Braitman A, Swerdel M R, Olsen S J, Tuomari A V, Lynch J S, Blue B, Michalik T, Field A K, Bonner D P, Clark J M
Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Antimicrob Agents Chemother. 1991 Jul;35(7):1464-8. doi: 10.1128/AAC.35.7.1464.
The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.
新型抗病毒核苷SQ 34,514 [(1R-1α,2β,3α)-2-氨基-9-[2,3-双(羟甲基)环丁基]-6H-嘌呤-6-酮],即消旋体SQ 33,054(环丁-G)的活性R异构体,在小鼠疱疹病毒感染治疗中的疗效得到了评估。SQ 34,514在1型单纯疱疹病毒(HSV-1)全身感染、脑内HSV-2感染、去卵巢小鼠阴道诱发的HSV-2感染以及全身性小鼠巨细胞病毒感染中口服有效。在这些实验性感染的治疗中,SQ 34,514与阿昔洛韦和更昔洛韦相比具有优势。在小鼠中,基于尿排泄,SQ 34,514的口服生物利用度为80%。SQ 34,514在人类HSV和巨细胞病毒感染的治疗中可能具有潜在价值。