Enzyme inhibitors

Claim 1

A compound of the formula: wherein: A is hydrogen, or R-, RCO- or RSO 2 -, where R is alkyl, cycloalkyl, aryl, heterocyclic, heterocyclic alkyl, heterocyclic aryl, aryloxy alkyl, heterocyclic aryloxy alkyl, aryl alkyl, heterocyclic aryl alkyl, heterocyclic oxyalkyl, and R- may be substituted by amino, hydroxy, alkyl, halo, and alkoxy groups. B and D can independently be absent or can be: E is or or, in the case where G is absent, E may be: E may also be: G is R or is: J is -O- or, in the case where R 4 does not equal hydrogen, may be absent. K is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl alkyl, cycloalkyl alkyl, heterocyclic, heterocyclic alkyl, each of which may be substituted by up to three members selected from amino, alkyl amino, dialkyl amino, trialkyl ammonium, hydroxy, alkoxy, aryloxy, arylalkoxy, alkanoylamino, arovlamino, or halo. K may also be where n' is 3 to 5 and R is as defined below. K may also be of the formula: -(CH 2 ) p -NH-L where p is 1 to 2 and L is or A as defined above. R 1 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkyl alkyl, aryl alkyl, heterocyclic, heterocyclic alkyl, each of which may be substituted by up to three groups selected from alkyl, halo, amino and alkoxy groups. n is 0, 1. R 2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkyl alkyl, aryl, aryl alkyl, heterocyclic, heterocyclic alkyl, each of which may be substituted by up to three groups selected from alkyl, hydroxy, halo, amino, alkylamino, dialkylamino, and alkoxy groups. R 3 is O H, NH , NHR 3 , NR 3 R 3 , OR where R a , R b , and R are separately alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkyl alkyl, aryl, aryl alkyl, heterocyclic, heterocyclic alkyl, each of which may be substituted by up to three groups selected from amino, alkyl amino, dialkyl amino, trialkyl ammonium, hydroxy, alkoxy, aryloxy, aryl alkoxyl, or halo. may also be -CO-V- wherein is alkyl or aryl; and are hydrogen or alkyl; V is -O-or -NH-. R 4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, each of which may be substituted by amino, alkyl amino, dialkyl amino, trialkyl ammonium, hydroxy, alkoxy, halo or alkyl groups. R 4 may also be -CO-V- wherein is alkyl or aryl; and are hydrogen or alkyl; V is -O- or -NH-. R 5 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, cycloalkyl alkyl, aryl alkyl, heterocyclic, heterocyclic alkyl, aryloxy alkyl, heterocyclic oxy alkyl, heterocyclic oxy oxy, each of which may be substituted by amino, alkyl amino, dialkyl amino, trialkyl ammonium, hydroxy, alkoxy, carboxy, alkoxycarbonyl, alkylthio, arylthio, thiol, guanidino, carboxamido and alkanoylamino groups. R 6 is hydrogen, methyl. R 7 can be R 5 and taken together with NR 8 may be a cyclic amino acid of formulas: where is hydrogen, phenyl, hydroxyphenyl; X is -S- or -CH 2 - or -CH- ; m is 1 or 2; and is cyclohexyl, phenylthio; W and Z are bonds or -CH 2 -, and R 3 is as defined above. R 8 is hydrogen, methyl and cycloalkyl including cyclopentyl and indanyl. When R 8 is cycloalkyl, R 6 and R 7 are hydrogen. R 9 is hydroxy, , -NH 2 , , , where and are as defined above. When A and B are both absent, R 9 can be where R 3 , R 5 and R 6 are as defined above. R 10 is alkyl, aryl alkyl, heterocyclic, heterocyclic alkyl, where each of these may be substituted by up to three groups selected from amino, alkyl amino, dialkyl amino, trialkyl ammonium, hydroxy, alkoxy, thiol, carboxamido, and alkanoylamino or aroylamino groups. R 11 is hydrogen or -OR 4 , where R 4 is as defined above. R 12 and R 13 may independently be hydrogen, alkyl, alkenyl, alkynyl, aryl, aryl alkyl, each of which may be substituted by up to three groups selected from hydroxy, alkyl, amino, alkyl amino, dialkyl amino, trialkyl ammonium, halo, alkanoylamino, aroylamino, alkoxy, and aryloxy groups; and pharmaceutically acceptable salts thereof.