Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Research Abstract Details 

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Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Abstract Text:

Joachim Rudolph,William P Esler,Stephen O'connor,Philip D G Coish,Philip L Wickens,Michael Brands,Donald E Bierer,Brian T Bloomquist,Georgiy Bondar,Libing Chen,Chih-Yuan Chuang,Thomas H Claus,Zahra Fathi,Wenlang Fu,Uday R Khire,James A Kristie,Xiao-Gao Liu,Derek B Lowe,Andrea C McClure,Martin Michels,Astrid A Ortiz,Philip D Ramsden,Robert W Schoenleber,Tatiana E Shelekhin,Alexandros Vakalopoulos,Weifeng Tang,Lei Wang,Lin Yi,Stephen J Gardell,James N Livingston,Laurel J Sweet,William H Bullock,Joachim Rudolph,William P Esler,Stephen O'connor,Philip D G Coish,Philip L Wickens,Michael Brands,Donald E Bierer,Brian T Bloomquist,Georgiy Bondar,Libing Chen,Chih-Yuan Chuang,Thomas H Claus,Zahra Fathi,Wenlang Fu,Uday R Khire,James A Kristie,Xiao-Gao Liu,Derek B Lowe,Andrea C McClure,Martin Michels,Astrid A Ortiz,Philip D Ramsden,Robert W Schoenleber,Tatiana E Shelekhin,Alexandros Vakalopoulos,Weifeng Tang,Lei Wang,Lin Yi,Stephen J Gardell,James N Livingston,Laurel J Sweet,William H Bullock,

The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine-substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Publishing Authors By Initials

J Rudolph,WP Esler,S O'connor,PD Coish,PL Wickens,M Brands,DE Bierer,BT Bloomquist,G Bondar,L Chen,CY Chuang,TH Claus,Z Fathi,W Fu,UR Khire,JA Kristie,XG Liu,DB Lowe,AC McClure,M Michels,AA Ortiz,PD Ramsden,RW Schoenleber,TE Shelekhin,A Vakalopoulos,W Tang,L Wang,L Yi,SJ Gardell,JN Livingston,LJ Sweet,WH Bullock,J Rudolph,WP Esler,S O'connor,PD Coish,PL Wickens,M Brands,DE Bierer,BT Bloomquist,G Bondar,L Chen,CY Chuang,TH Claus,Z Fathi,W Fu,UR Khire,JA Kristie,XG Liu,DB Lowe,AC McClure,M Michels,AA Ortiz,PD Ramsden,RW Schoenleber,TE Shelekhin,A Vakalopoulos,W Tang,L Wang,L Yi,SJ Gardell,JN Livingston,LJ Sweet,WH Bullock,

For similar pathological conditions, signs and symptoms: signs and symptoms: body weight: body weight changes: weight loss research abstracts see: pathological conditions, signs and symptoms: signs and symptoms: body weight: body weight changes: weight loss research

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Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of medicinal chemistry

VOLUME: 50

Page Numbers: 5202-16

Journal Abbreviation: J. Med. Chem.

ISSN: 0022-2623

DAY: 21

MONTH: 09

YEAR: 2007

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Information

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LANGUAGE: eng

NlmUniqueID: 9716531

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Keywords Mesh Terms:

KEYWORDS: Weight Loss

MESH TERMS: drug effects

Chemical & Substance for Abstract: Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. Information

Substance Name: Receptors, Ghrelin

Registry Number: 0

Grant and Affiliation Information for Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

AFFILIATION: Department of Chemistry Research, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, Connecticut 06516, USA. rudolph.joachim@gene.com

Country: United States

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MEDLINETA: J Med Chem

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