Patent TW-401401-B (TW)
Title: Cyclic amidino agents useful as nitric oxide synthase inhibitors
Inventor: HANSOEN JR DONALD W
IPC: C07D207/22
Filed: 1996-06-08
Granted: 2000-08-11
Abstract: The current invention discloses useful amidino derivative useful as nitric oxide synthase inhibitors. A compound having the formula: R1 is selected from the group consisting of cycloalkyl, heterocyclyl, and aryl, which may optionally be substituted by one or more of the following: lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, thiol, lower thioalkoxy, S(O)R9, S(O)2R9, halogen, nitro, amino, alkylamino, dialkylamino, aminoalkyl, dialkylaminoalkyl, arylamino, aminoaryl, alkylaminoaryl, acylamino, amidino, carboxyl, carboalkoxy, carboaryloxy, carboarylalkyloxy, cyano, aminocarbonylalkoxy, aminocarbonylamino, aminocarbonylaminoalkyl, haloalkyl, SO2NR7R9, wherein all said substitutions may be optionally substituted with one or more of the following: halogen, lower alkyl, amino, alkylamino, dialkylamino, aminoalkyl, aminoacyl, carboxyl, carboalkoxy, carboaryloxy, carboalkylaryloxy, hydroxy, lower alkoxy; L is selected form the group consisting of lower alkylene, lower alkenylene, lower alkynylene, and -(CH2)m-D-(CH2)n-; D is selected form this group consisting of O, S, SO, SO2, SO2NR7, NR7SO2, NR8, POOR7, PON(R7)2, POOR7NR7, NR7POOR7, C(O), C(O)O R7 is hydrogen, lower alkyl, or aryl; R8 is hydrogen, lower alkyl, COR9, or CO2R9; R9 is lower alkyl, or aryl; m = 0 to about 7; n = 0 to about 5; wherein L may optionally be substituted by one or more of the following: lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, thiol, lower thioalkoxy, S(O)R9, S(O)2R9, halogen, nitro, amino, alkylamino, dialkylamino, aminoalkyl, dialkylaminoalkyl, arylamino, aminoaryl, alkylaminoaryl, acylamino, carboxyl, carboalkoxy, carboaryloxy, carboarylalkyloxy, cyano, aminocarbonylalkoxy, aminocarbonylamino, aminocarbonylaminoalkyl, haloalkyl, SO2NR7R9, cycloalkyl, heterocyclyl, aryl, heteroaryl, lactonyl, lactamyl, amidino, isourea, isothiourea, guanidino, substituted guanidino, wherein all said substitutions may be optionally substituted with one or more of the following; lower alkyl, amino, alkylamino, dialkylamino, aminoalkyl, aminoacyl, carboxyl, carboalkoxy, carboaryloxy, carboalkylaryloxy, hydroxy, lower alkoxy, nitro, amidino, guanidino, substituted guanidino, isourea, isothiourea and X is selected form the group consisting of NH, O, S, (CH2)p, and CH=CH; p = 0 to about 4; A is selected from the group consisting of O, NR7, (CH2)q, CH=CH; q = 1 to about 2; B is selected from the group consisting of (CH2)v, CH=CH; v=1 to about 2; R2, R3, and R4 are independently selected from hydrogen, lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, thiol, lower thioalkoxy, S(O)R9, S(O)2R9, halogen, nitro, amino, alkylamino, dialkylamino, aminoalkyl, dialkylaminoalkyl, arylamino, aminoaryl, alkylaminoaryl, acylamino, carboxyl, carboalkoxy, carboaryloxy, carboarylalkyloxy, cyano, aminocarbonylalkoxy, aminocarbonylamino, aminocarbonylaminoalkyl, haloalkyl, SO2NR7R9, wherein all said substitutions may be optionally substituted with one or more of the following: halogen, lower alkyl, amino, alkylamino, dialkylamino, aminoalkyl, aminoacyl, carboxyl, carboalkoxy, carboaryloxy, carboalkylaryloxy, hydroxy, lower alkoxy, and and R2, R3, may optionally be taken together to form an exocyclic double bond, alicyclic hydrocarbon, heterocyclyl or aromatic hydrocarbon and said optionally formed unit may be optionally substituted with one or more of the following: lower alkyl, lower alkenyl, lower alkynyl which may be optionally substituted with carboxyl, carboalkoxy, carboaryloxy, carboxyalkylaryloxy and lower alkoxy; and R5, R6 are independently selected from the group consisting of hydrogen, hydroxy, and alkyloxy.