- ESTROGEN RECEPTOR TARGETING ANTAGONISTS
-
The present disclosure relates to compounds that act as antagonists via binding to the ER ligand binding domain non-covalently or covalently, or act as both antagonists and ER protein degraders, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases, including cancer, particularly breast cancer, and especially ER+ breast cancer.
- -
-
Paragraph 0031; 0106-0108
(2020/05/07)
-
- Oxygenophilic Lewis Acid Promoted Synthesis of 2-Arylindoles from Anilines and Cyanoepoxides in Alcohol
-
A convenient synthetic method to indoles from anilines and cyanoepoxides was developed under the catalysis of BF3·OEt2 or AlCl3 in alcohols. The reaction involves a tandem reaction of the regiospecific ring-opening of cyanoepoxides with anilines, elimination of cyanide, intramolecular aromatic electrophilic substitution, and water elimination. The Lewis acid generated protic acid is an efficient catalyst. The method features readily accessible starting materials, wide substrate scope, transition-metal-free environment, and regiospecificity in the ring-opening of cyanoepoxides.
- Xu, Chuangchuang,Xu, Jiaxi
-
p. 14733 - 14742
(2018/11/27)
-
- METHODS OF PREPARING BAZOEDOXIFENE
-
The present invention relates to novel bazedoxifene or to a method for producing a pharmaceutically acceptable salt thereof. The production method according to the present invention can provide the bazedoxifene with high purity and high yield, and is economical and environmentally friendly in terms of time and cost due to a relatively simple manufacturing process to be usefully applied to mass production.COPYRIGHT KIPO 2018
- -
-
Paragraph 0095-0100
(2018/10/16)
-
- Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles as non-competitive antagonists of GluK1/GluK2 receptors
-
This paper reports the thermal stability and thermal degradation of six derivatives of indole by means of TG-DSC (in air) and TG-FTIR (in nitrogen) techniques. The compounds were also characterized by infrared spectroscopy. In addition, IR spectra were ca
- Bartyzel, Agata,Kaczor, Agnieszka A.,G?uchowska, Halina,Pitucha, Monika,Wróbel, Tomasz M.,Matosiuk, Dariusz
-
p. 935 - 944
(2018/03/21)
-
- Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles
-
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.
- 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)
-
- Synthesis and molecular docking of indole and carbazole derivatives with potential pharmacological activity
-
Indole and carbazole derivatives were designed as non-competitive antagonists of the GluK2 receptor. The synthesized compounds were found to interact with the transduction domain of the receptor. The binding pocket is situated within one receptor subunit.
- Kaczor, Agnieszka A.,Pihlaja, Kalevi,Sinkkonen, Jari,Wiinamaeki, Kirsti,Kronbach, Christiane,Unverferth, Klaus,Wrobel, Tomasz,Stachal, Tomasz,Matosiuk, Dariusz
-
p. 103 - 109
(2014/07/07)
-
- Novel non-competitive antagonists of kainate GluK1/GluK2 receptors
-
A series of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles is synthesized by Fisher or Bischler method, followed by alkylation with an appropriate alkyl or aryl halide. Two compounds exhibit non-competitive antagonism towards GluK1 and six - towards GluK2 receptor. The values of IC 50 are in micromolar range. The investigated compounds belong to the most active GluK1 non-competitive inhibitors and are the first known negative allosteric modulators of GluK2 receptor. The observed pattern of activity is rationalized by molecular modelling, in particular by construction of the pharmacophore model.
- Kaczor, Agnieszka Anna,Kronbach, Christiane,Unverferth, Klaus,Pihlaja, Kalevi,Wiinam?ki, Kirsti,Sinkkonen, Jari,Kijkowska-Murak, Urszula,Wróbel, Tomasz,Stacha, Tomasz,Matosiuk, Dariusz
-
p. 891 - 898
(2013/02/22)
-
- Tethered indoles as functionalizable ligands for the estrogen receptor
-
To create ligands for the estrogen receptor that contain pendant groups for tethering to a poly(amido)amine (PAMAM) dendrimer, we have explored a class of N-substituted 2-phenyl indoles. Attachment of tethers of different length and chemical nature to thi
- Trogden, Bridget G.,Kim, Sung Hoon,Lee, Shuyi,Katzenellenbogen, John A.
-
scheme or table
p. 485 - 488
(2011/03/20)
-
- 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations
-
The present invention relates to new formulations containing one or more estrogens and 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below:
- -
-
-
- 2-phenylindoles as antiestrogenic pharmaceutical agents
-
PCT No. PCT/EP95/03000 Sec. 371 Date May 14, 1997 Sec. 102(e) Date May 14, 1997 PCT Filed Jul. 27, 1995 PCT Pub. No. WO96/03375 PCT Pub. Date Feb. 8, 1996Novel 2-phenyl indoles are disclosed of general formula (I), wherein: R1 represents one of the rests -(CH2)n-S(O)m-R4, -(CH2)n-NR6-SO2-R4, (a), and n' being integers between 4 and 12 and m and m' are 0, 1 or 2; X represents a methylene group, an imino group =NR6, or an oxygen or sulphur atom; R2 and R3 independently of one another represent a hydrogen atom, a C1-C10 alkyl group, a benzyl, alkanoyl or alkanoyloxy, or carbarnoyl rest of formula -C(O)R5 or -C(O)NR6R7 or a tetrahydropyranyl group; R4 represents a hydrogen atom, a C1-C10 alkyl, a completely or partially fluorinated alkyl group -(CH2)o-(CF2)pCF3, o and p being independently of one another integers between 0 and 6, an (alkyl)amino or (alkyl)carbamoyl group of formula (CH2)q-Y-NR8R9, q being an integer between 0 and 6 and Y representing a direct bond, a methylene or carbamoyl group (a condition being that q cannot be 0 when Y is a carbonyl group and m is 2), an aryl, aralkyl or heteroaryl group; R5 represents a C1-C10 alkyl group or a C1-C10 alkoxy group, a phenyl or benzyl group; R6, R7, R8 and R9 independently of one another represent a hydrogen atom, a C1-C10 alkyl group, or a benzyl group; and R10 represents a methyl group and R11 represents a hydrogen atom, or R10 and R11 both represent a di-, tri- or tetramethylene bridge which can also have a C-C double bond at any location in the bridge. These novel compounds have strong and selective anti-oestrogen properties and are suitable for use in particular in the treatment of oestrogen-related diseases.
- -
-
-
- 2-PHENYL-1-[4-(2-AMINOETHOXY)-BENZYL]-INDOLES AS ESTROGENIC AGENTS
-
The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below: STR1
- -
-
-
- Syntheses of Zindoxifene and Analogues by Titanium-Induced Oxo-Amide Coupling
-
Highly reactive titanium on graphite is used to reductively cyclize electron-rich acylamino carbonyl compounds 7, 8, 12, 14, and 16 to the corresponding indole derivatives 9, 10, 13, 15, and 17.Compound 9b is a known precursor of the mammary tumor-inhibiting compound zindoxifene (2).The other products are new analogues of this anticancer drug, exhibiting the substitution pattern previously recognized to be essential for high pharmacological activity. - Key Words: Indoles, 2-aryl- / Titanium graphite / Zindoxifene / Tumor-growth inhibitors / Alkylidenation, intramolecular
- Fuerstner, Alois,Jumbam, Denis N.,Seidel, Guenter
-
p. 1125 - 1130
(2007/10/02)
-
- 2-Phenylindoles. Relationship between Structure, Estrogen Receptor Affinity, and Mammary Tumor Inhibiting Activity in the Rat
-
A number of 2-phenylindole derivatives with one hydroxy group in the meta or para position of the phenyl ring and a second one in position 5, 6, or 7 of the indole nucleus were synthesized.In addition, different alkyl groups were introduced into positions
- Angerer, Erwin von,Prekajac, Jelica,Strohmeier, Josef
-
p. 1439 - 1447
(2007/10/02)
-