Madak, Joseph T.; Cuthbertson, Christine R.; Miyata, Yoshinari; Tamura, Shuzo; Petrunak, Elyse M.; Stuckey, Jeanne A.; Han, Yanyan; He, Miao; Sun, Duxin; Showalter, Hollis D.; Neamati, Nouri published an article in Journal of Medicinal Chemistry. The title of the article was 《Design, Synthesis, and Biological Evaluation of 4-Quinoline Carboxylic Acids as Inhibitors of Dihydroorotate Dehydrogenase》.Application of 70298-88-3 The author mentioned the following in the article:
We pursued a structure-guided approach toward the development of improved dihydroorotate dehydrogenase (DHODH) inhibitors with the goal of forming new interactions between DHODH and the brequinar class of inhibitors. Two potential residues, T63 and Y356, suitable for novel H-bonding interactions, were identified in the brequinar-binding pocket. Analogs were designed to maintain the essential pharmacophore and form new electrostatic interactions through strategically positioned H-bond accepting groups. This effort led to the discovery of potent quinoline-based analogs 41 (DHODH IC50 = 9.71 ± 1.4 nM) and 43 (DHODH IC50 = 26.2 ± 1.8 nM). A cocrystal structure between 43 and DHODH depicts a novel water mediated H-bond interaction with T63. Addnl. optimization led to the 1,7-naphthyridine 46 (DHODH IC50 = 28.3 ± 3.3 nM) that forms a novel H-bond with Y356. Importantly, compound 41 possesses significant oral bioavailability (F = 56%) and an elimination t1/2 = 2.78 h (PO dosing). In conclusion, the data supports further preclin. studies of our lead compounds toward selection of a candidate for early-stage clin. development. The results came from multiple reactions, including the reaction of 2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3Application of 70298-88-3)
2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Application of 70298-88-3
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics