Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses.
Kertesz DJ, Brotherton-Pleiss C, Yang M, Wang Z, Lin X, Qiu Z, Hirschfeld DR, Gleason SK, Mirzadegan T, Dunten PW, Harris SF, Villaseñor AG, Hang JQ, Heilek GM, Klumpp K
Bioorganic & medicinal chemistry letters (2010), Volume 20, Page 4215
Abstract:
An analysis of the binding motifs of known HIV-1 non-nucleoside reverse transcriptase inhibitors has led to discovery of novel piperidine-linked aminopyrimidine derivatives with broad activity against wild-type as well as drug-resistant mutant viruses. Notably, the series retains potency against the K103N/Y181C and Y188L mutants, among others. Thus, the N-benzyl compound 5k has a particularly attractive profile. Synthesis and SAR are presented and discussed, as well as crystal structures relating to the binding motifs.
Polymerases:
Topics:
Mutational Analysis, Structure and Structure/Function, Reverse Transcriptase
Status:
| new | topics/pols set | partial results | complete | validated |
Results:
| Polymerase | Reference | Property | Result | Context |
|---|---|---|---|---|
| HIV RT | Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses. | Reverse Transcriptase Activity | Yes |
Entry validated by:
Structures:
