Sokolova A S, Yarovaya O I, Semenova M D, Shtro A A, Orshanskaya I R, Zarubaev V V, Salakhutdinov N F
Novosibirsk Institute of Organic Chemistry , Siberian Branch of the Russian Academy of Sciences , Lavrentjev Avenue 9 , 630090 Novosibirsk , Russia . Email:
Novosibirsk State University , Pirogova St. 2 , 630090 Novosibirsk , Russia.
Medchemcomm. 2017 Mar 3;8(5):960-963. doi: 10.1039/c6md00657d. eCollection 2017 May 1.
Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1N1). Compounds , and containing a morpholine fragment exhibited the highest efficiency as agents inhibiting the replication of the influenza virus A(H1N1) with selectivity indices of 82, 45 and 65, correspondingly. Derivatives (SI = 23) and (SI = 25) containing a 1-methylpiperazine motif showed moderate antiviral activity. Structure-activity analysis of this new series of borneol derivatives revealed that a 1,7,7-trimethylbicyclo[2.2.1]heptan scaffold is required for the antiviral activity.
在此，我们展示了一系列新型（-）-冰片和（-）-异冰片杂环衍生物的设计与合成，这些衍生物是甲型流感病毒的有效抑制剂。所有化合物都针对其对MDCK细胞的毒性以及对甲型流感病毒A/波多黎各/8/34（H1N1）的病毒抑制活性进行了测试。含有吗啉片段的化合物、和作为抑制甲型流感病毒A（H1N1）复制的试剂表现出最高的效率，其选择性指数分别为82、45和65。含有1-甲基哌嗪基序的衍生物（SI = 23）和（SI = 25）表现出中等抗病毒活性。对这一系列新的冰片衍生物的构效分析表明，抗病毒活性需要1,7,7-三甲基双环[2.2.1]庚烷支架。
