| 摘要 |
4-(Hetero)aryl-pyrazole derivatives (I), substituted in the 1-position by a cyclic or acyclic nitrogen-containing group (optionally linked via a hydrocarbon group), are new. Pyrazole derivatives of formula (I) (including racemates, enantiomers, diastereomers and their mixtures) and their tautomers and salts are new. [Image] R 1>NR 6>R 7>, 4-7C azacycloalkyl, 5-7C azacycloalkenyl, 5-9C azabicycloalkyl or 5-9C azabicycloalkenyl (all optionally substituted (os) by one or more of 1-5C alkyl, 3-5C cycloalkyl or halo); A : direct bond; or 1-6C alkyl, 3-6C alkenyl, 3-6C alkynyl, cycloalkyl or cycloalkenyl (all os by one or more of 1-5C alkyl, 2-5C alkenyl, 2-5C alkynyl, cycloalkyl, cycloalkenyl, aralkyl, heteroaralkyl, aryl, heteroaryl or halo); provided that A-R 1> is such that the N in R 1> and the 1-N of the pyrazole are separated by at least 2C; R 3>H, halo, OH, SH, NH 2, OR c, SR c, SOR a, SO 2R a, NHCHO, NR aR b, NHC(O)R a, NHC(S)R a or NHSO 2R a; R 4>aryl or heteroaryl (both os by one or more of halo, CN, NO 2, NH 2, OH, SH, COOH, CHO, CONH 2, CSNH 2, SO 2H, SO 2NH 2, NHCHO, COR a, COOR a, CONR aR b, CSNR aR b, SOR a, SO 2R a, SO 2NR aR b, OR c, SR c, OCOR a, OCSR a, NR aR b, NHCOR a, NHCSR a, NHCONH 2, NHCONHR aR b, NHSO 2R a, aryl, heteroaryl, heterocycloalkyl, polyfluoroalkyl, SCF 3, OCF 3, 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl, the substituents being themselves os by one or more of alkyl, OH, OCH 3 or halo); R 5>H, halo, CF 3, CHF 2, CH 2F, alkyl or cycloalkyl; R a1-6C alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl or polyfluoroalkyl; and R bH or R a; or NR aR b5-7-membered saturated or unsaturated ring, optionally containing an additional heteroatom (e.g. O, S or N) and os by one or more alkyl or halo; R c1-6C alkyl, 3-6C alkenyl, 3-6C alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, fluoroalkyl, polyfluoroalkyl, COR 8>, CSR 8> or SO 2R 8>; R 6>, R 7>H, 1-6C alkyl, 3-6C alkenyl, 3-6C alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aralkyl or heteroaralkyl; or NR 6>R 7>ring as defined for NR aR b; and R 8>H or NR aR b; Cycloalkyl moieties have 3-7C, cycloalkenyl moieties 5-7C and heterocycloalkyl moieties 4-7C. An independent claim is included for the preparation of (I). ACTIVITY : Nootropic; neuroprotective; neuroleptic; antiaddictive; antibacterial; virucide; antiinflammatory; antiulcer; antiarthritic; antirheumatic; dermatological; antiseborrheic; antidiarrheic; analgesic; antimigraine; vulnerary; cerebroprotective; vasotropic; antiparkinsonian; anticonvulsant; antidepressant; tranquilizer; anorectic; hypnotic; antismoking; antialcoholic. MECHANISM OF ACTION : alpha 7-Nicotinic receptor ligand. (I) generally have K i values of less than 10 mu M in alpha 7-nicotinic receptor binding assays (no specific values for individual compounds given). |
