13708-58-2Relevant academic research and scientific papers
SYNTHESIS AND ISOMERIZATION RECYCLIZATION OF PYRAZINOINDOLES
Terenin, V. I.,Kabanova, E. V.,Baranova, N. A.,Bundel', Yu. G.
, p. 284 - 288 (1995)
A method for synthesis of pyrazinoindoles with alkyl substituents in position I was developed based on indole and isomerization recyclization of their quaternary salts into 9-aminopyridoindole derivatives was conducted.
Scaffold tailoring by a newly detected pictet-spenglerase activity of strictosidine synthase: From the common tryptoline skeleton to the rare piperazino-indole framework
Wu, Fangrui,Zhu, Huajian,Sun, Lianli,Rajendran, Chitra,Wang, Meitian,Ren, Xin,Panjikar, Santosh,Cherkasov, Artem,Zou, Hongbin,St?ckigt, Joachim
, p. 1498 - 1500 (2012)
The Pictet-Spenglerase strictosidine synthase (STR1) has been recognized as a key enzyme in the biosynthesis of some 2000 indole alkaloids in plants, some with high therapeutic value. In this study, a novel function of STR1 has been detected which allows for the first time a simple enzymatic synthesis of the strictosidine analogue 3 harboring the piperazino[1,2-a]indole (PI) scaffold and to switch from the common tryptoline (hydrogenated carboline) to the rare PI skeleton. Insight into the reaction is provided by X-ray crystal analysis and modeling of STR1 ligand complexes. STR1 presently provides exclusively access to 3 and can act as a source to generate by chemoenzymatic approaches libraries of this novel class of alkaloids which may have new biological activities. Synthetic or natural monoterpenoid alkaloids with the PI core have not been reported before.
Novel multi-target compounds in the quest for new chemotherapies against Alzheimer's disease: An experimental and theoretical study
Martínez, Alberto,Zahran, Mai,Gomez, Miguel,Cooper, Coreen,Guevara, Johnny,Ekengard, Erik,Nordlander, Ebbe,Alcendor, Ralph,Hambleton, Sarah
, p. 4823 - 4840 (2018)
The lack of any effective therapy along with the aging world population anticipates a growth of the worldwide incidence of Alzheimer's disease (AD) to more than 100 million cases by 2050. Accumulation of extracellular amyloid-β (Aβ) plaques, intracellular tangles in the brain, and formation of reactive oxygen species (ROS) are the major hallmarks of the disease. In the amyloidogenic process, a β-secretase, known as BACE 1, plays a fundamental role in the production of Aβ fragments, and therefore, inhibition of such enzymes represents a major strategy for the rational design of anti-AD drugs. In this work, a series of four multi-target compounds (1–4), inspired by previously described ionophoric polyphenols, have been synthesized and studied. These compounds have been designed to target important aspects of AD, including BACE 1 enzymatic activity, Aβ aggregation, toxic concentrations of Cu2+ metal ions and/or ROS production. Two other compounds (5 and 6), previously reported by some of us as antimalarial agents, have also been studied because of their potential as multi-target species against AD. Interestingly, compounds 3 and 5 showed moderate to good ability to inhibit BACE 1 enzymatic activity in a FRET assay, with IC50′s in the low micromolar range (4.4 ± 0.3 and 1.7 ± 0.3 μM, respectively), comparable to other multi-target species, and showing that the observed activity was in part due to a competitive binding of the compounds at the active site of the enzyme. Theoretical docking calculations overall agreed with FRET assay results, displaying the strongest binding affinities for 3 and 5 at the active site of the enzyme. In addition, all compounds selectively interacted with Cu2+ metal ions forming 2:1 complexes, inhibited the production of Aβ-Cu2+ catalyzed hydroxyl radicals up to a ～100% extent, and scavenged AAPH-induced peroxyl radical species comparably to resveratrol, a compound used as reference in this work. Our results also show good anti-amyloidogenic ability: compounds 1–6 inhibited both the Cu2+-induced and self-induced Aβ(1–40) fibril aggregation to an extent that ranged from 31% to 77%, while they disaggregated pre-formed Aβ(1–40) mature fibrils up to a 37% and a 69% extent in absence and presence of Cu2+, respectively. Cytotoxicity was additionally studied in Tetrahymena thermophila and HEK293 cells, and compared to that of resveratrol, showing that compounds 1–6 display lower toxicity than that of resveratrol, a well-known non-toxic polyphenol.
COMPOUNDS AND METHODS FOR THE MODULATION OF AhR
-
Paragraph 0206, (2019/08/29)
Provided herein are compounds, compositions and methods of using the compounds and compositions for the treatment of diseases modulated, as least in part, by AhR. The compounds are represented by formula: (I) wherein the letters and symbols a, b, c, d, e, f, A, R1, X1, Ar1 and Ar2 have the meanings provided in the specification.
CINNAMIC ACID AMIDE DERIVATIVE
-
Paragraph 0060; 0070, (2015/11/24)
The present invention provides a cinnamic acid amide derivative having an excellent analgesic action. The cinnamic acid amide derivative of the present invention is a compound showing excellent analgesic actions to not only a nociceptive pain model animal but also a neuropathic pain model animal, which is very useful as an agent for treating various pain diseases showing acute or chronic pains or neuropathic pains.
Diversity-oriented synthesis of polycyclic diazinic scaffolds
Gigant, Nicolas,Claveau, Elise,Bouyssou, Pascal,Gillaizeau, Isabelle
supporting information; experimental part, p. 844 - 847 (2012/03/26)
An efficient and versatile synthesis of a polycyclic diazinic system starting from oxazine has been developed using a two-step Michael/retro Michael and cyclization sequence. The substrates were synthesized with good to high yields giving rapid access to molecular diversity.
2-And 3-phenylsulfonylindoles-synthetic equivalents of unsubstituted indole in n-alkylation reactions
Karchava,Shuleva,Ovcharenko,Yurovskaya
, p. 291 - 301 (2011/04/22)
The N-alkylation of 2- and 3-phenylsulfonylindoles under various conditions and the subsequent removal of the activating phenylsulfonyl group by reductive desulfonylation using Raney nickel leads to N-alkylindoles in high yield. 2-Phenylsulfonylindole readily undergoes the Mitsunobu reaction, while isomeric 3-phenylsulfonylindole is relatively inert under these conditions.
Electrooxidative cyclization of hydroquinolyl alcohols, hydroquinolylamines, and dimethyl aminomalonates
Okimoto, Mitsuhiro,Yoshida, Takashi,Hoshi, Masayuki,Hattori, Kazuyuki,Komata, Masashi,Numata, Kaori,Tomozawa, Kenta
, p. 236 - 242 (2008/02/11)
Several hydroquinolyl alcohols and amines were electrochemically oxidized in methanol in the presence of sodium methoxide and potassium iodide to afford the corresponding intramolecular cyclization products. Furthermore, several amino malonates were electrochemically oxidized to yield the corresponding heterocyclic compounds through an intramolecular carbon-carbon bond formation in the presence of sodium cyanide in methanol. CSIRO 2007.
Highly efficient one-pot synthesis of 1-substituted-1,2,3,4- tetrahydropyrazino[1,2-a]indoles
Tiwari, Rakesh K.,Singh, Jaspal,Singh, Devender,Verma, Akhilesh K.,Chandra, Ramesh
, p. 9513 - 9518 (2007/10/03)
A practical and general one-pot synthesis of 1-substituted-10-methyl-1,2,3, 4-tetrahydropyrazino[1,2-a]indoles is described. The approach uses 2-(3-methyl-1H-indol-1-yl) ethylamine, benzotriazole and aldehydes in the presence of catalytic amount of acid catalysts (AlCl3, ZnCl 2, ZnBr2, p-TsOH, CH3SO3H) and proceeds in high yields via iminium cation intramolecular cyclization. The mechanism of the observed intramolecular cyclization reaction has been investigated theoretically by means of PM3 semiempirical method and results were consistent with the experimental results.
1-(2-alkanamidoethyl)-6-methoxyindole derivatives: A new class of potent indole melatonin analogues
Tarzia, Giorgio,Diamantini, Giuseppe,Di Giacomo, Barbara,Spadoni, Gilberto,Esposti, Daniele,Nonno, Romolo,Lucini, Valeria,Pannacci, Marilou,Fraschini, Franco,Stankov, Bojidar Michaylov
, p. 2003 - 2010 (2007/10/03)
A new series of indole melatonin analogues, bearing the amido ethyl side chain attached at the N-1 position of the indole nucleus, were synthesized and tested for their affinity for the melatonin receptor isolated from quail optic tecta in a series of in
