(2S,3R)-2-(4-(2-(PIPERIDIN-1-YL)ETHOXY)PHENYL)-2,3-DIHYDRO-3-(4-HYDROXYPHENYL)BENZO[B][1,4]OXATHIIN-6-OL | 412052-74-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (2S,3R)-2-(4-(2-(PIPERIDIN-1-YL)ETHOXY)PHENYL)-2,3-DIHYDRO-3-(4-HYDROXYPHENYL)BENZO[B][1,4]OXATHIIN-6-OL
• 英文别名: (2S,3R)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol
• CAS: 412052-74-5
• 化学式: C₂₇H₂₉NO₄S
• 分子量: 463.598
• InChiKey: TWZNCTCQAGRUGQ-RRPNLBNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  87.5
• 氢给体数：
  2
• 氢受体数：
  6

ADMET

代谢

(2S,3R)-3-(4-羟基-苯基)-2-[4-(2-哌啶-1-基-乙氧基)-苯基]-2,3-二氢-苯并[1,4]恶噻吩-6-醇已知的人体代谢物包括3-(4-羟基苯基)-4-氧代-2-[4-(2-哌啶-1-基乙氧基)苯基]-2,3-二氢-1,4lambda4-苯并恶噻吩-6-醇和3-(4-羟基苯基)-2-[4-[2-(戊氨基)乙氧基]苯基]-2,3-二氢-1,4-苯并恶噻吩-6-醇。

(2S,3R)-3-(4-Hydroxy-phenyl)-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-2,3-dihydro-benzo[1,4]oxathiin-6-ol has known human metabolites that include 3-(4-hydroxyphenyl)-4-oxo-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4lambda4-benzoxathiin-6-ol and 3-(4-hydroxyphenyl)-2-[4-[2-(pentylamino)ethoxy]phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-(4-(2-(PIPERIDIN-1-YL)ETHOXY)PHENYL)-2,3-DIHYDRO-3-(4-HYDROXYPHENYL)BENZO[B][1,4]OXATHIIN-6-OL 在 碳酸氢钠 、 sodium hydrogensulfite 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-[2-(4-{(2S,3R,4S)-6-(tert-Butyl-dimethyl-silanyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-oxo-3,4-dihydro-2H-4λ⁴-benzo[1,4]oxathiin-2-yl}-phenoxy)-ethyl]-piperidine
  参考文献：
  名称：

  Estrogen Receptor Ligands. II. Discovery of Benzoxathiins as Potent, Selective Estrogen Receptor α Modulators

  摘要：

  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.

  DOI：

  10.1021/jm034243o
• 作为产物：
  描述：

  (2S,3R)-2-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-(4-triisopropylsilanyloxy-phenyl)-2,3-dihydro-benzo[1,4]oxathiin-6-ol 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3R)-2-(4-(2-(PIPERIDIN-1-YL)ETHOXY)PHENYL)-2,3-DIHYDRO-3-(4-HYDROXYPHENYL)BENZO[B][1,4]OXATHIIN-6-OL
  参考文献：
  名称：

  Estrogen Receptor Ligands. II. Discovery of Benzoxathiins as Potent, Selective Estrogen Receptor α Modulators

  摘要：

  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.

  DOI：

  10.1021/jm034243o

文献信息

• 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. Part 4: The SAR of the syn-dihydrobenzoxathiin SERAMs
  作者：Seongkon Kim、Jane Wu、Helen Y. Chen、Elizabeth T. Birzin、Wanda Chan、Yi Tien Yang、Lawrence Colwell、Susan Li、Johanna Dahllund、Frank DiNinno、Susan P. Rohrer、James M. Schaeffer、Milton L. Hammond

  DOI：10.1016/j.bmcl.2004.03.074

  日期：2004.6

  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.
• 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.
• 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.