76875-22-4Relevant articles and documents
Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors
Guo, Jing,Zhao, Fan,Yin, Wenbo,Zhu, Mingyue,Hao, Chenzhou,Pang, Yu,Wu, Tianxiao,Wang, Jian,Zhao, Dongmei,Li, Haitao,Cheng, Maosheng
, p. 197 - 209 (2018/06/12)
We have previously described the identification of indolin-2-one-5-carboxamides as potent PAK4 inhibitors. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds, 2 and 3. A series of novel derivatives was designed, synthesized, and evaluated in biochemical and cellular assay. Most of this series displayed nanomolar biochemical activity and potent antiproliferative activity against A549 and HCT116 cells. The representative compound 10a exhibited excellent enzyme inhibition (PAK4 IC50 = 25 nM) and cellular potency (A549 IC50 = 0.58 μM, HCT116 IC50 = 0.095 μM). An X-ray structure of compound 10a bound to PAK4 was obtained. Crystallographic analysis confirmed predictions from molecular modeling and helped refine SAR results. In addition, Compound 10a displayed focused multi-targeted kinase inhibition, good calculated drug-likeness properties. Further profiling of compound 10a revealed it showed weak inhibitory activity against various isoforms of human cytochrome P450.
Synthesis, antimicrobial and antimycobacterial evaluation of [2-(substituted phenyl)-imidazol-1-yl]-pyridin-3-yl-methanones
Narasimhan, Balasubramanian,Sharma, Deepika,Kumar, Pradeep,Yogeeswari, Perumal,Sriram, Dharmarajan
experimental part, p. 720 - 727 (2012/04/04)
A series of [2-(substituted phenyl)-imidazol-1-yl]-pyridin-3-yl-methanones (111) were synthesized and screened for their antimicrobial and antimycobacterial activities. Further, a series of [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones (1220) reported in our earlier study was also screened for their antimycobacterial activity. The antimycobacterial activity results indicated that [2-(4-Nitro-phenyl)-imidazol- 1-yl]-pyridin-3-yl-methanone (8, minimum inhibitory concentration [MIC]=3.13 g) was equipotent as standard drug ciprofloxacin and [2-(4-Nitro-phenyl)- benzimidazol-1-yl]-pyridin-3-yl-methanone (16, MIC=1.56 g) was equipotent as standard drug ethambutol. The results of antimicrobial screening demonstrated that 2-[1-(Pyridine-3-carbonyl)-1H-imidazol-2-yl]-benzoic acid (compound 11, MIC=0.002 g) was two times more effective than standard drug ciprofloxacin (MIC=0.004 g) against tested bacterial strains and [2-(2,5-Dimethyl-phenyl)- imidazol-1-yl]-pyridin-3-yl-methanone (compound 3, MIC=0.005 g) was equipotent to the reference compound, fluconazole against tested fungal strains.
An efficient preparation of 2-imidazolines and imidazoles from aldehydes with molecular iodine and (diacetoxyiodo)benzene
Ishihara, Midori,Togo, Hideo
, p. 227 - 230 (2007/10/03)
2-Imidazolines were easily prepared in quite good yields from the reaction of aldehydes and ethylenediamine with molecular iodine in the presence of potassium carbonate. Moreover, 2-imidazolines obtained were smoothly oxidized to the corresponding imidazoles in good yields using (diacetoxyiodo)benzene at room temperature. Georg Thieme Verlag Stuttgart.
