Table 1.

Cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-one analogs 12-25.

Analog	Northern Aryl Substitution R1	Southern Aryl Substitution R2, R3, R4	HCT-116 Cytotoxicity IC50, μM
12	OMe	H, H, H	0.39
13	OMe	Cl, H, H	13
14	OMe	OMe, H, H	3.2a
15	OMe	Me, H, H	10
16	OMe	Cl, Cl, H	4
17	OMe	H, Cl, H	8
18	OMe	H, H, Cl	8
19	OMe	H, NH-LCBb, H	>25
20	OMe	NH-LCBb, H, H	25
21	OMe	N3, H, H	25
22	O-LCBb	H, H, H	17
23	OMe	H, NH2, H	>25
24	OH	H, H, H	9
25	OBn	H, H, H	8.9

^aAssay conducted by National Cancer Institutes Developmental Therapeutics Program.

^bLCB = (+)-biotinyl-6-aminohexanoic acid.

^cThe cytotoxicity experiments were done as previously described³² except that the cells were incubated for 48 h after the addition of the compounds.