N[S(4-aryl-triazol-3-yl)α-mercaptoacetyl]-
View Patent ↗A series of S-triazolyl α-mercaptoacetanilides having N-(α-mercaptoacetyl) p amino benzoic acid derivatives. are provided, where Q is CO 2 H, or a salt or ester thereof, or a C(O) N-linked amino acid. The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.
1. A method of inhibiting HIV reverse transcriptase, the method comprising contacting HIV reverse transcriptase with a compound of formula 1:
wherein:
R 1 is Cl, Br, I, CH 3 , CF 3 , CHF 2 or CH 2 F;
R 3 is H or CH 3 ;
R o is Cl, Br, CF 3 or methyl;
X is O or NH;
R 2 is H, a pharmaceutically acceptable cation or C 1-3 alkyl, when X is O; or
XR 2 is NHCH 2 CH 2 COOR 13 or NHCH(R 12 )COOR 13 ; where
R 12 is C 1-4 alkyl or aryl-C 1-4 alkyl; and
R 13 is a pharmaceutically acceptable cation or C 1-3 alkyl;
Ar is selected from the group consisting of (a), (b), (c) and (d):
wherein
R P is selected from the group consisting of methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, and C 3-6 cycloalkyl;
R 4 , R 5 and R 6 are independently selected from the group consisting of H, F, Cl, Br, CF 3 , CFH 2 , CF 2 H, ethyl, isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 ;
R 7 is selected from the group consisting of Cl, Br, I, CF 3 , OCH 3 , isopropyl, cyclopropyl, tent-butyl, and cyclobutyl; and
R 8 , R 9 , R 10 and R 11 are independently H or CH 3 .
2. The method of claim 1 , wherein the HIV reverse transcriptase is a mutated reverse transcriptase.
3. The method of claim 2 , wherein the mutated reverse transcriptase is a K103N, Y181C or Y188L mutant.
4. The method of claim 1 , wherein the inhibition occurs in vitro.
5. The method of claim 1 , wherein the inhibition occurs in vivo.
6. The method of claim 1 , wherein the compound of formula 1 is 4-[2-(5-bromo-4-[4-cyclopropyl-7-methoxynaphthalen-l-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid.
7. The method of claim 5 , wherein the compound of formula 1 is 4-[2-(5-bromo-4-[4-cyclopropyl-7-methoxynaphthalen-l-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid.
8. The method of claim 1 , wherein the compound of formula 1 is a pharmaceutically acceptable salt of 4-[2-(5-bromo-4-[4-cyclopropyl-7-methoxynaphthalen-1-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid, R 2 being a pharmaceutically acceptable cation.
9. The method of claim 1 , wherein the compound of formula 1 is a methyl, ethyl or propyl ester of 4-[2-(5-bromo-4-[4-cyclopropyl-7-methoxynaphthalen-l-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid, R 2 being methyl, ethyl, or propyl.