234082-05-4Relevant articles and documents
New and convergent synthesis of AZD 4547
Bu, Lehao,Chen, Wenxin,Gao, Lei,Mao, Yongjun,Sun, Cong,Wang, Han
, p. 276 - 282 (2020/06/10)
A practical and convergent synthetic route of AZD 4547 was developed successfully. The intermediate 5-(3,5-dimethoxyphenylethyl)-1H-pyrazol-3-amine (7) was prepared from 3,5-dimethoxybenzaldehyde through 6 simple steps in 52.3% yield. Another intermediate 4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzoic acid (14) was synthesized from ethyl 4-fluorobenzoate and (2R,6S)-2,6-dimethylpiperazine in 62% yield over 2 steps. Finally, AZD 4547 was obtained from 7 and 14 in 73% yield and 99.1% purity. Purification methods of the intermediates and the final product involved in the route were developed.
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.
Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
, (2018/09/27)
A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
