(+)-4-((2S,3R)-6-(benzyloxy)-3-{3-[(triisopropylsilyl) oxy] phenyl}-2,3-dihydro-1,4-benzoxathiin-2-yl)phenol | 412052-05-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (+)-4-((2S,3R)-6-(benzyloxy)-3-{3-[(triisopropylsilyl) oxy] phenyl}-2,3-dihydro-1,4-benzoxathiin-2-yl)phenol
• 英文别名: 4-[(2S,3R)-6-phenylmethoxy-3-[4-tri(propan-2-yl)silyloxyphenyl]-2,3-dihydro-1,4-benzoxathiin-2-yl]phenol
• CAS: 412052-05-2
• 化学式: C₃₆H₄₂O₄SSi
• 分子量: 598.879
• InChiKey: BJFAMJOCNMCGEN-MPQUPPDSSA-N

物化性质

• 沸点：
  662.6±55.0 °C(predicted)
• 密度：
  1.127±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.49
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+)-4-((2S,3R)-6-(benzyloxy)-3-{3-[(triisopropylsilyl) oxy] phenyl}-2,3-dihydro-1,4-benzoxathiin-2-yl)phenol 在 钯 偶氮二甲酸二异丙酯 、 甲酸铵 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain

  摘要：

  An optimized side chain for dihydrobenzoxathim SERAMs was discovered and attached to four dihydrobenzoxathim platforms. The novel SERAMs show exceptional estrogen antagonist activity in uterine tissue and an MCF-7 breast cancer cell assay. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.089
• 作为产物：
  描述：

  4'-hydroxy-2-bromo-2-(4-triisopropylsilyloxy-phenyl)-acetophenone 在 三乙基硅烷 、 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (+)-4-((2S,3R)-6-(benzyloxy)-3-{3-[(triisopropylsilyl) oxy] phenyl}-2,3-dihydro-1,4-benzoxathiin-2-yl)phenol
  参考文献：
  名称：

  Estrogen receptor ligands. Part 4: The SAR of the syn-dihydrobenzoxathiin SERAMs

  摘要：

  A series of estrogen receptor ligands based on a dihydrobenzoxathiin scaffold is described and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The most active analogue, 22, was found to be 40-fold ERalpha selective in a competitive binding assay, and 22 demonstrated very potent in vivo antagonism of estradiol driven proliferation in an immature rat uterine weight gain assay. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.074

文献信息

• [EN] ESTROGEN RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RECEPTEURS D'OESTROGENE
  申请人：MERCK & CO INC

  公开号：WO2003091239A1

  公开（公告）日：2003-11-06

  The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, and cancer, in particular of the breast, uterus and prostate.

  本发明涉及化合物及其衍生物，它们的合成以及作为雌激素受体调节剂的用途。本发明的化合物是雌激素受体的配体，因此可能用于治疗或预防与雌激素功能相关的各种疾病，包括：骨质疏松、骨折、骨质疏松症、软骨退化、子宫内膜异位症、子宫肌瘤病、潮热、低密度脂蛋白胆固醇水平升高、心血管疾病、认知功能受损、脑退行性疾病、再狭窄、男性乳房发育、血管平滑肌细胞增殖、肥胖、失禁和癌症，尤其是乳腺、子宫和前列腺癌。
• Estrogen receptor ligands. Part 8: Dihydrobenzoxathiin SERAMs with heteroatom-substituted side chains
  作者：Timothy A Blizzard、Frank DiNinno、Jerry D Morgan、Jane Y Wu、Helen Y Chen、Seongkon Kim、Wanda Chan、Elizabeth T Birzin、Yi Tien Yang、Lee-Yuh Pai、Zhoupeng Zhang、Edward C Hayes、Carolyn A DaSilva、Wei Tang、Susan P Rohrer、James M Schaeffer、Milton L Hammond

  DOI：10.1016/j.bmcl.2004.05.073

  日期：2004.8

  A series of benzoxathiin SERAMs with heteroatom-substituted amine side chains was prepared. Minor modifications in the side chain resulted in significant effects on biological activity, especially in uterine tissue. (C) 2004 Elsevier Ltd. All rights reserved.
• Estrogen Receptor Ligands. II. Discovery of Benzoxathiins as Potent, Selective Estrogen Receptor α Modulators
  作者：Seongkon Kim、Jane Y. Wu、Elizabeth T. Birzin、Katalin Frisch、Wanda Chan、Lee-Yuh Pai、Yi Tien Yang、Ralph T. Mosley、Paula M. D. Fitzgerald、Nandini Sharma、Johanna Dahllund、Ann-Gerd Thorsell、Frank DiNinno、Susan P. Rohrer、James M. Schaeffer、Milton L. Hammond

  DOI：10.1021/jm034243o

  日期：2004.4.1

  The discovery and synthesis of dihydrobenzoxathiins as potent, ERalpha subtype selective ligands are described. The most active analogue, 4-D, was found to be 50-fold selective in a competitive binding assay and 100-fold selective in a transactivation assay in HEK-293 cells. The alpha selectivity was postulated to lie in the interaction of the sulfur atom of the benzoxathiin ring with the two discriminating residues in the binding pocket of the receptor isoforms.
• Estrogen receptor ligands. Part 7: Dihydrobenzoxathiin SERAMs with bicyclic amine side chains
  作者：Timothy A Blizzard、Frank DiNinno、Jerry D Morgan、Helen Y Chen、Jane Y Wu、Candido Gude、Seongkon Kim、Wanda Chan、Elizabeth T Birzin、Yi Tien Yang、Lee-Yuh Pai、Zhoupeng Zhang、Edward C Hayes、Carolyn A DaSilva、Wei Tang、Susan P Rohrer、James M Schaeffer、Milton L Hammond

  DOI：10.1016/j.bmcl.2004.05.074

  日期：2004.8

  A series of benzoxathiin SERAMs with bicyclic amine side chains was prepared. Minor modifications in the side chain resulted in significant effects or, biological activity, especially in uterine tissue. (C) 2004 Elsevier Ltd. All rights reserved.
• Estrogen receptor ligands. Part 9: Dihydrobenzoxathiin SERAMs with alkyl substituted pyrrolidine side chains and linkers
  作者：Timothy A. Blizzard、Frank DiNinno、Jerry D. Morgan、Helen Y. Chen、Jane Y. Wu、Seongkon Kim、Wanda Chan、Elizabeth T. Birzin、Yi Tien Yang、Lee-Yuh Pai、Paula M.D. Fitzgerald、Nandini Sharma、Ying Li、Zhoupeng Zhang、Edward C. Hayes、Carolyn A. DaSilva、Wei Tang、Susan P. Rohrer、James M. Schaeffer、Milton L. Hammond

  DOI：10.1016/j.bmcl.2004.10.036

  日期：2005.1

  A series of dihydrobenzoxathiin SERAMs with alkylated pyrrolidine side chains or alkylated linkers was prepared. Minor modifications in the side chain or linker resulted in significant effects on biological activity, especially in uterine tissue.