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Theoretical Indane: "Keflomoxindamine"....Any opinions please?

So trifluoromethyl is more potent but more neurotoxic.... However the dimethyl group would balance out the neurotoxicity while retaining the increased serotonergic potency.

Atleast thats how I see it.

What is the benefit of the O? I understand the methoxy, but the oxygen has me stumped.
 
Slapdragonx said:
So trifluoromethyl is more potent but more neurotoxic.... However the dimethyl group would balance out the neurotoxicity while retaining the increased serotonergic potency.

Atleast thats how I see it.

What is the benefit of the O? I understand the methoxy, but the oxygen has me stumped.
Click to expand...

Read the aboe posts by Murphy....he explains it all.
Hydroxys if in the right spot can be very advantageous. It is mostly a matter of hydrophylicity and electrn donor/acceptor issue.
 
/navarone/ said:
About the MeO...well i really dont know...for some reason i have some sort of disregard towards hydroxy groups (dont ask me why cayuse I dont even know why) anyway it's god that you pointed out the problem with changing a OH with a MeO.

For sure that keto must be removed since, as you delightfully drew above, could fuck up the whole stability of the molecule and turn it into God knows what..possibly even a carcinogenic/neurotoxic compound.

While rushing throuhg Wiki i became fascinated by 5-Iodo-2-aminoindane....it fully substitutes for MDMA though that Iodine is freaking bulky and causes inevitably some kind of serotonergic neurotoxicity...shit.

Also if the serotonergic mechanism works just like parahaloamphetamines, that is..the bigger the halogen the stronger the serotonergic effect but the higher the induced neurotoxicity (even if PIA seems to have greater DARI potential than its halo twins), that would suck pretty much even in the case of indanes.

What intrigued me about 8-OH-DPAT was its 5-HT1a selective agonism and its remarkable 5-HT7 RI/RA activity, also a possible selective D3 agonistic activity along with some very low activity at other serotonin receptors. Ow and BTW IIRC I think i read somewhere that 8-OH-DPAT also had some NMDA activity.....correct me if I'm wrong.

About the amine alkyl conjugagtion I have no freaking idea, IMO a methyl, a dimethyl or a pyridine group seem to me the best choice...but i cant say nothing for sure since i dont get what kind of effet do those dipropyl chains have on DPAT. Help me out on this one guys..

So if i have to correct my molecule while still pursuing the goal of finding a novel non-neurotoxic MDMA entactogenic stimulant I would also take some inspiration from Para-methylamphetamine and switch that fluorine with a methyl.

So basically my new proposition, would be:

5-methyl-7-hydroxy-aminoindane (with some possible alkyl conjugation on the amine)

What do you guys think?
Murphy?
Click to expand...

Sorry to barge in here but I saw this thread and couldn't help but ask you why you do this? I could be off the mark completely, but my own concepts oppose yours.

Such arbitrary decisions being made... Having a "disregard" to hydroxy? That's the strangest thing I've ever heard. And thereby switching it to a methoxy... well your error has been pointed out already. Changing a fluorine to a methyl, again... I do not really understand the point of this. How could you draw a molecule and expect anyone to know the activity... To predict structure activity relationships you need to do more than look at its 2D structure, you need to screen it.

Changing from methyl/ethyl/propyl to a pyridine could have huge effects on selectivity or affinity - as the alkyl chains have free rotation and different steric effects... a pyridine is tighter and rigid. Why would you make so many changes at once, it is like trying to design a paper aeroplane that flies better by making 10 different folds instead of just 1... there could be good changes and bad, it's not a good way to approach the improvement of anything. But again, there is absolutely no way to ever know unless you have a way of actually testing your compound beyond comparing its 2D structure to other compounds on Wikipedia.
 
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this is a question not even David Nichols could answer...

to the OP, your inquiry would be useful if you at least had a sample of the compound...otherwise, it's all speculation.
 
souls_at_zero said:
Sorry to barge in here but I saw this thread and couldn't help but ask you why you do this? I could be off the mark completely, but my own concepts oppose yours.

Such arbitrary decisions being made... Having a "disregard" to hydroxy? That's the strangest thing I've ever heard. And thereby switching it to a methoxy... well your error has been pointed out already. Changing a fluorine to a methyl, again... I do not really understand the point of this. How could you draw a molecule and expect anyone to know the activity... To predict structure activity relationships you need to do more than look at its 2D structure, you need to screen it.

Changing from methyl/ethyl/propyl to a pyridine could have huge effects on selectivity or affinity - as the alkyl chains have free rotation and different steric effects... a pyridine is tighter and rigid. Why would you make so many changes at once, it is like trying to design a paper aeroplane that flies better by making 10 different folds instead of just 1... there could be good changes and bad, it's not a good way to approach the improvement of anything. But again, there is absolutely no way to ever know unless you have a way of actually testing your compound beyond comparing its 2D structure to other compounds on Wikipedia.
Click to expand...

My activity deductions are based on the information and properties regarding other similar substances that I listed and linked in my previous posts.
About the amine alkylation, well that i still have to research some more but it seems that methyl and dimethyl have stronger stimulant activity in such compounds, I hope hopwevr that changing the dipropyl pof 8-OH-DPAT wont compromise its interesting properties.
Im looking forwards for someone to throw some light on fy field of ignorance regarding amine alkylation.

Even if i obviously made some mistakes in my previous assumptions, I would like you to read carfully the information that I gave (along with the links) in the following posts.

Ciao
 
wungchow said:
this is a question not even David Nichols could answer...

to the OP, your inquiry would be useful if you at least had a sample of the compound...otherwise, it's all speculation.
Click to expand...

I wish I had a sample, though i would be carefull about testinjg it on myself first.

I could ask the neuropharmacology and chemestry department of my Uni to make a sample and test it ....but i doubt it's gonna be so easy to convince them to do so unless i provide some convincing theories rather than 'speculations'.

Currently the department is all dedicated on Imidazenyl and possible analogues.
 
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