Sciencemadness Discussion Board

TRPV1 antagonist synthesis

Jessenius - 22-6-2022 at 01:43

Hey, there have been some threads here about TRPV1 modulation, mostly using capsazepine, but I haven’t spotted anyone actually synthesizing such an antagonist.
This is a report from my home synthesis of A-425619, an even more potent TRPV1 antagonist (IC50 ~ 2 nM), which is not exactly OTC, but it was made completely in a home lab and I guess some of you might take it as an interesting inspiration.
Enjoy!



[Edited on 22-6-2022 by Jessenius]

[Edited on 22-6-2022 by Jessenius]

Attachment: A-425619_compressed.pdf (730kB)
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Jessenius - 22-6-2022 at 01:46

Please, don’t be afraid to comment on any mistakes in the article, I would love to hear your feedback!
And if you want the original version with high resolution pictures, just tell me and I’ll send it via email.

xdragon - 22-6-2022 at 01:58

Wonderful report, had a blast reading this. Definitely inspiring.

Diachrynic - 22-6-2022 at 02:11

In figure one, the structure is a quinoline, while in the rest of the document it's an isoquinoline. I assume this is an error and should really be an isoquinoline there as well.
Impressive work!

Jessenius - 22-6-2022 at 12:18

Thanks, this and more corrected.

Dr.Bob - 23-6-2022 at 10:38

Great write up. Maybe this can allow me to finally eat spicy foods better. :-)

Some very nice chemistry, impressive to get hold of triphosgene, its hard to order now even at a research institute. There are a growing number of chemicals that are getting hard to obtain, sadly. But we must keep going at it.

clearly_not_atara - 23-6-2022 at 20:23

Please be aware that TRPV1 antagonists can cause severe hyperthermia by inhibiting sweating and the ordinary perception of heat. Internal use is not advised and topical use should not be habitual. Pharmacological development of TRPV1 antagonists for pain relief was halted for this reason.