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 compound of formula
wherein:
R 1 is selected from the group consisting of Cl, Br, I, CH 3 , CF 3 , CHF 2 , and CH 2 F;
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 a pharmaceutically acceptable cation or C 1-3 alkyl;
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 selected from the group consisting of methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, and 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, ethyl, isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 .
2. The compound of claim 1 , wherein X is O.
3. The compound of claim 2 , wherein none of R 4 , R 5 , and R 6 is OH, NH 2 or NHCH 3 .
4. The compound of claim 2 , wherein at least one of R 4 , R 5 , and R 6 is other than H or CH 3 .
5. The compound of claim 3 wherein at least one of R 4 , R 5 , and R 6 is other than H or CH 3 .
6. The compound of claim 3 , wherein 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 7 , wherein R P is cyclopropyl.
9. The compound of claim 7 , which is 4-[2-(5-bromo-4-[4-cyclopropylnaphthalen-1-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid or an ester or a pharmaceutically acceptable salt thereof.
10. The compound of claim 9 , wherein R 2 is H.
11. The compound of claim 6 , wherein R 1 is Br and R 0 is Cl.
12. The compound of claim 6 , wherein Ar is 7-substituted naphthyl.
13. The compound of claim 12 , wherein R 4 is 7-ethyl, 7-OCH 3 , or 7-cyclopropyl, and each of R 5 and R 6 are H.
14. The compound of claim 13 , which is 4-[2-(5-bromo-4-[7-methoxy-4-methylnaphthalen-1-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid or an ester or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14 , wherein R 2 is H.
16. The compound of claim 6 , where R 0 is Cl.
17. The compound of claim 16 , wherein R P is cyclopropyl.
18. The compound of claim 17 , which is 4-[2-(5-bromo-4-[4-cyclopropyl-7-methoxynaphthalen-1-yl]-4H-1,2,4-triazol-3-ylthio)acetamido]-3-chlorobenzoic acid or an ester or a pharmaceutically acceptable salt thereof.
19. The compound of claim 18 , wherein R 2 is H.