[sharbeldam]

As i look at the chemical structures of retinoids, they look similar and ofcourse that is a given since it's the same family, but why is adapelene (and other third generation retinoids) are considered Retinoids since they there is nothing similar about them... is it because they are synthesized from older generations? or do they give same metabolites as older generations?

[pgk]

Adapelene is a retinoid bioisostere and not a retinoid compound. However and in terms of biological activity, it is classified as a retinoid.
Anyway, there is a clear structural similarity of alitretinoin with adapalene (and other 3rd generation retinoids). Can you see it?
Hint: Take a closer look at these molecules.
Bioisostere,
https://en.wikipedia.org/wiki/Bioisostere
Retinoid,
https://en.wikipedia.org/wiki/Retinoid
 

[sharbeldam]

Thank you.
In their chemical structures, I see resemblence in carboxylic acid (At the end) and R-OR Group also with second generation.
But 1 question, i understand that its not a retenoid now, but what does a compound specifically needs to have to officially be retenoid (not just biological activity wise)

[pgk]

It's not only that.
1). How many double bonds are conjugated with the carboxylic group and the same geometrical isomerism, in both cases?
2). How many carbon atom bonds are contained in the shortest distance between the cycloaliphatic ring and the carboxylic group, in both cases?

[pgk]

Officially, adapalene is a 3rd generation retinoid, which is a subclass of retinoids and not just a retinoid “in general”.

[sharbeldam]

I understand better but just to be more specific, for a molecule to be retinoid in general, what does it have to contain in its chemical structure?
according to wikipedia: " cyclic end group, a polyene side chain and a polar end group " but that is also true for adapelene which you said is not a retinoid "in general".
I appreciate it and sorry if i complicated it

[pgk]

There are two systems for drugs classification:
1). Classification by chemical family (e.g. terpenoids, alkaloids, etc.).
2). Classification by biological activity (e.g. vitamins, antibiotics, etc.).
But both classification systems have their own ads and cons:
1). Although being more convenient for chemists, members of the same chemical family or even enantiomers may have different biological activity (e.g. quinine and quinidine).
2). Although being more convenient for physicians, the activity classification is sometimes unsuccessful (e.g. sulfonamides that are not antibiotics but often classified as antibiotics).
Therefore, it is actually preferred the (unofficial up to date) drugs classification by generations that indicates both biological activity and the chemical structure; and often the adverse effects (e.g. antibiotics).

[pgk]

Getting to the point:
1). Retinoid (in general) refers to the biological activity.
2). Xth Generation retinoid refers to both biological activity and (with emphasis to) the chemical structure. Thus:
1st generation retinoids are cycloaliphatic derivatives (terpenoid derivatives),
2nd generation retinoids are aromatic derivatives,
3rd generation retinoids are polyaromatic derivatives,
4th generation retinoids are pyranone derivatives,
5th generation retinoids will be ?
and so on………..

[sharbeldam]

Thank you pgk!