Identification of anti-HIV agents with a novel benzo[4,5]isothiazolo[2,3-a]pyrimidine scaffold.
3,4-Dihydro-2H-benzo[4,5]isothiazolo[2,3-a]pyrimidine is a newly identified antiviral agent against human immunodeficiency virus type 1 (HIV-1) infection, derived from 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182). The introduction of the hydrophobic 8-aryl substituent on the benzene substructure improved its anti-HIV activity, resulting in the identification of 6-fold more potent analogs. In addition, it was demonstrated that these isothiazolopyrimidine derivatives exert anti-HIV effects at an early stage of viral infection.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Shiho
S
Okazaki
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Tsukasa
T
Mizuhara
Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Kazuya
K
Shimura
Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Hiroto
H
Murayama
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Hiroaki
H
Ohno
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: soishi@pharm.kyoto-u.ac.jp.
Shinya
S
Oishi
Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Masao
M
Matsuoka
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: nfujii@pharm.kyoto-u.ac.jp.
Nobutaka
N
Fujii
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology
C586214:6H-6-imino-(2,3,4,5-tetrahydropyrimido)(1,2-c)-(1,3)benzothiazine; D019380:Anti-HIV Agents; D007097:Imines; D011743:Pyrimidines; D013843:Thiazines; C030986:pyrimidine
Anti-HIV agent; Isothiazolopyrimidine; PD 404182; Pyrimidobenzothiazine