183557-77-9Relevant articles and documents
Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors
Wei, Manman,Peng, Xia,Xing, Li,Dai, Yang,Huang, Ruimin,Geng, Meiyu,Zhang, Ao,Ai, Jing,Song, Zilan
, p. 9 - 28 (2018/05/28)
Starting from the phase II clinical FGFR inhibitor lucitanib (2), we conducted a medicinal chemistry approach by opening the central quinoline skeleton coupled with a scaffold hopping process thus leading to a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives. Compound 25a was identified to show selective and equally high potency against FGFR1/2 and VEGFR2 with IC50 values less than 5.0 nM. Significant antiproliferative effects on both FGFR1/2 and VEGFR2 aberrant cancer cells were observed. In the SNU-16 xenograft model, compound 25a showed tumor growth inhibition rates of 25.0% and 81.0% at doses of 10 mg/kg and 50 mg/kg, respectively, with 5% and 10%body weight loss. In view of the synergistic potential of FGFs and VEGFs in tumor angiogenesis observed in preclinical studies, the FGFR/VEGFR2 dual inhibitor 25a may achieve better clinical benefits.
A Method for Identifying and Developing Functional Group Tolerant Catalytic Reactions: Application to the Buchwald-Hartwig Amination
Richardson, Jeffery,Ruble, J. Craig,Love, Elizabeth A.,Berritt, Simon
, p. 3741 - 3750 (2017/04/11)
Transition-metal catalysis has revolutionized organic synthesis, but difficulties can often be encountered when applied to highly functionalized molecules, such as pharmaceuticals and their precursors. This results in discovery collections that are enrich
Nitrogenous Heterocyclic Derivatives And Their Application In Drugs
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Paragraph 0570, (2015/03/31)
The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.