Patent TW-336932-B (TW)
Title: Amino-substituted pyrazoles
Inventor: BRIGHT GENE MICHAEL
IPC: A61P25/28
Filed: 1993-10-23
Granted: 1998-07-21
Abstract: A compound having the general formula (I) and pharamaceutically acceptable acid to form a salt, where A is CH2; X1 is covalent bond, CH2, O or S; R1, R2 and R3 are each linear chain C1-C6 alkyl, branched chain C3-C8 alkyl, C3-C8 ene, in which when X1 is oxygen or sulfur, the double bond is not adjacent to N or X1, or C3-C6 cyclolkyl (CH2)n, in which n is 0, 1, 2, 3 or 4; or R1 and R2 together with nitrogen atom form a saturated six-member ring which can be randomly condensed with benzene; and R3 can also be (CH2)qQ1R10, in which q is 0, 1 or 2, Q1 is O, S, NH, N(C1-C6 alkyl) or covalent bond when X1 is not covalent bond, and R19 is hydrogen, linear chain C1-C6 alkyl, branched chain C3-C8, C3-C8 ene, or C3-C6 cycloalkyl (CH2)n, in which, n is 0 to 4; Y is phenyl, pyrazyl, pyrimidyl, imidazyl, benzoimidazyl, furan, benzofuran, thiazolyl, benzothiazolyl, isothiazolyl, benzoisothiazolyl, isoxazolyl, benzoisoxazolyl, triazolyl, pyrazinyl, pyrrolyl, indolyl, acrindolyl, oxazolyl, benzoxazolyl, pyridylalkyl, thiazolylalkyl, morpholine or piperidyl, the above said can be substitued by one or three fluorine, chlorine, bromine, or methyl or a trifluoromethyl; the proviso being Y is not an unsubstitued phenyl and Z is as shown in (a) formula (II), in which B ring is phenyl substitutable by methyl, fluorine, chlorine, bromine or iodine; or saturated 5 or 6-member carbon ring or unsaturated ring with one or two double bonds; R4 is hydrogen; R5 is hydrogen, linear chain C1-C6 alkyl, branched chain C3-C8 alkyl, C3-C8 ene, or (CH2)o-X2-(CH2)r-Q2-R6; R6 is hydrogen, C1-C6 alkyl, branched chain C3-C8 alkyl, C3-C8 ene; X2 and Q2 is respectively O, S, NH, N(C1-C6 alkyl) or one of X2 and Q2 can be covalent; m is o or 1; o is 1 or 2; p is 1 or 2; and r is 0, 1, or 2; (b) formula (III) where R4 and R5 are as defined above, and t and u each is 1 or 2; (c)-NR7R8, in which R7 and R8 are respectively hydrogen, C1-C6 linear chain alkyl, branched chain C3-C8 alkyl, C3-C8 ene, (CH2)vCH2OOH, (CH2)vNR9N20, in which v is 0 to 3, and R9 and R10 are respectively hydrogen or linear chain C1-C6 alkyl; C1-C12 cycloalkyl; (C3-C12 cycloalkyl) (CH2)n, (C6-C10 dicycloalkyl) (CH2)n, in which n is 0 to 4; benzo C3-C8 cycloalkyl, C1-C6 hydroxyalkyl, phenyl, phenyl (C1-C3 alkylene), the above said can be substituted by one or two hydrooxy, fluorine, chlorine, bromine, C1-C5 alkyl, or C1-C5 alkoxy; or R7 and R8 together with nitrogen atom form a saturated or partially unsaturated 5- to 7-member ring containing S and substituable by C1-C6 alkyl, hydroxy or phenyl, wherein none of the double bonds are adjacent to any hetero atom; (d)O(CH2)vR11 in which v is 0 to 3 and R11 is linear chain C1-C6 alkyl, branched chain C3-C8 alkyl, phenyl, naphthyl, 1, 2,3,4-tetrahydronaphthyl, pyrazyl, pyrimidyl, imidazyl, benzoimidazyl, furan, benzofuran, thiazolyl, benzothiazolyl, isothiazolyl, benzoisothiazolyl, isoxazolyl, benzoisoxazolyl, triazolyl, pyrazinyl, pyrrolyl, indolyl, acrindolyl, oxazolyl, benzoxazolyl, pyridylalkyl, thiazolylalkyl, morpholine, piperidyl or thiamine, the above said can be substituted by one or two fluorine, chlorine, bromine, methyl, or trifluoromethyl; or (e) formula (VII) in which A is defined as above and linked to position 1 or 2, R14 individually is attached to 2 or 1; F, G, H, I, J and K each are C or N, under the condition that no more than three in H, I, J and K are N and no more than two adjacent nitrogen; R12 and R13 each are hydrogen, linear chain C1-C6 alkyl, branched chain C3-C8 alkyl, C3-C8 ene, fluorine, chlorine, bromine, trifluorimethyl, hydroxy, sufuryl, C1-C12 alkoxy, C1-C12 thioalkyl, or C3-C12 ene-oxy, in which the double bond is not adjacent to O or S, or -X2-(CH2)rQ2R6, in which X2, r, Q2 and R6 are as defined as in (a), the proviso being Q2 is not S or R14 is NR15R16, in which R15 and R16 each are hydrogen linear chain C1-C6 alkyl, branched chain C3-C8 alkyl, C3-C8 ene, in which the double bond is not adjacent to nitrogen or C3-C7 cycloalkyl-(CH2)n, in which n is as defined above or R15 and R16 together with nitrogen atom form a saturated 5 or 6 member ring which can be randomly condensed with benzene.