Table 3.

IC₅₀ values and selectivity ratios for substituted A-ring analogues.

No	3-R	RCC4 IC50 μM	RCC4/VHL IC50 μM	Ratioa	No	2-R	RCC4 IC50 μM	RCC4/VHL IC50 μM	Ratioa
18	Ph	11.6	33.2	2.9	39	2-Ph	19.1	40.0	2.1
19	4-pyridyl	13.8	34.0	2.5	40	Ph-4-Ac	38.8	33.4	0.9
20	Ph-4-CF3	12.8	22.6	1.8	41	4-pyridyl	28.9	38.0	1.3
21	Ph-4-iPr	>40	>40	ND	42	2-pyridyl-6-F	>40	>40	ND
22	Ph-4-CONH2	4.1	1.6	1.6	43	5-pyrimidine	26.4	37.0	1.4
23	Ph-4-CONpiperazine-N-methyl	12.8	>40	>3.1	44	4-(1H-indole)	3.1	4.5	1.5
24	Ph-4-CONH(CH2)3NMe2	4.0	3.9	1.0	45	3-thiophene	8.7	>40	>4.6
25	Ph-4-SO2CH3	1.6	13.4	8.4	46	4-(3,5-dimethyloxazole)	3	36.5	12
26	Ph-4-SO2NHtBu	4.5	22.5	5.0	47	3-pyrazole	0.48	20.0	14
27b	Ph-4-Ac	3.9	35.1	9	48	4-(1-methylpyrazole)	5.2	8.1	1.6
28b	C≡CCH2OH	0.24	2.9	11.9	49	4-(1-benzylpyrazole)	2.2	66.1	30
29b	C≡CCH2OMe	0.62	27.9	45	50	4-(1-benzyltriazole)	2.1	14.0	6.7
30	C≡C(CH2)2OH	1.1	2.8	2.5	51	4-methylpiperazine	11.5	31.6	2.8
31	C≡C(CH2)3OH	6.3	0.3	0.1	52	NH(CH2)2Nmorpholine	3.7	8.0	2.2
32	C≡CCH2Nmorpholine	0.57	2.3	4.0	53	O(CH2)2Nmorpholine	7.0	21.1	3.0
33	C≡CCH2Npiperazine-4-Me	2.6	2.2	0.9	54	O(CH2)3NMe2	6.0	8.8	1.5
34	4-(1-benzyltriazole)	>40	>40	ND
35	4-methylpiperazine	2.6	6.6	2.5
36	NH(CH2)2Nmorpholine	19.5	27.9	1.4
37	O(CH2)2Nmorpholine	0.32	0.88	2.8
38	O(CH2)3NMe2	2.7	20.2	7.4

^aRatio = IC₅₀ (RCC4/VHL)/IC₅₀ (RCC4).

^bData from reference 20.