Table 2.

Structure Activity Relationship of isoxazoles and oxadiazoles 43–105.^{26,27,31–33}

Entry	Substituent X	pIC50 ± SEM X4 (X5 = CH)	Entry	pIC50 ± SEM X5 (X4 = CH)
43	CH	< 5	-	-
44	N	5.57 ± 0.03	-	-
-	N	-	61	< 5
45	−CC(O)CF3	6.91 ± 0.02	62	5.74 ± 0.03
46	−CC(O)CH3	6.91 ± 0.03	63	< 5
47	−CCF3	6.67 ± 0.03	64	< 5
48	−CSO2Me	6.41 ± 0.03	65	< 5
49	−CC(O)tBu	6.32 ± 0.04	-	-
50	−CCN	6.24 ± 0.05	66	< 5
51	−CC(O)OMe	6.20 ± 0.04	67	< 5
52	−CCHO	5.82 ± 0.02	68	< 5
53	−CI	5.63 ± 0.07	-	-
54	−CCl	5.62 ± 0.05	69	< 5
55	−CCONMe2	5.47 ± 0.03	70	< 5
56	−COMe	< 5	71	< 5
57	−CBr	< 5	72	< 5
58	−CMe	< 5	73	< 5
59	−CSMe	< 5	74	< 5
60	−CC(O)NHMe	< 5	75	< 5

Entry	Substituent X	X4	X5	pIC50 ± SEM
76	-phenyl	CX	CH	5.06 ± 0.08
77	pyridin-2-yl	CX	CH	< 5
78	pyridin-4-yl	CX	CH	< 5
79	-phenyl	CH	CX	< 5
80–84	Mono substituted phenyl (e.g. 2, 3 or 4-F, −COCF3, −OMe)	CH	CX	< 5
85–87	Mono substituted pyridine (e.g. 4-Me, −OMe, −CF3)	CH	CX	< 5
88	furan-2-yl	CX	N	6.03 ± 0.03
89	6-cyanopyridin-2-yl	CX	N	5.98 ± 0.05
90	thiophen-2-yl	CX	N	5.71 ± 0.04
91	6-bromopyridin-2-yl	CX	N	5.69 ± 0.06
92	pyridin-2-yl	CX	N	5.56 ± 0.04
93–96	methyl-6-picolinate, 6-picolinic acid, 6-chloropyridin-2-yl, 6- iodopyridin-2-yl	CX	N	< 5
97–101	furan-2-yl, pyridin-2-yl, pyridin- 3-yl, pyridin-4-yl, Ph	N	CX	< 5
102–105	R = C(O)OMe, thiophen-2-yl, furan-2-yl, pyridin-2-yl			< 5