Patent EP-1097921-A1 (EP)
Inventor: LABEEUW BERNARD
IPC: A61K31/439
Filed: 1996-04-11
Abstract: 1-Phenyl pyrazole-3-carboxamides of formula (I), their salts, quaternary ammonium salts formed with tertiary amines, and their solvates, are new. R1 = TCN, C(NH2)=NOH, C(=NOH)NH(CH2)rNR5R6, TC(NR12R13)=NR14, C(NH2)=NO(CH2)rNR5R6, TCONRaRb, TCONR7Rc, YCOOR7, ORd, TNR5R6 (provided R5 and R6 are not both H when T is a direct bond), TN(R7)CORe, SO2NRaRb, TN(R7)SO2R'7, TNR27R28; NRaRb = NR5R6, NR9(CH2)sCR7R8(CH2)tNR5R6, NR21(CH)sCR7R8(CH2)tN<+>R22R23R24Q<-> , a gp. of formula (i)-(v), NR7(CH2)qCN, NR7(CH2)qC(NR12R13)=NR14, NR7(CH2)qCONH2, NR7(CH2)qCOOR7, NR21(CH2)sCR7R8(CH2)tNR25R26; Rc = XOR7, CH2R20COOR7 or (CH2)4CH(NH2)COOR7; Rd = XNR5R6, YCONR5R6, YCOOR7, YSO2NR5R6, or a gp. of formula (vi) or (vii); Re = R16, YNR5R6, YNHCOR16, CH(R17)NR5R6, YN<+>R22R23R24Q<->, a gp. (vi), (CH2)qCN, (CH2)qC(NR12R13)=NR14 or NR18R19; R2, R3 = H, 1-6C alkyl, (3-8C cycloalkyl)-methyl, 3-8C cycloalkyl, halo, nitro, CF3, OR4, NR5R6, pyrrol-1-yl, cyano or carbamoyl; or R2+R3 = trimethylene, tetramethylene, or pentamethylene; R4 = H, 1-6C alkyl, 3-4C alkenyl, 3-8C cycloalkyl, (3-8C cycloalkyl)methyl, (1-4C alkoxy)(1-4C alkylene), or benzyl; R5, R6 = H, 1-6C alkyl, 3-8C alkenyl, (3-8C cycloalkyl)methyl, or benzyl; or NR5R6 = pyrrolidine, piperidine, morpholine, thiomorpholine, (4-R9)-piperazine, aziridine, azetidine or perhydroazepine ring; R5', R6' = H or 1-6C alkyl; or NR5'R6' = pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine or (4-(1-6C alkyl)-piperazine; R7' = 1-4C alkyl; phenyl opt. substd by one or more 1-4C alkyl; or XNR5R6; R7 = H, 1-4C alkyl, or benzyl; R8 = H, 1-4C alkyl or OH; or CR7R8 = 3-5C cycloalkane; R9 = H, 1-4C alkyl, benzyl, XOH, XNR5'R6' or 3-8C alkenyl; R10 = H, 1-4C alkyl, benzyl, carbamoyl, or cyano; R11 = H, 1-4C alkyl, XOH, or XNR5'R6'; R12, R13 = H or 1-4C alkyl; R14 = H; or may be 1-4C alkyl when R12 = H and R13 = alkyl; or R13+R14 = Z; R15 = H, 1-4C alkyl or (CH2)sNR5R6; R16 = H, 1-8C alkyl, 3-8C cycloalkyl, phenyl, or piperid-2-, -3- or -4-yl; R17 = 1-6C alkyl, phenyl, benzyl, hydroxy-(1-4C alkyl), or amino(1-4C alkyl); R18, R19 = H or 1-4C alkyl; R18 may also be (CH2)qNR5R6; or NR18R19 = pyrrolidine, piperidine, morpholine, thiomorpholine or (4-R9)-piperazine; R20 = H, 1-4C alkyl, benzyl, hydroxyphenylmethyl, hydroxy(1-4C alkyl), mercapto(1-4C alkyl), (CH2)3NHC(=NH)NH2, (CH2)4NH2, or CH2-Im; Im = imidazol-4-yl; R21 = 1-4C alkyl, allyl, or benzyl; R22, R23 = 1-6C alkyl; or NR22R23 = pyrrolidine, piperidine, morpholine, or perhydroazepine; R24 = 1-4C alkyl, benzyl, allyl, hydroxy(1-4C alkyl), or (1-4C alkoxy)(1-4C alkyl); Q<-> = an anion; R25 = H or 1-6C alkyl; R26 = (1-4C alkoxy)carbonyl, benzyloxycarbonyl, or (1-4C alkyl)carbonyl; R27 = H, 1-4C alkyl, (1-4C alkyl)carbonyl, CO(CH2)rOH, or SO2R'7; R28 = XNR5R6; s, t = 0-3, with the proviso that (s+t) in the same group is 1 or more; r = 2-5; q = 1-5; T = a direct bond or 2-7C alkylene; X = 2-7C alkylene; Y = 2-7C alkylene; Z = 2-6C alkylene; AECN = a 4-7 membered saturated heterocycle, opt. substd by one or more 1-4C alkyl; NHAA(OH) = NHC(Xa)(Xa')COOH; Xa = H, and Xa' = H, 1-5C alkyl or a non-aromatic 3-15C carbocycle; or CXaXa' = a 3-15C non-aromatic carbocycle; and NGNL = piperazine, imidazolidine or imidazoline, all opt. substd. by 1 or more 1-4C alkyl. A number of intermediates for the preparation of these compounds are also claimed.