3610-42-2Relevant academic research and scientific papers
Synthesis of Vinca Alkaloids and Related Compounds, XXXIV: Synthesis of (3S,14S,16S)-Bromovincamines and Bromoapovincamines by Regioselective Bromination
Szabo, Lajos,Dobay, Laszlo,Kalaus, Gyoergy,Gacs-Baitz, Eszter,Tamas, Jozsef,Szantay, Csaba
, p. 781 - 789 (1987)
By bromimation of the iminium salt 2a (X=Cl), the 9-bromo derivative 2c (X=ClO4) is obtained in isomer-free state.Bromination of the lactam 8d leads to ca. 7.5:1 mixture of 11-bromo (8c) and 9-bromo (8a) lactams.These precursors have been used to synthesize 9-, 10- and 11-bromovincamines (11a-c), and 9-, 10- and 11-bromoapovincamines (12a-c).
1-BENZYLSPIRO[PIPERIDINE-4,1′-PYRIDO[3,4-b]indole] ‘co-potentiators’ for minimal function CFTR mutants
Son, Jung-Ho,Phuan, Puay-Wah,Zhu, Jie S.,Lipman, Elena,Cheung, Amy,Tsui, Ka Yi,Tantillo, Dean J.,Verkman, Alan S.,Haggie, Peter M.,Kurth, Mark J.
, (2020/10/26)
We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency. Structure-activity relationship studies established that analog 2i, with 6′-methoxyindole and 2,4,5-trifluorobenzyl substituents, had the greatest potency for activation of N1303K-CFTR, with EC50 ～600 nM representing an ～17-fold improvement over the original compound identified in a small molecule screen.
Metal-Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous-Flow
Ranjan, Prabhat,Ojeda, Gerardo M.,Sharma, Upendra K.,Van der Eycken, Erik V.
, p. 2442 - 2446 (2019/01/29)
A metal-free, phosphine-catalyzed intramolecular “umpolung Michael addition” on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five- and six-membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous-flow conditions. Triphenylphosphine-catalyzed nucleophilic activation of alkynes allows the exclusive formation of exo-product under mild reaction conditions.
Synthesis of 1-methoxyindoles and related analogs of pimprinine, (±)-chelonin A and B, based on 1-hydroxy-indole chemistry
Aoki, Kazuko,Nagahama, Yoshiyuki,Sugaya, Katsuko,Maeda, Yuki,Sato, Haruhiko,Nakagawa, Kyoko,Somei, Masanori
, p. 236 - 270 (2019/08/01)
The total synthesis of pimprinine, (±)-chelonin A and B, and their analogs are achieved based on 1-hydroxyindole chemistry.
Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents
Xiong, Runde,He, Dongxiu,Deng, Xiangping,Liu, Juan,Lei, Xiaoyong,Xie, Zhizhong,Cao, Xuan,Chen, Yanming,Peng, Junmei,Tang, Guotao
, p. 573 - 583 (2019/04/30)
A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3′-C5′ positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.
Facile in Vitro Biocatalytic Production of Diverse Tryptamines
McDonald, Allwin D.,Perkins, Lydia J.,Buller, Andrew R.
, p. 1939 - 1944 (2019/07/08)
Tryptamines are a medicinally important class of small molecules that serve as precursors to more complex, clinically used indole alkaloid natural products. Typically, tryptamine analogues are prepared from indoles through multistep synthetic routes. In the natural world, the desirable tryptamine synthon is produced in a single step by l-tryptophan decarboxylases (TDCs). However, no TDCs are known to combine high activity and substrate promiscuity, which might enable a practical biocatalytic route to tryptamine analogues. We have now identified the TDC from Ruminococcus gnavus as the first highly active and promiscuous member of this enzyme family. RgnTDC performs up to 96 000 turnovers and readily accommodates tryptophan analogues with substituents at the 4, 5, 6, and 7 positions, as well as alternative heterocycles, thus enabling the facile biocatalytic synthesis of >20 tryptamine analogues. We demonstrate the utility of this enzyme in a two-step biocatalytic sequence with an engineered tryptophan synthase to afford an efficient, cost-effective route to tryptamines from commercially available indole starting materials.
Preparation method of 5-bromoindole derivative
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, (2017/10/23)
The invention discloses a preparation method of a 5-bromoindole derivative tert-butyl 2-(5-bromo-1H-indole-3-yl)ethyl carbamate. The preparation method comprises the following steps: taking 5-bromoindole as an initial raw material, and performing a Friedel-Craft reaction, amidation, reduction and a tert-butyloxycarbonyl protection reaction to obtain the target product. The compound is an important medical intermediate compound.
Marine AChE inhibitors isolated from Geodia barretti: Natural compounds and their synthetic analogs
Olsen, Elisabeth K.,Hansen, Espen,Moodie, Lindon W. K.,Isaksson, Johan,Sep?i?, Kristina,Cergolj, Marija,Svenson, Johan,Andersen, Jeanette H.
, p. 1629 - 1640 (2016/02/09)
Barettin, 8,9-dihydrobarettin, bromoconicamin and a novel brominated marine indole were isolated from the boreal sponge Geodia barretti collected off the Norwegian coast. The compounds were evaluated as inhibitors of electric eel acetylcholinesterase. Barettin and 8,9-dihydrobarettin displayed significant inhibition of the enzyme, with inhibition constants (Ki) of 29 and 19 μM respectively towards acetylcholinesterase via a reversible noncompetitive mechanism. These activities are comparable to those of several other natural acetylcholinesterase inhibitors of marine origin. Bromoconicamin was less potent against acetylcholinesterase, and the novel compound was inactive. Based on the inhibitory activity, a library of 22 simplified synthetic analogs was designed and prepared to probe the role of the brominated indole, common to all the isolated compounds. From the structure-activity investigation it was shown that the brominated indole motif is not sufficient to generate a high acetylcholinesterase inhibitory activity, even when combined with natural cationic ligands for the acetylcholinesterase active site. The four natural compounds were also analysed for their butyrylcholinesterase inhibitory activity in addition and shown to display comparable activities. The study illustrates how both barettin and 8,9-dihydrobarettin display additional bioactivities which may help to explain their biological role in the producing organism. The findings also provide new insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
Asymmetric dearomatization of indoles through a Michael/Friedel-Crafts-Type cascade to construct polycyclic spiroindolines
Zhao, Xiaohu,Liu, Xiaohua,Mei, Hongjiang,Guo, Jing,Lin, Lili,Feng, Xiaoming
supporting information, p. 4032 - 4035 (2015/03/30)
A highly efficient asymmetric dearomatization of indoles was realized through a cascade reaction between 2-isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N-dioxide/MgII catalyst. Fused polycyclic indolines containing three stereocenters were afforded in good yields with excellent diastereo- and enantioselectivities through a Michael/Friedel-Crafts/Mannich cascade. When 2-substituted 2-isocyanoethylindoles were used, spiroindoline derivatives were obtained through a Michael/Friedel-Crafts reaction.
Alpha-ethyltryptamines as dual dopamine-serotonin releasers
Blough, Bruce E.,Landavazo, Antonio,Partilla, John S.,Decker, Ann M.,Page, Kevin M.,Baumann, Michael H.,Rothman, Richard B.
, p. 4754 - 4758 (2015/01/09)
The dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter releasing activity and serotonin-2A (5-HT2A) receptor agonist activity of a series of substituted tryptamines are reported. Three compounds, 7b, (+)-7d and 7f, were found to be potent dual DA/5-HT releasers and were >10-fold less potent as NE releasers. Additionally, these compounds had different activity profiles at the 5-HT2Areceptor. The unique combination of dual DA/5-HT releasing activity and 5-HT2Areceptor activity suggests that these compounds could represent a new class of neurotransmitter releasers with therapeutic potential.
