Table 2. Optimization of Thiazolo[5,4-b]pyridine Agonists^a.

compd	Z	R1	R2	hS1P1 RI EC50, μM (% efficacy)	hS1P3 Ca2+ EC50, μM (% efficacy)
4d	N	H	H	0.199 (92)	0.478 (94)
5a	N	Me	H	0.035 (99)	0.877 (44)
5b	N	H	Me	0.038 (87)	0.996 (45)
5c	N	Me	Me	0.033 (103)	2.51 (64)
5d	N	-(CH2)2-		0.002 (98)	0.888 (26)
5e	N	-(CH2)3-		0.119 (124)	1.31 (68)
5f	N	-(CH2)4-		0.026 (76)	12% @ 2.5 μM
5g	N	-(CH2)5-		0.033 (108)	0.836 (41)
6	CH	-(CH2)2-		0.038 (93)	4.67 (56)

^aData represents an average of at least two determinations. % efficacy is reported as in Table 1. For statistical analysis, see the Supporting Information