Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents

Agonists of the 5-HT sub(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 sub(2B) receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-02, Vol.20 (3), p.1128-1133
Main Authors: Ahmad, Saleem, Ngu, Khehyong, Miller, Keith J, Wu, Ginger, Hung, Chen-Pin, Malmstrom, Sarah, Zhang, Ge, O'Tanyi, Eva, Keim, William J, Cullen, Mary Jane, Rohrbach, Kenneth W, Thomas, Michael, Ung, Thao, Qu, Qinling, Gan, Jinping, Narayanan, Rangaraj, Pelleymounter, Mary Ann, Robl, Jeffrey A
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page 1133
container_issue 3
container_start_page 1128
container_title Bioorganic & medicinal chemistry letters
container_volume 20
creator Ahmad, Saleem
Ngu, Khehyong
Miller, Keith J
Wu, Ginger
Hung, Chen-Pin
Malmstrom, Sarah
Zhang, Ge
O'Tanyi, Eva
Keim, William J
Cullen, Mary Jane
Rohrbach, Kenneth W
Thomas, Michael
Ung, Thao
Qu, Qinling
Gan, Jinping
Narayanan, Rangaraj
Pelleymounter, Mary Ann
Robl, Jeffrey A
description Agonists of the 5-HT sub(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 sub(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 sub(2C) agonists with no detectable agonism of the 5-HT sub(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.
doi_str_mv 10.1016/j.bmcl.2009.12.014
format article
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_21296186</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>21296186</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_212961863</originalsourceid><addsrcrecordid>eNqNjU1OwzAQhb0AifJzga5mhWARY5s0atYVqAfIgl3lOBOYaGpDxqmUnr5B4gCsnvT0ve8ptbZGW2Orl0G3x8DaGVNr67Sx5ZVamboyxbYuP27UrchgltaU5UoNzUhhDkwBOvqauzH9TBT9OTHFFFHAC8R0QoZNsW9ApvbJ7Z5BkDFkOiH42EEaPfMM2PcUfKA0LbOYqUgtCuUZ_CfGLPfquvcs-PCXd-rx_a3Z7Yvv31OUfDiSBGT2ERfFwVlXV3Zbvf4bvAByQFGe</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21296186</pqid></control><display><type>article</type><title>Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents</title><source>ScienceDirect Freedom Collection</source><creator>Ahmad, Saleem ; Ngu, Khehyong ; Miller, Keith J ; Wu, Ginger ; Hung, Chen-Pin ; Malmstrom, Sarah ; Zhang, Ge ; O'Tanyi, Eva ; Keim, William J ; Cullen, Mary Jane ; Rohrbach, Kenneth W ; Thomas, Michael ; Ung, Thao ; Qu, Qinling ; Gan, Jinping ; Narayanan, Rangaraj ; Pelleymounter, Mary Ann ; Robl, Jeffrey A</creator><creatorcontrib>Ahmad, Saleem ; Ngu, Khehyong ; Miller, Keith J ; Wu, Ginger ; Hung, Chen-Pin ; Malmstrom, Sarah ; Zhang, Ge ; O'Tanyi, Eva ; Keim, William J ; Cullen, Mary Jane ; Rohrbach, Kenneth W ; Thomas, Michael ; Ung, Thao ; Qu, Qinling ; Gan, Jinping ; Narayanan, Rangaraj ; Pelleymounter, Mary Ann ; Robl, Jeffrey A</creatorcontrib><description>Agonists of the 5-HT sub(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 sub(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 sub(2C) agonists with no detectable agonism of the 5-HT sub(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.</description><identifier>ISSN: 0960-894X</identifier><identifier>DOI: 10.1016/j.bmcl.2009.12.014</identifier><language>eng</language><ispartof>Bioorganic &amp; medicinal chemistry letters, 2010-02, Vol.20 (3), p.1128-1133</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Ahmad, Saleem</creatorcontrib><creatorcontrib>Ngu, Khehyong</creatorcontrib><creatorcontrib>Miller, Keith J</creatorcontrib><creatorcontrib>Wu, Ginger</creatorcontrib><creatorcontrib>Hung, Chen-Pin</creatorcontrib><creatorcontrib>Malmstrom, Sarah</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>O'Tanyi, Eva</creatorcontrib><creatorcontrib>Keim, William J</creatorcontrib><creatorcontrib>Cullen, Mary Jane</creatorcontrib><creatorcontrib>Rohrbach, Kenneth W</creatorcontrib><creatorcontrib>Thomas, Michael</creatorcontrib><creatorcontrib>Ung, Thao</creatorcontrib><creatorcontrib>Qu, Qinling</creatorcontrib><creatorcontrib>Gan, Jinping</creatorcontrib><creatorcontrib>Narayanan, Rangaraj</creatorcontrib><creatorcontrib>Pelleymounter, Mary Ann</creatorcontrib><creatorcontrib>Robl, Jeffrey A</creatorcontrib><title>Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents</title><title>Bioorganic &amp; medicinal chemistry letters</title><description>Agonists of the 5-HT sub(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 sub(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 sub(2C) agonists with no detectable agonism of the 5-HT sub(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.</description><issn>0960-894X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqNjU1OwzAQhb0AifJzga5mhWARY5s0atYVqAfIgl3lOBOYaGpDxqmUnr5B4gCsnvT0ve8ptbZGW2Orl0G3x8DaGVNr67Sx5ZVamboyxbYuP27UrchgltaU5UoNzUhhDkwBOvqauzH9TBT9OTHFFFHAC8R0QoZNsW9ApvbJ7Z5BkDFkOiH42EEaPfMM2PcUfKA0LbOYqUgtCuUZ_CfGLPfquvcs-PCXd-rx_a3Z7Yvv31OUfDiSBGT2ERfFwVlXV3Zbvf4bvAByQFGe</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Ahmad, Saleem</creator><creator>Ngu, Khehyong</creator><creator>Miller, Keith J</creator><creator>Wu, Ginger</creator><creator>Hung, Chen-Pin</creator><creator>Malmstrom, Sarah</creator><creator>Zhang, Ge</creator><creator>O'Tanyi, Eva</creator><creator>Keim, William J</creator><creator>Cullen, Mary Jane</creator><creator>Rohrbach, Kenneth W</creator><creator>Thomas, Michael</creator><creator>Ung, Thao</creator><creator>Qu, Qinling</creator><creator>Gan, Jinping</creator><creator>Narayanan, Rangaraj</creator><creator>Pelleymounter, Mary Ann</creator><creator>Robl, Jeffrey A</creator><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20100201</creationdate><title>Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents</title><author>Ahmad, Saleem ; Ngu, Khehyong ; Miller, Keith J ; Wu, Ginger ; Hung, Chen-Pin ; Malmstrom, Sarah ; Zhang, Ge ; O'Tanyi, Eva ; Keim, William J ; Cullen, Mary Jane ; Rohrbach, Kenneth W ; Thomas, Michael ; Ung, Thao ; Qu, Qinling ; Gan, Jinping ; Narayanan, Rangaraj ; Pelleymounter, Mary Ann ; Robl, Jeffrey A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_212961863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmad, Saleem</creatorcontrib><creatorcontrib>Ngu, Khehyong</creatorcontrib><creatorcontrib>Miller, Keith J</creatorcontrib><creatorcontrib>Wu, Ginger</creatorcontrib><creatorcontrib>Hung, Chen-Pin</creatorcontrib><creatorcontrib>Malmstrom, Sarah</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>O'Tanyi, Eva</creatorcontrib><creatorcontrib>Keim, William J</creatorcontrib><creatorcontrib>Cullen, Mary Jane</creatorcontrib><creatorcontrib>Rohrbach, Kenneth W</creatorcontrib><creatorcontrib>Thomas, Michael</creatorcontrib><creatorcontrib>Ung, Thao</creatorcontrib><creatorcontrib>Qu, Qinling</creatorcontrib><creatorcontrib>Gan, Jinping</creatorcontrib><creatorcontrib>Narayanan, Rangaraj</creatorcontrib><creatorcontrib>Pelleymounter, Mary Ann</creatorcontrib><creatorcontrib>Robl, Jeffrey A</creatorcontrib><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic &amp; medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahmad, Saleem</au><au>Ngu, Khehyong</au><au>Miller, Keith J</au><au>Wu, Ginger</au><au>Hung, Chen-Pin</au><au>Malmstrom, Sarah</au><au>Zhang, Ge</au><au>O'Tanyi, Eva</au><au>Keim, William J</au><au>Cullen, Mary Jane</au><au>Rohrbach, Kenneth W</au><au>Thomas, Michael</au><au>Ung, Thao</au><au>Qu, Qinling</au><au>Gan, Jinping</au><au>Narayanan, Rangaraj</au><au>Pelleymounter, Mary Ann</au><au>Robl, Jeffrey A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents</atitle><jtitle>Bioorganic &amp; medicinal chemistry letters</jtitle><date>2010-02-01</date><risdate>2010</risdate><volume>20</volume><issue>3</issue><spage>1128</spage><epage>1133</epage><pages>1128-1133</pages><issn>0960-894X</issn><abstract>Agonists of the 5-HT sub(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 sub(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 sub(2C) agonists with no detectable agonism of the 5-HT sub(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.</abstract><doi>10.1016/j.bmcl.2009.12.014</doi></addata></record>
fulltext fulltext
identifier ISSN: 0960-894X
ispartof Bioorganic & medicinal chemistry letters, 2010-02, Vol.20 (3), p.1128-1133
issn 0960-894X
language eng
recordid cdi_proquest_miscellaneous_21296186
source ScienceDirect Freedom Collection
title Tricyclic dihydroquinazolinones as novel 5-HT sub(2C) selective and orally efficacious anti-obesity agents
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T03%3A57%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tricyclic%20dihydroquinazolinones%20as%20novel%205-HT%20sub(2C)%20selective%20and%20orally%20efficacious%20anti-obesity%20agents&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Ahmad,%20Saleem&rft.date=2010-02-01&rft.volume=20&rft.issue=3&rft.spage=1128&rft.epage=1133&rft.pages=1128-1133&rft.issn=0960-894X&rft_id=info:doi/10.1016/j.bmcl.2009.12.014&rft_dat=%3Cproquest%3E21296186%3C/proquest%3E%3Cgrp_id%3Ecdi_FETCH-proquest_miscellaneous_212961863%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=21296186&rft_id=info:pmid/&rfr_iscdi=true