Table 2.

Structure-activity relationships of bastadin-5 (3) and analogues.^a

Entry	Compound	Skeleton	X	Y	EC50 (μM)b	IC50 (μM)c
1	3	A	–	–	2.2 ± 0.1	–
2	(±)-4	B	NO2	H	20.9 ±10.8	–
4	(±)-5	B	NH2	H	33.0 ±12.2	–
5	(±)-6	B	N3	H	–	63 ±8.1
6	(±)-7	B	Br	H	10.9 ±2.6	–
7	(±)-8	B	Br	Br	>100	–
8	(±)-9	B	H	H	>100	–
9	(±)-10	B	I		28.6 ±14.2	–
10	11	C	NO2	H	24 ± 3.9	–
11	12	C	NH2	H	21 ±5.7	–
12	13	C	N3	H	20.0 ± 2.3	–
13	14	C	Br	H	–	6.2 ±1.2
14	(±)-15	C	Br	Br	–	47 ± 15
15	49	D	Br	H	>100
16	52	D	Br	Br	6.5 ±0.7
17	53				>100

^aEquilibrium binding of 1 nM [³H]-ryanodine to skeletal junctional sarcoplasmic reticulum (SR) was performed in assay buffer containing 250 mM KCl, 15 mM NaCl, 20 mM HEPES, 20 μM Ca²⁺, pH 7.4. Nonspecific binding was determined in the presence of 1 μM cold ryanodine.

^bagonist-like activity (enhanced ³[H]-ryanodine binding)

^cantagonist-like (reduced ³[H]- ryanodine binding)