Synthesis of new 1-[2-Azido-2-(2,4-dichlorophenyl)ethyl]-1H/-imidazoles and in vitro evaluation of their antifungal activity

Figures & data

Figure 1 Antifungals used in therapeutic, and general structure of new synthesized compounds 3 and 6a-f (R = H, butyl, vinyl, allyl, propargyl, phenyl, benzyl).

Scheme 1 Synthesis of compounds 2 and 3. Reagent: (a) BF₃.Et₂O, NaN₃, THF, 0°C; (b) MsCl, NEt₃, CH₂Cl₂, 0°C, 99%; (c) NaN₃, DMF, RT, 92%.

Scheme 2 Synthesis of compounds 5a-f and 6a-f. Reagents: (a) i-RMgBr, ii-RZnBr or iii-BuLi, THF; (b) BF₃·Et₂O, NaN₃, THF, 0°C.

Table I.  MIC₉₀ for the tested compounds against several fungal strains.

		MIC90^* (μg/mL)
		Candida glabrata
Compounds	R	parent	mutant	C. albicans	A. fumigatus
1	H	>250	>250	>250	>250
3		31	8	31	4
5a	(CH2)3CH3	>250	>250	125	>250
6a		>250	>250	16	>250
5b	CH = CH2	8	4	31	31
6b		4	1	250	>250
5c	CH2-CH = CH2	1	16	16	4
6c		2	4	8	8
5d	CH2-C = CH	4	16	16	62
6d		8	4	16	31
5e	C6H5	>250	>250	250	>250
6e		8	2	16	16
5f	CH2-C6H5	0.25	4	2	16
6f		2	8	31	>250
fluconazole		8	>250	2	>250
voriconazole		0.5	>250	0.062	8

^* Minimum Inhibitory Concentration required to inhibit at least 90% of the fungal growth compared to the drug-free control.