Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor

Saleem Ahmad; William N Washburn; Andres S Hernandez; Sharon Bisaha; Khehyong Ngu; Wei Wang; Mary Ann Pelleymounter; Daniel Longhi; Neil Flynn; Anthony V Azzara; Kenneth Rohrbach; James Devenny; Suzanne Rooney; Michael Thomas; Susan Glick; Helen Godonis; Susan Harvey; Hongwei Zhang; Brian Gemzik; Evan B Janovitz; Christine Huang; Lisa Zhang; Jeffrey A Robl; Brian J Murphy

doi:10.1021/acs.jmedchem.6b00676

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Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor

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Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor

Saleem Ahmad, William N Washburn, Andres S Hernandez, Sharon Bisaha, Khehyong Ngu, Wei Wang, Mary Ann Pelleymounter, Daniel Longhi, Neil Flynn, Anthony V Azzara, …

Journal of medicinal chemistry, v 59(19), pp 8848-8858

13 Oct 2016

DOI: https://doi.org/10.1021/acs.jmedchem.6b00676

PMID: 27564419

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Abstract

Animals

Anti-Obesity Agents - chemistry

Anti-Obesity Agents - pharmacokinetics

Anti-Obesity Agents - pharmacology

Anti-Obesity Agents - therapeutic use

Dogs

Halogenation

Humans

Macaca fascicularis

Male

Mice

Obesity - drug therapy

Pyrimidines - chemistry

Pyrimidines - pharmacokinetics

Pyrimidines - pharmacology

Pyrimidines - therapeutic use

Rats

Receptors, Somatostatin - antagonists & inhibitors

Receptors, Somatostatin - metabolism

Structure-Activity Relationship

The potent MCHR1 in vitro and in vivo antagonist activity of a series of cyclic tertiary alcohols derived from compound 2b is described. Subsequent pharmacokinetic and pharmacodynamic studies identified BMS-814580 (compound 10) as a highly efficacious antiobesity agent with a relatively clean in vitro and in vivo safety profile.

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14 citations in Web of Science

12 citations in Scopus

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Title: Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor
Creators: Saleem Ahmad - Bristol-Myers Squibb (United States)
William N Washburn - Bristol-Myers Squibb (United States)
Andres S Hernandez - Bristol-Myers Squibb (United States)
Sharon Bisaha - Bristol-Myers Squibb (United States)
Khehyong Ngu - Bristol-Myers Squibb (United States)
Wei Wang - Bristol-Myers Squibb (United States)
Mary Ann Pelleymounter - Bristol-Myers Squibb (United States)
Daniel Longhi - Bristol-Myers Squibb (United States)
Neil Flynn - Bristol-Myers Squibb (United States)
Anthony V Azzara - Bristol-Myers Squibb (United States)
Kenneth Rohrbach - Bristol-Myers Squibb (United States)
James Devenny - Bristol-Myers Squibb (United States)
Suzanne Rooney - Bristol-Myers Squibb (United States)
Michael Thomas - Bristol-Myers Squibb (United States)
Susan Glick - Bristol-Myers Squibb (United States)
Helen Godonis - Bristol-Myers Squibb (United States)
Susan Harvey - Bristol-Myers Squibb (United States)
Hongwei Zhang - Bristol-Myers Squibb (United States)
Brian Gemzik - Bristol-Myers Squibb (United States)
Evan B Janovitz - Bristol-Myers Squibb (United States)
Christine Huang - Bristol-Myers Squibb (United States)
Lisa Zhang - Bristol-Myers Squibb (United States)
Jeffrey A Robl - Bristol-Myers Squibb (United States)
Brian J Murphy - Bristol-Myers Squibb (United States)
Publication Details: Journal of medicinal chemistry, v 59(19), pp 8848-8858
Publisher: American Chemical Society (ACS)
Resource Type: Journal article
Language: English
Academic Unit: Pharmacology and Physiology
Web of Science ID: WOS:000385607100011
Scopus ID: 2-s2.0-84991392264
Other Identifier: 991021902531604721

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Web of Science research areas: Chemistry, Medicinal

Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor

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Abstract

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Details

UN Sustainable Development Goals (SDGs)

InCites Highlights

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