5296-86-6Relevant academic research and scientific papers
Optimization and SAR investigation of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as EGFR and BRAFV600E dual inhibitors with potent antiproliferative and antioxidant activities
Gomaa, Hesham A.M.,Shaker, Mohamed E.,Alzarea, Sami I.,Hendawy,Mohamed, Fatma A.M.,Gouda, Ahmed M.,Ali, Asmaa T.,Morcoss, Martha M.,Abdelrahman, Mostafa H.,Trembleau, Laurent,Youssif, Bahaa G.M.
, (2022/01/26)
Using a single drug to treat cancer with dual-targeting is an unusual approach when compared to other drug combinations. Dual-targeting agents were developed as a result of insufficient efficacy and drug resistance when single-targeting agents were used.
Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity
Mohamed, Fatma A.M.,Gomaa, Hesham A.M.,Hendawy,Ali, Asmaa T.,Farghaly, Hatem S.,Gouda, Ahmed M.,Abdelazeem, Ahmed H.,Abdelrahman, Mostafa H.,Trembleau, Laurent,Youssif, Bahaa G.M.
supporting information, (2021/05/26)
New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17–19 showed superior antiproliferative activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19 increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19 demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.
Substituted indole - 2 - formic acid (by machine translation)
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Paragraph 0045; 0046, (2017/10/28)
This invention relates to a substituted indole - 2 - carboxylic acid synthesis method, is to replace the phenyl hydrazine hydrochloride or arylhydrazines as raw materials, through with pyruvic acid ethyl ester cheng zong, Fischer indole synthesis by reaction of substituted indole - 2 - carboxylic acid ethyl ester, hydrolysis to obtain the substituted - 2 - carboxylic acid. Product purity is greater than 97%, the reaction yield is 64%. Synthesis method of the invention with non-harsh conditions, the operation is simple, and environmental friendliness, it has certain economic benefits. It is a kind of raw materials are easy, simple operation, three wastes, high yield of indole - 2 - carboxylic acid synthesis method. (by machine translation)
ZnO nanoparticles as reusable heterogeneous catalyst for efficient one pot three component synthesis of imidazo-fused polyheterocycles
Swami, Suman,Devi, Nisha,Agarwala, Arunava,Singh, Virender,Shrivastava, Rahul
, p. 1346 - 1350 (2018/03/26)
An efficient, simple, environmentally benign synthetic protocol is developed for synthesis of biologically and medicinally relevant pyrazole coupled imidazo[1,2-a]pyridine derivatives via three component reaction of alkyl-4-formyl-1-phenyl-1H-pyrazole-3-c
Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole derivatives: A new method for synthesis pyranoindoles
Xie, Hui,Yang, Jian-Xin,Bora, Pranjal Protim,Kang, Qiang
, p. 3014 - 3021 (2016/05/19)
A direct and highly stereoselective approach for the synthesis of Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A variety of pyranoindoles were obtained in 44-93% yields. Moreover, a more convenient synthesis of pyranoindoles starting from terminal alkyne was realized via a Cu-Rh sequentially catalyzed one-pot cascade reaction.
Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup
Devasthale, Pratik,Wang, Wei,Hernandez, Andres S.,Moore, Fang,Renduchintala, Kishore,Sridhar, Radhakrishnan,Pelleymounter, Mary Ann,Longhi, Daniel,Huang, Ning,Flynn, Neil,Azzara, Anthony V.,Rohrbach, Kenneth,Devenny, James,Rooney, Suzanne,Thomas, Michael,Glick, Susan,Godonis, Helen,Harvey, Susan,Cullen, Mary Jane,Zhang, Hongwei,Caporuscio, Christian,Stetsko, Paul,Grubb, Mary,Huang, Christine,Zhang, Lisa,Freeden, Chris,Li, Yi-Xin,Murphy, Brian J.,Robl, Jeffrey A.,Washburn, William N.
, p. 2793 - 2799 (2015/06/08)
Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in
Synthesis and biological activity of functionalized indole-2-carboxylates, triazino- and pyridazino-indoles
El-Gendy, Adel A.,Said, Mohamed M.,Ghareb, Nagat,Mostafa, Yasser M.,El-Ashry, El Sayed H.
experimental part, p. 294 - 300 (2009/04/11)
Condensation of aryl hydrazines with ethyl pyruvate gave the respective hydrazones 4-6; Fischer indolization led to substituted-1H-indole-2-carboxylic acid ethyl esters 7-9. The Mannich reaction of these compounds with formaldehyde and morpholine yielded ethyl 3-(morpholinomethyl)-substituted-1H-indole-2- carboxylates 10-12. The 5,7-dichloro-1H-indole-2-carbohydrazide 13 was cyclized with methyl orthoformate in DMF to give 6,8-dichloro[1,2,4]triazino[4,5-a]indol- 1(2H)-one 14. Vilsmeier-Haack formylation of 7-9 gave ethyl 3-formyl- substituted-1H-indole-2-carboxylates 15-17 whose 2,2′-((5-chloro-2- (ethoxycarbonyl)-1H-indol-3-yl)methylene)bis-(sulfanediyl) diacetic acid 18 was prepared. The reaction of 15 and 16 with substituted anilines by conventional and microwave methods gave ethyl 3-(N-aryliminomethyl)-5-halo-1H-indole-2- carboxylates 19-29. In a cyclocondensation reaction of 19-25 with thiolactic acid or thioglycolic acid substituted indolylthiazolidinones 30-33 were prepared. Reaction of hydrazine hydrate with 15-17 did not give the respective hydrazones but directly led to the cyclized products substituted-3H- pyridazino[4,5-b]indol-4(5H)-ones 34-36, while a reaction with 2,4-dichlorophenylhydrazine yielded the uncyclized hydrazones. The chlorination of 35 and 36 with POCl3 gave pyridazino[ 4,5-b]indoles 39 and 40, respectively; reaction of the latter compounds with morpholine gave 4-(substituted-5H-pyridazino[4,5-b]indol-4-yl)morpholine 41 and 42. Mannich reaction of 34 with formaldehyde and N-ethylpiperazine gave 8-chloro-3-((4- ethylpiperazin-1-yl)methyl)-3H-pyridazino[ 4,5-b]indol-4(5H)-one 43. The microwave assistance of selected reactions has a profound effect on the reaction speed. The structures of the new compounds were confirmed by both analytical and spectral data. Some compounds were subjected to investigations concerning their antimicrobial, tranquilizing, and anticonvulsant activities.
Indoline Analogues of Idazoxan: Potent α2-Antagonists and α1-Agonists
Fagan, Gay P.,Chapleo, Christopher B.,Lane, Anthony C.,Myers, Malcolm,Roach, Alan G.,et al
, p. 944 - 948 (2007/10/02)
The synthesis and α-adrenergic activity of a series of substituted 2-imidazolinylindolines are described.Substitution in the indoline ring generated compounds with a spectrum of adrenoceptor antagonist/agonist profiles that proved sensitive to both the nature and position of the substituent.Many of the derivatives possess greater presynaptic antagonist potency that the corresponding benzodioxan 1, dihydrobenzofuran 2, and indan 3 analogues; however, this α2-antagonism is often accompanied by α1-agonist activity.It was not possible to separate α2-antagonist from α1-agonist properties in this series.Compounds of most interest proved to be the N-ethyl 6, 5-chloro-N-methyl 18 and 5-chloro-N-ethyl 23 derivatives, all being potent α2-antagonists and α1-agonists.Substitution at the 4- and 7-position of the indoline ring generally gave compounds with nonselective agonist properties.
