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Can anyone extrapolate the structure 4 these MAT allosteric ligand-binding enhancers?

Nagelfar said:
These spirocyclic tropanyl-Δ(2)-isoxazolines reportedly enhance re-uptake inhibitor ligands at SERT & DAT. Does anyone have access to a source that could give me the IUPAC to as many of these and if possible draw them up in molecular-2D for me? I'd like to contribute them to WP.
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The only active compound was 3'-methoxy-8-methyl-spiro[8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole], and it only worked on SERT, not DAT
 
Nagelfar said:
Someone know a program that will render it with that nomenclature? (Marvin Beans doesn't recognize it, it's gets specific with the R/S)
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Opsin

3'-methoxy-8-methyl-spiro%5B8-azabicyclo%5B3.2.1%5Doctane-3%2C5'(4'H)-isoxazole%5D.png
 
This is the closest I can get to naming it. Just imagine 1 benzene ring fused to the 2 and 3 positions of the cyclopentane ring. Also just imagine the correct stereochemistry in your head as well.

4-carbomethoxy-8-methyl-spiro%5B8-azabicyclo%5B3.2.1%5Doctane-3%2C5'-cyclopentane%5D.png


NET inhibition = 140nM
DAT inhibition = >2000nM
 
This? =

YbZjQ.jpg


(Is the stereochemistry the same as cocaine?)

i.e. =

YFO9G.jpg


The double-bond I had to add in each case on the benzene, is it a double like the benzene or a single along the cyclopentane? Does the stereochemistry extend to any part of the cyclopentane as I added or no?
 
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aced126 said:
Yup that's it.
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Are there any other compounds in that paper alluded to that are closer to my cyclized benzoyloxy? (in terms of carbon skeleton only, of course, not the multi-bond sulfur mania), the one given has the same bond length of the phenyltropanes, but you'd think they'd try the phenyl coming off of the cyclopentane with a bond instead of the benzene directly fused on, as that's the same bond-distance/length as cocaine itself.
 
aced126 said:
Not any which had appreciable B-CFT inhibition.
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But is there a staple one of that kind that you may be able to give me the name for, it's affinity (or lack thereof) w/ image (or description good enough that I can draw my own again)? I'm compiling as many attested analogs as possible; efficacy is only an interesting aside (and showing that such a structure has low affinity, still tells something of the QSAR that is, after-all, quite important)

Thanks for keeping up with me here, aced. It really is highly valuable to me and greatly appreciated.
 
In fact, the above compound is the only one where they assayed it and obtained reuptake inhibition values.

The other compound they made was one where carbon 4 on the cyclopentane was replaced with C-S(O2)-C, a sulfonyl group, and they didn't even assay that. All other compounds described in the article were intermediates in the synthesis towards the final one you drew.
 
aced126 said:
In fact, the above compound is the only one where they assayed it and obtained reuptake inhibition values.

The other compound they made was one where carbon 4 on the cyclopentane was replaced with C-S(O2)-C, a sulfonyl group, and they didn't even assay that. All other compounds described in the article were intermediates in the synthesis towards the final one you drew.
Click to expand...

Oh OK, thanks aced.
 
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