Efavirenz Mannich bases: synthesis, anti-HIV and antitubercular activities.
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.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, India. dsriram@bits-pilani.ac.in
Banerjee
Debjani
D
Yogeeswari
Perumal
P
D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D003521:Cyclopropanes; D005557:Formaldehyde / Q000737:chemistry; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000737:chemistry; D013329:Structure-Activity Relationship
D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D008352:Mannich Bases; D010879:Piperazines; D005557:Formaldehyde; C098320:efavirenz