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Any way to tell what, if any, in vivo activity something will have?

CloudyHazeD

CloudyHazeD

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By looking at a chemical (it's formula, it's structure, etc) is there any way to theorize what its effects ,in vivo, will be?

What receptors it will play on?

Its basic bio-availability?
 
A look at the chemical structure might give you some ideas as to what the potential activity of a molecule may be, or alternatively a computer can make predictions based on the structure. These sorts of guesses are never 100% accurate though, and activity can really only be determined experimentally (ideally this means in vivo testing).
 
Yes, yes and yes. That's the short answer. It's called structure activity studies (SAR).
 
Thanks, you have provided a great jump point for the information I am seeking.......

Can you recomend any basic or must have literature on SAR theory and practice?
 
Whoa!

3D QSAR in Drug Design: Volume 1: Theory Methods and Applications (Three-Dimensional Quantitative Structure Activity Relationships) (Hardcover)
by H. Kubinyi (Editor)

List Price: $573.00
Click to expand...

Fuckin' ouch!
 
Yah, SAR's are what you want.

You can determine a lot of them simply by looking at structures, and their binding affinities to certain receptor targets. Plotting molecules in 3D will help, use something like Chem3D for this (or equivalent) - it'll help you identify active stereoisomers too.

There are also papers which strictly deal with SARs. Just search Google Scholar.
Some receptors are better researched than others. The opiods are one of the most researched I believe...

At the high end you can use molecule docking software that "docks" molecules into simulated receptor targets, but I have no idea whatsoever on what these are nor where to get them nor where to obtain receptor models from - if anyone knows, it'be greatly appreciated if you could speak about it a bit :) .
 
"By looking at a chemical (it's formula, it's structure, etc) is there any way to theorize what its effects ,in vivo, will be?"

Theorizing you can,but if you look at a new molecule,its only guesses (the closer it is to a known molecule,the better the prediction.Yeah,really).To dampen the other posters "its never 100% accurate",I would say if you get 10% right,you are a genius.Particularly if you wanna be specific about receptor binding profiles or bioavailability.The proof of the pudding is indeed in the eating,as dademurphy said and as Sashas favourite line goes!You never know when you fall off of what appears to be a line or/and start to dive into a complete Another area of activity.

Though I know a company who appears to have a computerprogram for designing structures with an amazing hit success,but its property and a therefore a secret.And haven't heard of them since a while.

Figure out the world is a dream who took many victims.
 
I'd recommend getting a damn thorough knowledge of chemistry first. Just looking at a structure isn't going to tell you anything unless you know what exactly you're looking at. You've got to be able to think and understand what possible effects various substituents and structures will have. Yeah there are a lot of programs out there and models available, but none of them are perfect descriptors of the real world. And it takes a lot of knowledge to know under what conditions those models will work and under what conditions those models start to break down. I'm not trying to dissuade you or discourage you, but I'd recommend getting the basics down first before you try to dive into that monster of a text.
 
Yep, I'm afraid it's a lot of organic chemistry re: spatial orientation, hybridization, optical activity & absolute configuration. It helps a hell of a lot if you are good at visualizing things in 3D or the structural side will just be a real slog to get through. After a while of looking at SAR studies, you start to recognize certain features as being important to the activity; this leads to an eventual concept of a pharmacophore - which is like a design template to match molecules to.

I could go on for hours (I usually do!), but I tend to forget that not everyone has my affection for organic chem & SAR stuff :D
 
Whenever I tell my fiancee, who's a biologist, "I discovered some wonderful SARs today!" she always thinks I'm talking about the disease. Totally irrelevant, but funny, as it's happened multiple times.
 
fastandbulbous said:
I could go on for hours (I usually do!), but I tend to forget that not everyone has my affection for organic chem & SAR stuff :D
Click to expand...


I have your affection... and would like to learn as much as possible... please go on (or PM me?)
 
^seems that there are enough drug nerds listening for f&b to open a online college.

just a pity that normal drug users are about to loose interest when you throw in the first methyl.
 
Some drugs have wacky profiles. SPA (Lefetamine) is an amphetamine stimulant AND an opiate pain killer. I mean, what a boon!
 
haribo1 said:
Some drugs have wacky profiles. SPA (Lefetamine) is an amphetamine stimulant AND an opiate pain killer. I mean, what a boon!
Click to expand...

quite a few of the DAT inhibitors /Dopamine reuptake inhibitors have stimulant and opioid effects and vice versa
Fencamfamine is another example of a stimulant with opioid effects
meperidine is a analglesic with DAT inhibitor effects. etc.
V
 
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