Zhaosen Zeng

Bio: Zhaosen Zeng is an academic researcher from Fudan University. The author has contributed to research in topics: Diarylpyrimidines & Nucleoside Reverse Transcriptase Inhibitor. The author has an hindex of 7, co-authored 12 publications receiving 223 citations.

Structural Modifications of DAPY Analogues with Potent Anti‐HIV‐1 Activity

Abstract: A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild-type HIV-1.A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were synthesized and evaluated for their in vitro activity against HIV in MT-4 cells. All compounds exhibited strong activity against wild-type HIV-1. The most active compound showed activity against wild-type HIV-1 with an EC(50) value of 2.35 nM and against the double mutant strain (K103N+Y181C) with an EC(50) value of 6.6 microM, with a selectivity index greater than 60 000 against wild-type HIV-1. Additionally, some compounds also showed activity against HIV-2 (EC(50)=5.82 microM).

Design, synthesis, and SAR of naphthyl-substituted Diarylpyrimidines as non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Abstract: A series of 38 2-naphthyl-substituted diarylpyrimidine (DAPY) analogues, characterized by various substitution patterns on the pyrimidine and naphthalene rings, was synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of the HIV-1 wild-type and double mutant (K103N+Y181C) strains. Most of the compounds displayed strong activity against wild-type HIV-1. The most active compound, with a cyano group at position C6 on the naphthalene ring, exhibited activity against wild-type HIV-1 with an EC50 value of 0.002 microM and against the double mutant strain with an EC50 value of 0.24 microM; the selectivity index (SI) against wild-type is >180 000, the highest SI value among DAPY analogues. The structure-activity relationship (SAR) of the newly synthesized DAPYs is presented herein.

Lead optimization of diarylpyrimidines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Abstract: Over the past few years, considerable efforts have been devoted to the structural modification of diarylpyrimidines (DAPYs), a family of non-nucleoside reverse transcriptase inhibitors (NNRTIs) with remarkable anti-HIV-1 activity, leading to the development of etravirine (1), rilpivirine (TMC278, 2) and other highly potent compounds against both wild type and mutant strains of HIV-1 reverse transcriptase (RT).

HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design.

Abstract: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) nowadays represent very potent and most promising anti-AIDS agents that specifically target the HIV-1 reverse transcriptase (RT). However, the effectiveness of NNRTI drugs can be hampered by rapid emergence of drug-resistant viruses and severe side effects upon long-term use. Therefore, there is an urgent need to develop novel, highly potent NNRTIs with broad spectrum antiviral activity and improved pharmacokinetic properties, and more efficient strategies that facilitate and shorten the drug discovery process would be extremely beneficial. Fortunately, the structural diversity of NNRTIs provided a wide space for novel lead discovery, and the pharmacophore similarity of NNRTIs gave valuable hints for lead discovery and optimization. More importantly, with the continued efforts in the development of computational tools and increased crystallographic information on RT/NNRTI complexes, structure-based approaches using a combination of traditional medicinal chemistry, structural biology, and computational chemistry are being used increasingly in the design of NNRTIs. First, this review covers two decades of research and development for various NNRTI families based on their chemical scaffolds, and then describes the structural similarity of NNRTIs. We have attempted to assemble a comprehensive overview of the general approaches in NNRTI lead discovery and optimization reported in the literature during the last decade. The successful applications of medicinal chemistry strategies, crystallography, and computational tools for designing novel NNRTIs are highlighted. Future directions for research are also outlined.

Phosphorous derivatives as kinase inhibitors

Abstract: The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

Strategies for the Design of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Lessons from the Development of Seven Representative Paradigms

Abstract: Transcriptase Inhibitors: Lessons from the Development of Seven Representative Paradigms Dongyue Li,† Peng Zhan,† Erik De Clercq,‡ and Xinyong Liu*,† †Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P. R. China ‡Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

Compounds for inhibiting cell proliferation in egfr-driven cancers

Abstract: The invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of formula (I), wherein the variables are as defined herein.