SAR of Indole-type u-agonists?

[Ham-milton]

I was wondering if there has been any research done on the structure-activity relationships of indole u-agonists, like 7-hydroxymitragynine, and less so mitragynine itself?

I couldn't find anything about any research done, but this seems like a good job for a grad student.

Anything you know would be greatly appreciated.

 

[hussness]

I have a good review and a few articles on this subject. PM me with an email address if you want them.

 

[Ham-milton]

Thanks much appreciated.

 

[Ham-milton]

Great articles hussness!! Very much appreciated.

My new question, without starting a new thread, is: Has a Mitragynine pseudoindoxyl -derivative with other substitutents at the the 7 and 9 position been tested? It has the top substitutents for the typical Mitragynine-type drug, but it's quite a bit different.

Is there anything that could be done to make a Mytragynine pseudoindoxyl analogue that'd be more resistant to catabolisis?? Assuming that Takayama is correct about why it's not as effective as it should be based on binding data.

 

[hussness]

^I'll have to think about that. I think it is mentioned in that same article that mitragynine with an acetyl group instead of the methyl ether is completely inactive. I never figured that one out. Another question I've wondered about is whether or not the cis substituents shown on the bottom ring are at all relevant to binding.

 

[Ham-milton]

Yeah, it doesn't make a lot of sense to me why the 9 and 7 positions are so important. You mean everything below the 4th ring (counting right to left)?

It doesn't seem like there's been a whole lot of work done on this.