102308-97-4Relevant articles and documents
Novel anellated pyrazoloquinolin-3-ones: Synthesis and in vitro BZR activity
Ferlin, Maria Grazia,Chiarelotto, Gianfranco,Dall'Acqua, Stefano,MacIocco, Elisabetta,Mascia, Maria Paola,Pisu, Maria Giuseppina,Biggio, Giovanni
, p. 3531 - 3541 (2005)
A series of pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-one derivatives 6, 7a-c, 8a,b, 9a,b and 10-12 were synthesized as modified pyrazoloquinolinone analogs (PQs) and evaluated for their ability to inhibit radioligand to central and peripheral benzodiazepin
Discovery of N-(1-(3-fluorobenzoyl)-1H-indol-5-yl)pyrazine-2-carboxamide: a novel, selective, and competitive indole-based lead inhibitor for human monoamine oxidase B
Elkamhawy, Ahmed,Paik, Sora,Kim, Hyeon Jeong,Park, Jong-Hyun,Londhe, Ashwini M.,Lee, Kyeong,Pae, Ae Nim,Park, Ki Duk,Roh, Eun Joo
, p. 1568 - 1580 (2020)
Herein, two new series of N-substituted indole-based analogues were rationally designed, synthesized via microwave heating technology, and evaluated as noteworthy MAO-B potential inhibitors. Compared to the reported indazole-based hits VI and VII, compounds 4b and 4e exhibited higher inhibitory activities over MAO-B with IC50 values of 1.65 and 0.78?μM, respectively. When compared to the modest selectivity index of rasagiline (II, a well-known MAO-B inhibitor, SI > 50), both 4b and 4e also showed better selectivity indices (SI > 60 and 120, respectively). A further kinetic evaluation of the most potent derivative (4e) displayed a competitive mode of inhibition (inhibition constant (K i)/MAO-B = 94.52 nM). Reasonable explanations of the elicited biological activities were presented via SAR study and molecular docking simulation. Accordingly, the remarkable MAO-B inhibitory activity of 4e (N-(1-(3-fluorobenzoyl)-1H-indol-5-yl)pyrazine-2-carboxamide), with its selectivity and competitive inhibition, advocates its potential role as a promising lead worthy of further optimization.
Chemoselective transfer hydrogenation of nitroarenes by highly dispersed Ni-Co BMNPs
Zhang, Jia-Wei,Lu, Guo-Ping,Cai, Chun
, p. 25 - 29 (2016)
Highly dispread Ni-Co bimetallic nanoparticles (Ni-Co BMNPs) are synthesized and applied as an efficient catalyst in the chemoselective transfer hydrogenation of nitroarenes (CTH) using hydrazine hydrate as the hydrogen donor. The BMNPs can efficiently catalyze the reduction reaction without any additives under mild conditions with high TOF. Significantly higher activity is achieved when compared with corresponding single-component catalysts, optimal composition of the Ni-Co BMNPs was screened which was proved to be crucial in both the selectivity and yields. Excellent performance of Ni-Co BMNPs can be ascribed to the improved dispersion of active sites on the BMNPs surface (compared with Ni NPs) and the electron transfer from cobalt to nickel.
Direct C-H bond arylation: Selective palladium-catalyzed C2-arylation of N-substituted indoles
Lane, Benjamin S.,Sames, Dalibor
, p. 2897 - 2900 (2004)
(Equation Presented) We present a new, practical method by which N-substituted indoles may be selectively arylated in the C2-position with good yields, low catalyst loadings, and a high degree of functional group tolerance. Our investigation found that two competitive processes, namely, the desired cross-coupling and biphenyl formation, were operative in this reaction. A simple kinetic model was formulated that proved to be instructive and provided useful guidelines for reaction optimization; the approach described within may prove to be useful in other catalytic cross-coupling processes.
Method for preparing amine through catalytic reduction of nitro compound by cyclic (alkyl) (amino) carbene chromium complex
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Paragraph 0015, (2021/04/17)
The cyclic (alkyl) (amino) carbene chromium complex is prepared from corresponding ligand salt, alkali and CrCl3 and used for catalyzing pinacol borane to reduce nitro compounds in an ether solvent under mild conditions to generate corresponding amine. The method for preparing amine has the advantages of cheap and accessible raw materials, mild reaction conditions, wide substrate application range, high selectivity and the like, and is simple to operate.
Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity
Nimbarte, Vijaykumar D.,Wirmer-Bartoschek, Julia,Gande, Santosh L.,Alshamleh, Islam,Seibert, Marcel,Nasiri, Hamid Reza,Schnütgen, Frank,Serve, Hubert,Schwalbe, Harald
, p. 1667 - 1679 (2021/03/24)
Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.
Scaffold repurposing of in-house small molecule candidates leads to discovery of first-in-class cdk-1/her-2 dual inhibitors: In vitro and in silico screening
Elkamhawy, Ahmed,Ammar, Usama M.,Paik, Sora,Abdellattif, Magda H.,Elsherbeny, Mohamed H.,Lee, Kyeong,Roh, Eun Joo
supporting information, (2021/09/08)
Recently, multitargeted drugs are considered a potential approach in treating cancer. In this study, twelve in-house indole-based derivatives were preliminary evaluated for their inhibitory activities over VEGFR-2, CDK-1/cyclin B and HER-2. Compound 15l showed the most inhibitory activities among the tested derivatives over CDK-1/cyclin B and HER-2. Compound 15l was tested for its selectivity in a small kinase panel. It showed dual selectivity for CDK-1/cyclin B and HER-2. Moreover, in vitro cytotoxicity assay was assessed for the selected series against nine NCI cell lines. Compound 15l showed the most potent inhibitory activities among the tested compounds. A deep in silico molecular docking study was conducted for compound 15l to identify the possible binding modes into CDK-1/cyclin B and HER-2. The docking results revealed that compound 15l displayed interesting binding modes with the key amino acids in the binding sites of both kinases. In vitro and in silico studies demonstrate the indole-based derivative 15l as a selective dual CDK-1 and HER-2 inhibitor. This emphasizes a new challenge in drug development strategies and signals a significant milestone for further structural and molecular optimization of these indole-based derivatives in order to achieve a drug-like property.
