Table 1.

Ligand yields, lipophilicities and mGlu₅ affinities.

Entry	X	R1	R2	Yield (%)	cLogDa	Ki (nM)b
1	FCH2	F	CN	NA	3.66 (2.18)14	0.03614
2	Me	F	CN	NA	3.42	0.08 ± 0.0217
6a	NH2	H	CN	71	2.52	0.90 ± 0.19
6b	NH2	F	CN	62	3.06	0.25 ± 0.04
6c	NH2	H	CH2CN	86	2.49	5.90 ± 0.95
6d	NH2	H	OMe	89	2.72	18.6 ± 0.38
7a	Cl	H	CN	56c	2.88	0.27 ± 0.04
7b	Cl	F	CN	64c	3.41	0.40 ± 0.09
7c	Cl	H	CH2CN	67c	2.99	3.10 ± 0.46
7d	Cl	H	OMe	48c	3.44	8.10 ±1.36
8a	Br	H	CN	32d	3.38	3.70± 0.25
8b	Br	F	CN	48	3.95	0.95 ± 0.10
8c	Br	H	CH2CN	61	3.48	3.30 ± 0.53
8d	Br	H	OMe	59	3.86	22.3 ± 0.50
9a	I	H	CN	83	3.56	4.20 ± 0.50
9b	I	F	CN	71	4.21	1.30 ± 0.23
9c	I	H	CH2CN	62	3.63	23.3 ± 3.53
9d	I	H	OMe	50	3.96	132.9 ± 2.54
10a	F	H	CN	24, 75e	3.12	1.60 ± 0.11*
10b	F	F	CN	35, 72e	3.58	0.28 ± 0.05*
10c	F	H	CH2CN	43, 78 e	3.18	3.90 ± 0.56
10d	F	H	OMe	33, 65e	3.56	22.7 ± 0.28
10e	F	H	H	46, 78f	3.38	122 ± 3.3

^aThe cLogD was calculated with Pallas 3.4.0 software (Compudrug), except value in parenthesis which is a measured value.

^bValues were determined in triplicate from rat brain homogenates, except those marked

^*(n = 6).

^cObtained by coupling from compound 5.

^dValue reported in reference ²².

^eFrom the 2-bromo and 2-chloro-thiazoles, respectively (each treated with KF in DMSO at 130 °C).

^fFrom the 2-bromo- and 2-chloro-thiazoles, respectively.²⁴

NA = Not applicable.