610802-16-9Relevant articles and documents
Novel indole derivative and medicine containing the same (by machine translation)
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Paragraph 0152; 0154, (2018/06/30)
[A] formation of Amyloid fibrils can be compounds, including therapeutic or prophylactic agent for neurodegenerative disease Amyloid fibrils formation inhibitor compound and of. (I) or its pharmaceutically acceptable compound represented by the formula [a] or a salt or solvate thereof includes the, Amyloid fibrils formation inhibitor. [R1 And R2 Each independently is H, an alkyl group, a cyano group or the like; R3 And R4 Each independently is H, or an alkyl group; R3 And R4 The, joint may form a ring; Ar1 And Ar2 The substituted or unsubstituted heteroaryl group are independently substituted/unsubstituted aryl groups /; X and Y are each independently a single bond, - (=O) - C etc., Z is O or CH2 ; N is an integer of 1 - 3][Drawing] no (by machine translation)
Synthesis and biological evaluation of piperazine derivatives as novel isoform selective voltage-gated sodium (Nav) 1.3 channel modulators
Juki?, Marko,Frlan, Rok,Chan, Fiona,Kirby, Robert W.,Madge, David J.,Tytgat, Jan,Peigneur, Steve,Anderluh, Marko,Kikelj, Danijel
, p. 2366 - 2380 (2015/04/16)
Sponges of the genus Agelas produce compounds that modulate the activity of voltage-gated sodium ion channels and contribute novel scaffolds for the development of compounds with activity against a plethora of biological targets. In particular, clathrodin and dibromosceptrin were reported to decrease the average maximum amplitude of inward sodium currents in isolated chick embryo sympathetic ganglia cells; we envisaged these compounds as a starting point to design novel Nav channel modulators. This endeavor was part of our long-term goal of designing a comprehensive library of Agelas alkaloid analogs that would cover a broader chemical space and allow us to examine the activity of such compounds on Nav channels. Our series of compounds was designed by maintaining the terminal structural features found in clathrodin while rigidizing the central part of the molecule and replacing the 3-aminopropene linker with a 4-methylenepiperazine moiety. Synthesised compounds were screened for inhibitory action against the human voltage-gated sodium channel isoforms Nav 1.3, Nav 1.4, cardiac Nav 1.5, and Nav 1.7 using an automated patch clamp electrophysiology technique. The results demonstrate that we have obtained a series of compounds with a modest but selective inhibitory activity against the Nav 1.3 channel isoform. The most potent compound showed selective activity against the Nav 1.3 channel isoform with an IC50 of 19 μM and is a suitable starting point for further development of selective Nav 1.3 channel modulators. Such compounds could prove to be beneficial as a pharmacological tool towards the development of novel therapeutically useful compounds in the treatment of pain.
