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Strategies towards Improving the Pharmacokinetic Profile of ε‐Substituted Lysinol‐Derived HIV Protease Inhibitors
Author(s) -
Rajapakse Hemaka A.,
Walji Abbas M.,
Moore Keith P.,
Zhu Hong,
Mitra Aurpon W.,
Gregro Alison R.,
Tinney Elizabeth,
Burlein Christine,
Touch Sinoeun,
Paton Brenda L.,
Carroll Steven S.,
DiStefano Daniel J.,
Lai MingTain,
Grobler Jay A.,
Sanchez Rosa I.,
Williams Theresa M.,
Vacca Joseph P.,
Nantermet Philippe G.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000395
Subject(s) - protease , substituent , human immunodeficiency virus (hiv) , pharmacokinetics , truncation (statistics) , pharmacology , potency , computational biology , chemistry , computer science , medicine , stereochemistry , virology , biochemistry , enzyme , biology , in vitro , machine learning
Compounds that are all HAART: Subsequent to accessing the S2 subpocket of HIV protease from the novel lysinol series of HIV protease inhibitors, we now report a comprehensive structure–activity relationship study at this position. Balancing physical properties via truncation of the substituent binding in the S1′ subpocket enabled the discovery of inhibitors with improved pharmacokinetic properties, while maintaining the functional potency of these inhibitors.