Patent IL-101312-A (IL)
Title: Aminoguanidines, their preparation and pharmaceutical compositions containing them
IPC: C07D333/58
Filed: 1992-03-20
Abstract: Compounds active in the treatment of gastrointestinal motility disorders and migraine of the formula R5R6Z R7NYNH-B R1N wherein R1 is hydrogen; C1-6 alkyl; (C1-6 alkyl) carbonyl; benzoyl; or phenyl C1-4 alkyl- carbonyl; R5 is hydrogen; halogen; C1-6 alkyl; hydroxy; nitro; amino; C1-4 alkylamino; C1-10 alkylcarbonylamino; C2-6 alkoxycarbonyl; SO2NRaRb wherein each of Ra independently is hydrogen or C1-6 alkyl; cyano; or trimethylsilyl; C1-6 alkyl substituted by -SO2-C1-6 alkyl, -SO2NRaRb, -CONRaRb, -NH-SO2-C1-6 alkyl, -N(C1-6 alkyl) -SO2 - (C1-6 alkyl), -NRaR(b wherein R(b is hydrogen or C1-6 alkyl, C2-6 alkoxycarbonyl or -PO(C1-4 alkyl)2; carboxy; -CONRaRb; -PO(C1-4 alkyl)2; OCONRcRd, wherein each of Rc and Rd independently is C1-6 alkyl; R6 is hydrogen or, when R5 is OH, R6 is hydrogen or halogen, Z is -CR4 = wherein R4 is hydrogen, halogen, hydroxy or C1-6 alkyl or, when R5 is hydrogen or hydroxy, Z is also -N=, R7 is hydrogen, halogen, C1-6 alkyl or C1-6 alkoxy, X--Y is -CR8=N- or -CH(R8) -NH- wherein R8 is hydrogen or C1-6 alkyl, and B is a radical of the formula CH2)n A1NX1 or R10NX2 (a)(b) wherein n is 1 or 2, A1 is C=O or CH2, X1 is S; NR11 wherein R11 is hydrogen, C1-6 alkyl) carbonyl, benzoyl or phenyl C1-4 alkyl-carbonyl; or CR12R13, wherein each of R12 and R13 independently is hydrogen or C1-4 alkyl, R10 is hydrogen; C1-12 alkyl; C1-6 alkyl substituted by hydroxy, aryl, aryloxy, adamantyl, a heterocyclic radical, -NR15-CO-R16 or -NH-SO2 -aryl; C5-7 cycloalkyl; adamantyl; (C1-10 alkyl) carbonyl; benzoyl; phenyl (C1-4 alkyl) carbonyl; or -CONHR14( wherein R14 is C1-10 alkyl or C5-7 cycloalkyl, R15 is hydrogen or C1-4 alkyl, and R16 is C1-6 alkyl, C5-7 cycloalkyl, C5-7 cycloalkyl- C1-4 alkyl, aryl or aryl C1-4 alkyl, wherever "aryl" appears as is or in the significances "aryloxy", "-NH-SO2 -aryl" or "aryl (C1-4 alkyl)" in the above definition, it is phenyl or phenyl substituted by halogen, C1-4 alkyl or C1-6 alkoxy; and wherever "heterocyclic radical" appears in the above definition, it is pyridyl, imidazolyl, benzimidazolyl, pyrrolidinyl, pyrrolidonyl, piperidino, pyrazinyl, perhydroindolyl or a radical of the formula OR22-NN- B1OEE1N-O or G(CH2)n( wherein R22 is hydrogen or C1-4 alkyl, B1 is -CH2CH2-, -COCH2 - or - (CH2)3 - in which one or two H thereof can be replaced by C1-4 alkyl, or 1, 2-phenylene, E is -CH2CH2-, -CH2N(R17) - or -(CH2)3 - in which one or two H thereof can be replaced by C1-6 alkyl, or 1, 2-phenylene, E1 is CO or CH2, R17 is hydrogen or C1-4 alkyl, G is CO, -CHCOOR18, -CHCOR19, 5,5-dimethyl-1, 3-dioxan-2-ylidene or 1,3-dioxolan-2-ylidene, wherein R18 is hydrogen or C1-6 alkyl and R19 is C1-6 alkyl, and n( is 0 or 1 and X2 is -SR20 or -NR3R(10 wherein R20 is C1-6 alkyl, R3 is hydrogen or C1-6 alkyl and R(10 together with the nitrogen atom to which they are attached form a heterocyclic radical as defined above; with the proviso that where B is a radical of formula (b), only one of R10 and R(10 can be other than hydrogen and X2 can be -SR20 only when R10 is hydrogen, and a physiologically-hydrolysable and -acceptable ether or ester thereof when R5 is hydroxy, in free form or in salt form.