8-Hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors.
A series of potent novel 8-hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 12 is active against replication of HIV-1 in cell culture with a CIC(95) of 0.31microM. Further SAR exploration led to the preparation of pseudosymmetrical tricyclic pyrrolopyrazine inhibitors 23 and 24 with further improvement in antiviral activity.
Fisher
Thorsten E
TE
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. thor_fisher@merck.com
Kim
Boyoung
B
Staas
Donnette D
DD
Lyle
Terry A
TA
Young
Steven D
SD
Vacca
Joseph P
JP
Zrada
Matthew M
MM
Hazuda
Daria J
DJ
Felock
Peter J
PJ
Schleif
William A
WA
Gabryelski
Lori J
LJ
Anari
M Reza
MR
Kochansky
Christopher J
CJ
Wai
John S
JS
D045744:Cell Line, Tumor; D019427:HIV Integrase / Q000502:physiology; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000821:virology
D019428:HIV Integrase Inhibitors; D011719:Pyrazines; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1