7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methyl-2,3-dihydro-4H-benzopyran-4-one | 209324-81-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methyl-2,3-dihydro-4H-benzopyran-4-one
• 英文别名: 7-(methoxymethoxy)-3-[4-(methoxymethoxy)phenyl]-3-methylchroman-4-one；7-Methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylchroman-4-one；7-(methoxymethoxy)-3-[4-(methoxymethoxy)phenyl]-3-methyl-2H-chromen-4-one
• CAS: 209324-81-2
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: YANYLVOJMCKLCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methyl-2,3-dihydro-4H-benzopyran-4-one 在 正丁基锂 、 4-甲基苯磺酸吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 9-[7-methoxymethyloxy-3-(4-methoxymethyloxyphenyl)-3-methylchroman-4-yl]nonyl methanesulfonate
  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：

  (+/-)-2,3-Dihydro-7-(methoxymethoxy)-3-<4-(methoxymethoxy)phenyl>-4H-1-benzopyran-4-on 、 碘甲烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以82%的产率得到7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methyl-2,3-dihydro-4H-benzopyran-4-one
  参考文献：
  名称：

  3-methyl -chromane or thiochromane derivatives

  摘要：

  本发明涉及3-甲基-色环或硫代色环衍生物，其药学上可接受的盐，立体异构体或水合物，以及一种抗雌激素药物组合物，其包括上述化合物作为活性成分。

  公开号：

  US20030013756A1

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。
• [EN] NOVEL BENZOPYRAN DERIVATIVES<br/>[FR] NOUVEAUX DERIVES DE BENZOPYRANE
  申请人：C & C RESEARCH LABORATORIES

  公开号：WO1998025916A1

  公开（公告）日：1998-06-18

  (EN) 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, and to a process for preparation thereof and a pharmaceutical composition having anti-estrogenic activity which contains the compound (I) as an active component.(FR) La présente invention concerne un nouveau dérivé de benzopyrane possédant une activité anti-oestrogénique. La présente invention concerne plus particulièrement un nouveau dérivé de benzopyrane représenté par la formule (I) et des sels de celui-ci pharmaceutiquement acceptables, dans laquelle ----- représente une liaison simple ou une liaison double; R1 et R2 représentent, indépendamment l'un de l'autre, hydrogène, hydroxy ou un groupe OR dans lequel R représente acyle ou alkyle; R3 représente hydrogène, alkyle inférieur ou halogéno alkyle inférieur à condition que lorsque ----- représente hydrogène ou alkyle inférieur, R3 ne soit pas présent; R4 représente hydrogène ou alkyle inférieur; A représente un groupe de formule (a), (b), (c), ou (d); R5, R6 et R7 représentent, indépendamment l'un de l'autre, hydrogène, alkyle, halogénoalkyle, alcényle ou halogénoalcényle, ou R6 et R7 peuvent former conjointement avec un atome d'azote, auquel ils sont liés, un noyau hétérocyclique de 4 à 8 chaînons pouvant être substitué par R5; X représente O, S ou NR8 dans lequel R8 représente hydrogène ou alkyle inférieur; m représente un nombre entier compris entre 2 et 15; n représente un nombre entier compris entre 0 et 2; et p représente un nombre entier compris entre 0 et 4. La présente invention concerne également un procédé de préparation des composés précités et une composition pharmaceutique présentant une activité anti-oestrogénique renfermant le composé (I) comme composant actif.

  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，本发明涉及一种由公式（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分别独立地表示氢，羟基或OR基团，其中R表示酰基或烷基；R3表示氢，低烷基或卤代低烷基，但当-----表示双键时，R3不存在；R4表示氢或低烷基；A表示公式（a），（b），（c）或（d）的基团；R5，R6和R7独立地表示氢，烷基，卤代烷基，烯基或卤代烯基，或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，并且本发明还涉及其制备方法和含有化合物（I）作为活性成分的抗雌激素活性的药物组合物。
• Novel benzopyran or thiobenzopyran derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US20040102479A1

  公开（公告）日：2004-05-27

  The present invention relates to a novel benzopyran or thiobenzopyran derivative represented by formula (1): pharmaceutically acceptable salt or stereoisomer thereof, in which X, R 1 , R 2 , R 3 , R 4 and A are defined as described in the specification, and to a process for preparation thereof and a pharmaceutical composition having anti-estrogenic activity which contains the compound (1) as an active component.

  本发明涉及一种由式（1）表示的新型苯并吡喃或硫代苯并吡喃衍生物：其药学上可接受的盐或立体异构体，其中X，R1，R2，R3，R4和A的定义如说明书中所述，以及制备过程和具有抗雌激素活性的制剂，其含有化合物（1）作为活性成分。
• 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.