Sriram Dharmarajan, Yogeeswari Perumal, Reddy Sushma Pobba
Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2113-6. doi: 10.1016/j.bmcl.2006.01.064. Epub 2006 Feb 7.
A series of pyrazinamide (PAZ) Mannich bases has been synthesized by reacting PAZ, formaldehyde, and various substituted piperazines using microwave irradiation with the yield ranging from 46% to 86%. The synthesized compounds were evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB). Among the synthesized compounds, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-4-((pyrazine-2-carboxamido)methyl)piperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (17) was found to be the most active compound in vitro with MIC of 0.39 and 0.2 microg/mL against MTB and multidrug-resistant MTB, respectively. In the in vivo animal model 17 decreased the bacterial load in lung and spleen tissues with 1.86 and 1.66-log10 protections, respectively.
通过微波辐射使吡嗪酰胺（PAZ）、甲醛与各种取代哌嗪反应，合成了一系列吡嗪酰胺（PAZ）曼尼希碱，产率在46%至86%之间。对合成的化合物进行了体外和体内抗结核分枝杆菌活性评估，以对抗结核分枝杆菌H37Rv（MTB）。在合成的化合物中，发现1-环丙基-6-氟-1,4-二氢-8-甲氧基-7-(3-甲基-4-((吡嗪-2-甲酰胺基)甲基)哌嗪-1-基)-4-氧代喹啉-3-羧酸（17）是体外活性最强的化合物，对MTB和耐多药MTB的最低抑菌浓度分别为0.39和0.2微克/毫升。在体内动物模型中，化合物17分别使肺和脾组织中的细菌载量降低了1.86和1.66个对数10级。
