Amides as inhibitors of human secreted phospholipase A2
Methods and compounds useful for inhibiting a phoshpolipase A 2 are provided, the methods comprising contacting the phoshpolipase A 2 with a compound having the structure A, or pharmaceutically acceptable salts thereof: wherein R 1 is H, F, NH 2 , or COOH; R 2 is, H, linear saturated or unsaturated alkyl, alkenyl, or alkynyl; each of R 3 and R 4 is independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl; R 5 is H, (C 1 -C 6 ) alkyl such as methyl or ethyl; X is aryl or substituted aryl, such as phenyl or a substituted phenyl; and Y is O or S.
1. A compound having the structure A, or pharmaceutically acceptable salts thereof:
wherein:
R 1 is H, F, NH 2 , or COOH;
R 2 is H, linear saturated or unsaturated unsubstituted (C 2 -C 10 )alkyl, alkenyl, or alkynyl;
each of R 3 and R 4 is independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl;
R 5 is H or (C 1 -C 6 )alkyl;
X is aryl or substituted aryl; and
Y is O or S.
2. The compound of claim 1 , wherein R 5 is H, methyl, or ethyl; and X is phenyl or substituted phenyl.
3. The compound of claim 1 , wherein the compound has the formula 9:
4. A method of inhibiting a phoshpolipase A 2 , comprising contacting the phoshpolipase A 2 with a compound having the structure A, or pharmaceutically acceptable salts thereof:
wherein:
R 1 is H, F, NH 2 , or COOH;
R 2 is H, linear saturated or unsaturated unsubstituted (C 2 -C 10 )alkyl, alkenyl, or alkynyl;
each of R 3 and R 4 is independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl;
R 5 is H or (C 1 -C 6 )alkyl;
X is aryl or substituted aryl; and
Y is O or S.
5. The method of claim 4 , wherein R 5 is H, methyl, or ethyl; and X is phenyl or substituted phenyl.
6. The method of claim 4 , wherein the compound has the formula 9: