New indazole derivatives useful as antiasthmatic, antiallergic, neuroprotective agents and for treatment of inflammation and immune disorders

摘要

1,3,5-Trisubstituted-1H-Indazole derivatives (I) and their addition, base and quaternary salts are new. 1,3,5-Trisubstituted-1H-indazole derivatives of formula (I) and their addition, base and quaternary salts are new: X = -SO2-; -SO-; -(CH2)p-; -(CH2)p-O-; -(CH2)p-C(O)-; -(CH2)p-C(O)-NH-; -(CH2)p-CHOH-; -CHOH-(CH2)p-; -(CH2)p-CH=CH-; or -CH=CH-(CH2)p-; Y = -(CH2)p-; -(CH2)p-O-; -(CH2)p-C(O)-; -(CH2)p-C(O)-NH-; -(CH2)p-C(O)-NH-(CH2)p-; -(CH2)p-CHOH-; -CHOH-(CH2)p-; -(CH2)p-CH=CH-; or -CH=CH-(CH2)p-; Z = -O-; -S-; -SO-; -SO2-; -O-(CH2)p-; -NH-; -NH-C(O)-; -NH-C(O)-NH-; -NH-C(O)-O-; -NH-CH2-C(O)-; or -NH-C(O)-CH2-; p = 1-4; R1, R2 and R3 = a 5-14 membered carbocycle (especially phenyl, naphthyl, anthranyl or fluorenyl) or 5-15 membered heterocycle containing 1-6 hetero (preferably N, O and S) atoms (especially thiophenyl, pyridinyl, isoxazolyl, benzimidazolyl, benz(1,3)dioxolyl, pyrimidinyl, quinolyl, quinazolinyl, morpholinyl, pyrrolidinyl, pyrrolyl, phenyl(1,2,4)oxadiazolyl or phenylthiazolyl) (each mono-, bi- or tricyclic, saturated or mono- or poly-unsaturated and optionally substituted with 1 or more Q); or R1 = H except when X = CH2; or R3-Z = NO2; Q = 1-6C alkyl; 1-6C alkoxy; 3-7C cycloalkyloxy; a 3-14 membered carbocycle or 5-15 membered heterocycle containing 1-6 hetero (preferably N, O and S) atoms (each mono-, bi- or tricyclic and saturated or mono- or poly-unsaturated); F; Cl; Br; I; OH; SH; NO2; NH2; NH(1-6C alkyl); N(1-6C alkyl)2; NH(6-14C aryl); N(6-14C aryl)2; N(1-6C alkyl)(6-14C aryl); NHCO(1-6C alkyl); NHCO(6-14C aryl); CONH(1-6C alkyl); CONH(6-14C aryl); CONHSO2(1-6C alkyl); CONHSO2(6-14C aryl); CN; C(O)-1-6C alkyl; C(S)-1-6C alkyl; COOH; C(O)O-1-6C alkyl; O-6-14C aryl; O-C(O)-1-6C alkyl; O-C(O)-6-14C aryl; benzyl; benzyloxy; S-1-6C alkyl; S-6-14C aryl; CF3; -(CH2)p-COOH; -(CH2)p-C(O)O-1-6C alkyl; SO2-1-6C alkyl; or SO2-6-14C aryl; compounds (I) are excluded when (i) Y = -(CH2)p-C(O)- or -(CH2)p-C(O)-NH- and R2 = pyridinyl, piperazinyl, pyrimidinyl or tetrahydropyridinyl; and (ii) when Z' = -NH-C(O)-, -NH-C(O)-NH-, NH-C(O)-O- or -NH-C(O)-CH2-, R1 = phenyl substituted with 1 or more COOH, C(O)O-1-6C alkyl, -(CH2)p-COOH, -(CH2)p-C(O)O-1-6C alkyl, CONH(1-6C alkyl), CONH(6-14C aryl), CONHSO2(1-6C alkyl), CONHSO2(6-14C aryl) or 1H-tetrazol-5-yl and R2 = phenyl substituted with 1 or more CN, halo, 1-4C alkyl, 1-4C alkoxy or CF3; and (iii) when R3-Z = NO2, R1-X = benzyl or 4-methoxybenzyl and R2-Y = benzyl or 2-picolyl. An Independent claim is also included for the preparation of compounds (I).