Process development of fluorinated-pyrrolidin analogue #memo #organic_chemistry

Here is an interesting article for efficient synthesis of fluorinated pyrrolidin synthesis from pfizer.https://pubs.acs.org/doi/abs/10.1021/acs.oprd.9b00245 Fluorine containing building blocks are often used medicinal chemistry. So efficient synthetic route is very useful for us. Some years ago, I synthesized similar compounds 1-fluoro-2-amino cyclic amine derivatives. I tried to use almost same synthetic scheme described in scheme1. 1)

Recent trends of Flow Chemistry #memo #chemistry #technology

I enjoyed reading the article in my lunch break. Researchers at Abbie published nice review about the flow chemistry in the pharmaceutical industry. The URL is below. https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01760 The review describes wide range of the flow chemistry from large scale synthesis to lab scale synthesis. Flow chemistry can run the reaction under high temperature and

Change properties of approved oral drugs

When I learned drug discovery long time ago, I read the article about Role of five which is a rule of thumb to evaluate druglikeness. https://www.sciencedirect.com/science/article/pii/S0169409X00001290?via%3Dihub You can read nice review about the druglikess scores in following URL. ( Written in Japanese ;-) ) View at Medium.com By the way, recently there are many articles

Applicable Domain on Deep Neural Networks #JCIM #chemoinformatics

I read interesting article from JCIM. Dissecting Machine-Learning Prediction of Molecular Activity: Is an Applicability Domain Needed for Quantitative Structure−Activity Relationship Models Based on Deep Neural Networks? URL is below. https://pubs.acs.org/doi/10.1021/acs.jcim.8b00348 The pros of DNN is feature extraction. And there are many articles which use DNN for molecular activity prediction. BTW, is it true that

(new?) medchem tool box for compound synthesis

This mini perspective shows recent progress of the direct C-H alkylation with Alkyl Sulfinates. https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01303 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

Similar but not similar compounds….

Some months ago I wrote a blog post about biased ligand. It is still exciting area for me. https://iwatobipen.wordpress.com/2018/02/10/rational-design-of-gpcr-biased-ligand/ 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

Read a letter.

To design molecule, I care about not only biological activity but also molecular properties. Because if chemist do molecular design only focused on biological activity, it will produce many problems. I read short letter of J. Med. Chem. lett. ASAP article. The letter shows some interesting data. I often use LE, LLE but not used