70298-88-3Relevant articles and documents
Design, Synthesis, and Biological Evaluation of 4-Quinoline Carboxylic Acids as Inhibitors of Dihydroorotate Dehydrogenase
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
, p. 5162 - 5186 (2018/05/15)
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. Analogues 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 analogues 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. Additional 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 preclinical studies of our lead compounds toward selection of a candidate for early-stage clinical development.
Preparation technology for 1-(3-amino-4-pyridyl) aceton
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Paragraph 0005; 0012-0013; 0020-0021; 0028-0029; 0036-0037, (2018/03/01)
The invention discloses a preparation technology for 1-(3-amino-4-pyridyl) aceton. The preparation technology is characterized by comprising the following steps: (1) by taking 3-aminopyridine as a raw material, participating into amidation reaction, thereby generating 3-teramidyl pyridine; (2) generating N-(4-aceton pyridine-3-group) trimethyl acetamide through the substitution reaction of the 3-teramidyl pyridine; and (3) hydrolyzing the N-(4-aceton pyridine-3-group) trimethyl acetamide, thereby acquiring the target product 1-(3-amino-4-pyridyl) aceton. The raw materials in process route are low in cost and easily acquired, the operation condition is mild and easily controlled and the preparation technology is beneficial to the industrial application.
Amine Activation: Synthesis of N-(Hetero)arylamides from Isothioureas and Carboxylic Acids
Zhu, Yan-Ping,Sergeyev, Sergey,Franck, Philippe,Orru, Romano V. A.,Maes, Bert U. W.
supporting information, p. 4602 - 4605 (2016/09/28)
A novel method for N-(hetero)arylamide synthesis based on rarely explored amine activation, rather than classical acid activation, is reported. The activated amines are easily prepared using a three-component reaction with commercial reagents. The new method shows a broad scope including challenging amides not (efficiently) accessible via classical protocols.
