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Discovery of structurally novel, potent and orally efficacious GPR119 agonists.
Alper, Phil; Azimioara, Mihai; Cow, Christopher; Mutnick, Daniel; Nikulin, Victor; Michellys, Pierre-Yves; Wang, Zhiliang; Reding, Esther; Paliotti, Michael; Li, Jing; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Zimmerman, Matthew; Groessel, Todd; Tuntland, Tove; Joseph, Sean B; McNamara, Peter; Seidel, H Martin; Epple, Robert.
Afiliação
  • Alper P; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States. Electronic address: palper@gnf.org.
  • Azimioara M; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Cow C; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Mutnick D; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Nikulin V; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Michellys PY; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Wang Z; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Reding E; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Paliotti M; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Li J; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Bao D; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Zoll J; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Kim Y; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Zimmerman M; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Groessel T; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Tuntland T; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Joseph SB; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • McNamara P; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Seidel HM; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States.
  • Epple R; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, United States. Electronic address: repple@gnf.org.
Bioorg Med Chem Lett ; 24(10): 2383-7, 2014 May 15.
Article em En | MEDLINE | ID: mdl-24751443
ABSTRACT
Screening hit 5 was identified in a biochemical screen for GPR119 agonists. Compound 5 was structurally novel, displayed modest biochemical activity and no oral exposure, but was structurally distinct from typical GPR119 agonist scaffolds. Systematic optimization led to compound 36 with significantly improved in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse model at a dose of 10mg/kg.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirazóis / Pirimidinas / Receptores Acoplados a Proteínas G Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirazóis / Pirimidinas / Receptores Acoplados a Proteínas G Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2014 Tipo de documento: Article