雷洛昔芬C衍生物的合成研究与评价
Synthesis Studies and the Evaluation of C Raloxifene Derivatives.
作者信息
Williams David R, Taylor Levin, Miter Gabriel A, Sheiman Johnathan L, Wallace Joseph M, Allen Matthew R, Kohler Rachel, Medeiros Claudia
机构信息
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.
Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana 46202, United States.
出版信息
ACS Med Chem Lett. 2024 Jun 3;15(6):879-884. doi: 10.1021/acsmedchemlett.4c00078. eCollection 2024 Jun 13.
Abstract
Methodology is described for the synthesis of C derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies have explored the incorporation of electron-withdrawing substituents at C of the benzothiophene core. Efficient processes are also examined to introduce hydrogen bond donor and acceptor functionality. Raloxifene derivatives are evaluated with testing to determine estrogen receptor (ER) binding affinity and gene expression in MC3T3 cells.
摘要
描述了用于合成雷洛昔芬C衍生物的方法，雷洛昔芬是一种用于治疗和预防骨质疏松症的处方药。研究探索了在苯并噻吩核心的C位引入吸电子取代基。还研究了引入氢键供体和受体官能团的有效方法。通过测试评估雷洛昔芬衍生物，以确定其雌激素受体（ER）结合亲和力和在MC3T3细胞中的基因表达。
相似文献
1
Synthesis Studies and the Evaluation of C Raloxifene Derivatives.雷洛昔芬C衍生物的合成研究与评价
ACS Med Chem Lett. 2024 Jun 3;15(6):879-884. doi: 10.1021/acsmedchemlett.4c00078. eCollection 2024 Jun 13.
2
Raloxifene: a selective estrogen-receptor modulator for postmenopausal osteoporosis - a clinical update on efficacy and safety.雷洛昔芬：一种用于绝经后骨质疏松症的选择性雌激素受体调节剂——疗效与安全性的临床最新进展
Womens Health (Lond). 2006 Mar;2(2):199-210. doi: 10.2217/17455057.2.2.199.
3
Structure-activity relationships of selective estrogen receptor modulators: modifications to the 2-arylbenzothiophene core of raloxifene.选择性雌激素受体调节剂的构效关系：雷洛昔芬2-芳基苯并噻吩核心结构的修饰
J Med Chem. 1997 Jan 17;40(2):146-67. doi: 10.1021/jm9606352.
4
The cardiovascular effects of selective estrogen receptor modulators.选择性雌激素受体调节剂的心血管效应。
Ann N Y Acad Sci. 2006 Dec;1092:374-84. doi: 10.1196/annals.1365.034.
5
Rationale for using raloxifene to prevent both osteoporosis and breast cancer in postmenopausal women.使用雷洛昔芬预防绝经后妇女骨质疏松症和乳腺癌的理论依据。
Maturitas. 2008 Jun 20;60(2):92-107. doi: 10.1016/j.maturitas.2008.04.009. Epub 2008 Jun 4.
6
Raloxifene-driven benzothiophene derivatives: Discovery, structural refinement, and biological evaluation as potent PPARγ modulators based on drug repurposing.基于药物再利用的强效 PPARγ 调节剂：雷洛昔芬驱动的苯并噻吩衍生物的发现、结构优化和生物学评价。
Eur J Med Chem. 2024 Apr 5;269:116325. doi: 10.1016/j.ejmech.2024.116325. Epub 2024 Mar 15.
7
Benefit-risk assessment of raloxifene in postmenopausal osteoporosis.雷洛昔芬用于绝经后骨质疏松症的获益-风险评估
Drug Saf. 2005;28(8):721-30. doi: 10.2165/00002018-200528080-00006.
8
Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents.雷洛昔芬单磺酰胺和双磺酰胺作为双靶点药物的合成、生物学评价及稳定性研究
Bioorg Med Chem. 2024 Mar 1;101:117645. doi: 10.1016/j.bmc.2024.117645. Epub 2024 Feb 16.
9
Synthesis and evaluation of raloxifene derivatives as a selective estrogen receptor down-regulator.雷洛昔芬衍生物作为选择性雌激素受体下调剂的合成与评价
Bioorg Med Chem. 2016 Jul 1;24(13):2914-2919. doi: 10.1016/j.bmc.2016.04.068. Epub 2016 May 7.
10
Donor-acceptor tetrahydrochrysenes, inherently fluorescent, high-affinity ligands for the estrogen receptor: binding and fluorescence characteristics and fluorometric assay of receptor.供体-受体四氢 Chrysene，本质上具有荧光性，是雌激素受体的高亲和力配体：结合与荧光特性及受体的荧光测定法。
Biochemistry. 1992 Nov 24;31(46):11536-45. doi: 10.1021/bi00161a035.
引用本文的文献
1
Effects of novel raloxifene analogs alone or in combination with mechanical loading in the Col1a2 murine model of osteogenesis imperfecta.新型雷洛昔芬类似物单独或联合机械加载对 Col1a2 型成骨不全症小鼠模型的作用。
Bone. 2024 Feb;179:116970. doi: 10.1016/j.bone.2023.116970. Epub 2023 Nov 17.
本文引用的文献
1
Effects of novel raloxifene analogs alone or in combination with mechanical loading in the Col1a2 murine model of osteogenesis imperfecta.新型雷洛昔芬类似物单独或联合机械加载对 Col1a2 型成骨不全症小鼠模型的作用。
Bone. 2024 Feb;179:116970. doi: 10.1016/j.bone.2023.116970. Epub 2023 Nov 17.
2
Synthesis of raloxifene-like quinoxaline derivatives by intramolecular electrophilic cyclization with disulfides.用二硫化物进行分子内亲电环化合成雷洛昔芬类似物喹喔啉衍生物。
Bioorg Med Chem Lett. 2023 Sep 1;93:129415. doi: 10.1016/j.bmcl.2023.129415. Epub 2023 Aug 1.
3
Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in mutant breast cancer cells.立体选择性拉索昔芬衍生物揭示了雌激素受体α稳定性与突变型乳腺癌细胞中拮抗活性的相互作用。
Elife. 2022 May 16;11:e72512. doi: 10.7554/eLife.72512.
4
Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection.重新利用雌激素受体调节剂雷洛昔芬治疗 SARS-CoV-2 感染。
Cell Death Differ. 2022 Jan;29(1):156-166. doi: 10.1038/s41418-021-00844-6. Epub 2021 Aug 17.
5
Design, synthesis, and biological evaluation of new raloxifene analogues of improved antagonist activity and endometrial safety.新型雷洛昔芬类似物的设计、合成及改善拮抗活性和子宫内膜安全性的生物学评价。
Bioorg Chem. 2021 Jan;106:104482. doi: 10.1016/j.bioorg.2020.104482. Epub 2020 Nov 17.
6
6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding.6'-甲氧基雷洛昔芬类似物可增强小鼠骨骼特性，同时降低雌激素受体结合力。
Bone Rep. 2020 Jan 17;12:100246. doi: 10.1016/j.bonr.2020.100246. eCollection 2020 Jun.
7
Synthesis and evaluation of raloxifene derivatives as a selective estrogen receptor down-regulator.雷洛昔芬衍生物作为选择性雌激素受体下调剂的合成与评价
Bioorg Med Chem. 2016 Jul 1;24(13):2914-2919. doi: 10.1016/j.bmc.2016.04.068. Epub 2016 May 7.
8
Structural features underlying raloxifene's biophysical interaction with bone matrix.雷洛昔芬与骨基质生物物理相互作用的潜在结构特征。
Bioorg Med Chem. 2016 Feb 15;24(4):759-67. doi: 10.1016/j.bmc.2015.12.045. Epub 2015 Dec 29.
9
Direct synthesis of diverse 2-aminobenzo[b]thiophenes via palladium-catalyzed carbon-sulfur bond formation using Na2S2O3 as the sulfur source.以硫代硫酸钠为硫源，通过钯催化的碳-硫键形成直接合成多种2-氨基苯并[b]噻吩。
Org Lett. 2014 Oct 3;16(19):5040-3. doi: 10.1021/ol502381e. Epub 2014 Sep 17.
10
From empirical to mechanism-based discovery of clinically useful Selective Estrogen Receptor Modulators (SERMs).从基于经验到基于机制发现临床有用的选择性雌激素受体调节剂（SERMs）。
Steroids. 2014 Nov;90:30-8. doi: 10.1016/j.steroids.2014.07.013. Epub 2014 Jul 30.
Zotero 插件