Delving into the Latest Updates on BMS-363131 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Tryptase

Mechanism

Tryptase inhibitors

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Allergic asthma

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC28H40N6O5

InChIKeyFHCQLMSOTXBNCN-AKFKNWHVSA-N

CAS Registry384829-65-6

Azetidinones such as BMS-363131 (2) and BMS-363130 (3), which contain a guanidine group in the C-3 side chain were previously shown to be very potent inhibitors of human tryptase with high selectivity versus other serine proteases, including trypsin. In this letter, we describe the discovery of a number of potent azetidinone tryptase inhibitors in which the guanidine moiety at the ring C-3 position is replaced with primary or secondary amine or aminopyridine functionality. In particular, BMS-354326 (4) is a highly potent tryptase inhibitor (IC(50)=1.8 nM), which has excellent selectivity against trypsin and most other related serine proteases.

01 Nov 2002·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Synthesis of potent and highly selective inhibitors of human tryptase

Q4 · MEDICINE

Article

Author: Martin L. Ogletree ; Ming-Hsing Huang ; Glenn Jacobs ; Uwe Treuner ; William A. Slusarchyk ; James C. Sutton ; Steven M. Seiler ; Zulan Pi ; Gregory S. Bisacchi ; Wei Meng ; William A. Schumacher ; Karen S. Hartl ; Scott A. Bolton ; Robert Zahler ; Guohua Zhao

The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC(50)<1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin.

100 Deals associated with BMS-363131

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