Solipsis
Bluelight Crew
- Joined
- Mar 12, 2007
- Messages
- 15,509
Firstly: I agree with Nuke's post.
Secondly: this is IMO a typical case of SAR abuse. There is something called the SAR paradox which adresses the fact that often when we think we can see a pattern going on between structure and activity of a drug there are other factors that come into play to mess with our assumptions. How well a drug binds and what reactions and risks that yields depends on a great number of factors which indeed include the size of groups, electronegativity and how rigidly they are positioned.
Such rules as proposed in this thread are extremely instable which as is already said can be illustrated by comparing 2C-X's with their NBOMe counterparts. Adding the NBOMe group makes the whole molecule fit into a receptor differently. The halogens fit in a certain 'pocket' in the receptor and which halogen group fits better depends on how the rest of the molecule binds.
With a number of N-benzyl substituted 2C-X it seems indeed that the iodides are the most potent: they fit best to give the most activation of the receptor. I agree with Nuke that problems arising from this can be that these compounds act so well that the resulting activity can cause complications. In other words: in these cases the best explanation we seem to have for hospitalisations is that too much 5-HT2A activity can kill. Toxicity is not always a result of something inherently abnormal, destructive and alien going on, it is often the result of "too much of a good thing".
The fact that this seems the case with N-benzyl phens that have an iodide on the 4-position says nothing about whether for example 5-halogen-DMT drugs are a bad idea because "the halogen is alien". (In by far most cases the halogen group cannot "fall off" to cause problematic metabolites so that is not it either.) 5-halogen-DMT drugs may be bad or good only because of how the entire thing acts on receptors and what effects and side-effects that results in.
Another illustration is that there are bio-isosteres which means that some groups can act alike because they have properties that are similar like size and electronegativity. With research chemicals being developed, this is often used to create a drug that is similar to something else but not the same. IMO saying that some groups are by definition bad is misunderstanding that chemistry doesn't discriminate, there are only reactions to molecules having certain properties and if you can simulate the important properties well enough to make an analogue, receptors won't say "fuck you, I am not familiar with this", they will only react to how the ligand is built up in size and dipoles, etc etc.
Excusing this as correlations doesn't make it right - it is still an attempt to draw conclusions in a way that is only conductive to junk science.
Yes, the correlation you quote that is about halogens in the 2C-X range is definitely real within the 2C-X range of compounds, but this is nothing new and it seems like a pretty boring thing to say unless you are trying to take that point and applying it something else to draw conclusions.
Sorry to be blunt, it is not personal.
Secondly: this is IMO a typical case of SAR abuse. There is something called the SAR paradox which adresses the fact that often when we think we can see a pattern going on between structure and activity of a drug there are other factors that come into play to mess with our assumptions. How well a drug binds and what reactions and risks that yields depends on a great number of factors which indeed include the size of groups, electronegativity and how rigidly they are positioned.
Such rules as proposed in this thread are extremely instable which as is already said can be illustrated by comparing 2C-X's with their NBOMe counterparts. Adding the NBOMe group makes the whole molecule fit into a receptor differently. The halogens fit in a certain 'pocket' in the receptor and which halogen group fits better depends on how the rest of the molecule binds.
With a number of N-benzyl substituted 2C-X it seems indeed that the iodides are the most potent: they fit best to give the most activation of the receptor. I agree with Nuke that problems arising from this can be that these compounds act so well that the resulting activity can cause complications. In other words: in these cases the best explanation we seem to have for hospitalisations is that too much 5-HT2A activity can kill. Toxicity is not always a result of something inherently abnormal, destructive and alien going on, it is often the result of "too much of a good thing".
The fact that this seems the case with N-benzyl phens that have an iodide on the 4-position says nothing about whether for example 5-halogen-DMT drugs are a bad idea because "the halogen is alien". (In by far most cases the halogen group cannot "fall off" to cause problematic metabolites so that is not it either.) 5-halogen-DMT drugs may be bad or good only because of how the entire thing acts on receptors and what effects and side-effects that results in.
Another illustration is that there are bio-isosteres which means that some groups can act alike because they have properties that are similar like size and electronegativity. With research chemicals being developed, this is often used to create a drug that is similar to something else but not the same. IMO saying that some groups are by definition bad is misunderstanding that chemistry doesn't discriminate, there are only reactions to molecules having certain properties and if you can simulate the important properties well enough to make an analogue, receptors won't say "fuck you, I am not familiar with this", they will only react to how the ligand is built up in size and dipoles, etc etc.
Excusing this as correlations doesn't make it right - it is still an attempt to draw conclusions in a way that is only conductive to junk science.
Yes, the correlation you quote that is about halogens in the 2C-X range is definitely real within the 2C-X range of compounds, but this is nothing new and it seems like a pretty boring thing to say unless you are trying to take that point and applying it something else to draw conclusions.
Sorry to be blunt, it is not personal.
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