Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa.

Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Research Abstract Details 

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Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Abstract Text:

John I Trujillo,Horng-Chih Huang,William L Neumann,Matthew W Mahoney,Scott Long,Wei Huang,Danny J Garland,Carrie Kusturin,Zaheer Abbas,Michael S South,David B Reitz,

Herein is described the design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors were designed to explore replacement and variation of the P1 amidine described previously [J. Med. Chem.2003, 46, 4050]. The P1 needle replacements were selected based upon their reduced basicity compared to the parent phenyl amidine (pKa approximately 12). A contributing factor towards the oral bioavailability of a compound is the ionization state of the compound in the intestinal tract. The desired outcome of the study was to identify an orally bioavailable TF-VIIa inhibitor.

Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Publishing Authors By Initials

JI Trujillo,HC Huang,WL Neumann,MW Mahoney,S Long,W Huang,DJ Garland,C Kusturin,Z Abbas,MS South,DB Reitz,

For similar proteins: blood proteins: blood coagulation factors: thromboplastin research abstracts see: proteins: blood proteins: blood coagulation factors: thromboplastin research

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Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry letters

VOLUME: 17

Page Numbers: 4568-74

Journal Abbreviation: Bioorg. Med. Chem. Lett.

ISSN: 0960-894X

DAY: 6

MONTH: 06

YEAR: 2007

Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9107377

Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Keywords Mesh Terms:

KEYWORDS: Thromboplastin

MESH TERMS: antagonists & inhibitors

Chemical & Substance for Abstract: Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa. Information

Substance Name: Factor VIIa

Registry Number: EC 3.4.21.21

Grant and Affiliation Information for Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa.

AFFILIATION: Department of Medicinal Chemistry, Pfizer Global Research and Development, Chesterfield, MO 63017, USA. john.i.trujillo@pfizer.com

Country: England

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MEDLINETA: Bioorg Med Chem Lett

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