(new?) medchem tool box for compound synthesis

This mini perspective shows recent progress of the direct C-H alkylation with Alkyl Sulfinates.

There are many heterocyclic moieties such as pyridine, pyrrole etc. in drug like molecules.
The C-H alkylation reaction of heterocycles is useful but difficult to conduct it under mild reaction conditions.
So mild and universal reaction is very attractive for chemists I think.

In the article, Phil S. Baran’s group reported many examples of their developed reaction.
They used alkyl sulfinates as a radical precursors and developed many kind of commercial sulfinates, fluoroalkyl, heterocyclic, alkyl, aromatic and linker-type.

Surprisingly most of the reactions proceed room temperature. Also they shows reactivity guid lines, it is very practical!

And also this reaction can apply not only early stage of synthesis but also late stage of synthesis.
It means that this is very specific reaction.
I had few successful cases C-H alkylation with sulfinate…. I would like to use the reaction condition when I have chance.



I like my town. This town is comfortable for me to live in, because it is not too urban like Tokyo or rural.

There are many beautiful place and following pictures are my favorite place.  The water in this river is very clean. I can see firefly in summer around here.

I want to  this scenery to continue forever.

After walk, I went to see a doctor, my finger is getting well. I hope my finger get well soon…

Enjoyed RDKitUGM2018 #RDKit

I got back Japan from Cambridge today. Time flies when you’re having fun.
This is the first time I participate RDKit UGM and RDKit Hackathon. It was amazing experience for me.
Twitter Hash Tag was very attractive. If reader who is interested in, I recommend to search #RDKitUGM2018 in twitter.
I could talk face to face many people who I’m following twitter. Thank you for talking with me. ;-)
There were many exiting topics in the meeting. Especially I enjoyed Dr. Segler’s talk about computer aided synthesis planning. It was nice work! His system can analyze retrosynthetic route very efficiently.

And Gregs’s presentation gave me very important message.
Pros of open source is good community and contribution of users. I agree his opinion. I would like to have ab internal discussion about it.

I really surprised that I could meet my blog reader and could get many positive comment about the blog.
I was so happy that I cried….

This blog is memo for myself, but it make me happy that my blog be someone’s help.

I really thank the meeting organizer and participants.
I hope I can meet everyone next year

Enjoy summer vacation

I and my family enjoyed camp in this weekend. This is third time for us.
The campsite is located near the river. Kids enjoyed playing in the water and caught crabs.

This tent site was very humid because after a typhoon has passed. It was
terrible dew condenses on the tent….

In this morning, I enjoyed coffee and hot sand. My new partner, coleman 413H 2 burner worked very well. It made us delicious breakfast. ;-)

I would like to go camp again near the feature!

Dual Kinase inhibitor for Autoimmune disease

There are lots of JAK/TYK inhibitor project in drug discovery area.
Here is an article from pfizer. Pfizer discovered and launched JAK inhibitor ‘tofacitinib’.
Tofacitinib inhibits JAK3, JAK1 and JAK3.

It is well known that JAK2 uniquely forms a homodimer, which is important in hematopoiesis via signal transduction associated with erythropoietin (EPO), thrombopoietin (TPO), and IL-3. Inhibition of JAK2 is concerned about reduction in hemoglobin/Amemia.

They focused to obtain JAK1/TYK2 dual inhibitor to block INF alpha. I think the strongest point is that they can use PK/PD relationship of tofacinib’s JAK2 inhibition.
By using their clinical knowledge, they could define the clear criteria of the project.

Their lead compound is pyrimidine derivative with 4 diversity points. They changed R4 group from cyanoacetyl group to cyclopropyamidel group to improve hydrohobic interactions. And finally they found difluoro cyclopropyl amide moiety. Genentec published Tyk2 inhibitor and the compound has cyclopropyl moiety too but different binding mode. Hmm, cyclopropyl group is interesting parts for medicinal chemist.

Finally they found compound 23 and the compound showed good efficacy in vivo AIA model (PF-06700841). And this compound studies in Ph II trials now.

BTW, In fig1 shows Jak inhibitors on the market and in late stage clinical development.

It is very interesting for me baricitinib and ruxolitinib is quite similar structure. It is because that both compounds are developed by same company Incyte Biopharmaceutical Company. I did not check patents of both compounds. I would like to know claim strategy of them.

第17回 サマーカップinエコパの応援行った #ドッジボール

 長男が所属しているドッチボールチームの参加する大会、第17回 サマーカップinエコパ ということで、掛川のエコパアリーナまで応援に行ってきました。