Literature DB >> 22778800

Rational Drug Design Leading to the Identification of a Potent 5-HT(2C) Agonist Lacking 5-HT(2B) Activity.

Gang Chen1, Sung Jin Cho, Xi-Ping Huang, Niels H Jensen, Andreas Svennebring, Maria F Sassano, Bryan L Roth, Alan P Kozikowski.   

Abstract

The 5-HT(2C) receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT(2C) receptor agonists. After expanding our structure-function library, we were able to combine our datasets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT(2B)/5-HT(2C) agonists, which has led to the identification of a highly selective 5-HT(2C) agonist, (+)-trans-[2-(2-cyclopropylmethoxyphenyl)cyclopropyl]methylamine hydrochloride, with an EC(50) of 55 nM and no detectable agonism at the 5-HT(2B) receptor.

Entities:  

Year:  2011        PMID： 22778800      PMCID： PMC3390974          DOI： 10.1021/ml200206z

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  23 in total

1.  HTS and rational drug design to generate a class of 5-HT(2C)-selective ligands for possible use in schizophrenia.

Authors:  Alan P Kozikowski; Sung Jin Cho; Niels H Jensen; John A Allen; Andreas M Svennebring; Bryan L Roth
Journal:  ChemMedChem       Date:  2010-08-02       Impact factor: 3.466

Review 2.  5-HT2C receptor modulators: a patent survey.

Authors:  Junwon Lee; Myung Eun Jung; Jinhwa Lee
Journal:  Expert Opin Ther Pat       Date:  2010-09-17       Impact factor: 6.674

Review 3.  Pharmacological profile of the 5-HT(2C) receptor agonist WAY-163909; therapeutic potential in multiple indications.

Authors:  John Dunlop; Karen L Marquis; H K Lim; Louis Leung; John Kao; Cynthia Cheesman; Sharon Rosenzweig-Lipson
Journal:  CNS Drug Rev       Date:  2006 Fall-Winter

4.  Pharmacophore-directed homology modeling and molecular dynamics simulation of G protein-coupled receptor: study of possible binding modes of 5-HT2C receptor agonists.

Authors:  Zhili Zuo; Gang Chen; Xiaomin Luo; Chummok Puah; Weiliang Zhu; Kaixian Chen; Hualiang Jiang
Journal:  Acta Biochim Biophys Sin (Shanghai)       Date:  2007-06       Impact factor: 3.848

Review 5.  The molecular biology of serotonin receptors: therapeutic implications for the interface of mood and psychosis.

Authors:  W K Kroeze; B L Roth
Journal:  Biol Psychiatry       Date:  1998-12-01       Impact factor: 13.382

Review 6.  Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity.

Authors:  Keith J Miller
Journal:  Mol Interv       Date:  2005-10

7.  Compulsive behavior in the 5-HT2C receptor knockout mouse.

Authors:  Jennifer M Chou-Green; Todd D Holscher; Mary F Dallman; Susan F Akana
Journal:  Physiol Behav       Date:  2003-04

Review 8.  Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases.

Authors:  Dean A Wacker; Keith J Miller
Journal:  Curr Opin Drug Discov Devel       Date:  2008-07

9.  Mild conditions for Pd-catalyzed carboamination of N-protected hex-4-enylamines and 1-, 3-, and 4-substituted pent-4-enylamines. Scope, limitations, and mechanism of pyrrolidine formation.

Authors:  Myra Beaudoin Bertrand; Joshua D Neukom; John P Wolfe
Journal:  J Org Chem       Date:  2008-10-23       Impact factor: 4.354

Review 10.  Hallucinogens, serotonin and obsessive-compulsive disorder.

Authors:  P L Delgado; F A Moreno
Journal:  J Psychoactive Drugs       Date:  1998 Oct-Dec
View more
  6 in total

1.  Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents.

Authors:  Jianjun Cheng; Patrick M Giguère; Oluseye K Onajole; Wei Lv; Arsen Gaisin; Hendra Gunosewoyo; Claire M Schmerberg; Vladimir M Pogorelov; Ramona M Rodriguiz; Giulio Vistoli; William C Wetsel; Bryan L Roth; Alan P Kozikowski
Journal:  J Med Chem       Date:  2015-02-10       Impact factor: 7.446

2.  Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz.

Authors:  Dhwanil A Dalwadi; Seongcheol Kim; Shahnawaz M Amdani; Zhenglan Chen; Ren-Qi Huang; John A Schetz
Journal:  Pharmacol Res       Date:  2016-05-06       Impact factor: 7.658

3.  Design and Synthesis of (2-(5-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methanamine as a Selective Serotonin 2C Agonist.

Authors:  Jianjun Cheng; Patrick M Giguere; Wei Lv; Bryan L Roth; Alan P Kozikowski
Journal:  Tetrahedron Lett       Date:  2015-06-03       Impact factor: 2.415

4.  Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models.

Authors:  Jianjun Cheng; Patrick M Giguere; Claire M Schmerberg; Vladimir M Pogorelov; Ramona M Rodriguiz; Xi-Ping Huang; Hu Zhu; John D McCorvy; William C Wetsel; Bryan L Roth; Alan P Kozikowski
Journal:  J Med Chem       Date:  2016-01-13       Impact factor: 7.446

5.  We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders.

Authors:  Jianjun Cheng; Alan P Kozikowski
Journal:  ChemMedChem       Date:  2015-10-28       Impact factor: 3.466

6.  Imaging evaluation of 5HT2C agonists, [(11)C]WAY-163909 and [(11)C]vabicaserin, formed by Pictet-Spengler cyclization.

Authors:  Ramesh Neelamegam; Tim Hellenbrand; Frederick A Schroeder; Changning Wang; Jacob M Hooker
Journal:  J Med Chem       Date:  2014-02-12       Impact factor: 7.446
  6 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.