99532-52-2Relevant academic research and scientific papers
A radical addition and cyclization relay promoted by Mn(OAc)3?2H2O: Synthesis of 1,2-oxaphospholoindoles and mechanistic study
Xu, Meng-Meng,Kou, Lu-Yao,Bao, Xiao-Guang,Xu, Xiao-Ping,Ji, Shun-Jun
supporting information, p. 1915 - 1919 (2021/03/09)
Novel and efficient Mn(OAc)3?2H2O promoted radical addition-[4 + 1] cyclization relay of 3-indolymethanols and phosphites was disclosed, which afforded 1,2-oxaphospholoindole derivatives in moderate to good yields. Based on the experimental and computational studies, a mechanism involving radical addition and intramolecular cyclization cascade was proposed.
Design, synthesis and biological evaluation of quinoline-indole derivatives as anti-tubulin agents targeting the colchicine binding site
Li, Wenlong,Shuai, Wen,Sun, Honghao,Xu, Feijie,Bi, Yi,Xu, Jinyi,Ma, Cong,Yao, Hequan,Zhu, Zheying,Xu, Shengtao
, p. 428 - 442 (2018/12/13)
A series of novel isocombretastatin A-4 (isoCA-4) analogs were designed and synthesized by replacing 3,4,5-trimethoylphenyl and isovanillin of isoCA-4 with quinoline and indole moieties, respectively. The structure activity relationships (SARs) of these synthesized quinoline-indole derivatives have been intensively investigated. Two compounds 27c and 34b exhibited the most potent activities against five cancer cell lines with IC50 values ranging from 2 to 11 nM, which were comparable to those of Combretastatin A-4 (CA-4, 1). Further mechanism investigations revealed that 34b effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Further cellular mechanism studies elucidated that 34b disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, induced apoptosis and depolarized mitochondria of K562 cells. Moreover, 34b displayed potent anti-vascular activity in both wound healing and tube formation assays. Importantly, 27c and 34b significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, suggesting that 27c and 34b deserve further research as potent antitumor agents for cancer therapy.
Rhodium(III)-Catalyzed Regioselective Direct C4-Alkylation and C2-Annulation of Indoles: Straightforward Access to Indolopyridone
Biswas, Aniruddha,Samanta, Rajarshi
, p. 1426 - 1436 (2018/04/06)
A straightforward RhIII-catalyzed strategy was developed for the site-selective C4-alkylation and C2-annulation of indole by using electronically variable diazo esters. The transformation was accomplished with the assist of an oxime directing group at the C3 position of the indole core with wide scope and functional-group tolerance. The method directly provided an indolopyridone core. The selectivity was triggered by the reactivity of the diazo coupling partner.
Palladium-catalyzed regioselective C-H fluoroalkylation of indoles at the C4-position
Borah, Arun Jyoti,Shi, Zhuangzhi
supporting information, p. 3945 - 3948 (2017/04/11)
An exclusive catalytic C4-selective fluoroalkylation of indoles with highly active (1H, 1H-perfluoroalkyl)mesityliodonium triflate has been described. The key to its high regioselectivity is the appropriate choice of an easily accessible, cheap and removable directing group at the C3 position in the presence of a Pd(OAc)2 catalyst. Besides indole fluoroalkylation, the application of this strategy in other heteroarenes such as benzo[b]thiophene is also described.
Synthesis of 3-acylindoles by oxidative rearrangement of 2-aminochalcones using a hypervalent iodine reagent and cyclization sequence
Nakamura, Akira,Tanaka, Satoshi,Imamiya, Akira,Takane, Reo,Ohta, Chiaki,Fujimura, Kazuma,Maegawa, Tomohiro,Miki, Yasuyoshi
, p. 6702 - 6705 (2017/08/22)
An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in mo
Chemical exploration of 4-(4-fluorobenzyl)piperidine fragment for the development of new tyrosinase inhibitors
Ferro, Stefania,De Luca, Laura,Germanò, Maria Paola,Buemi, Maria Rosa,Ielo, Laura,Certo, Giovanna,Kanteev, Margarita,Fishman, Ayelet,Rapisarda, Antonio,Gitto, Rosaria
, p. 992 - 1001 (2016/11/11)
Tyrosinase is involved in the production of melanin through the hydroxylation of monophenols to o-diphenols. The role of this enzyme was extensively studied in order to identify new therapeutics preventing skin pigmentation and melanoma. In this work we initially identified the 3-(4-benzylpiperidin-1-yl)-1-(1H-indol-3-yl)propan-1-one (1a) as promising mushroom tyrosinase inhibitor (IC50= 252 μM). Then, several chemical modifications were performed and new analogues related to compound 1a were synthesized. Biochemical assays demonstrated that several obtained compounds proved to be effective inhibitors showing IC50values lower both than “lead compound” 1a and reference inhibitor kojic acid, as a well-known tyrosinase inhibitor. The inhibition kinetics analyzed by Lineweaver–Burk plots revealed that compounds 2 a-c and 10b act as non-competitive inhibitors while the most active inhibitor 2d (IC50= 7.56 μM) is a mixed-type inhibitor. Furthermore, experimental and computational structural studies were performed in order to clarify the binding mode of the derivative 2d.
Targeting GluN2B-containing N-methyl- D -aspartate receptors: Design, synthesis, and binding affinity evaluation of novel 3-substituted indoles
Buemi, Maria Rosa,De Luca, Laura,Ferro, Stefania,Gitto, Rosaria
, p. 533 - 539 (2014/08/18)
In an effort to improve our knowledge about structure-affinity relationships (SARs) for a class of 3-substituted-indole derivatives as GluN2B-containing N-methyl-D-aspartate-type receptor (NMDAR) ligands, we herein describe the design, synthesis, and preliminary screening of a new series of molecules. The in vitro determination of binding affinities suggested that 5-hydroxy- and 6-hydroxyindole derivatives 12 and 13 were active ligands. Generally, the novel compounds proved to be less potent than their homologs previously reported as promising neuroprotective agents. In fact, our lead compound 3-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethan-1-one (2) was about 10-fold more active than the new propan-1-one derivative (12). To rationalize the low potency of the new analog 12, docking studies were also performed and the in silico results were consistent with the in vitro data.
Novel and simple methodology for the synthesis of 3-acetylindoles and their N-alkyl derivatives using TBAB as phase transfer catalyst
Venkatanarayana,Dubey, Pramod K.
experimental part, p. 656 - 662 (2012/06/01)
Using 5% aq. NaOH, a simple method for the transformation of 3-cyanoacetylindoles 2(a-e) into 3-acetylindoles 3 (a-e), in good yields, is reported. Tetrabutylammoniumbromide (TBAB) is found to be an efficient phase transfer catalyst for the synthesis of N-alkyl derivatives 5(a-t) of 3-acetylindoles 3(a-e) giving products in excellent yields. 2 (a-e) were themselves obtained from simple indoles 1 (a-e) by reaction with cyano acetic acid in the presence of propionic anhydride at 100 °C for 5-10 min. Partial hydrolysis of 2 (a-e) under hot acidic conditions yielded the corresponding carboxamides α-(3-indolecarboxoyl)acetamides 4(a-e). Which could be readily transformed into the respective 3(a-e) by refluxing with 5% aq. NaOH for 2-2.5 h.
A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series
De Luca, Laura,Barreca, Maria Letizia,Ferro, Stefania,Iraci, Nunzio,Michiels, Martine,Christ, Frauke,Debyser, Zeger,Witvrouw, Myriam,Chimirri, Alba
, p. 2891 - 2895 (2008/12/21)
We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described.
A Convenient Synthesis of 3-Acylindoles via Friedel-Crafts Acylation of 1-(Phenylsulfonyl)indole. A New Route to Pyridocarbazole-5,11-quinones and Ellipticine
Ketcha, Daniel M.,Gribble, Gordon W.
, p. 5451 - 5457 (2007/10/02)
A Friedel-Crafts acylation of 1-(phenylsulfonyl)indoles (1) with carboxylic acid anhydrides and acid chlorides in the presence of aluminum chloride gives 3-acyl-1-(phenylsulfonyl)indoles (2) in 81-99percent yields.Base hydrolysis converts 2 to 3-acylindoles (3) in 79-96percent yields.The reaction of 1-(phenylsulfonyl)indole (1a) with oxalyl chloride gives acid chloride 2h, which is converted to 3-cyanoindole (7) in three steps (75percent yield).Although a similar Friedel-Crafts alkylation of 1 was unsuccessful, in some cases the 3-acyl-1-(phenylsulfonyl)indoles 2a,e,f could be reduced to 3-alkyl-1-(phenylsulfonyl)indoles 8a,b,c in nearly quantitative yield with sodium borohydride in trifluoroacetic acid.The acid chloride derived from keto acid 9 did not cyclize to the desired pyridocarbazole-5,11-quinone 24 but rather to chloro keto lactam 10.However, acylation of 1a with acid chloride 22 followed by strong-base-mediated cyclization gives 24.Since quinone 24 has been previously converted to the alkaloid ellipticine 26, this route to 24 represents a new synthesis of ellipticine.Related synthetic schemes give rise to quinones 16 and 20.
