N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
A series of N1-alkyl pyrimidinediones were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our efforts identified compound 10b, which represents the lead compound in this series with pharmacokinetics and antiviral potency that may support once-daily dosing.
Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. mmitchell@gilead.com
Michael L
ML
Mitchell
Jong Chan
JC
Son
Hongyan
H
Guo
Yun-A
YA
Im
Eun Jung
EJ
Cho
Jianhong
J
Wang
Jaclyn
J
Hayes
Michael
M
Wang
Amber
A
Paul
Eric B
EB
Lansdon
James M
JM
Chen
Doris
D
Graupe
Gerry
G
Rhodes
Gong-Xin
GX
He
Romas
R
Geleziunas
Lianhong
L
Xu
Choung U
CU
Kim
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004285:Dogs; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D013941:Thymine