- An Efficient and Facile Synthesis of Functionalized Indole-3-yl Pyrazole Derivatives Starting from 3-Cyanoacetylindole
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The versatile hitherto reported 3-(1H-indol-3-yl)-1H-pyrazol-5-amine (4) was synthesized by the reaction of 3-cyanoacetylindole (3) with hydrazine hydrate in refluxing ethanol and used as a key intermediate for the synthesis of novel pyrazolo[1,5-a]pyrimidines via its reactions with appropriate 1,3-biselectrophilic reagents or through three-component condensations with triethyl orthoformate and compounds possessing an activated methylene group. Besides, the applicability and synthetic potency of (4) to attain polyfunctionally substituted imidazo[1,2-b]pyrazole, pyrazolo[1,5-a][1,3]diazepine and pyrazolo[1,5-c][1,3,5]thiadiazine derivatives of an expected pharmaceutical interest have been investigated. The mechanistic aspects for the formation of the newly synthesized compounds are discussed.
- El-Mekabaty, Ahmed,Mesbah, Ahmed,Fadda, Ahmed A.
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- Synthesis of Some New Fused Pyrazole Derivatives Bearing Indole Moiety as Antioxidant Agents
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3-(1H-Indol-3-yl)-1H-pyrazol-5-amine 3 was prepared in a quantitative yield by heating 3-(1H-indol-3-yl)-3-oxopropanenitrile 2 in dry ethanol with hydrazine hydrate, and utilized as key intermediate for the synthesis of some new pyrazolo[1,5-a]pyrimidines and pyrazolo[5,1-c]triazines. Structures of the newly synthesized compounds were established by elemental analysis and spectral data and evaluated as antioxidant agents. Most of the tested compounds belonging to the pyrazolo[1,5-a]pyrimidine series exhibited better activities than members of the pyrazolotriazine one.
- El-Mekabaty, Ahmed,Etman, Hassan A.,Mosbah, Ahmed
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- 5-(1H-Indol-3-yl)-pyrazolyl derivatives as colorimetric sensor for anions
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The synthesis, characterisation and binding and deprotonation studies with anions for four 5-(1H-indol-3-yl)-pyrazolyl derivatives (2-5) have been described. It is worthy to mention that sensor 2 shows a drastic change in absorption spectrum (ca. 335 nm) and colour (colourless to blue) upon addition of F- in DMSO solution due to the deprotonation of indole -NH proton, as confirmed by 1H NMR titration. Sensor 4 recognizes F- and CN- ions by deprotonation mechanism with visible colour change of the solution in a similar manner to that of 2. However, in contrary to 2 and 4, sensor 3 binds with F-, CN-, H2PO4 -, AcO- and PhCOO- ions exploiting hydrogen-bonding interaction with the shifting of absorption band to longer wavelength and subsequent colour change of the solution. Compound 5 recognizes F- without any visual colour change and its binding is studied by 1H NMR titration to acquire the important information about the nature of binding between F- and 5.
- Ahmad, Israr,Mishra, Neeraj Kumar,Ghosh, Tamal
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- Synthesis and cytotoxic activity of novel mono-and bis-indole derivatives: Analogues of marine alkaloid nortopsentin
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Background: The oceans cover more than 70% of the earth’s surface, which represents over 95% of the biosphere. Therefore, oceans provide a wealth of marine invertebrates, especially sponges, ascidians, bryozoans and molluscs that produce structurally unique bioactive metabolites such as alkaloids. The bioactive scaffolds of marine alkaloids exhibit cytotoxic activities against human cancer cell lines. Objective: To prepare analogues of the marine alkaloid nortopsentin [having 2,4-bis(3'-indolyl)imidazole scaffold] as cytotoxic agents via structural modification of the core imidazole ring and one of the side indole rings. Method: Four series of nortopsentin analogues were synthesized in which the imidazole ring was replaced by pyrazole, pyrido[2,3-d]pyrimidinone and pyridine rings. Furthermore, one of the side indole rings was replaced by substituted phenyl moiety. The target compounds were tested for their in vitro cytotoxic activity against HCT-116 cell-line and the most potent compound was sub-jected to further investigation on its effect on HCT-116 cell cycle progression. Results: The cytotoxic screening of the synthesized compounds revealed that bis-indolylpyridine-dicarbonitriles 8a-d exhibited the most potent cytotoxic activity with IC50=2.6-8.8 μM. Compound 8c was further tested by flow cytometry analysis to explore its effect on HCT-116 cell cycle progression that, in turn, indicated its anti-proliferative effect. Conclusion: Marine-derived bis-indole alkaloids (nortopsentins) have emerged as a new class of indole-based antitumor agents. The design of new analogues involved several modifications in or-der to obtain more selective and potent cytotoxic agents. Indole derivatives bearing a pyridine core displayed more potent cytotoxic activity than those containing pyrido[2,3-d]pyrimidin-4(1H)-one moiety.
- Kamel, Mona Monir,Abdel-Hameid, Mohamed Kamal,El-Nassan, Hala Bakr,El-Khouly, Eman Adel
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p. 779 - 789
(2021/04/02)
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- Synthesis and cytotoxicity evaluation of novel indole derivatives as potential anti-cancer agents
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Background: Marine sponges and tunicates have been a wealthy source of cytotoxic compounds such as indole alkaloids. Most of the indole alkaloids show in vitro cytotoxic and antineoplastic activities against a wide range of cancer cell lines. Objective: Three series of bioisosteres of marine indole alkaloids (meridianins) were synthesized and the compounds were tested for their in vitro anti-proliferative activity against HCT-116 cellline. In the design of the targeted analogues, the 2-aminopyrimidine ring of merdianins was replaced with 5-aminopyrazole, pyrazolo[1,5-a]pyrimidine and pyrazolo[3,4-b]pyridine rings. Results: The cytotoxic screening of the synthesized compounds revealed that pyrazolo[1,5- a]pyrimidines (compounds 9c and 11a) had the most potent cytotoxic activity with IC50 = 0.31 μM and 0.34 μM respectively. Compounds 9c and 11a were further investigated for their kinase inhibitory potencies toward six kinases (CDK5/p25, CK1e/ε, GSK-3α/β, Dyrk1A, Erk2, and CLK1). They exhibited effective inhibition of GSK-3α/β (IC50 = 0.196 μM and 0.246 μM, respectively) and Erk2 (IC50 = 0.295 μM and 0.376 μM, respectively). Conclusion: Meridianins emerged as promising lead structures that need further development to obtain more selective and potent cytotoxic agents. One of these modifications involved the replacement of 2-aminopyrimidinyl ring of meridianins with other heterocyclic rings. Both pyrazolo[ 1,5-a]pyrimidine and pyrazolo[3,4-b]pyridine rings showed promising cytotoxic activity compared to the five membered 5-aminopyrazole.
- Abdel-hameid, Mohamed K.,El-Khouly, Eman A.,El-Nassan, Hala B.,Kamel, Mona M.
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p. 873 - 882
(2020/01/25)
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- NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS
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The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
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Page/Page column 126
(2008/12/07)
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