Evaluation of secondary amide replacements in a series of CCR5 antagonists as a means to increase intrinsic membrane permeability. Part 1: Optimization of gem-disubstituted azacycles
Replacement of a secondary amide with an N-acyl or N-sulfonyl gem-disubstituted azacyle in a series of CCR5 antagonists led to the identification of compounds with excellent in vitro HIV antiviral activity and increased intrinsic membrane permeability.
Lemoine, Remy C.,Petersen, Ann C.,Setti, Lina,Wanner, Jutta,Jekle, Andreas,Heilek, Gabrielle,deRosier, Andre,Ji, Changhua,Berry, Pamela,Rotstein, David
scheme or table
p. 704 - 708
(2010/07/04)
OCTAHYDROPYRROLO [3, 4-C] PYRROLE DERIVATIVES AN THEIR USE AS ANTIVIRAL AGENTS
Chemokine receptor antagonists, in particular, 3,7-diazabicyclo [3.3.0] octane compounds according to formula (I) wherein R1-R3 and Ar are as defined herein are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are alleviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula (I).
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(2008/06/13)
Oximino-piperidino-piperidine-based CCR5 antagonists. Part 2: Synthesis, SAR and biological evaluation of symmetrical heteroaryl carboxamides
The synthesis, SAR and biological evaluation of symmetrical amide analogues of our clinical candidate SCH 351125 are described. A series of potent and orally bioavailable CCR5 antagonists containing symmetrical 2,6-dimethyl isonicotinamides and 2, 6-dimethyl pyrimidines amides were generated with enhanced affinity for the CCR5 receptor.
Palani, Anandan,Shapiro, Sherry,Clader, John W.,Greenlee, William J.,Vice, Susan,McCombie, Stuart,Cox, Kathleen,Strizki, Julie,Baroudy, Bahige M.
p. 709 - 712
(2007/10/03)
Piperazine-based CCR5 antagonists as HIV-1 inhibitors. III: Synthesis, antiviral and pharmacokinetic profiles of symmetrical heteroaryl carboxamides
The unsymmetrical nicotinamide-N-oxide moiety in compound 1 was replaced with symmetrical isonicotinamides as well as 4,6-dimethyl pyrimidine-5-carboxamides. Compound 16 from the latter set reduced the number of rotamers, improved potency of inhibiting UIV entry, slightly diminished the affinity for the muscarine receptors and showed very good oral absorption.
McCombie, Stuart W.,Tagat, Jayaram R.,Vice, Susan F.,Lin, Sue-Ing,Steensma, Ruo,Palani, Anandan,Neustadt, Bernard R.,Baroudy, Bahige M.,Strizki, Julie M.,Endres, Michael,Cox, Kathleen,Dan, Niya,Chou, Chuan-Chu
p. 567 - 571
(2007/10/03)
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