Tricyclic Dihydroquinazolinones As Novel 5-HT2C Selective and Orally Efficacious Anti-obesity Agents

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2009 Dec 22

PMID 20022752

Citations 3

Authors

Saleem Ahmad

Khehyong Ngu

Keith J Miller

Ginger Wu

Chen-Pin Hung

Sarah Malmstrom

Ge Zhang

Eva OTanyi

William J Keim

Mary Jane Cullen

Kenneth W Rohrbach

Michael Thomas

Thao Ung

Qinling Qu

Jinping Gan

Rangaraj Narayanan

Mary Ann Pelleymounter

Jeffrey A Robl

Affiliations

Soon will be listed here.

Abstract

Agonists of the 5-HT(2C) receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT(2B) receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT(2C) agonists with no detectable agonism of the 5-HT(2B) receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing.

Citing Articles

Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT Modulators.

Kim J, Jo H, Lee H, Choo H, Kim H, Pae A Molecules. 2017; 22(9).

PMID: 28846591 PMC: 6151589. DOI: 10.3390/molecules22091416.

Diversity oriented synthesis and IKK inhibition of aminobenzimidazole tethered quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines.

Dadiboyena S, Arfaoui A, Amri H, Piedrafita F, Nefzi A Bioorg Med Chem Lett. 2014; 25(3):685-9.

PMID: 25522820 PMC: 4311523. DOI: 10.1016/j.bmcl.2014.11.078.

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

Kozikowski A, Cho S, Jensen N, Allen J, Svennebring A, Roth B ChemMedChem. 2010; 5(8):1221-5.

PMID: 20533502 PMC: 2951742. DOI: 10.1002/cmdc.201000186.