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Your search keyword '"Hazen RJ"' showing total 6 results
Start Over Author "Hazen RJ" Journal bioorganic medicinal chemistry letters
6 results on '"Hazen RJ"'

1. Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.

Author

Miller JF, Andrews CW, Brieger M, Furfine ES, Hale MR, Hanlon MH, Hazen RJ, Kaldor I, McLean EW, Reynolds D, Sammond DM, Spaltenstein A, Tung R, Turner EM, Xu RX, and Sherrill RG

Subjects
HIV Protease Inhibitors chemistry, Molecular Structure, Sulfonamides chemistry, HIV Protease Inhibitors pharmacology, Sulfonamides pharmacology
Abstract

A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.

Published
2006
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2. Synthesis and antiviral activities of novel N-alkoxy-arylsulfonamide-based HIV protease inhibitors.

Author

Sherrill RG, Furfine ES, Hazen RJ, Miller JF, Reynolds DJ, Sammond DM, Spaltenstein A, Wheelan P, and Wright LL

Subjects
Benzene Derivatives chemistry, Drug Design, Drug Resistance, Multiple, Viral, HIV Protease drug effects, Humans, Structure-Activity Relationship, Sulfonamides pharmacology, Virus Replication drug effects, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, HIV Protease Inhibitors pharmacology, Sulfonamides chemical synthesis
Abstract

A series of novel N-alkoxy-arylsulfonamide HIV protease inhibitors with low picomolar enzyme activity and single digit nanomolar antiviral activity is disclosed.

Published
2005
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3. Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles.

Author

Miller JF, Brieger M, Furfine ES, Hazen RJ, Kaldor I, Reynolds D, Sherrill RG, and Spaltenstein A

Subjects
Animals, Anti-HIV Agents chemical synthesis, Dogs, Drug Resistance, Multiple, Viral genetics, HIV genetics, HIV Protease Inhibitors chemical synthesis, Inhibitory Concentration 50, Mutation, Rats, Structure-Activity Relationship, Virus Replication genetics, Anti-HIV Agents pharmacology, Drug Resistance, Multiple, Viral drug effects, HIV drug effects, HIV Protease Inhibitors pharmacology, Virus Replication drug effects
Abstract

A novel series of tyrosine-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus.

Published
2005
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4. Optimization of pyrrolidinone based HIV protease inhibitors.

Author

Sherrill RG, Andrews CW, Bock WJ, Davis-Ward RG, Furfine ES, Hazen RJ, Rutkowske RD, Spaltenstein A, and Wright LL

Subjects
HIV Protease Inhibitors chemistry, Models, Molecular, Pyrrolidinones chemistry, HIV Protease Inhibitors pharmacology, Pyrrolidinones pharmacology
Abstract

Optimization of P1-substituted pyrrolidinone based HIV protease inhibitors has yielded analogs with very potent antiviral activity.

Published
2005
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5. Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains.

Author

Miller JF, Furfine ES, Hanlon MH, Hazen RJ, Ray JA, Robinson L, Samano V, and Spaltenstein A

Subjects
Animals, Anti-HIV Agents chemical synthesis, Cell Line, Drug Resistance, Multiple, Viral drug effects, HIV drug effects, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, Humans, Molecular Structure, Mutation, Rats, Structure-Activity Relationship, Sulfonamides chemical synthesis, Anti-HIV Agents pharmacology, Drug Resistance, Multiple, Viral genetics, HIV genetics, HIV Protease drug effects, HIV Protease Inhibitors pharmacology, Sulfonamides pharmacology
Abstract

A novel series of P1' chain-extended arylsufonamides was synthesized and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized.

Published
2004
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6. Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.

Author

Spaltenstein A, Almond MR, Bock WJ, Cleary DG, Furfine ES, Hazen RJ, Kazmierski WM, Salituro FG, Tung RD, and Wright LL

Subjects
Anti-HIV Agents chemical synthesis, Anti-HIV Agents chemistry, Anti-HIV Agents pharmacology, Drug Design, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors chemical synthesis, HIV Protease Inhibitors pharmacology, Thiazoles chemistry
Abstract

A novel series of HIV protease inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based antiviral assay.

Published
2000

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