| 摘要 |
<p>#CMT# #/CMT# 1-Benzylpyrazole compounds (I) and their acid or base addition salts, hydrates or solvates are new. #CMT# : #/CMT# 1-Benzylpyrazole compounds of formula (I) and their acid or base addition salts, hydrates or solvates are new. Y 1-N(R 7)CO-, -N(R 7)CO-N(R 7)-, -OCO- or -N(R 7)S(O) n; R 1H or 1-4C alkyl; R 2, R 4H, halo, 1-4C alkyl, 1-4C alkoxy or -CF 3; R 3, R 5halo, 1-4C alkyl, 1-4C alkoxy, -CF 3, -OCF 3, CN or S(O) mAlk; R 61-6C alkyl (optionally substituted by one or more substituents comprising halo, OH, 1-4C alkoxy or OCF 3), phenyl (optionally substituted by R 8), benzyl or benzhydryl, heterocyclic radical comprising thienyl, furyl or pyrrolyl (optionally substituted by halo, 1-4C alkyl or CF 3), 3-12C non-aromatic carbocyclic radical (optionally substituted by one or more halo, 1-4C alkyl, 1-4C alkoxy, OH or CN), 3-7C cycloalkylmethyl (optionally substituted by one or more 1-4C alkyl) or aryloxymethyl (optionally substituted on methyl by one or more two alkyl groups, in which aryloxy represents phenoxy group (optionally substituted by one or more R 8)); R 7H or 1-4C alkyl; R 8halo, 1-4C alkyl, CF 3, CN, 1-4C alkoxy, OCF 3, phenyl, 3-7C cycloalkyl or NHS(O) nAlk; n : 1 or 2; m : 0-2; and Alk : 1-4C alkyl. Independent claims are included for: (1) the preparation of (I); and (2) a substituted 1-benzylpyrazole compound of formula (XII). W 1OH or NH 2; and R 3, R 5halo, 1-4C alkyl, 1-4C alkoxy or -CF 3. #CMT#[Image]#/CMT# #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Immunomodulator; Analgesic; Gastrointestinal-Gen; Cardiovascular-Gen; Nephrotropic; Cytostatic. #CMT#MECHANISM OF ACTION : #/CMT# Cannabinoid receptor antagonist. The ability of (I) to inhibit cannabinoid receptor was tested in cell lines. The result showed that (I) exhibited an IC 5 0 value of 0.1-500 nM. #CMT#USE : #/CMT# (I) is useful for: the preparation of medicament for treating or preventing diseases comprising immune disorders, pain, gastrointestinal disorders, and cardiovascular and renal disorders; and useful in anticancer chemotherapy (all claimed). #CMT#ADVANTAGE : #/CMT# (I) has good in vitro affinity. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (Claimed): Preparation of (I) comprises: either treating 1-benzylpyrazole compound of formula (II) with an acid derivative of formula (R 6COOH) (III) to give (I) (Y 1 is NHCO or OCO); or treating (II) with an isocyanate compound of formula (R 6N=C=O) (IV) to give (I) (Y 1 is NH-CO-NH); or treating (II) with a halogen derivative of formula (R 6S(O) nHal) to give (I) (Y 1 is NH-S(O) n). X : NH or N(R 7); and Hal : halo, preferably chloride. #CMT#[Image]#/CMT# #CMT#ADMINISTRATION : #/CMT# Administration of (I) is oral (0.01-100 (preferably 0.1-50) mg/kg), sublingual, buccal, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal. #CMT#SPECIFIC COMPOUNDS : #/CMT# 2 Compounds (I) are specifically claimed i.e. N-((1-(3,4-dichlorobenzyl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)methyl)-2,2-dimethylpropanamide of formula (Ia) and N-((1-(3,4-dichlorobenzyl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)methyl)-2-methylpropane-2-sulfonamide. #CMT#[Image]#/CMT# #CMT#EXAMPLE : #/CMT# 1-(1-(3,4-Dichlorobenzyl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)methanamine (0.50 g) and pivaloic acid (0.15 g) were placed in dimethylformamide (50 ml) in presence of benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate, then triethylamine (0.28 ml). The resulting mixture was agitated at an ambient temperature and the solvent was evaporated. The resulting mixture was worked up to give N-((1-(3,4-dichlorobenzyl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)methyl)-2,2-dimethylpropanamide (0.36 g).</p> |
