Delving into the Latest Updates on SB-568849 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MCHR1

Mechanism

MCHR1 inhibitors(Melanin-concentrating hormone receptor 1 inhibitors)

Therapeutic Areas

Endocrinology and Metabolic DiseaseOther Diseases

Active Indication-

Inactive Indication

Anxiety DisordersObesity

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability.

01 Sep 2006·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849

Q4 · MEDICINE

Article

Author: Dieter Hamprecht ; Andrea Haynes ; Geoffrey Stemp ; Phillip Jeffrey ; David R. Witty ; Kamal Al-Barazanji ; Christopher N. Johnson ; Kevin Thewlis ; Alison I. Muir ; Kim Y. Winborn ; Alex J. Stevens ; Guillaume J. Hervieu ; John Bateson ; Peter J. O’Hanlon

A strategy of systematically targeting more rigid analogues of the known MCH R1 receptor antagonist, SB-568849, serendipitously uncovered a binding mode accessible to N-aryl-phthalimide ligands. Optimisation to improve the stability of this compound class led to the discovery of novel N-aryl-quinazolinones, benzotriazinones and thienopyrimidinones as selective ligands with good affinity for human melanin-concentrating hormone receptor 1.

100 Deals associated with SB-568849

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