A question regarding napthoylindole SAR

[pr0d1gy]

So I recently decided to toss together some compounds loosely based on napthoylindole SAR. I'm interested in testing, but my lack of pharma/biochem knowledge leaves me cautious. Because friedel crafts and acyl chloride synth are sort of effort, I was a bit limited with what aromatic hydrocarbons I would be using. I've not seen any indole cannabinoid with an unsubstituted benzene ring substituted for the naphthalene ring. This is puzzling as it seems like a fairly rational train of thought. See the attached image please. The two non-indole heterocycles I just made for shits and grins and will never ingest. However, compound (1) seems fairly kosher as far as known synthetic cannabinoids. I'd appreciate any speculation as to whether (1) might be worth a try. It just seems like such an obvious evolution from nathoylindole structures that I can't imagine why I cannot find information regarding it. I assume it's just an extremely uninteresting compound relative to others. Still, I am keen to know whether or not it might be even a bit worthwhile.

 

[adder]

I'm not really familiar with synthetic cannabinoids SAR, but from the comparison of substituents at position 3 of the indole it simply looks like unsubstituted phenyl either doesn't reach far enough or it's electronically less efficient for strong interaction with some residue. Judging by substituents used on the phenyl ring, it's the latter, so your first compound may be much less potent and less selective for cannabinoid receptors than substituted benzoylindoles.

 

[pr0d1gy]

Thanks for your reply. That does seem to be a very reasonable estimate of why unsubstituted phenylmethanones don't seem to have any presence in literature. Out of sheer curiosity, I've started to assay the thianaphthene @ 200 ug and increasing by 100 ug per hour. I think I may have been getting something @ 1.4 mg but it may have been placebo and I'm not willing to increase the dose further until I get some consultation about possible toxicity. It's absolutely something I'd not smoke so dosing has been oral.

The indole-3-phenylmenthanone seems the most promising, but as you said it may be inactive or far less potent. I know dosage conjecture is pretty futile, but any guesses as to where a good place to start titrating from would be awesome. Submilligram doses are always appropriate, but it may take forever to get to an active dose with (1) if at all.

Are their any databases that can be used to mathematically estimate toxicity? Sort of like a toxicological scifinder.

 

[pr0d1gy]

If anyone is at all interested, have assayed (1) and (2). As speculated the indole-3-methanone was very weak relative to most JWH compounds. A dose of 15mg vaporized produced primarily peripheral effects, but it was certainly more then placebo. Typical cotton mouth, bloodshot eyes, and increased appetite were noticeable, but the cannabinoid head space was not present at all really. Very little cognitive effects were noted and a moderate headache occurred, which is enough to detour future trials. I'm not experienced with synth CBDs, I only tried 018 once and had an incredible panic attack. The compound in question was pure as far as can be assessed by 500 mhz HNMR and TLC; which isn't saying a whole lot I suppose.

The thianapthene compound scares me quite a bit and I'm not keen to try it via vaporization. Am I wrong in thinking that it could lead to some nasty metabolites?

 

[Deleted member 81238]

It is normally called *nicotine*.

 

[sekio]

Can you even make S-alkyl benzothiophenes? I would have guessed the answer was 'no' and no.2 there was a typo.

Who's doing the NMR and TLC, the guys who sell you the compoounds?

 

[pr0d1gy]

Can you even make S-alkyl benzothiophenes? I would have guessed the answer was 'no' and no.2 there was a typo.

Who's doing the NMR and TLC, the guys who sell you the compoounds?

Yes, s-alkylation of thiophene and many of its derivatives is possible. It's a bit obscure so they don't teach it in 2000 level OCHEM. I won't go into synthesis detail, but the literature is out there. I've spent most of my graduate research working with sulfur heterocycles. Compounds similar to the one above are IME very unstable and can decompose @ just above ambient temperature in a rotovape; hence I said it wouldn't be a good compound to vaporize. I sincerely doubt any shady RC producer would be willing to make the effort to make such a compound; both due to difficulty in synthesis and poor prospects as a marketable CBD. I took the NMR and also the massive undertaking that is TLC (note sarcasm).

I can understand skepticism as a lot of BS is posted in ADD. If you think I'm full of shit, delete the thread and we can go back to the usual hypothetical SAR circle jerk. It's just sort of amusing that because you can't understand the chemistry, you automatically assume I'm some dickwad buying random garbage from china and claiming otherwise.