On March 15, 2014, Xiao, Dong; Zhu, Xiaohong; Yu, Younong; Shao, Ning; Wu, Jie; McCormick, Kevin D.; Dhondi, Pawan; Qin, Jun; Mazzola, Robert; Tang, Haiqun; Rao, Ashwin; Siliphaivanh, Phieng; Qiu, Hongchen; Yang, Xiaoxin; Rivelli, Maria; Garlisi, Charles G.; Eckel, Steve; Mukhopadhyay, Gitali; Correll, Craig; Rindgen, Diane; Aslanian, Robert; Palani, Anandan published an article.Electric Literature of 35444-44-1 The title of the article was Quality by design (QbD) of amide isosteres: 5,5-Disubstituted isoxazolines as potent CRTh2 antagonists with favorable pharmacokinetic and drug-like properties. And the article contained the following:
Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide I to isoxazole II. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted isoxazolines III (R1, R2 = alkyl, aryl) were introduced. The chirality at 5 position of isoxazolines controlled the switch between two modes of actions, which led to a novel series of pure antagonists. This non-planar motif also conferred a change of shape of these mols., which avoided flat structures and improved their phys. properties. The experimental process involved the reaction of Methyl 6-chloro-6-oxohexanoate(cas: 35444-44-1).Electric Literature of 35444-44-1
The Article related to isoxazoline amide isostere crth2 antagonist design, agonism/antagonism switch, amide isostere, crth(2) antagonists, drug-like properties, isoxazolines, quality by design (qbd) and other aspects.Electric Literature of 35444-44-1
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics