Reasonably Potent and HIGHLY selective 5-HT2A Agonist

[SeenSoFar]

So, I was reading some research papers, and I came across mention of the following compound:

It was originally synthesized as part of Martin Hansen's thesis "Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain"^[1] and it seems to be a very interesting chemical. It isn't that potent, with a K_i of 2.5 ± 0.1 nM, however it has a 124x selectivity for 5-HT_2A over 5-HT_2C^[2]. I do believe that this would make it one of the most selective 5-HT_2A agonists there is.

To me, this seems like it might be a special compound. I would definitely interested in seeing more of this. I am wondering what everyone else thinks of this one. It definitely seems like it has potential. I'm not sure but I also believe that the structure is different enough from regular PEA-NBOMe-series compounds that it would probably fall outside the NBOMe catch-all clauses of the UK and other such places. Thoughts?

[1] Martin Hansen PhD. Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain. University of Copenhagen, 2011.

[2] Juncosa, J. I.; Hansen, M.; Bonner, L. A.; Cueva, J. P.; Maglathlin, R.; McCorvy, J. D.; Marona-Lewicka, D.; Lill, M. A. et al. (2012). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience 4: 120717095020003. doi:10.1021/cn3000668.

 

[ebola?]

I do believe that this would make it one of the most selective 5-HT2A agonists there is.

On paper, 25i matches this selectivity (we need more data on the compound you note, as measures of binding affinity can differ a lot study-to-study).

ebola

 

[endotropic]

So, I was reading some research papers, and I came across mention of the following compound:

It was originally synthesized as part of Martin Hansen's thesis "Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain"^[1] and it seems to be a very interesting chemical. It isn't that potent, with a K_i of 2.5 ± 0.1 nM, however it has a 124x selectivity for 5-HT_2A over 5-HT_2C^[2]. I do believe that this would make it one of the most selective 5-HT_2A agonists there is.

To me, this seems like it might be a special compound. I would definitely interested in seeing more of this. I am wondering what everyone else thinks of this one. It definitely seems like it has potential. I'm not sure but I also believe that the structure is different enough from regular PEA-NBOMe-series compounds that it would probably fall outside the NBOMe catch-all clauses of the UK and other such places. Thoughts?

[1] Martin Hansen PhD. Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain. University of Copenhagen, 2011.

[2] Juncosa, J. I.; Hansen, M.; Bonner, L. A.; Cueva, J. P.; Maglathlin, R.; McCorvy, J. D.; Marona-Lewicka, D.; Lill, M. A. et al. (2012). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience 4: 120717095020003. doi:10.1021/cn3000668.

It's my understanding that 5-HT2C activity is desirable for psychedelic activity. For a research tool, that kind of selectivity is fantastic. For a glowing experience some "off-target" effects might be desirable.

 

[atara]

2C affinity seems to be more attractive with low intrinsic activity than high intrinsic activity. 2C-halogens are entactogenic, unlike most related psychedelics; on the contrary, mCPP produces nausea and anorexia.

 

[SeenSoFar]

2C affinity seems to be more attractive with low intrinsic activity than high intrinsic activity. 2C-halogens are entactogenic, unlike most related psychedelics; on the contrary, mCPP produces nausea and anorexia.

My thoughts exactly. I'm well aware that 5-HT2A agonism does not automatically equal a valuable compound for our purposes. I know this compound is not a guaranteed winner but I think it warrants some exploration. I've always wondered why constraining the alpha- and n- alkyl into a piperidine (not piperazine) ring was not considered more with the PEAs or even tryptamines. It seems like a logical avenue of exploration.

@ebola: I am aware that this is by no means a complete picture, and that in vitro and in vivo results can have radically different, even opposite results, depending on the methodology used in the in vitro experiments. I just thought it might be interesting to let people know about this compound, since it seems like no one has ever discussed it in this or similar communities, at least as far as I have been able to find. Thanks so much for replying and giving your thoughts everyone, I really appreciate it!