Nonnucleoside reverse transcriptase inhibitors

1. A method for treating an existing HIV infection comprising administering to a host in need thereof a therapeutically effective amount of a compound of formula I

wherein:

X 1 is selected from the group consisting of R 5 O, R 5 S(O) n , R 5 CH 2 , R 5 CH 2 O, R 5 CH 2 S(O) n , R 5 OCH 2 , R 5 S(O) n , CH 2 and NR 5 R 6 ;

X 2 is selected from the group consisting of O, S, and NR 7 ;

R 1 and R 2 are

(i) each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, C 1-6 haloalkoxy, C 1-6 haloalkylthio, halogen, amino, alkylamino, dialkylamino, aminoacyl, nitro and cyano; or,

(ii) taken together are —CH—CH—CH═CH—, or

(iii) taken together along with the carbons to which they are attached to form a five- or six-membered heteroaromatic or heterocyclic ring with a one or two heteroatoms independently selected from the group consisting of O, S and NH;

R 3 and R 4 are each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 1-6 haloalkylthio, halogen, amino, alkylamino, dialkylamino, aminoacyl, nitro and cyano;

R 5 is selected from the group consisting of phenyl, naphthyl, pyrdinyl, pyridinyl N-oxide, indolyl, indolyl N-oxide, quinolinyl, quinolinyl N-oxide, pyrimidinyl, pyrazinyl and pyrrolyl; wherein, said phenyl, said naphthyl, said pyrdinyl, said pyridinyl N-oxide said indolyl, said indolyl N-oxide, said quinolinyl, said quinolinyl N-oxide, said pyrimidinyl, said pyrazinyl and said pyrrolyl groups are optionally substituted with one to three substituents independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, C 1-6 haloalkoxy, C 1-6 haloalkylthio, halogen, amino, alkylamino, dialkylamino, aminoacyl, acyl, alkoxycarbonyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, nitro and cyano;

R 6 is hydrogen, C 1-6 alkyl, or acyl;

R 7 is hydrogen or C 1-6 alkyl optionally substituted with one or two substituents independently selected from the group consisting of hydroxy, alkoxy, thiol, alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, halogen, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, and dialkylamino;

n is an integer from 0 to 2; or acid addition salts thereof.

2. A method according to claim 1 wherein:

X 1 is OR 5 ;

R 1 is methyl, ethyl, trifluoromethyl or halogen;

R 2 and R 4 are independently selected from the group consisting of hydrogen, fluoro, chloro, methyl and ethyl;

R 3 is hydrogen or fluoro; and,

R 5 is optionally substituted phenyl.

3. A method for treating HIV infection according to claim 1 further comprising co-administering at least one compound selected from the group consisting of HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, CCR5 inhibitors and viral fusion inhibitors.

4. A method according to claim 3 wherein the reverse transcriptase inhibitor is selected from the group consisting of zidovudine, lamivudine, didanosine, zalcitabine, stavudine, rescriptor, sustiva, viramune, efavirenz, nevirapine and delavirdine and/or the protease inhibitor is selected from the group consisting of saquinavir, ritonavir, nelfinavir, indinavir, amprenavir and lopinavir.

5. A method according to claim 2 for inhibiting a HIV reverse transcriptase.

6. A method according to claim 5 wherein the host is infected with a strain of HIV expressing a reverse transcriptase with at least one mutation compared to wild type virus.

7. A method according to claim 6 wherein said strain of HIV exhibits reduced susceptibility to efavirenz, nevirapine or delavirdine.