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 A
wherein:
Q is selected from the group consisting of a salt of COOH, CONR′R″, SO 3 H or a salt thereof, and SO 2 NR′R″;
P is selected from the group consisting of (a), (b), (c) and (d)
R 1 is selected from the group consisting of Cl, Br, I, CH 3 , CF 3 , CHF 2 , and CH 2 F;
R 3 is H or CH 3 ;
R′ and R″ are independently selected from the group consisting of H, lower alkyl, and lower alkyl substituted with one or more OR, CO 2 R, NHR, NR 2 , or CF 3 groups wherein R is H or lower alkyl, or
R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
R O is selected from the group consisting of Cl, Br, CF 3 and methyl;
R P is selected from the group consisting of halogen, methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, and C 3 -C 6 eyeloalkyl;
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 ;
U and U′ are independently selected from N and CH;
R 7 is selected from the group consisting of Cl, Br, I, CH 3 , CF 3 , OCH 3 , isopropyl, cyclopropyl, tert-butyl, and cyclohutyl; and
R 8 , R 9 , R 10 and R 11 are independently H or CH 3 ;
with the provisos that,
when Q is SO 2 NH 2 , R 1 is not methyl unless R P is halogen, cyclopropylmethyl or C 3 -C 6 cycloalkyl, and
R 7 is methyl only if R 6 is methyl.
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 O is Cl.
6. The compound of claim 1 , wherein P is a substituted quinoline or isoquinoline and R 1 is selected from the group consisting of Br, CF 3 , CFH 2 , and CF 2 H.
7. The compound of claim 6 , wherein each of R 4 , R 5 , and R 6 is H.
8. The compound of claim 6 , wherein R P is cyclopropyl.
9. The compound of claim 6 , wherein R 1 is Br and R O is Cl.
10. The compound of claim 1 , wherein Q is a salt of COOH and wherein the salt is Na+, K+, Ca++, Mg++, or DABCO salt.
11. A pharmaceutical composition comprising a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.
12. The compound of claim 1 , which is
2-[5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-chloro-4-sulfamoyl-phenyl)-acetamidc or
2-[5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-chloro-4-carbamoyl-phenyl)-acetamide.
13. The compound of claim 1 , which is
2-[5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-sulfamoyl-phenyl)-acetamide or
2-[5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-carbamoyl-phenyl)-acetamide.