1001397-19-8Relevant articles and documents
Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure
Harada, Kazuhito,Mizukami, Jun,Watanabe, Takashi,Mori, Genki,Ubukata, Minoru,Suwa, Katsunori,Fukuda, Sumiaki,Negoro, Tamotsu,Sato, Motohide,Inaba, Takashi
, p. 373 - 379 (2019)
We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which linked potency and lipophilicity. Subsequent optimization studies of 8 for improvement of solubility afforded representative 21. Compound 21 had no inhibitory activity against six CYP isoforms and showed favorable pharmacokinetic properties and hypoglycemic activity in rats.
Facile reductive amination of aldehydes with electron-deficient anilines by acyloxyborohydrides in TFA: Application to a diazaindoline scale-up
Boros, Eric E.,Thompson, James B.,Katamreddy, Subba R.,Carpenter, Andrew J.
scheme or table, p. 3587 - 3590 (2009/09/05)
A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive animation of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9