. 2011 Apr 18;2(7):538–543. doi: 10.1021/ml200070g

Table 1. Structures and KHK Inhibition Results for Derivatives of 1 with Variation of R₁.

graphic file with name ml-2011-00070g_0005.jpg

compd^a	R₁	R₂	IC₅₀ (nM)^b
2	2-MeC₆H₄	Me	400
3	2-MeC₆H₄	CH₂-c-Pr	210
4	Ph	CH₂-c-Pr	3200
5	3-MeC₆H₄	CH₂-c-Pr	2800
6	2-MeOC₆H₄	CH₂-c-Pr	100
7	2-EtOC₆H₄	CH₂-c-Pr	200
8	2-MeSC₆H₄	CH₂-c-Pr	12
9	3-MeSC₆H₄	CH₂-c-Pr	2000
10	4-MeSC₆H₄	CH₂-c-Pr	>9000
11	2-MeSO₂C₆H₄	CH₂-c-Pr	>9000
12	2-EtSC₆H₄	CH₂-c-Pr	>9000
13	2-CF₃SC₆H₄	CH₂-c-Pr	3000
14	2-EtC₆H₄	CH₂-c-Pr	130
15	2-(i-Pr)C₆H₄	CH₂-c-Pr	5000
16	2-(c-Pr)C₆H₄	CH₂-c-Pr	380
17	2-FC₆H₄	CH₂-c-Pr	1500
18	2-ClC₆H₄	CH₂-c-Pr	540
19	2-BrC₆H₄	CH₂-c-Pr	170
20	c-Pr	CH₂-c-Pr	>9000
21	c-hexyl	CH₂-c-Pr	>9000

New compounds were purified by HPLC and characterized by ESI-MS and ¹H NMR (see the Supporting Information).

Inhibition of recombinant human hepatic KHK (KHK-C) in terms of IC₅₀ values; >9000 nM relates to <50% inhibition at 9 μM.

Table 1. Structures and KHK Inhibition Results for Derivatives of 1 with Variation of R1.