189393-17-7Relevant articles and documents
Non-nucleoside reverse transcriptase inhibitors
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, (2008/06/13)
Provided are compounds of the general formula I: wherein R2 is selected from the group consisting of H, F, Cl, (C1-4) alkyl, (C3-4) cycloalkyl and CF3; R4 is H or Me; R5 is H, Me or Et, wit
Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 8. 8- Aryloxymethyl- and 8-arylthiomethyldipyridodiazepinones
Cywin, Charles L.,Klunder, Janice M.,Hoermann, MaryAnn,Brickwood, Janice R.,David, Eva,Grob, Peter M.,Schwartz, Racheline,Pauletti, Daniel,Barringer, Kevin J.,Shih, Cheng-Kon,Sorge, Christopher L.,Erickson, David A.,Joseph, David P.,Hattox, Susan E.
, p. 2972 - 2984 (2007/10/03)
Nevirapine (I) is the first human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitor to reach regulatory approval. As a result of a second generation program around the tricyclic core system of nevirapine, 2-chloro-5,11-dihydro-11-ethyl-5-methyl-8-(2- (pyridin-4-yl)ethyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (II)1a and 2-chloro-5,11dihydro-11-ethyl-5-methyl-8-phenylethyl-6H-dipyrido[3-2- b:2',3'-e][1,4]diazepin-6-one (III)1a were identified as broad spectrum HIV-1 RT inhibitors. A detailed examination of replacing either of the methylenes of the 8-ethyl linker of II or III is presented. It was found that 8-aryloxymethyl and 8-arylthiomethyl are the preferred pattern of substitution for potency against RT. The most potent compounds were further evaluated against a panel of clinically significant mutant RT enzymes (K103N, V106A, G190A, P236L) and in cytotoxicity and in vitro metabolism assays. The most potent compound was 2-chloro-8-phenylthiomethyl analogue 37 which displayed sub-100 nM activity against all HIV-1 RT enzymes tested.