| Optimization of orally bioavailable alkyl amine renin inhibitors. | |
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MedLine Citation:
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PMID: 19959358 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension. |
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Authors:
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Zhenrong Xu; Salvacion Cacatian; Jing Yuan; Robert D Simpson; Lanqi Jia; Wei Zhao; Colin M Tice; Patrick T Flaherty; Joan Guo; Alexey Ishchenko; Suresh B Singh; Zhongren Wu; Brian M McKeever; Boyd B Scott; Yuri Bukhtiyarov; Jennifer Berbaum; Jennifer Mason; Reshma Panemangalore; Maria Grazia Cappiello; Ross Bentley; Christopher P Doe; Richard K Harrison; Gerard M McGeehan; Lawrence W Dillard; John J Baldwin; David A Claremon |
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Publication Detail:
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Type: Journal Article Date: 2009-12-01 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-04-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 694-9 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Amines / chemical synthesis, chemistry*, pharmacokinetics Animals Binding Sites Blood Pressure / drug effects Carbamates / chemical synthesis, chemistry*, pharmacokinetics Crystallography, X-Ray Drug Design Enzyme Inhibitors / chemical synthesis, chemistry*, pharmacokinetics Haplorhini Humans Piperidines / chemical synthesis, chemistry*, pharmacokinetics Rats Rats, Transgenic Renin / antagonists & inhibitors*, blood, metabolism Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Amines; 0/Carbamates; 0/Enzyme Inhibitors; 0/Piperidines; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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