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The discovery of diazepinone-based 5-HT3 receptor partial agonists.
Manning, David D; Guo, Cheng; Zhang, Zhenjun; Ryan, Kristen N; Naginskaya, Jennifer; Choo, Sok Hui; Masih, Liaqat; Earley, William G; Wierschke, Jonathan D; Newman, Amy S; Brady, Catherine A; Barnes, Nicholas M; Guzzo, Peter R.
Afiliação
  • Manning DD; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States. Electronic address: David.Manning@amriglobal.com.
  • Guo C; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Zhang Z; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Ryan KN; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Naginskaya J; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Choo SH; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Masih L; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Earley WG; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Wierschke JD; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
  • Newman AS; Celentyx Ltd, Birmingham Research Park, Vincent Drive, Edgbaston, Birmingham B15 2SQ, UK.
  • Brady CA; Celentyx Ltd, Birmingham Research Park, Vincent Drive, Edgbaston, Birmingham B15 2SQ, UK.
  • Barnes NM; Celentyx Ltd, Birmingham Research Park, Vincent Drive, Edgbaston, Birmingham B15 2SQ, UK; Clinical and Experimental Medicine, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
  • Guzzo PR; Albany Molecular Research Inc. (AMRI), 26 Corporate Circle, Albany, NY 12212-5098, United States.
Bioorg Med Chem Lett ; 24(11): 2578-81, 2014 Jun 01.
Article em En | MEDLINE | ID: mdl-24755431
Serotonin type 3 (5-HT3) receptor partial agonists have been targeted as potential new drugs for the symptomatic relief of irritable bowel syndrome (IBS). Multiple diazepinone-based compounds have been discovered, which exhibit nanomolar binding affinity for the h5-HT3A receptor and display a range of intrinsic activities (IA=7-87% of 5-HT Emax) in HEK cells heterologously expressing the h5-HT3A receptor. Favorable physicochemical properties and in vitro ADME profile coupled with oral activity in the murine von Bezold-Jarisch reflex model demonstrates the series has promise for producing low to moderate IA partial agonists suitable for an IBS indication.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Azepinas / Síndrome do Intestino Irritável / Receptores 5-HT3 de Serotonina / Descoberta de Drogas 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: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Azepinas / Síndrome do Intestino Irritável / Receptores 5-HT3 de Serotonina / Descoberta de Drogas Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2014 Tipo de documento: Article