Your browser doesn't support javascript.
loading
Discovery of a Potent and Selective ROMK Inhibitor with Pharmacokinetic Properties Suitable for Preclinical Evaluation.
Walsh, Shawn P; Shahripour, Aurash; Tang, Haifeng; Teumelsan, Nardos; Frie, Jessica; Zhu, Yuping; Priest, Birgit T; Swensen, Andrew M; Liu, Jessica; Margulis, Michael; Visconti, Richard; Weinglass, Adam; Felix, John P; Brochu, Richard M; Bailey, Timothy; Thomas-Fowlkes, Brande; Alonso-Galicia, Magdalena; Zhou, Xiaoyan; Pai, Lee-Yuh; Corona, Aaron; Hampton, Caryn; Hernandez, Melba; Bentley, Ross; Chen, Jing; Shah, Kashmira; Metzger, Joseph; Forrest, Michael; Owens, Karen; Tong, Vincent; Ha, Sookhee; Roy, Sophie; Kaczorowski, Gregory J; Yang, Lihu; Parmee, Emma; Garcia, Maria L; Sullivan, Kathleen; Pasternak, Alexander.
Afiliação
  • Walsh SP; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Shahripour A; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Tang H; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Teumelsan N; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Frie J; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Zhu Y; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Priest BT; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Swensen AM; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Liu J; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Margulis M; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Visconti R; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Weinglass A; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Felix JP; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Brochu RM; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Bailey T; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Thomas-Fowlkes B; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Alonso-Galicia M; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Zhou X; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Pai LY; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Corona A; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Hampton C; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Hernandez M; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Bentley R; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Chen J; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Shah K; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Metzger J; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Forrest M; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Owens K; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Tong V; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Ha S; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Roy S; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Kaczorowski GJ; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Yang L; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Parmee E; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Garcia ML; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Sullivan K; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
  • Pasternak A; Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
ACS Med Chem Lett ; 6(7): 747-52, 2015 Jul 09.
Article em En | MEDLINE | ID: mdl-26191360
ABSTRACT
A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a new mechanism diuretic. Robust pharmacodynamic effects in both SD rats and dogs have been demonstrated.
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2015 Tipo de documento: Article