Discovery of aminoheterocycles as potent and brain penetrant prolylcarboxypeptidase inhibitors.

Wu, Zhicai; Yang, Cangming; Graham, Thomas H; Verras, Andreas; Chabin, Renee M; Xu, Suoyu; Tong, Xinchun; Xie, Dan; Lassman, Mike E; Bhatt, Urmi R; Garcia-Calvo, Margarita M; Shen, Zhu; Chen, Qing; Bleasby, Kelly; Sinharoy, Ranabir; Hale, Jeffrey J; Tata, James R; Pinto, Shirly; Colletti, Steven L; Shen, Dong-Ming

Wu, Zhicai; Yang, Cangming; Graham, Thomas H; Verras, Andreas; Chabin, Renee M; Xu, Suoyu; Tong, Xinchun; Xie, Dan; Lassman, Mike E; Bhatt, Urmi R; Garcia-Calvo, Margarita M; Shen, Zhu; Chen, Qing; Bleasby, Kelly; Sinharoy, Ranabir; Hale, Jeffrey J; Tata, James R; Pinto, Shirly; Colletti, Steven L; Shen, Dong-Ming.

Affiliation

Wu Z; Department of Discovery Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. zhicai_wu@merck.com

Bioorg Med Chem Lett ; 22(4): 1727-30, 2012 Feb 15.

Article de En | MEDLINE | ID: mdl-22290078

ABSTRACT

ABSTRACT

Efforts were dedicated to develop potent and brain penetrant prolylcarboxypeptidase (PrCP) inhibitors by replacing the amide group of original leads 1 and 2 with heterocycles. Aminopyrimidines including compound 32a were identified to display good PrCP inhibitory activity (32a, IC(50)=43 nM) and impressive ability to penetrate brain in mice (brain/plasma ratio 1.4).

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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Encéphale / Carboxypeptidases / Antienzymes / Découverte de médicament / Amines / Composés hétérocycliques Limites: Animals Langue: En Journal: Bioorg Med Chem Lett Sujet du journal: BIOQUIMICA / QUIMICA Année: 2012 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

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