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New Atypical Antipsychotic Drug Designs.

MedicinalUser247

MedicinalUser247

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Aug 2, 2023
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When it comes to Atypical Antipsychotics the best one is clozapine. The downside is that it can cause a drop in the leucocyte or white blood cell count. There is a way to stop this though. I figured if you were to add a ketone such as 10,11-dihydro-10-oxo- to the carbon-carbon double bond of clozapines dibenzodiazapines ring on clozapines chemical structure it would have no effect on the white blood cell count. Of course this is all a hypothesis. I've also gone into more complex designs basing it on clozapine. Trying to design it so it would be free from side effects. One in which I decided to remove the 8-chloro along with leaving out the Ketone. The chemical name is 11-(4-Methylpiperazine-1-yl)-5H-dibenzo(b,f)(1,4)thiazepine-5-carboxamide. It has the same piperazine structure as clozapine. It has the main part of the chemical structure that's identical to Seroquel and has the added link to the carbon-carbon double bond which adds on the link which gives part of the structure the look of carbamazepine. One of the reasons I thought of changing the structure from two of my original designs, one with a simple azepine, the other with (1,4)diazepine and instead went with a (1,4)thiazepine was because I speculated that changing this part of it would decrease any chance in the drug producing side effects that are seen in clozapine or carbamazepine. Of course this is all hypothetical work so I don't think it will ever be put into production.
 
What is your rationale for these changes?
 
As for how I got these ideas. I got them by looking at different chemical structures and comparing them to each other. I just wanted to design a more effective antipsychotic and everything in the design is based on pure speculation. That's why it's purely hypothetical.
 

Wait - where are you adding a ketone?

I studied clozapine long, long ago and I know people have got to the level of swapping H for D in different places to improve it's safety profile, but nothing has come of it so far. Likely won't. It is an old drug.

I know that it acts on NMDA as well as dopamine which lead to NMDA modulators being produced more recently... they failed in trials.
 
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MedicinalUser247 said:
The Ketone is on the middle of the N of the clozapine analog to the left side on top.
Click to expand...

That would make that an AMIDE, not an amine. A basic nitrogen is absolutely required for activity so no, sorry.

Compare it to olanzapine. See how the both have a piperazine ring?
 
Well I did compare it to Olanzapine and Seroquel before I designed it. The thing is I wanted it to keep it as closely looking like Clozapine as possible. Olanzapines right bottom ring looks totally different.
 
On paper - the 2 aromatic rings are more or less interchangable.

With respect, you need to learn a lot more medicinal chemistry. 'Rational Design' as the name suggests means you have a rational reason to change something.... but changing an amine to an amide isn't rational.

It's a lot of work, but just look at the patent on olanzapine - dozens of people for over a decade, Formally it takes 8 years but in truth, those 8 years are just to learn the toolkit.
 
Thanks for some of your answers. If anyone wants to get an idea of what my design basically looks like. It looks like a cross between Oxcarbazepine and Clozapine except I dropped the 8-chloro in the compound. Now I'm wondering why a cross between the two compounds wouldn't work. If you can give me an answer go ahead and give me one. Thanks.
 
It would work too well, based on my experience with samidorphan, which was dysphoric as all get out.
 
If you want to learn how to post structures, try

opsin.ch.cam.ac.uk

Insert the name of the compound into the query box. The structure you want will pop up. If you get an error message, keep playing with it.

Now, select all the name in the query box and copy. Now, manually type in the url box, opsin.ch.cam.ac.uk/opsin/<the text you just copied>.png

Viola, your virtual molecule now has a shape and its own website. Go to this new site and select all then copy the url.

Now, make a post. Treat it as an image being inserted by typing [ I M G ] Paste [ / I M G ] without the spaces.
 
Wait, I'm confused again. Drawing the structure makes chemical communication 100x easier. If I wanted to make clozapine friendlier, I would swap the chloro with a methoxy.
 
I think the new docking tools would be nice in this case. You can dock a current compound and look at all the ligand-protein interaction sites like where are all the hydrogen bonds n whatnot. This could help you get a better idea of what changes to make to get a better for for your target or worse fit for off target proteins
 
Yes, and adding an element with a heavier atom such as bromine or iodine would hypothetically make it stronger, but that's not part of my cross design of Oxcarbazepine and Clozapine. I'm not even sure if adding one of those atoms is necessary in the case. But... To each his own design.
 
MedicinalUser247 said:
Yes, and adding an element with a heavier atom such as bromine or iodine would hypothetically make it stronger, but that's not part of my cross design of Oxcarbazepine and Clozapine. I'm not even sure if adding one of those atoms is necessary in the case. But... To each his own design.
Click to expand...

Why would a heavier halogen make it stronger? Ever consider that ALL the halogens were tried...... try reading the patent.

BTW Please ignore Rectify - (s)he knows NOTHING about medicinal chemistry and because they became so annoying, we gave them their own thread called 'Drawing Random Molecules' for them to waste their own time and not other peoples. REALLY, try reading through it AFTER reading the clozapine patent.....
 
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