Design, Synthesis, and X-ray Studies of Potent HIV-1 Protease Inhibitors Incorporating Aminothiochromane and Aminotetrahydronaphthalene Carboxamide Derivatives As the P2 Ligands

Overview

Journal Eur J Med Chem

Specialty Chemistry

Date 2018 Oct 20

PMID 30340140

Citations 1

Authors

Arun K Ghosh

Ravindra D Jadhav

Hannah Simpson

Satish Kovela

Heather Osswald

Johnson Agniswamy

Yuan-Fang Wang

Shin-Ichiro Hattori

Irene T Weber

Hiroaki Mitsuya

Affiliations

Soon will be listed here.

Abstract

We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.

Citing Articles

Design, Synthesis, and Biological Evaluation of Darunavir Analogs as HIV-1 Protease Inhibitors.

Ur Rehman M, Chuntakaruk H, Amphan S, Suroengrit A, Hengphasatporn K, Shigeta Y ACS Bio Med Chem Au. 2024; 4(5):242-256.

PMID: 39431267 PMC: 11487539. DOI: 10.1021/acsbiomedchemau.4c00040.

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