Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides

Table 6

SAR and MIC of tetrahydropyrazolopyrimidine carboxamides.

Compounds	R^1	R^2	R^3	MIC (µM)		Solubility^b (mM, pH 6.8)	PPB (%)^c(h/m)
65			CF3	0.15 ± 0.04	6.3	<4	>99.0/99.0
66			CF3	0.44 ± 0.1	4.4	9	96.1/95.8
67			CF3	0.13 ± 0.06	5.5	<4	>99.0/99.0
68			CF3	0.87 ± 0.18	4.8	<4	98.2/98.4
69			CF3	0.44 ± 0.04	4.1	6	98.1/98.5
70			CF3	0.73 ± 0.1	5.1	9	97.3/97.6
71			CF3	0.47 ± 0.15	5.1	<4	>99.0/99.0
72			CF3	0.83 ± 0.24	4.9	<4	>99.0/99.0
73			CHF2	0.60 ± 0.2	4.6	212	95.7/94.8
74			CF3	52.2 ± 24.1	3.2	347	81.9/87.2
75			CF3	3.7 ± 0.6	3.2	20	87.8/89.2

: high throughput measured octanol/water partition coefficient, ^bsolubility: high throughput equilibrium solubility, ^cPPB: plasma protein binding measured by rapid equilibrium dialysis (RED) device.