Patent TW-366337-B (TW)
Title: 3-amidopyrazole derivatives, process for preparing these and pharmaceutical compositions containing them
Inventor: BOIGEGRAIN ROBERT
IPC: C07D401/12
Filed: 1991-08-19
Granted: 1999-08-11
Abstract: 3-amidopyrazole for formula (I) or (I'), in which, R1 represents: a group where R1, R' and R"1 each independently represents a hydrogen atom, a halogen atom, a hydroxyl, a linear or branched C1-C4 alkyl group, a C1-C4 alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a nitro group, a carboxyl group or an amino group; a carboxyalkyl or alkoxycarbonylalkyl group in which the alkyls are C1-C4 groups; a cycloalkyl group in which the alkyls are C3-C6 groups; a tetrahydronaphthyl group; a pyridyl group; a naphthyl group substituted with R1, R'1 and R"1 as defined above; a benzyl group substituted with R1, R'1 and R"1 as defined above; a cinnamyl group optionally substituted on the aromatic ring with a halogen, a hydroxyl or a C1-C4 alkoxy; a quinolyl or isoquinolyl group optionally substituted with R1, R'1 and R"1 as defined above; a 2-benzothiazolyl group; a quinoxalinyldione group; a 1-phthalazinyl group; a benzothiadiazolyl group; a methylene group substituted with a 5- or 6-membered heterocyclic group such as, in particular, a pyridyl and a thienyl; RIa represents a benzyl group substituted with R1, R'1 and R"1, as defined above; R represents 0, 1, 2 or 3; either X represents hydrogen and X' represents hydrogen; a linear or branched C1-C6 alkyl; an aryl; a C1-C4 aminoalkyl; a C1-C4 hydroxyalkyl; a carboxyalkyl in which the alkyl group is a C1-C4 group; an acetamidoalkylcysteine in which the alkyl group is a C1-C4 group; a guanidinoalkyl in which the alkyl group is a C1-C4 group; a nitroguanidinoalkyl in which the alkyl group is a C1-C4 group; a C3-C7 cycloalkyl; and arylalkyl in which the alkyl is a C1-C4 group and in which the aryl is optionally substituted with a halogen or a hydroxyl or with a C1-C3 alkyl; a heteroarylalkyl in which the heteroaryl represents an imidazolyl or an indolyl unsubstituted or substituted with a C1-C4 alkyl; with a hydroxyl or with a C1-C4 alkoxy and in which the alkyl is a C1-C4 group; or, when n is equal to zero, X represents hydrogen and X' and -N-R considered together form a ring, unsubstituted or substituted with a hydroxyl, or formula, with m=2, 3 or 4, or a ring-system of formula, with t=1 or 2, or a ring-system of formula, with t=1 or 2, or an indolinyl, perhydroindole or 4,5,6,7-tetrahydrothieno [2,3-c]pyrid-6-yl ring-system; or X and X' each independently represent a C1-C4 alkyl or a C3-C6 cycloalkyl; a phenyl; or X and X' are linked and form together a cycloalkyl group having 2 to 12 carbon atoms, optionally substituted with a C1-C3 alkyl; or X, X' and the carbon atom to which they are linked form an adamantyl group; an adamantyl group substituted with one or two methyl groups or with a hydroxyl, a C1-C3 alkoxy or a halogen atom; a 1-azaadamantyl group; a quinuclidinyl group; a 4-piperidyl group optionally N-substituted with a benzyl group, a 2,2,6,6-tetramethylpiperidyl group; a tetrahydronaphthyl group; a tetrahydropyran-4-yl or tetrahydrothiopyran-4-yl group; a 2,3-dihydro-4H-benzopyran-4-yl group; a 2,3-dihydro-4H-benzothiopyran-4-yl group; a group for formula, in which n1=0 or 1, n'1=1 or 2, n2=1, n3=2 or 3 and W represents a carbon atom or an oxygen atom, this group of formula (a) being attached to -N(R)- and to -C(O)-Z as defined above through one carbon atom of one or other of the rings, or a group of formula b; in which N4=2, 3, or 4, n3=2 or 3 and W represents a carbon or oxygen atom, this group of formula (b) being attached to -N(R)- and to -C(O)-Z as defined above through one carbon atom or one or other of the rings, it being possible for the rings of the above groups a and b be optionally substituted on one and/or other of the rings with one or two C1-C4 alkyl groups and it not being possible for the amino acid to be at the alpha-position with respect to W when W represents oxygen; a bicycle[2.2.1] hept-5-en-2-yl group; an 8-oxabicyclo[3.2.1] oct-6-en-3-yl group; and 8-thiabicyclo-[3.2.1]oct-3-yl groups; or X represents hydrogen and X' is an adamantyl group; an adamantyl group substituted with one or two methyls, with a hydroxyl, a C1-C3 alkoxy or a halogen atom; a 1-azaadamantyl group; a group of formula a or b as defined above, it not being possible for the bond between these ring-systems and the carbon carrying -COZ and -N-R to be at the alpha-position with respect to W when the latter represents oxygen; Z represents a hydroxyl group or a C1-C6 alkoxy group; an oxygen atom substituted with a carboxylic acid-protecting group such as a tert-butyl, a benzyl, benzyl substituted with a halogen atom, a C1-C6 alkyl, a trifluoromethyl, a trifluoromethoxy or a carboxyl group; an amino group; a nitrogen atom substituted with a carboxyalkyl in which the alkyl is a linear or branched C1-C6 group, with the limitation that, if Z represents a nitrogen atom substituted as defined above and it n=O, then, when X=H, X1 cannot be a group; in which x=1 or 2 and Q is a hydroxyl, a free amino or amino substituted with a C1-C6 dialkyl or a C1-C6 alkoxy; RIv represents a hydrogen atom, a halogen atom or a C1-C6 alkyl; Rv represents; a group where R5, R'5 and R"5 each independently represent a hydrogen atom, a halogen atom, a linear or branched C1-C4 alkyl, a hydroxyl, a C1-C4 alkoxy, a nitro, a trifluoromethyl, a trifluoromethoxy, a cyano, an amino, a carboxyl, a C1-C4 carboxyalkyl or a phenyl; a naphthyl group unsubstituted or substituted with a C1-C4 alkyl; a styryl group unsubstituted or substituted with a C1-C4 alkyl; or alternatively, RIv and Rv considered together represent a group in which the phenyl group substitutes the pyrazole at position 5 and the group -(CH2)i- in which i=1 to 3 substitutes the pyrazole at position 4, W1, W2 and W3 substitute the benzene ring and independently represent hydrogen, a halogen or a hydroxyl group; or one of its possible salts with organic or inorganic acids or with inorganic bases.