17450-68-9Relevant articles and documents
Design, synthesis, and LFA-1/ICAM-1 antagonist activity evaluation of Lifitegrast analogues
An, Yuanlong,Du, Guoxin,Du, Weiwei,Gong, Qi,Hao, Feifei,He, Wei,He, Xiangdong,Jiang, Hualiang,Tong, Xiaochu,Wang, Minnan,Zhang, Donglei,Zheng, Mingyue
, p. 555 - 579 (2022/02/22)
The interaction between Lymphocyte function-associated antigen 1 (LFA-1) and intercellular-adhesion molecule-1 (ICAM-1) plays important roles in the cell-mediated immune response and inflammation associated with dry eye disease. LFA-1/ICAM-1 antagonists can be used for the treatment of dry eye disease, such as Lifitegrast which has been approved by the FDA in 2016 as a new drug for the treatment of dry eye disease. In this study, we designed and synthesized some new structure compounds that are analogues to Lifitegrast, and their biological activities were evaluated by in vitro cell-based assay and also by in vivo mouse dry eye model. Our results demonstrated that one of these analogues of Lifitegrast (compound 1b) showed good LFA-1/ICAM-1 antagonist activity in in vitro assay; meanwhile, it also significantly reduced ocular surface epithelial cells damage, increased goblet cell density in dry eye mouse and highly improved the symptoms of dry eye mouse. [Figure not available: see fulltext.]
Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors
Wang, Yazhou,Huang, Wei,Xin, Minhang,Chen, Pan,Gui, Li,Zhao, Xinge,Tang, Feng,Wang, Jia,Liu, Fei
, p. 75 - 83 (2016/12/22)
Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.
Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds
Nguyen, Son T.,Williams, John D.,Butler, Michelle M.,Ding, Xiaoyuan,Mills, Debra M.,Tashjian, Tommy F.,Panchal, Rekha G.,Weir, Susan K.,Moon, Chaeho,Kim, Hwa-Ok,Marsden, Jeremiah A.,Peet, Norton P.,Bowlin, Terry L.
, p. 3366 - 3372 (2014/07/22)
Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/ Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC 50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications.