Silicon Switch Approach in TRPV1 Antagonist MK-056 and its Analogues
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 10 November 2009
Minsun, Chang , Seol-Rin, Park , Juhyun, Kim , Mijung, Jang , Jeong Hyun, Park , ...
In searching for opportunities to exploit the benefits of silicon in TRPV1 research, we tried to investigate the pharmacological effects of sila-substitution (C/Si exchange) of tert-butyl group in the MK-056 series. Compound 13a, with a 4-positioned trimethylsilanyl group on the B ring in place of tert-butyl group, exhibited the most potent antagonist activity with IC50 values of 0.15 μM, which is almost equipotent with that of MK-056. This is the first example that tert-butyl group on MK-056 series can be replaced to the other substituent without loss of activity.
