Table 8.

In Vitro DMPK Profiling of Select 5-Chloropyridin-2-yl Ether Analogues

no.	R	cLogPa	LLEb	mGlu3 IC50 (nM)	fold vs mGlu5	rat plasma Fuc	rat CLhep (mL/min/kg)d
99	2-cyano-5-fluorophenyl	3.29	2.99	529	>56	0.045	47.7
100	pyridin-2-yl	2.57	3.91	328	>91	0.051	69.5
101	pyridin-3-yl	2.16	4.06	608	>49	0.118	42.0
106	2-fluoropyridin-3-yl	2.67	3.74	392	>76	0.083	36.9
107	4-fluoropyridin-3-yl	2.26	4.06	482	>62	0.085	36.0
108	5-fluoropyridin-3-yl	2.26	4.06	481	>62	0.092	26.6
109	5-cyanopyridin-3-yl	1.88	4.34	605	>49	0.078	22.8

^aCalculated using Dotmatics Elemental (www.dotmatics.com/products/elemental/).

^bLLE (ligand-lipophilicity efficiency) = pIC₅₀ – cLogP.

^cF_u = fraction unbound.

^dPredicted hepatic clearance based on intrinsic clearance in rat liver microsomes.