Table 2. Activity analysis of MS-0022 chemotype (See structure in figure 1B).

ID	R1	R2	R3	X	Y	MW	IC50 (Shh-L2,nM)	IC50 (nM, BODIPY- cyclopamine inhib.)	cLogP	PSA
MS-0022	CH3	H	2-bromophenyl	C	C	406.3	100	259	5.44	46.4
MS-0030	CH3	CH3	2-bromophenyl	C	C	420.3	630	–	5.86	46.4
MS-0031	CH3	H	2-bromophenyl	C	N	407.3	2300	–	3.88	59.29
MS-0032	CH3	H	2-fluorophenyl	C	C	345.4	161	93	4.39	46.2
MS-0033	H	H	4-methoxyphenyl	C	C	343.4	181	287	4.24	55.63
MS-0034	–	H	2-methoxyphenyl	N	C	344.4	>10,000	–	3.21	68.5
MS-0035	–	H	4-methoxyphenyl	N	C	344.4	877	–	3.1	68.52
MS-0036	–	H	3,5-dimethylphenyl	N	C	342.4	3,700	–	4.06	59.29
MS-0037	–	H	3-chlorophenyl	N	C	348.8	1,870	–	3.87	59.29
MS-0038	–	H	2-trifluoromethylphenyl	N	C	382.3	1,150	–	2.98	59.3

Biological activity of side group analogues of MS-0022 measured by pathway inhibition in Shh induced Shh-L2 cells and by BODIPY-cyclopamine competition, including cLogP (computed LogP, octanol/water partition coefficient) and polar surface area (PSA).