Why do 2Cs act as serotonin agonists when they look more similar to dopamine?

[Ziiirp]

Not really related to 2c-c, but can someone in this thread describe in a few notes, why the 2c's are primarily known as 5HT2-agonists, when they look much more like dopamine, 2c-d in particular ?

 

[sekio]

this is the tyranny of SAR

activity of drugs is not determined by how they look on paper, but rather the 3d spatial arrangement of atoms and electrical charges and how the molecule interacts with protiens (i.e. receptors)

 

[Pomzazed]

2C doesn't look "more" like dopamine.

You cannot only looking on 2D stucture on paper and determine that.
What to do is to look at its 3D orientation, including the shape, the electron densities at each spot, its spatial arrangement etc.
before you can say it look like this more than that

 

[SeenSoFar]

I've had this same question (as well as many similar ones) asked to me countless times. This is how I explain it:

Think about a simple childish drawing of a person. This drawing gets its point across, that yes, it is in fact supposed to be a person, but it doesn't come close to telling the whole story. You don't see the intricacies of the human form, the miniscule muscle movements, the variations in skin-tone and all the other things that make a human a human.

Think of the 2D chemical line drawing as a simple child's picture of a man, and the actual molecule as a real living human. This isn't even the whole story though, because many of the properties that define the activity of a compound are not visible to the naked eye, even if you were able to enlarge the molecule to a size that would permit you to examine it unaided. If you look up the 3D structure of a compound though, you will often find that most compounds that have activity at a particular site have certain structural features in common that might not be obvious from the 2D structure. For example, perhaps one part of the structure that appears to dangle off to one side in the line drawing actually curls around and produces something that is geometrically very similar to the closed ring of another compound with similar activity. Sorry for being so vague, but I'm posting from my mobile and I can't produce diagrams to explain my point, but when I get home I will add examples.

Anyway, hopefully this explains things in a way that's a bit easier to understand for those who are not as familiar with such concepts.

 

[Nately's Whore]

^So by that logic would a 3d image of a chemical structure be akin to a portrait by a semi-skilled artist and/or graphic design program?

I don't know much about chemistry but I just thought that up and figured I'd take a shot in the dark.

 

[SeenSoFar]

^So by that logic would a 3d image of a chemical structure be akin to a portrait by a semi-skilled artist and/or graphic design program?

I don't know much about chemistry but I just thought that up and figured I'd take a shot in the dark.

I think that's a very good way to look at it. With a typical 3D molecular model you are certainly gaining another level of complexity, just as you are with your extension to the analogy. Both are trying to capture something in a medium that will never record the subject in a perfectly accurate way. The 3D model does a better job of communicating the message, and someone who is knowledgeable in chemistry can mentally fill in a lot of the rest, just as you can imagine or visualise what a scene or subject that has been drawn, painted or modeled by someone of some level of skill might be like in real life. The thing with a molecular diagram or model is that much of the symbols or glyphs used are visual placeholders for non-visual phenomena, such as bonds, just as an artist may use symbols or glyphs to convey smell or sound. Where I'm going with this is, you have done an excellent job of extending the analogy. Kudos.