Solid phase synthesis of novel pyrrolidinedione analogs as potent HIV-1 integrase inhibitors.
A novel series of HIV-1 integrase inhibitors were identified from a 100 member (4R(1) x 5R(2) x 5R(3)) library of pyrrolidinedione amides. A solid-phase route was developed which facilitates the simultaneous variation at R(1), R(2), and R(3) of the pyrrolidinedione scaffold. The resulting library samples were assayed for HIV-1 integrase activity and analyzed to determine the R(1), R(2), and R(3) reagent contributions towards the activity.
Pendri
Annapurna
A
Bristol-Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA. annapurna.pendri@bms.com
Troyer
Timothy L
TL
Sofia
Michael J
MJ
Walker
Michael A
MA
Naidu
B Narasimhulu
BN
Banville
Jacques
J
Meanwell
Nicholas A
NA
Dicker
Ira
I
Lin
Zeyu
Z
Krystal
Mark
M
Gerritz
Samuel W
SW
D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019428:HIV Integrase Inhibitors; D013388:Succinimides