Efavirenz Mannich bases: Synthesis, anti-HIV and antitubercular activities

Figures & data

Table I.  Physical constants and biological activities of efavirenz Mannich bases.

Comp.	Ar	Yield%	m.p.°C	logP^a	EC50^b (nM)	CC50^c (μM)	MIC MTB (μg/ML/)^d	t1/2 (min)^e
4a	Phenyl	45	90	6.27	3.0	>10	>12.5	ND
4b	2-Pyridyl	36	105	5.65	12.1	NT	>12.5	ND
4c	4-Methoxyphenyl	35	119	6.15	6.69	NT	>12.5	ND
4d	4-Fluoro phenyl	46	122	6.43	3.6	NT	>12.5	ND
4e	3-Chloro phenyl	52	113	6.83	2.4	>10	>12.5	120
4f		85	155	6.42	2.58	>10	3.12	240
4 g		88	152	5.94	3.79	NT	1.56	ND
4 h		70	187	5.9	4.47	NT	0.4	ND
4i		78	197	6.09	2.4	>10	0.2	180
Efa	–	–	–	3.93	2.53	>10	>12.5

^alogP values calculated with Chem Office 2004 software, ^beffective concentration of compound achieving 50% protection in MT-4 cell lines against the cytopathic effect of HIV-1, ^cCC₅₀ cytotoxic concentration of compound required to reduce the viability of mock infected CEM cells by 50%, ^dminimum inhibitory concentration against M. tuberculosis, ^e At pH 7.4 at 37°C, 4f, 4i contains group at piperazine moiety. NT-Not tested. ND- Not determined.

Scheme 1.  Protocol for the synthesis of efavirenz prodrugs.