2199-51-1Relevant articles and documents
An improved synthesis of sunitinib malate via a solvent-free decarboxylation process
Meng, Ge,Liu, Chunyan,Qin, Shidong,Dong, Mengshu,Wei, Xiaomi,Zheng, Meilin,Qin, Liwen,Wang, Huihui,He, Xiaoshuang,Zhang, Zhiguo
, p. 8941 - 8954 (2015)
To search for an economical and convenient synthesis of sunitinib and its malate salt, optimization of a scalable synthetic route was explored by designing a standard experimental protocol on laboratory scale using commercially available materials including acetyl ethyl acetate, 4-fluoroaniline, and N 1,N 1-diethylethane-1,2-diamine. The optimal conditions were established based on investigating the main reaction steps, including cyclization, hydrolysis, decarboxylation, formylation, and condensation, giving optimized yields for each step of 94.4, 97.6, 98.5, 97.1, 91.0, 86.3, 85.5, 88.2, 99.1, 97.3, and 58.7 %, respectively. The synthesis process of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid as the important intermediate was significantly improved by using solvent-free decarboxylation instead of the traditional process in a high-boiling-point solvent. The subsequent formylation was conducted directly using the dichloromethane solution of the crude product from decarboxylation, leading to an almost quantitative combined yield of these two steps. The overall yields of sunitinib and its salt using the optimal synthesis process were 67.3 and 40.0 % based on acetyl ethyl acetate. The obtained data could be used as reference for future industrialization, especially for avoiding expensive solvents and reducing reaction time.
Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives
Rasal, Nishant K.,Sonawane, Rahul B.,Jagtap, Sangeeta V.
, (2020/10/22)
A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.
Transition metal-free cyclization of N-boc-N-propargylenamines
Chikayuki, Yuya,Higashiyama, Kimio,Ishikawa, Haruka,Kouno, Yasuaki,Sasaki, Shigeru,Teramoto, Hiroyoshi,Waki, Yoko,Yamauchi, Takayasu,Yonekawa, Shiori
, p. 719 - 746 (2020/07/13)
An efficient method for the synthesis of multi-substituted pyrroles was developed using basic cyclization of readily accessible N-Boc-N-propargylenamines. Despite the basic conditions, cleavage of the N-Boc group occurred easily. The process was rapid and afforded N-H-pyrroles with wide functional group tolerance in high yields.
