Delving into the Latest Updates on Indinavir Sulfate/L-756423 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

HIV-1 protease

Mechanism

HIV-1 protease inhibitors(HIV protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck Sharp & Dohme Corp.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC39H48N4O5

InChIKeyAOMZDQMIOCTPQP-QHQMVRJISA-N

CAS Registry216863-66-0

View All Structures (2)

Author: Emini, Emilio A. ; Olsen, David B. ; Hoffman, Jacob M. ; Darke, Paul L. ; Newton, Christina L. ; Zugay-Murphy, Joan A. ; Michelson, Stuart R. ; Levin, Rhonda B. ; Lin, Jiunn H. ; Rutkowski, Carrie A. ; Vacca, Joseph P. ; Chen, I-W. ; Holloway, M. Katharine ; McDaniel, Stacey L. ; Stahlhut, Mark W. ; Huff, Joel R. ; Schleif, William A. ; Dorsey, Bruce D. ; Kuo, Lawrence C. ; McDonough, Colleen

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

100 Deals associated with Indinavir Sulfate/L-756423

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