BIOMAT Database Logo BIOMAT Database Logo

N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase. 2011

Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455.

A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of Human Immunodeficiency Virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)-thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity-relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.

UI MeSH Term Description Entries

Related Publications

Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Design, synthesis and biological evaluation of 3-hydroxyquinazoline-2,4(1H,3H)-diones as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and integrase.
September 2019, Bioorganic & medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Rationally designed dual inhibitors of HIV reverse transcriptase and integrase.
July 2007, Journal of medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Synthesis of pyrimidine and quinolone conjugates as a scaffold for dual inhibitors of HIV reverse transcriptase and integrase.
February 2008, Bioorganic & medicinal chemistry letters,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
[Research progress of dual inhibitors targeting HIV-1 reverse transcriptase and integrase].
April 2013, Yao xue xue bao = Acta pharmaceutica Sinica,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Advances in rationally designed dual inhibitors of HIV-1 reverse transcriptase and integrase.
November 2016, Bioorganic & medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Rapid screening of HIV reverse transcriptase and integrase inhibitors.
April 2014, Journal of visualized experiments : JoVE,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.
December 2017, European journal of medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Evolution of HIV-1 reverse transcriptase and integrase dual inhibitors: Recent advances and developments.
October 2019, European journal of medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
6-Biphenylmethyl-3-hydroxypyrimidine-2,4-diones potently and selectively inhibited HIV reverse transcriptase-associated RNase H.
August 2018, European journal of medicinal chemistry,
Jing Tang, and Kasthuraiah Maddali, and Christine D Dreis, and Yuk Y Sham, and Robert Vince, and Yves Pommier, and Zhengqiang Wang
Pyrimidine 2,4-Diones in the Design of New HIV RT Inhibitors.
May 2019, Molecules (Basel, Switzerland),
Copied contents to your clipboard!