86847-59-8Relevant articles and documents
Copper- or Nickel-Enabled Oxidative Cross-Coupling of Unreactive C(sp3)-H Bonds with Azole C(sp2)-H Bonds: Rapid Access to β-Azolyl Propanoic Acid Derivatives
Tan, Guangying,Zhang, Luoqiang,Liao, Xingrong,Shi, Yang,Wu, Yimin,Yang, Yudong,You, Jingsong
, p. 4830 - 4833 (2017)
β-Azolyl propanoic acid derivatives are frequently found in biologically active molecules and pharmaceuticals. Here, we report the oxidative heteroarylation of unactivated C(sp3)-H bonds with azole C(sp2)-H bonds via copper or nickel catalysis with the aid of removable bidentate auxiliary, which provides a rapid pathway to β-azolyl propanoic acid derivatives. A variety of azoles such as oxazole, benzoxazole, thiazole, benzothiazoles, benzimidazole, purine, and even [1,2,4]triazolo[1,5-a]pyrimidine could be engaged in this protocol.
6H-THIENO[2,3-E][1,2,4]TRIAZOLO[3,4-C][1,2,4]TRIAZEPINE DERIVATIVE
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Paragraph 0311-0313, (2020/05/07)
The 6H-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,2,4]triazepine derivatives or salts thereof of the present invention have BRD4 inhibitory activity, and thus, they are useful as medicaments, in particular, as prophylaxis and/or therapeutic agents for diseases associated with BRD4.
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.
