Design, synthesis and evaluation of 3-(imidazol- 1-ylmethyl)indoles as antileishmanial agents. Part II

Figures & data

Figure 1.  Chemical structure of a potential inhibitor following the conclusions of the model.

Figure 2.  Synthetic route used for the preparation of 3-(imidazol-1-ylmethyl)indoles 5a-y.

Table 1.  Biological results of compounds 5a-l, 5r-t and comparison with predicted values of activity (boxes with * represent molecules used in the previous 3D-QSAR model).

Cpd	R	Z	X	Actual IC50 (μM)	Pred. IC50 (μM)
5a*			4-Br	8.4±0.3	4.10
5b	H	H	4-CN	13.1±2.0	2.96
5c			4-CF3	3.5±0.2	12.62
5d			4-Br	4.0±0.5	4.36
5e*	H	Br	4-CN	3.5±0.8	3.10
5f			4-CF3	3.0±0.3	10.38
5g			4-Br	4.8±0.2	1.52
5h	H	OCH3	4-CN	32.0±2.0	0.62
5i			4-CF3	4.3±0.3	4.29
5j*			4-Br	0.3±0.02	0.63
5k	CH3	H	4-CN	21.8±5.5	0.58
5l			4-CF3	4.9±0.1	2.60
5r			4-Br	2.3±0.6	0.61
5s	CH3	OCH3	4-CN	12.7±3.0	0.70
5t			4-CF3	6.1±0.2	0.72

Figure 3.  Craig Diagram (σ: Hammett electronic substituent constant and π: Hansch hydrophobicity substituent constant).

Figure 4.  Preparation of benzyl bromides 9a-e from benzaldehyde acetals.

Table 2.  Biological results of compounds 5m-q and 5u-y with alkyl side chains on para-position of the benzyl group.

Cpd	Z	X	Exp. IC50 (μM)
5m		Me	5.3±0.1
5n		Et	4.4±0.1
5o	H	n-Pr	3.2±0.2
5p		i-Pr	5.0±0.6
5q		n-Bu	2.6±0.1
5u		Me	5.4±0.2
5v		Et	5.1±0.1
5w	OMe	n-Pr	4.4±0.2
5x		i-Pr	2.5±0.4
5y		n-Bu	4.5±0.1