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Your search keyword '"Doerffler, Edward"' showing total 3 results
Start Over Author "Doerffler, Edward" Topic carboxylic acids
3 results on '"Doerffler, Edward"'

1. Discovery of GS-9451: an acid inhibitor of the hepatitis C virus NS3/4A protease.

Author

Sheng XC, Appleby T, Butler T, Cai R, Chen X, Cho A, Clarke MO, Cottell J, Delaney WE 4th, Doerffler E, Link J, Ji M, Pakdaman R, Pyun HJ, Wu Q, Xu J, and Kim CU

Subjects
Animals, Antiviral Agents pharmacokinetics, Antiviral Agents pharmacology, Biological Availability, Caco-2 Cells, Carboxylic Acids pharmacokinetics, Carboxylic Acids pharmacology, Crystallography, X-Ray, Dogs, Hepacivirus chemistry, Hepacivirus enzymology, Hepatitis C drug therapy, Hepatitis C virology, Humans, Macaca fascicularis, Models, Molecular, Quinolines pharmacokinetics, Quinolines pharmacology, Rats, Serine Proteinase Inhibitors pharmacokinetics, Serine Proteinase Inhibitors pharmacology, Structure-Activity Relationship, Viral Nonstructural Proteins chemistry, Antiviral Agents chemical synthesis, Carboxylic Acids chemical synthesis, Hepacivirus drug effects, Quinolines chemical synthesis, Serine Proteinase Inhibitors chemical synthesis, Viral Nonstructural Proteins antagonists & inhibitors
Abstract

The discovery of GS-9451 is reported. Modification of the P3 cap and P2 quinoline with a series of solubilizing groups led to the identification of potent HCV NS3 protease inhibitors with greatly improved pharmacokinetic properties in rats, dogs and monkeys., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
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2. Discovery of a 2′-fluoro-2′-C-methyl C-nucleotide HCV polymerase inhibitor and a phosphoramidate prodrug with favorable properties.

Author

Kirschberg, Thorsten A., Metobo, Sammy, Clarke, Michael O., Aktoudianakis, Vangelis, Babusis, Darius, Barauskas, Ona, Birkus, Gabriel, Butler, Thomas, Byun, Daniel, Chin, Gregory, Doerffler, Edward, Edwards, Thomas E., Fenaux, Martijn, Lee, Rick, Lew, Willard, Mish, Michael R., Murakami, Eisuke, Park, Yeojin, Squires, Neil H., and Tirunagari, Neeraj

Subjects
*DRUG development, *HEPATITIS C treatment, *PHOSPHORAMIDATES, *PRODRUGS, *CARBOXYLIC acids, *PHARMACOKINETICS, *THERAPEUTICS
Abstract

A series of 2′-fluorinated C -nucleosides were prepared and tested for anti-HCV activity. Among them, the triphosphate of 2′-fluoro-2′- C -methyl adenosine C -nucleoside ( 15 ) was a potent and selective inhibitor of the NS5B polymerase and maintained activity against the S282T resistance mutant. A number of phosphoramidate prodrugs were then prepared and evaluated leading to the identification of the 1-aminocyclobutane-1-carboxylic acid isopropyl ester variant ( 53 ) with favorable pharmacokinetic properties including efficient liver delivery in animals. [ABSTRACT FROM AUTHOR]

Published
2017
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3. Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

Author

Clarke, Michael O., Chen, Xiaowu, Cho, Aesop, Delaney, William E., Doerffler, Edward, Fardis, Maria, Ji, Mingzhe, Mertzman, Michael, Pakdaman, Rowchanak, Pyun, Hyun-Jun, Rowe, Tanisha, Yang, Cheng Y., Sheng, X. Christopher, and Kim, Choung U.

Subjects
*BIOMEDICAL materials, *PHOSPHINIC acid, *CHEMICAL inhibitors, *HEPATITIS C virus, *SERINE proteinases, *CARBOXYLIC acids, *PHARMACOKINETICS, *CONSTRAINTS (Physics), *MACROCYCLIC compounds
Abstract

Abstract: A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described. [Copyright &y& Elsevier]

Published
2011
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