Delving into the Latest Updates on SB-228357 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

5-HT2C receptor

Mechanism

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

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Anxiety DisordersDepressive Disorder

Originator Organization

Smithkline Beecham Plc

Active Organization-

Inactive Organization

Smithkline Beecham Plc

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Author: Wyman, Paul A. ; Ham, Peter ; Mulholland, Keith R. ; Davies, Susannah ; Duckworth, D. Malcolm ; Blaney, Frank E. ; Riley, Graham J. ; Lightowler, Sean ; Trail, Brenda ; Wood, Martyn D. ; Davies, David T. ; Clarke, Stephen E. ; Kennett, Guy A. ; Forbes, Ian T. ; Holland, Vicky ; Blackburn, Thomas P. ; Saunders, Damian V. ; Jones, Graham E. ; Gaster, Laramie M. ; Dabbs, Steven ; Middlemiss, Derek N. ; Bromidge, Steven M. ; King, Frank D.

The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5-HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

100 Deals associated with SB-228357

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