Title of article :
Orally bioavailable prodrugs of a BCS class 2 molecule, an inhibitor of HIV-1 reverse transcriptase
Author/Authors :
Todd R. Elworthy، نويسنده , , James P. Dunn، نويسنده , , J. Heather Hogg، نويسنده , , Grace Lam، نويسنده , , Y. David Saito، نويسنده , , Tania M.P.C. Silva، نويسنده , , Dimitrios Stefanidis، نويسنده , , Witold Woroniecki، نويسنده , , Eugenia Zhornisky، نويسنده , , Amy S. Zhou، نويسنده , , Klaus Klumpp، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Abstract :
The N-2 position of pyridazinone 1, a potent HIV-1 NNRTI that has limited aqueous solubility, was derivatized into a series of hydroxymethyl esters and carbonates as well as one phosphate. The derivatives served as prodrugs to effectively deliver 1 to rat plasma upon oral treatment at 50 mpk. Increases of 4.3- to 8.6-fold in 24-hour exposure of 1 (over that of parent) were observed while the prodrugs and the hydroxymethyl adduct 2 were undetectable.
Keywords :
HIV-1 reverse transcriptase inhibitor , Pyridazinone , prodrug , Oral bioavailability , Dissolution limiting pharmacokinetics , NNRTI , Hydroxymethyl derivatives , Class 2 molecule
Journal title :
Bioorganic & Medicinal Chemistry Letters
Journal title :
Bioorganic & Medicinal Chemistry Letters
