Karparov A, Galabov A S, Sidzhakova D, Danchev D
Arzneimittelforschung. 1985;35(8):1269-75.
1-Morpholinomethyl-tetrahydro-2(1H)-pyrimidinone (DD-13), a selective inhibitor of the alphaviral reproduction in vitro, manifests a pronounced antiviral activity in experimental infections with Semliki forest virus (SFV) and Sindbis virus in white mice (intraperitoneally inoculated with 10-10 000 LD50). Introduced subcutaneously in mice infected with SFV the compound was effective within the dose range of 4.7-300 mg/kg. The effective dose (ED)50 value of DD-13 is about 18.7 mg/kg and the maximum effect is reached with a 150-300 mg/kg dose. The protection index reached 80% and the mean survival time from approximately 7 days in the placebo group was lengthened to 26 days. This high antiviral effect is distinguished by its high selectivity, the selectivity ratio (LD50/ED50) being 385 (LD50 = 7200 mg/kg) and is manifested in infections with massive viral inocula (100-1000 LD50). The effective treatment schedule was determined: two divided daily doses of 37.5-150 mg/kg, beginning on the 3rd day after infection to the 8th day. After intravenous administration of DD-13 in mice infected with SFV a high protective effect was also observed, which was equal to that of the subcutaneous application, but with doses several times lower: in the 3-40 mg/kg. ED50 is about 3.5 mg/kg and the optimal effective dose is 10-20 mg/kg, i.e. 1/12-1/6 of LD50 (116 mg/kg). The selectivity ratio is about 33. The most effective treatment course is accomplished by a 10-20 mg/kg daily dose (in two applications) starting on the 2nd day after the virus inoculation up to the 8th day.(ABSTRACT TRUNCATED AT 250 WORDS)
1-吗啉甲基-四氢-2(1H)-嘧啶酮（DD-13）是一种体外甲病毒复制的选择性抑制剂，在白色小鼠感染塞姆利基森林病毒（SFV）和辛德毕斯病毒的实验感染中（腹腔注射10 - 10000个半数致死量）表现出显著的抗病毒活性。将该化合物皮下注射到感染SFV的小鼠体内，在4.7 - 300 mg/kg的剂量范围内有效。DD-13的有效剂量（ED）50值约为18.7 mg/kg，在150 - 300 mg/kg剂量时达到最大效果。保护指数达到80%，安慰剂组平均存活时间约7天延长至26天。这种高抗病毒效果以其高选择性为特征，选择性比率（LD50/ED50）为385（LD50 = 7200 mg/kg），并在大量病毒接种（100 - 1000个半数致死量）的感染中表现出来。确定了有效的治疗方案：每日分两次给予37.5 - 150 mg/kg的剂量，从感染后第3天开始至第8天。在感染SFV的小鼠静脉注射DD-13后也观察到高保护效果，与皮下给药相当，但剂量低几倍：3 - 40 mg/kg。ED50约为3.5 mg/kg，最佳有效剂量为10 - 20 mg/kg，即LD50（116 mg/kg）的1/12 - 1/6。选择性比率约为33。最有效的治疗疗程是从病毒接种后第2天开始至第8天，每日给予10 - 20 mg/kg的剂量（分两次给药）。（摘要截取自250字）
