Patent NZ-506721-A (NZ)
Title: Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors
Inventor: PITZEL BARNETT S
IPC: C07D333/24
Filed: 1999-03-04
Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: R1 can be optionally substituted and is selected from the group consisting of hydrogen, alkyl, alkenyl, and alkynyl; R2 can be optionally substituted and is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and either R or S alpha-amino acid; R3 and R4 can be optionally substituted and are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and NO2; R11 is selected from the group consisting of hydroxyl and R or S alpha-amino acid; G is selected from the group consisting of alkylene, alkenylene, and alkynylene, each of which is optionally substituted with one or more selected from the group consisting of halogen, hydroxy, trifluoromethyl, nitro, cyano, amino, alkyl, alkenyl, alkynyl, and alkoxy, each of which can be can be optionally substituted from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, hydroxy, lower alkoxy, aryloxy, thiol, lower thioalkoxy, halogen, cyano, nitro, amino, carboxy, carboxyalkyl, carboxyaryl, amidino, guanidino, trifluoromethyl, and nitro; or from the formula (CH2)p-(CX1X2)r-(CH2)s-Q-(CH2)t-(CX3X4)u(CH2)V where p, r, s, t, u, v are independently 0 to 3 and Q is oxygen, C=O, S(O)a wherein a is 0 to 2, with the proviso that when a is 1 or 2, G must contain halogen, or NR12 wherein R12 is hydrogen or alkyl which may be optionally substituted with one or more selected from the group consisting of alkyl, alkoxy, hydroxy, trifluoromethyl, nitro, cyano, amino, and halogen; or from the formula -(CH2)w-(CX5X6)y-(CH2)z-A-(CH2)k-(CX7X8)j-(CH2)h wherein w, y, z, k, j, h are independently 0 to 3 and A is a 3 to 6 membered carbocyclic radical or heterocyclic radical which may be optionally substituted with one or more selected from the group consisting of halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, nitro, cyano, and amino, each of which may be optionally substituted with halogen or alkyl, with the proviso that when G is selected from the formula -(CH2)w-(CX5X6)y-(CH2)z-A-(CH2)k-(CX7X8)j-(CH2)h, Y must contain halogen; X1, X2, X3, X4, X5, X6, X7, X8 are independently not present, hydrogen, halogen, alkyl alkenyl, or alkynyl, wherein the alkyl, alkenyl, and alkynyl can be optionally substituted from one or more of the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, hydroxy, lower alkoxy, aryloxy, thiol, lower thioalkoxy, halogen, cyano, nitro, amino, carboxy, carboxyalkyl, carboxyaryl, amidino, guanidino, trifluoromethyl, and nitro; Y is selected from the group consisting of heterocycle, haloalkyl, dihaloalkyl, trihaloalkyl, alkyl, cycloalkyl, alkenyl, and alkynyl, each of which is optionally substituted with one or more selected from the group consisting of halogen, hydroxy, trifluoromethyl, nitro, cyano, amino, alkyl, alkenyl, alkynyl, and alkoxy; Y can be NR9R10 wherein R9 and R10 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, nitro, amino, aryl, and alkaryl; with the proviso that at least one of G or Y contains a halogen.