Search

Your search keyword '"Rano TA"' showing total 3 results
Start Over Author "Rano TA" Topic indinavir
3 results on '"Rano TA"'

1. Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains.

Author

Cheng Y, Zhang F, Rano TA, Lu Z, Schleif WA, Gabryelski L, Olsen DB, Stahlhut M, Rutkowski CA, Lin JH, Jin L, Emini EA, Chapman KT, and Tata JR

Subjects
Animals, Area Under Curve, Dogs, Drug Resistance, HIV Protease drug effects, HIV Protease Inhibitors metabolism, HIV Protease Inhibitors pharmacokinetics, Humans, Indinavir metabolism, Indinavir pharmacokinetics, Inhibitory Concentration 50, Metabolic Clearance Rate, Structure-Activity Relationship, Tumor Cells, Cultured, HIV drug effects, HIV Protease Inhibitors chemical synthesis, Indinavir analogs & derivatives
Abstract

Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains.

Published
2002
Full Text
View/download PDF

2. A combinatorial library of indinavir analogues and its in vitro and in vivo studies.

Author

Cheng Y, Rano TA, Huening TT, Zhang F, Lu Z, Schleif WA, Gabryelski L, Olsen DB, Stahlhut M, Kuo LC, Lin JH, Xu X, Jin L, Olah TV, McLoughlin DA, King RC, Chapman KT, and Tata JR

Subjects
Animals, Area Under Curve, Combinatorial Chemistry Techniques, Dogs, Drug Evaluation, Preclinical, HIV Protease Inhibitors administration & dosage, HIV-1 drug effects, HIV-1 genetics, HIV-1 growth & development, Humans, Indinavir pharmacokinetics, Indinavir pharmacology, Inhibitory Concentration 50, Metabolic Clearance Rate, Mutation, Structure-Activity Relationship, Tumor Cells, Cultured, HIV Protease Inhibitors chemical synthesis, HIV Protease Inhibitors pharmacokinetics, Indinavir analogs & derivatives
Abstract

A combinatorial library of 300HIV protease inhibitors has been synthesized. The library was screened against recombinant wild-type and mutant HIV-1 protease enzymes. The pharmacokinetics of the library was evaluated by dosing in dogs. Compounds that are notably more potent than indinavir and have favorable pharmacokinetic properties were identified.

Published
2002
Full Text
View/download PDF

3. Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library.

Author

Rano TA, Cheng Y, Huening TT, Zhang F, Schleif WA, Gabryelski L, Olsen DB, Kuo LC, Lin JH, Xu X, Olah TV, McLoughlin DA, King R, Chapman KT, and Tata JR

Subjects
Animals, Cell Line, Dogs, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors pharmacology, Humans, Indinavir chemical synthesis, Indinavir pharmacokinetics, Indinavir pharmacology, Models, Molecular, Molecular Conformation, Molecular Structure, T-Lymphocytes, Combinatorial Chemistry Techniques, HIV Protease Inhibitors chemistry, Indinavir analogs & derivatives, Indinavir chemistry
Abstract

An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.

Published
2000
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results