4-[9-(t-butyldimethylsilyloxy)-1-nonynyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman | 209325-04-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 4-[9-(t-butyldimethylsilyloxy)-1-nonynyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman
• 英文别名: 4-[9-(t-Butyldimethylsilyloxy)1-nonynyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman；tert-butyl-[9-[7-methoxy-3-(4-methoxyphenyl)-3-methyl-2,4-dihydrothiochromen-4-yl]non-8-ynoxy]-dimethylsilane
• CAS: 209325-04-2
• 化学式: C₃₃H₄₈O₃SSi
• 分子量: 552.894
• InChiKey: ZUUMLCVVWHCFEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.22
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[9-(t-butyldimethylsilyloxy)-1-nonynyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman 在 palladium on activated charcoal sodium azide 、 四丁基氟化铵 、 氢气 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens

  摘要：

  In order to search for alternatives to the sulfoxide moiety in the long side chain of pure antiestrogens, several molecules that may interact with water in a fashion similar to ICI164,384 were designed and it was found that compounds with the carboxy, the sulfamide, or the sulfonamide instead of the sulfoxide moiety also functioned as pure antiestrogens. Interestingly, the compound possessing the carboxy moiety showed superior antiestrogen activity compared to ICI182,780 when dosed orally. Results of the pharmacokinctic evaluation indicated that the potent antiestrogen activity at oral dosing attributed to both the improved absorption from the intestinal wall and the metabolic stability of the compound in liver. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.090
• 作为产物：
  描述：

  ((7-bromoheptyl)oxy)(tert-butyl)dimethylsilane 在 正丁基锂 、 sodium cyanoborohydride 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 4-[9-(t-butyldimethylsilyloxy)-1-nonynyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman
  参考文献：
  名称：

  Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure–activity relationship

  摘要：

  In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.020

文献信息

• Benzopyran derivatives
  申请人：C & C Research Laboratories

  公开号：US06153768A1

  公开（公告）日：2000-11-28

  The present invention relates to a novel benzopyran derivative having anti-estrogenic activity. More specifically, the present invention relates to a novel benzopyran derivative represented by formula (I) and pharmaceutically acceptable salt thereof, in which ----- represents a single bond or a double bond; R1 and R2 independently of one another represent hydrogen, hydroxy or OR group, wherein R represents acyl or alkyl; R3 represents hydrogen, lower alkyl or halogeno lower alkyl, provided that when ----- represents a double bond, R3 is not present; R4 represents hydrogen or lower alkyl; A represents a group of formula a, b, c or d; R5, R6 and R7 independently of one another represent hydrogen, alkyl, halogenoalkyl, alkenyl or halogenoalkenyl, or R6 and R7 together with nitrogen atom to which they are bound can form a 4- to 8-membered heterocyclic ring which can be substituted with R5; X represents O, S, or NR8, wherein R8 represents hydrogen or lower alkyl; m denotes an integer of 2 to 15; n denotes an integer of 0 to 2; and p denotes an integer of 0 to 4.

  本发明涉及一种具有抗雌激素活性的新型苯并吡喃衍生物。更具体地，本发明涉及一种由式（I）表示的新型苯并吡喃衍生物及其药学上可接受的盐，其中-----表示单键或双键；R1和R2彼此独立地表示氢、羟基或OR基团，其中R表示酰基或烷基；R3表示氢、较低烷基或卤代较低烷基，但当-----表示双键时，R3不存在；R4表示氢或较低烷基；A表示a、b、c或d式的基团；R5、R6和R7彼此独立地表示氢、烷基、卤代烷基、烯基或卤代烯基，或者R6和R7与它们结合的氮原子一起可以形成一个4-至8-成员的杂环环，该环可以用R5取代；X表示O、S或NR8，其中R8表示氢或较低烷基；m表示2至15的整数；n表示0至2的整数；p表示0至4的整数。
• Benzopyran or thiobenzopyran derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06645951B1

  公开（公告）日：2003-11-11

  The present invention provides novel benzopyran compounds, pharmaceutically acceptable salts thereof and stereoisomers thereof where the benzopyran compounds of the invention are compounds according to Formula I: The present invention further provides pharmaceutical compositions which possess anti-estrogenic activity and comprise at least one benzopyran compound of the invention and a method of treating breast cancer by administration of an effective amount of a benzopyran compound provided by the present invention.

  本发明提供了新颖的苯并吡喃化合物，其药学上可接受的盐及其立体异构体，其中本发明的苯并吡喃化合物是根据式I的化合物：本发明还提供了具有抗雌激素活性的药物组合物，包括本发明的至少一种苯并吡喃化合物，并通过给予本发明提供的苯并吡喃化合物的有效量来治疗乳腺癌的方法。
• Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure–activity relationship
  作者：Yoshitake Kanbe、Myung-Hwa Kim、Masahiro Nishimoto、Yoshihito Ohtake、Nobuaki Kato、Toshiaki Tsunenari、Kenji Taniguchi、Iwao Ohizumi、Shin-ichi Kaiho、Kazumi Morikawa

  DOI：10.1016/j.bmc.2006.03.020

  日期：2006.7.15

  In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities. (c) 2006 Elsevier Ltd. All rights reserved.
• Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens
  作者：Yoshitake Kanbe、Myung-Hwa Kim、Masahiro Nishimoto、Yoshihito Ohtake、Toshiaki Tsunenari、Kenji Taniguchi、Iwao Ohizumi、Shin-ichi Kaiho、Yoshiaki Nabuchi、Setsu Kawata、Kazumi Morikawa、Jae-Chon Jo、Hee-An Kwon、Hyun-Suk Lim、Hak-Yeop Kim

  DOI：10.1016/j.bmcl.2006.04.090

  日期：2006.8

  In order to search for alternatives to the sulfoxide moiety in the long side chain of pure antiestrogens, several molecules that may interact with water in a fashion similar to ICI164,384 were designed and it was found that compounds with the carboxy, the sulfamide, or the sulfonamide instead of the sulfoxide moiety also functioned as pure antiestrogens. Interestingly, the compound possessing the carboxy moiety showed superior antiestrogen activity compared to ICI182,780 when dosed orally. Results of the pharmacokinctic evaluation indicated that the potent antiestrogen activity at oral dosing attributed to both the improved absorption from the intestinal wall and the metabolic stability of the compound in liver. (c) 2006 Elsevier Ltd. All rights reserved.