Structure-activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure.
A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenylnorstatine (Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) were designed and synthesized. From the structure-activity relationship of this series of compounds, SM-309515 was found to have potent antiviral activity against wild-type and resistant HIV-1s and to possess a desirable pharmacokinetic profile in dogs.
Mimoto
Tsutomu
T
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., Enoki 33-94, Suita, Osaka 564-0053, Japan. tsutomu-mimoto@ds-pharma.co.jp
Nojima
Satoshi
S
Terashima
Keisuke
K
Takaku
Haruo
H
Shintani
Makoto
M
Hayashi
Hideya
H
D000818:Animals; D004285:Dogs; D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D010654:Phenylbutyrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D010654:Phenylbutyrates; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid