198479-63-9Relevant academic research and scientific papers
Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1 H-indoles
Argaez, Aida Nelly Garcia,Dalla Via, Lisa,Hyeraci, Mariafrancesca,Kikelj, Danijel,Ma?i?, Lucija Peterlin,Passarella, Daniele,Secci, Daniela,Toma?i?, Tihomir,Zidar, Nace
, p. 691 - 697 (2020/07/14)
A series of 3-methyl-2-phenyl-1H-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI50 values of the most potent compounds (32 and 33) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition. The most potent derivative, 32, was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1H-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.
Cobalt-catalyzed intramolecular decarbonylative coupling of acylindoles and diarylketones through the cleavage of C-C bonds
Lu, Hong,Wei, Hao,Xu, Wen-Hua,Yu, Tian-Yang
, p. 12336 - 12340 (2020/12/08)
We report here cobalt-N-heterocyclic carbene catalytic systems for the intramolecular decarbonylative coupling through the chelation-assisted C-C bond cleavage of acylindoles and diarylketones. The reaction tolerates a wide range of functional groups such as alkyl, aryl, and heteroaryl groups, giving the decarbonylative products in moderate to excellent yields. This transformation involves the cleavage of two C-C bonds and formation of a new C-C bond without the use of noble metals, thus reinforcing the potential application of decarbonylation as an effective tool for C-C bond formation. This journal is
ANTIESTROGEN COMPOUNDS
-
Paragraph 0091, (2020/01/08)
A genus of proteolysis-targeting chimeras (PROTACs)-type compounds/antiestrogens has now been found that act as selective estrogen receptor degraders (SERDs) and estrogen receptor antagonists by degrading and antagonizing ERa in breast cancer cells. The compounds are of the following genus: The compounds described herein exhibit anti-proliferative effects, and are potentially useful, alone or in combination with other therapies, for the treatment of breast cancer. In general, these compounds combine a tight binding ERa targeting ligand tethered to a recognition motif or degron. Once bound, the degron recruits destructive cellular components and the targeted receptor (i.e., ERa) is degraded (i.e., destroyed) or antagonized.
PROCESS FOR THE PREPARATION OF BAZEDOXIFENE
-
Paragraph 0072-0074, (2020/01/12)
The invention relates to a process for preparation of the compound 3-methyl-5-benzyloxy-2-(4-benzyloxyphenyl)-1H-indole 5, an intermediate for the synthesis of bazedoxifene and bazedoxifene acetate.
INDOLE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
-
Paragraph 0432; 0435, (2018/04/21)
The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.
Ruthenium-Catalyzed Electrochemical Dehydrogenative Alkyne Annulation
Xu, Fan,Li, Yan-Jie,Huang, Chong,Xu, Hai-Chao
, p. 3820 - 3824 (2018/05/22)
A ruthenium-catalyzed electrochemical dehydrogenative annulation reaction of aniline derivatives and alkynes has been developed for the synthesis of indoles. Electric current is used to recycle the active ruthenium-based catalyst and promote H2 evolution. The electrolysis reaction is operationally convenient as it employs a simple undivided cell, proceeds efficiently in an aqueous solution, and is insensitive to air.
Efficient preparation method of bazedoxifene
-
Paragraph 0078-0083; 0096; 0110; 0117, (2017/08/30)
The invention discloses a preparation method of bazedoxifene. The preparation method comprises the following steps: (a) taking 1-(4-(2-(azepane-1-yl)ethoxy)benzyl)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole, adding a polar organic solvent, an aprotic lewis acid organic solution and a hydrogen ion provider, and stirring at 0-40 DEG C to obtain a reaction liquid; and (b) separating and purifying the reaction liquid obtained in the step (a) to obtain bazedoxifene. In the method disclosed by the invention, the low-cost and easily available aprotic lewis acid such as boron trifluoride is adopted as a catalyst for preparing bazedoxifene, the reaction conditions are mild, the operation is convenient, the safety is high, and the energy consumption is low; the obtained bazedoxifene has high yield and high purity, and the preparation difficulty and production cost of bazedoxifene are lowered; and the method brings a remarkable positive effect and is very suitable for industrialized use.
5-benzyloxy-2 - (4-benzyloxy-phenyl) - 3-methyl -1H-indole preparation method
-
Paragraph 0035-0037, (2017/02/24)
The invention discloses a preparation method for 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-indole as shown in the specification. The preparation method comprises the following steps: (1) subjecting a compound II and a compound III to a condensation reaction in an alcohol solvent under the action of alkali; and (2) mixing a reaction solution obtained in the step (1) with protonic acid and carrying out Bischler-Mohlau indole cyclization. Compared with the prior art, the invention has the following advantages: the condensation reaction in the first step and Bischler-Mohlau indole cyclization at the second step are integrated into a one-pot reaction, so operation is simple and convenient; a reaction product I is directly precipitated from the reaction solvent, so reaction post-treatment is substantially simplified, and high purity and high reaction yield are realized; and the method is applicable to enlarged production.
Piperazinone compounds and application thereof
-
, (2016/10/09)
The invention belongs to the technical field of medicine and relates to 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione as well as a medical application, a stereoisomer and pharmaceutically acceptable salt thereof. The structural formula of 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl] butyl]piperazine-2,3-dione is represented in the specification; 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione and pharmaceutically acceptable acid addition salt of the compound can be combined with existing drugs or can be independently used as an estrogen receptor modulator for treating or preventing various estrogen function related diseases such as bone loss, fracture, osteoporosis, hectic fever, LDL cholesterol level rise, cardiovascular disease, cognitive impairment, brain degeneration disease and anxiety, as well as depression, sexual dysfunction, hypertension, retinal degeneration and cancer caused by estrogen deficiency, especially osteoporosis.
Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles
Kelly, Patrick M.,Bright, Sandra A.,Fayne, Darren,Pollock, Jade K.,Zisterer, Daniela M.,Williams, D. Clive,Meegan, Mary J.
, p. 4075 - 4099 (2016/08/23)
Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We describe the design and synthesis of novel SERM type ligands based on the 2-arylindole scaffold to selectively target the estrogen receptor in hormone dependent breast cancers. Some of these novel compounds are designed as bisindole type structures, while others are conjugated to a cytotoxic agent based on combretastatin A4 (CA4) which is a potent inhibitor of tubulin polymerisation. The indole compounds synthesised within this project such as 31 and 86 demonstrate estrogen receptor (ER) binding and strong antiproliferative activity in the ER positive MCF-7 breast cancer cell line with IC50values of 2.71?μM and 1.86?μM respectively. These active compounds induce apoptotic activity in MCF-7 cells with minimal effects on normal peripheral blood cells. Their strong anti-cancer effect is likely mediated by the presence of two ER binding ligands for 31 and an ER binding ligand combined with a cytotoxic agent for 86.
