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Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1.
Humphrey, John M; Movsesian, Matthew; Am Ende, Christopher W; Becker, Stacey L; Chappie, Thomas A; Jenkinson, Stephen; Liras, Jennifer L; Liras, Spiros; Orozco, Christine; Pandit, Jayvardhan; Vajdos, Felix F; Vandeput, Fabrice; Yang, Eddie; Menniti, Frank S.
Afiliação
  • Humphrey JM; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Movsesian M; Division of Cardiovascular Medicine , University of Utah School of Medicine , 30 N 1900 E, Room 4A-100 , Salt Lake City , Utah 84132 , United States.
  • Am Ende CW; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Becker SL; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Chappie TA; Pfizer Worldwide Research and Development , 1 Portland Street , Cambridge , Massachusetts 02139 , United States.
  • Jenkinson S; Pfizer World Wide Research and Development , La Jolla , California 92121 , United States.
  • Liras JL; Pfizer Worldwide Research and Development , 1 Portland Street , Cambridge , Massachusetts 02139 , United States.
  • Liras S; Pfizer Worldwide Research and Development , 1 Portland Street , Cambridge , Massachusetts 02139 , United States.
  • Orozco C; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Pandit J; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Vajdos FF; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Vandeput F; Division of Cardiovascular Medicine , University of Utah School of Medicine , 30 N 1900 E, Room 4A-100 , Salt Lake City , Utah 84132 , United States.
  • Yang E; Pfizer World Wide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
  • Menniti FS; MindImmune Therapeutics, Inc., and the George & Anne Ryan Institute for Neuroscience , University of Rhode Island , 7 Greenhouse Road , Kingston , Rhode Island 02881 , United States.
J Med Chem ; 61(10): 4635-4640, 2018 05 24.
Article em En | MEDLINE | ID: mdl-29718668
ABSTRACT
We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S)-3 readily attains free plasma concentrations above PDE1 IC50 values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue. These compounds represent promising new tools to probe the value of PDE1 inhibition in the treatment of cardiovascular disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores de Fosfodiesterase / Quinazolinas / Nucleotídeo Cíclico Fosfodiesterase do Tipo 1 / Descoberta de Drogas / Miocárdio Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores de Fosfodiesterase / Quinazolinas / Nucleotídeo Cíclico Fosfodiesterase do Tipo 1 / Descoberta de Drogas / Miocárdio Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article