrazolylmethyl, N-(methyl)tetrazolylmethyl, tetrazolyl, N-(methyl)tetrazolyl, C(O)NR 6R 7, CH 2S(O) nAlk or C(O)OR 8; R 4, R 5 = phenyl (optionally substituted by one or more halo, 1-7C alkyl, OAlk, CF 3 or S(O) nAlk); R 6, R 7 = H or Alk; or NR 6R 7 = heterocyclic radical selected from pyrrolidino, piperidino, morpholino or piperazino (all optionally substituted by one or more Alk); R 8 = Alk; n = 0-2; and Alk = 1-4C alkyl. An independent claim is included for preparation of (I). #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Gastrointestinal-Gen.; Antiinflammatory; Neuroleptic; Antismoking; Tranquilizer; Antidepressant; Sedative; Nootropic; Antimigraine; Anticonvulsant; Antiparkinsonian; Neuroprotective; Immunomodulator; Antialcoholic; Vasotropic. #CMT#MECHANISM OF ACTION : #/CMT# Cannabinoid receptor antagonist. The ability of (I) to bind with cannabinoid receptor was tested using biological assays. The results showed that (I) exhibited IC 50 = 5 x 10 -7> M. #CMT#USE : #/CMT# (I) are useful to treat or prevent appetite disorders, metabolic disorders, gastrointestinal disorders, inflammatory disorders, immune disorders, psychotic disorders, alcoholic dependency and nicotinic dependency (all claimed). (I) are also useful for treatment of psychiatric disorders e.g. anxiety and depression, mood disorders, insomnia, delirious disorders, obsessional disorders, psychoses, schizophrenia, attention and hyperactivity disorders, migraine, stress, psychosomatic diseases, panic attacks, epilepsy, movement disorders, Parkinson's disease, mnemic disorders, cognitive disorders, senile dementia, Alzheimer's disease, ischemia, cranial traumatisms, neurodegenerative diseases, chorea, Huntington's chorea and Tourette's syndrome. #CMT#ADVANTAGE : #/CMT# (I) have good in vitro affinity to cannabinoid receptors. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (Claimed): Preparation of (I) comprises reacting pyrazole compound of formula (II) with sulfonyl halide of formula HalSO 2R 1 in the presence of base and solvent to give sulfur substituted pyrazole compound of formula (III) (R 31 = R 3 or precursor of R 3) and transforming (III) to obtain (I). #CMT#[Image]#/CMT# #CMT#ADMINISTRATION : #/CMT# Administration of (I) is oral at a dosage of 0.01-100 (preferably 0.02-50) mg/kg/day, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal. #CMT#SPECIFIC COMPOUNDS : #/CMT# 69 Compounds (I) are specifically disclosed e.g. 5-(4-chlorophenyl)-3-(3-chlorophenyl)sulfonylamino-methyl-1-(2,4-dichlorophenyl)-N,N-dimethyl-1H-pyrazole-4-carboxamide (Ia). #CMT#EXAMPLE : #/CMT# A solution of 5-(4-chlorophenyl)-3-(3-chlorophenyl)sulfonylamino-methyl-1-(2,4-dichlorophenyl)-1H-pyrazole-4-carboxylic acid (0.4 g) was added to dichloromethane (20 ml). To this reaction mixture benzotriazol-1-yloxy tris(dimethyl amino)-phosphonium hexafluorophosphate (0.37 g) and methylamine (0.05 g) was added and agitated. The resulting mixture was worked up to give 5-(4-chlorophenyl)-3-(3-chlorophenyl)sulfonylamino-methyl-1-(2,4-dichlorophenyl)-N,N-dimethyl-1H-pyrazole-4-carboxamide (0.35 g).</p> |
