Similar but not similar compounds….

Some months ago I wrote a blog post about biased ligand. It is still exciting area for me.

BYW, the post is about Rexulti developed by Otuka Pharmaceutical.
And the drug approved 19th Jan. 2018 in Japan for schizophrenia. Just by looking, Rexulit has very similar structure to Abilify.
I interested the patent strategy and got some U.S. patent from google patent.


U.S. patent number of Abilify is 5,006,528 filed in oct. 20, 1989 “CARBOSTYRIL DERIVERTIVES”.
Common structure is below.

R in the formula is limited substituted benzene.
In this patent, there are many in vivo data but no in vitro data.

Let’s move to next patent, rexulti.
I found following U.S. patent.
The claimed structure is below.

In the figure, Q is calbostyril moiety. Main difference is monocyclic benzene and benzothiophene.
In this patent, inventor differentiate competitors patents from pharmaceutical or structural side.
Let’s see background art!
WO2004/026864A1 discloses that acarbostyril derivative represented by the general formula.

It seems too similar I think. But they differentiate from biological activity.
However, there is no description in WO2004/026864A150 that carbostyril derivatives described in the document have D receptor partial agonist activity,5-HT2 receptor antagonist activity, a receptor antagonist activity and serotonin uptake inhibitory activity together and have a wide treatment spectrum.
Hmm. OK CNS area is very complex. It will be difficulty point for drug discovery but also will be chance.

Next patent WO 2005/019215A1 disclose the following formula.

The claimed structure is also similar. But the patent does not disclose the structure of rexuti.
However, WO 2005/019215 A1 does not specifically disclose the compounds of the present invention

There are lots of patents about Abilify and Rexulti. In this industry patent strategy is very important because finding new drug is needed long time and efforts.

This post shows only very easy part these drugs but I feel very difficult and interesting point of CNS area drug discovery.


Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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