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Your search keyword '"Chapman KT"' showing total 4 results
Start Over Author "Chapman KT" Topic pyrrolidines
4 results on '"Chapman KT"'

1. CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity.

Author

Lynch CL, Hale JJ, Budhu RJ, Gentry AL, Finke PE, Caldwell CG, Mills SG, MacCoss M, Shen DM, Chapman KT, Malkowitz L, Springer MS, Gould SL, DeMartino JA, Siciliano SJ, Cascieri MA, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller M, and Emini E

Subjects
Anti-HIV Agents pharmacokinetics, Biological Availability, Propionates pharmacokinetics, Pyrrolidines pharmacokinetics, Anti-HIV Agents pharmacology, CCR5 Receptor Antagonists, Propionates pharmacology, Pyrrolidines pharmacology
Abstract

[reaction: see text] A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.

Published
2003
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2. 1,3,4 Trisubstituted pyrrolidine CCR5 receptor antagonists bearing 4-aminoheterocycle substituted piperidine side chains.

Author

Willoughby CA, Rosauer KG, Hale JJ, Budhu RJ, Mills SG, Chapman KT, MacCoss M, Malkowitz L, Springer MS, Gould SL, DeMartino JA, Siciliano SJ, Cascieri MA, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller M, and Emini EA

Subjects
Animals, Anti-HIV Agents chemical synthesis, CHO Cells, Chemokine CCL4, Cricetinae, Half-Life, HeLa Cells, Humans, Hydrogen Bonding, Macrophage Inflammatory Proteins metabolism, Piperidines pharmacokinetics, Pyrrolidines pharmacokinetics, Rats, CCR5 Receptor Antagonists, Piperidines chemical synthesis, Piperidines pharmacology, Pyrrolidines chemical synthesis, Pyrrolidines pharmacology
Abstract

A new class of 4-(aminoheterocycle)piperidine derived 1,3,4 trisubstituted pyrrolidine CCR5 antagonists is reported. Compound 4a is shown to have good binding affinity (1.8 nM) and antiviral activity in PBMC's (IC(95)=50 nM). Compound 4a also has improved PK properties relative to 1.

Published
2003
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3. 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains.

Author

Lynch CL, Willoughby CA, Hale JJ, Holson EJ, Budhu RJ, Gentry AL, Rosauer KG, Caldwell CG, Chen P, Mills SG, MacCoss M, Berk S, Chen L, Chapman KT, Malkowitz L, Springer MS, Gould SL, DeMartino JA, Siciliano SJ, Cascieri MA, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller M, and Emini EA

Subjects
Animals, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents pharmacology, Dogs, Half-Life, Humans, Leukocytes, Mononuclear, Macaca mulatta, Metabolic Clearance Rate, Piperidines chemistry, Pyrrolidines chemical synthesis, Pyrrolidines pharmacology, Radioligand Assay, Rats, Structure-Activity Relationship, Tumor Cells, Cultured, Anti-HIV Agents chemical synthesis, CCR5 Receptor Antagonists, Pyrrolidines pharmacokinetics
Abstract

The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics.

Published
2003
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4. 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 4: synthesis of N-1 acidic functionality affording analogues with enhanced antiviral activity against HIV.

Author

Lynch CL, Hale JJ, Budhu RJ, Gentry AL, Mills SG, Chapman KT, MacCoss M, Malkowitz L, Springer MS, Gould SL, DeMartino JA, Siciliano SJ, Cascieri MA, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller M, and Emini EA

Subjects
Animals, Anti-HIV Agents pharmacokinetics, CHO Cells, Cell Membrane Permeability, Chemical Phenomena, Chemistry, Physical, Chemokine CCL4, Cricetinae, HeLa Cells, Humans, Indicators and Reagents, Macrophage Inflammatory Proteins antagonists & inhibitors, Pyrrolidines pharmacokinetics, Rats, Structure-Activity Relationship, Anti-HIV Agents chemical synthesis, Anti-HIV Agents pharmacology, CCR5 Receptor Antagonists, HIV-1 drug effects, Pyrrolidines chemical synthesis, Pyrrolidines pharmacology
Abstract

A series of alpha-(pyrrolidin-1-yl)acetic acids is presented as selective and potent antivirals against HIV. Several of the pyrrolidine zwitterions demonstrated reasonable in vitro properties, enhanced antiviral activities and improved pharmacokinetic profiles over pyrrolidine 1.

Published
2002
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