1216-21-3Relevant academic research and scientific papers
Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides
Doherty, Elizabeth M.,Fotsch, Christopher,Bo, Yunxin,Chakrabarti, Partha P.,Chen, Ning,Gavva, Narender,Han, Nianhe,Kelly, Michael G.,Kincaid, John,Klionsky, Lana,Liu, Qingyian,Ognyanov, Vassil I.,Tamir, Rami,Wang, Xianghong,Zhu, Jiawang,Norman, Mark H.,Treanor, James J. S.
, p. 71 - 90 (2007/10/03)
The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators, particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert- butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1), an antagonist that blocks the capsaicin-induced and pH-induced uptake of 45Ca2+ in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 ± 5 and 150 ± 80 nM, respectively. In this report, we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (Foral = 39% and 17%, respectively).
Tyrosine phosphatase inhibitors
-
, (2008/06/13)
A compound of the formula (I): wherein X1 and X2 are the same or different and each is a bond or a spacer having 1 to 20 atom(s) in the main chain; one of R1 and R2 is a cycle group having substituent(s) selected from 1) an optionally substituted carboxy-C1-6 alkoxy group and 2) an optionally substituted carboxy-C1-6 aliphatic hydrocarbon group, wherein the cycle group optionally has additional substituent(s), and the other is an optionally substituted cycle group or a hydrogen atom; and R3, R4 and R5 are the same or different and each is a hydrogen atom or a substituent, or R4 may link together with R3 or R5 to form an optionally substituted ring; provided that when R3 is a hydrogen atom, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-cyclohexylphenyl; when R3 is 4-methoxyphenyl, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-methoxyphenyl; and when R1 or R2 is a hydrogen atom, the adjacent X1 or X2 is not a C1-7 alkylene; or a salt thereof exhibits a protein tyrosine phosphatase inhibitory action and is useful as a prophylactic or therapeutic agent for diabetes or the like.
