Table 3. Biophysical Data of 4-Amino-6-(pyrazol-4-yl)pyrimidine Derivatives against MabPurC^a .

Compound	R1	R2	R3	X	ΔTm (°C)b	MabPurC Kd (μM)	LEd
9	CN	Me	H	N	+4.4	23 ± 3	0.39
12	CN		=o	N	+2.9	45 ± 5	0.27
13	CN		H	N	+3.5	52 ± 8	0.26
14	CN		H	N	+4.5	22 ± 0 8	0.32
15	CN		H	N	+2.6	47 ± 6	0.26
16	CN	3-pyridyl	H	N	+6.2	3.1 ± 0.3	0.36
17	CN	4-pyridyl	H	N	+6.0	7.5 ± 0.5	0.33
18	CN	5-methoxy-3-pyridyl	H	N	+6.5	2.1 ± 0.2	0.34
19	CN	3-fluorophenyl	H	N	+8.3	0.25 ± 0.03	0.41
20	CN	3-(trifluoromethyl)phenyl	H	N	+5.3	ND	-
21	CN	3-fluoro-5-methoxyphenyl	H	N	+8.8a	NDe	-
22	CN	4-fluorophenyl	H	N	+9.4	0.22 ± 0.02	0.41
23	CN	phenyl	H	N	+9.3	0.28 ± 0.03	0.43
24	CN	phenyl	Me	N	+7.5	0.53 ± 0.03	0.38
25	CN	benzyl	H	N	+5.3	ND	-
26	CN	3,5-difluorophenyl	H	N	+8.7e	0.24 ± 0.05	0.37
27	CN	3,4-difluorophenyl	H	N	+9.0	0.15 ± 0.02	0.37
28	Cl	3-fluorophenyl	H	N	+7.1	0.35 ± 0.02	0.39
29	CN	3-fluorophenyl	H	CH	+5.1	1.4 ± 0.06	0.36
30	Cl	3-fluorophenyl	H	CH	+2.6c	ND	-
31	H	3-fluorophenyl	H	N	+4.1	ND	-

^aND not determined.

^b1 mM ligand and 100 μM Mab PurC

^c0.5 mM ligand and 100 μM Mab PurC

^dkcal mol^–1 per heavy atom.

^eDue to poor solubility.