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

/navarone/

/navarone/

Bluelighter
Joined
Dec 26, 2003
Messages
1,322
Location
Under your bed, masturbating...
Ok guys I know u all hate when users come up with illogical nex molecules thinking they found the drug of the century..but after some research on indanes TRIs TRAs Tetralins excettera, I pictured a pontential interesting molecule in my stupid little brain and i sincerely want your opinions about what you think about this compound.

keflomoxindamine.png


I expect it to be a pretty intriguing, non neurotoxic TRI or TRagent but i cant saty nothing without the your oèpinion.

Ow and BTW sorry if i once again come up with random molecules but im drunk and i like fantasizing about molecules when im drunk.

Any info or suggestion would be greatly appreciated.

Cheers and remember drink beer!

Ciao
 
Just tell me how stupid this substance us and WHY esoecially.

PS: my inspirations came from 8-OH-DPAT and common psychoactive indanes,.Forget the keto...that might be a very unecessary group that I foolishlty added as an attempt to render thh drug more adrenergic.
 
!!

/navarone/ said:
my inspirations came from 8-OH-DPAT and common psychoactive indanes
Click to expand...

It has not much to do with 8-OH-DPAT. Some reasons:
1. Sizes of the aliphatic rings are different (6 vs. 5). Why so? This changes the geometry unnecessarily, in other words: the substituents point in different directions.
2. 8-OH-DPAT's hydroxy has become a methoxy in your case. What is the reasoning for this? While a -OH is both a hydrogen-bond-donor & -acceptor, a -OMe can act only as acceptor. Not speaking of increase in steric bulk...
3. Could you elaborate the reason for introducing the fluorine-substituent plz?!​

Furthermore do I have some doubts about the stability of the beta-carbonylamine. Tautomerization to the 1,2-enaminol occurs easily (new double-bond is still in conjugation with the benzene; the alcohol can form 6-membered ring via hydrogen-bond to nearby -OMe).


It would be nice if you could explain the reasoning behind your suggested molecule. Otherwise you have to live with comments like Vecktor's...


Peace! - Murphy



P.S. Some random thoughts why and how your compound looks unstable on first sight:



I don't say that these happen necessarily but they are at least realistic. The compound itself is already a reasonably strong base and could act as auto-catalyst.
 
Last edited:
^ Thanks for the extensive analisis. It is obvious that i rushed a bit too much while trying to comeing up with a non-neurotoxic MDMA-Methamphetamine substitute.

The reason for the fluorine was to increase serotonergic activity like seen in many halogenated amphetamines but after some revision I saw that that fluorine would cause some degree of neurotoxicity.

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?
 
MurphyClox said:
It has not much to do with 8-OH-DPAT. Some reasons:
1. Sizes of the aliphatic rings are different (6 vs. 5). Why so? This changes the geometry unnecessarily, in other words: the substituents point in different directions.
2. 8-OH-DPAT's hydroxy has become a methoxy in your case. What is the reasoning for this? While a -OH is both a hydrogen-bond-donor & -acceptor, a -OMe can act only as acceptor. Not speaking of increase in steric bulk...
3. Could you elaborate the reason for introducing the fluorine-substituent plz?!​

Furthermore do I have some doubts about the stability of the beta-carbonylamine. Tautomerization to the 1,2-enaminol occurs easily (new double-bond is still in conjugation with the benzene; the alcohol can form 6-membered ring via hydrogen-bond to nearby -OMe).


It would be nice if you could explain the reasoning behind your suggested molecule. Otherwise you have to live with comments like Vecktor's...


Peace! - Murphy



P.S. Some random thoughts why and how your compound looks unstable on first sight:



I don't say that these happen necessarily but they are at least realistic. The compound itself is already a reasonably strong base and could act as auto-catalyst.
Click to expand...

The dehydration of the enolamine is not possible. It is a net reduction of the molecule, so it would require a reducing agent. The bottom reaction to the imine is an oxidation, so it would require an oxidizer (O2?). The tautomerization is certainly possible.
 
/navarone/ said:
^ Thanks for the extensive analisis. It is obvious that i rushed a bit too much while trying to comeing up with a non-neurotoxic MDMA-Methamphetamine substitute.

The reason for the fluorine was to increase serotonergic activity like seen in many halogenated amphetamines but after some revision I saw that that fluorine would cause some degree of neurotoxicity.

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...

I think following a compound that has partial NMDA antagonist activity may be the way to go. I have heard somewhere that NMDA antagonists help protect against some of the neurotoxicity of MDMA. (That isn't to say NMDA antagonists may not have their own poblems especially if they start interacting with the AMPA receptors, as most full on AMPA agonists are neurotoxins.)

In addition, NMDA antagonism may provide more of a "trippy" feel to the compound. That combined with the seritogenic and dopamageneric effects of the compound would be pretty awesome.
 
MurphyClox said:
It has not much to do with 8-OH-DPAT. Some reasons:
1. Sizes of the aliphatic rings are different (6 vs. 5). Why so? This changes the geometry unnecessarily, in other words: the substituents point in different directions.
2. 8-OH-DPAT's hydroxy has become a methoxy in your case. What is the reasoning for this? While a -OH is both a hydrogen-bond-donor & -acceptor, a -OMe can act only as acceptor. Not speaking of increase in steric bulk...
3. Could you elaborate the reason for introducing the fluorine-substituent plz?!​

Furthermore do I have some doubts about the stability of the beta-carbonylamine. Tautomerization to the 1,2-enaminol occurs easily (new double-bond is still in conjugation with the benzene; the alcohol can form 6-membered ring via hydrogen-bond to nearby -OMe).


It would be nice if you could explain the reasoning behind your suggested molecule. Otherwise you have to live with comments like Vecktor's...


Peace! - Murphy



P.S. Some random thoughts why and how your compound looks unstable on first sight:



I don't say that these happen necessarily but they are at least realistic. The compound itself is already a reasonably strong base and could act as auto-catalyst.
Click to expand...

BTW what program do you use to draw such chemical pathways?
 
tryp2fun said:
The dehydration of the enolamine is not possible. It is a net reduction of the molecule, so it would require a reducing agent. The bottom reaction to the imine is an oxidation, so it would require an oxidizer (O2?). The tautomerization is certainly possible.
Click to expand...

Agreed about the reaction in the bottom line. Removing a cation (H+) can't of course lead to another cation (the depicted ammonium); electron balance is false in my scheme. :\

With respect to the dehydration, I wouldn't be so sure that it couldn't happen. In food chemistry is the dehydration-reaction of 1,2-enaminols well studied. I admit, the compounds in question (usually carbohydrate-derivatives; see "Maillard-reaction" or "Amadori-rearrangement") possess another hydroxy-function nearby (see this scheme for example) that makes actually the elimination. But still, having a fluoro-phenyl with electron-withdrawing properties in conjugation with the carbonyl does not really increase overall stability of this ring-system.


/navarone/ said:
BTW what program do you use to draw such chemical pathways?
Click to expand...
ChemDraw.


The bottom-line of this discussion is unfortunately, that apart from my (and others) criticism above, it is always recommended to provide more background and reasoning for suggested 'new' compounds. A simple "Oh look what I have drawn for a fancy molecule! Is it active?" is not helpful in any way.

PEACE! - Murphy
 
The bottom-line of this discussion is unfortunately, that apart from my (and others) criticism above, it is always recommended to provide more background and reasoning for suggested 'new' compounds. A simple "Oh look what I have drawn for a fancy molecule! Is it active?" is not helpful in any way.
Click to expand...

Yes, unfortunately unless all of the "look what I drew" conversations are nixed rapidly, there'll never be an impetus to introduce good detail and reasoning first (especially when it starts, I'm drunk, but...)
 
Hammilton said:
Yes, unfortunately unless all of the "look what I drew" conversations are nixed rapidly, there'll never be an impetus to introduce good detail and reasoning first (especially when it starts, I'm drunk, but...)
Click to expand...

AAGhhhh....C'mon! Have a beer mate! Or one of your mystical novel alcohol analogues since it seems that you are the alcohol guru around here.

Back on topic:
@ Slapdragonx
trifluoromethyl normally tends to increase serotonergic potency in amphetamine substitutes but still retains about half of the neurotoxicity compared to parafluoroamphetamine/aminoindane.

@MurphyClox
Cool...I use ACD (freeware) as well though I gues I still need to get a bit more confident with the program.
BTW i make a 3d optimized comparison between 5-Me-7-OH-dimethylamino indane and 8-OH-DPAT:

http://www.mediafire.com/?qmmoituvtjk

Unofrtunately i had some problems with copying the mol file in jpeg ormat so i had to uload it in RTF.
 
What exactly are we supposed to see in this picture?

And you better use imageShack or alike for posting pictures.

- Murphy
 
Copying the ACD 3DView image on paint made the image awfully fuzzy...thats the problem I was talking about before.
On the RTF file though it is very clear, it is an 3d optimized ball and stick mol image with space filling 'dots'.
Tried image shack but didnt work with any ACD 3DView file format.
If you could find a way to post the image in a satisfying quality I would be very gratefull.
 
When you are in ACD 3d viewer go to file -> export then select gif or jpg. Lets you save the molecule as an image.
 
Ow screw it! I'll just post the bmp/jpeg picture anyway. My freeare version doesn't allow me to transform 3d mol files into gif,jpg,jpeg...........I would need a screen shot in that case.

Anyway here is the comparison even if in bad quality.

5me7ohdai.png
 
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