Tetrahydroquinoline-Based selective estrogen receptor modulators (SERMs)

Wallace, Owen B.; Lauwers, Kenneth S; Jones, Scott A.; Dodge, Jeffrey A.

doi:10.1016/s0960-894x(03)00306-8

Cited by 88 publications

(40 citation statements)

References 14 publications

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“…These organic molecules have attracted attention of both synthetic and medicinal chemists. Quinoline nucleus has been found to possess a wide range of biological activities, such as anti-allergenic [3], antitumoral [4], antimalarial [5] …”

Section: Discussionmentioning

confidence: 99%

Crystal structure of 1,3-bis(6-methoxyquinolin-2-yl)benzene, C26H20N2O2

Duarte

Gutiérrez

Astudillo

et al. 2013

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialThe title compound, C 26 H 20 N 2 O 2 , was prepared by the reaction of p-anisidine with terephthaldialdehyde and N-vinyl-2-pyrrolidone at room temperature. A mixture of p-anisidine (3 mmol) and isophthalaldehyde (1.5 mmol) in anhydrous CH 3 CN (5 mL) under N 2 , was stirred at room temperature for 1 hour. BiCl 3 (20 mol %) was added. Over a period of 20 min, a solution the N-vinyl-2-pirrolidone (3.1 mmol) in CH 3 CN (5 mL) was added dropwise. The resulting mixture was stirred for 8-10 h. After completion of the reaction as indicated by TLC, the reaction mixture was diluted with (15 mL) and extracted with ethyl acetate (3´10 mL). The organic layer was separated, and dried with Na 2 SO 4 . The organic solvent was removed in vacuo and the resulting product was purified by column chromatography (silica gel, petroleum ether/EtOAc) to afford pure substances, tetrahydroquinoline and 1,3-bis(6-methoxyquinolin-2-yl)benzene. Analysis: Solid crystalline m.p. 224-227°C. 13 C NMR (400 MHz, CDCl 3 ) d: 157.4 (2), 154.6 (2), 144.1 (2), 140 (2), 135.2 (2), 130.9 (2), 128.3 (1), 127.9 (2), 127.6 (2), 126 (1), 122 (2), 119.1 (2), 104.7 (2), 55.2 (2). Experimental detailsH atoms were located in the difference Fourier map, but refined with fixed individual displacement parameters, using a riding model with C-H distances of 0.95 Å (for CH), 0.98 Å (for CH 3 ), with U iso (H) values of 1.2U eq (C) (for CH) and 1.5U eq (C) (for CH 3 ). DiscussionHeterocyclic compounds, especially those with nitrogen, are the most important class of compounds in the pharmaceutical and agrochemical industries [1]. Quinoline systems in particular constitute a privileged substructure and are found in numerous biologically active natural products and pharmacologically relevant therapeutic agents [2]. These organic molecules have attracted attention of both synthetic and medicinal chemists. (12) and 2.96(12)°. In the molecular structure, the most noticeable deviation from planarity are expressed by the torsion angles of the methoxy groups with respect to adjacent quinoline system [C8-O2-C26-C25 = 5.3(3) and C7-

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Section: Discussionmentioning

confidence: 99%

Crystal structure of 1,3-bis(6-methoxyquinolin-2-yl)benzene, C26H20N2O2

Duarte

Gutiérrez

Astudillo

et al. 2013

Zeitschrift Für Kristallographie - New Crystal Structures

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“…The SPA presently described here is highly accurate, rapid, robotics, simple, convenient, reproducible, and sensitive enough for HTS. The equilibrium binding constants of [ 3 H] estradiol and the affinities and kinetic rate constants for a set of standard compounds (17b-estradiol, raloxifene, and daidzein) were all in the previously published range [Labrie et al, 1999[Labrie et al, , 2001Meyers et al, 2002;Wallace et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

Novel estrogen receptor ligands and their structure-activity relationship evaluated by scintillation proximity assay for high-throughput screening

Xiang

Zhang

et al. 2005

Drug Dev. Res.

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The estrogen receptor (ER) is an important drug target with allosteric characteristics that binds orthotopic hormones and other ligands. A recently developed scintillation proximity (SPA)-based assay for high-throughput screening (HTS) of compound libraries was used to identify novel estrogen receptor ligands that might have ER subtype selective binding activity. Radioligand binding was determined in a multi-detector scintillation counter designed for microtitration plates. Equilibrium binding experiments and kinetic competition tests were performed with [ 3 H]-estradiol and human ERa and ERb receptors. A library of 6,000 structurally diverse compounds was screened. From this, several novel ligands were identified that showed pronounced subtype-selective differences in ligand binding for ERa and ERb. The observed equilibrium dissociation constant (K d ) for the binding of [ 3 H]estradiol to ERa and ERb receptors were approximately 0.25 and 0.64 nM, respectively. When 17b-estradiol, raloxifene and daidzein were tested for binding affinity to ERa in a competition assay, the IC 50 values were 0.34, 1.31, and 75.6 nM, respectively. When tested for binding affinity to ERb, the IC 50 values were 1.05, 11.4, and 10.6 nM, respectively. The results obtained show that the methodology is valid in comparison to previously published data regarding estradiol and other standard compounds (raloxifene and daidzein) binding characteristics of estrogen receptors. The assay is also well suited to applied research as a tool in HTS of compound libraries in the search of ER ligands. Several novel active compounds were identified and selected as potent ER subtype ligands. Drug Dev Res 64:203-212, 2005.

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“…Anthraquinone derivatives have been utilized for the activation of human telomerase reverse transcriptase expression [4]. Annulated arene heterocycles and carbocycles such as chromanones [5] chromans [6] quinolines [7] and tetrahydroquinolines [8] are present as important core structures in many biologically active natural products and pharmaceuticals. 2H-1-Benzopyrans (chromenes) and 3,4-dihydro-2H-1-benzopyrans (chromans) are important classes of oxygenated heterocycles that have attracted much synthetic interest because of the biological activity of naturally occurring representatives [9,10].…”

Section: Introductionmentioning

confidence: 99%