Sriram Dharmarajan, Banerjee Debjani, Yogeeswari Perumal
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, India.
J Enzyme Inhib Med Chem. 2009 Feb;24(1):1-5. doi: 10.1080/14756360902784425.
A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35-88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC(50) of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 microg/mL.
通过微波辐射使依非韦伦、甲醛与各种芳基取代的哌嗪反应，合成了一系列依非韦伦曼尼希碱（产率35 - 88%）。对合成的化合物进行了体外抗HIV和抗分枝杆菌活性评估。体外抗逆转录病毒活性表明，化合物7-(4-((6-氯-4-(2-环丙基乙炔基)-4-(三氟甲基)-2-氧代-2H-苯并[d][1,3]恶嗪-1(4H)-基)甲基)-3-甲基哌嗪-1-基)-1-环丙基-6-氟-1,4-二氢-8-甲氧基-4-氧代喹啉-3-羧酸（4i）与依非韦伦效力相当，其半数有效浓度（EC50）为2.4 nM。化合物4i对结核分枝杆菌也有抑制作用，最低抑菌浓度为0.2μg/mL。
