Delving into the Latest Updates on PF-4479745 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

PF 4479745, PF4479745

Target

5-HT2C receptor

Action

agonists

Mechanism

5-HT2C receptor agonists(Serotonin 2c (5-HT2c) receptor agonists)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Urinary Incontinence, Stress

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Pfizer Inc.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC17H22N4

InChIKeyIHHALLDEDARSAL-LBPRGKRZSA-N

CAS Registry1065110-43-1

Author: Conlon, Kelly M. ; Jessiman, Alan S. ; Roberts, Lee R. ; Root, James A. ; Wright, John ; Brennan, Paul E. ; Bungay, Peter J. ; Shanmugasundaram, Veerabahu ; Wheeler, Simon ; Storer, R. Ian ; Whitlock, Gavin A. ; McMurray, Gordon ; Corbett, Matthew S. ; Heifetz, Alexander ; Brown, Alan D. ; Westbrook, Dominique ; Ho, Danny K. H. ; de Oliveira, Cesar Augusto F. ; Shapiro, Michael J. ; Skerten, Melanie ; DePianta, Robert P. ; Fish, Paul V.

A series of 4-substituted pyrimido[4,5-d]azepines that are potent, selective 5-HT2C receptor partial agonists is described. A rational medicinal chemistry design strategy to deliver CNS penetration coupled with SAR-based optimization of selectivity and agonist potency provided compounds with the desired balance of preclinical properties. Lead compounds 17 (PF-4479745) and 18 (PF-4522654) displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems. Utilizing recent advances in the structural biology of GPCRs, homology modeling has been carried out to rationalize binding and agonist efficacy of these compounds.

100 Deals associated with PF-4479745

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