S-TRIAZOLYL ALPHA-MERCAPTO ACETANILIDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE
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 CONR′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 0 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 cycloalkyl;
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 cyclobutyl; and
R 8 , R 9 , R 10 and R 11 are independently H or CH 3 .
2 . The compound of claim 1 , wherein none of R 4 , R 5 , and R 6 are OH, NH 2 or NHCH 3 .
3 . The compound of claim 1 , wherein P is not substituted phenyl and at least one of R 4 , R 5 , and R 6 is other than H or CH 3 .
4 . The compound of claim 1 , wherein P is a substituted phenyl and R 6 is not methyl.
5 . The compound of claim 2 , wherein P is not substituted phenyl and at least one of R 4 , R 5 , and R 6 is other than H or CH 3 .
6 . (canceled)
7 . The compound of claim 2 , 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.
8 . The compound of claim 7 , wherein each of R 4 , R 5 , and R 6 is H.
9 . The compound of claim 7 , wherein R P is cyclopropyl.
10 . The compound of claim 7 , wherein R 1 is Br and R 0 is Cl.
11 . The compound of claim 2 , 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.
12 . The compound of claim 11 , wherein each of R 4 , R 5 , and R 6 is H.
13 . The compound of claim 11 , wherein R P is cyclopropyl.
14 . The compound of claim 11 , wherein R 1 is Br and R 0 is Cl.
15 . (canceled)
16 . (canceled)
17 . (canceled)
18 . A pharmaceutical composition comprising a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.
19 . A compound of Formula A
wherein:
R 1 is C 1-3 alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br, —NH 2 , or hydrogen;
R 2 is an aryl or heteroaryl moiety containing a cycloalkyl or heterocyclic group which can be further substituted with alkyl, cycloalkyl, aryl or heteroaryl moieties;
Q is a C 3-5 cycloalkyl;
W is S, O, or an optionally substituted amine;
R 3 is C 1-3 alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br; and
R 4 is —COR′, wherein R′ is —NH 2 or —NH(alkyl).
20 . A compound of Formula
wherein:
R 1 is C 1-3 alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br, —NH 2 , or hydrogen;
R 2 is an 4-Q-naphth-1-yl or 4-Q-phen-1-yl-;
Q is C 2-5 alkyl;
W is S, O or an optionally substituted amine;
R 3 is C 1-3 alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br; and
R 4 is —COR′, wherein R′ is —NH 2 or —NH(alkyl).