Delving into the Latest Updates on BMS-433796 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

γ-secretase

Action

inhibitors

Mechanism

γ-secretase inhibitors(Gamma-secretase inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Alzheimer Disease

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Author: Barten, Donna M. ; Gao, Qi ; Dangler, Charles ; Smith, David W. ; Polson, Craig T. ; Guss, Valerie L. ; Zheng, Ming ; Yeola, Suresh ; Bergstrom, Carl ; Wang, Jian ; Sleczka, Bogdan G. ; Corsa, Jason A. ; Vig, Shikha ; Hendrick, Joseph P. ; Prasad, C. V. C. ; Loo, Alice ; Roberts, Susan B. ; Robertson, Barbara J.

We report on the design of benzodiazepinones as peptidomimetics at the carboxy terminus of hydroxyamides. Structure-activity relationships of diazepinones were investigated and orally active gamma-secretase inhibitors were synthesized. Active metabolites contributing to Abeta reduction were identified by analysis of plasma samples from Tg2576 mice. In particular, (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796) was identified with an acceptable pharmacodynamic and pharmacokinetic profile. Chronic dosing of BMS-433796 in Tg2576 mice suggested a narrow therapeutic window and Notch-mediated toxicity at higher doses.

100 Deals associated with BMS-433796

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