S-triazolyl α-mercaptoacetanilides as inhibitors of HIV reverse transcriptase
View Patent ↗A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is CO 2 H, CONR 2 , SO 3 H, or SO 2 NR 2 . The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.
1. A compound of formula
wherein:
P is selected from the group consisting of (a):
R 1 is selected from the group consisting of Cl, Br, I, CF 3 , CHF 2 ; and CH 2 F;
R 2 and R 2′ are independently selected from the group consisting of H, optionally substituted C 1-5 acyl, 1-(C 2-4 acyloxy)C 1-4 alkoxycarbonyl, and an acyl group derived from an α-amino acid;
R 3 is H or CH 3 ;
R 0 is selected from the group consisting of Cl, Br, CF 3 and methyl;
R P is C 3-6 cycloalkyl; and
R 4 , R 5 and R 6 are independently selected from the group consisting of H, F, Br, CH 3 , CF 3 , CFH 2 , CF 2 H, isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 .
2. The compound of claim 1 , wherein
P is a substituted naphthyl and
R 1 is selected from the group consisting of Br, CF 3 , CFH 2 , and CF 2 H.
3. The compound of claim 2 , wherein each of R 4 , R 5 , and R 6 is H.
4. The compound of claim 2 , wherein R P is cyclopropyl.
5. The compound of claim 2 , wherein
R 1 is Br and
R 0 is Cl.
6. A method for inhibiting an HIV reverse transcriptase, comprising contacting the HIV reverse transcriptase with a compound of formula
wherein:
P is selected from the group consisting of (a):
R 1 is selected from the group consisting of Cl, Br, I, CF 3 , CHF 2 , and CH 2 F;
R 2 and R 2′ are independently selected from the group consisting of H, optionally substituted C 1-5 acyl, 1-(C 2-4 acyloxy)C 1-4 alkoxycarbonyl, and an acyl group derived from an α-amino acid;
R 3 is H or CH 3 ;
R 0 is selected from the group consisting of Cl, Br, CF 3 and methyl;
R P is C 3-6 cycloalkyl; and
R 4 , R 5 and R 6 are independently selected from the group consisting of H, F, Cl, Br, CH 3 , CF 3 , CFH 2 , CF 2 H, isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 .
7. The method of claim 6 , wherein the HIV reverse transcriptase is a mutated reverse transcriptase.
8. The method of claim 7 , wherein the mutated HIV reverse transcriptase is a K10Y, Y181C or Y188L mutant.