(2R)-2-{[N,N-di(4-flurophenyl)carbamoyloxy]methyl}-5-[(ethoxycarbonyl)methoxy]-2-hydroxy-1,2,3,4-tetrahydronaphthalene | 227951-71-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R)-2-{[N,N-di(4-flurophenyl)carbamoyloxy]methyl}-5-[(ethoxycarbonyl)methoxy]-2-hydroxy-1,2,3,4-tetrahydronaphthalene
• 英文别名: (2R)-2-{[N,N-di(4-fluorophenyl)-carbamoyloxy]methyl}-5-[(ethoxycarbonyl)methoxy]-2-hydroxy-1,2,3,4-tetrahydronaphthalene；ethyl 2-[[(6R)-6-[bis(4-fluorophenyl)carbamoyloxymethyl]-6-hydroxy-7,8-dihydro-5H-naphthalen-1-yl]oxy]acetate
• CAS: 227951-71-5
• 化学式: C₂₈H₂₇F₂NO₆
• 分子量: 511.522
• InChiKey: UFYVMSQKFOVTSB-MUUNZHRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R)-2-{[N,N-di(4-flurophenyl)carbamoyloxy]methyl}-5-[(ethoxycarbonyl)methoxy]-2-hydroxy-1,2,3,4-tetrahydronaphthalene 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-[[(6R)-6-[bis(4-fluorophenyl)carbamoyloxymethyl]-6-hydroxy-7,8-dihydro-5H-naphthalen-1-yl]oxy]acetic acid
  参考文献：
  名称：

  Metabolism investigation leading to novel drug design 2: Orally active prostacyclin mimetics. Part 5

  摘要：

  A metabolism study of FK788 (2) led to the discovery of new diphenylcarbamoyl derivatives as prostacyclin mimetics without the PG skeleton. We designed and evaluated PGI(2) mimetics based on blocking the main metabolic pathway of FK788. The new compound 7c was found to be equipotent to FK788 towards PGI(2) agonist activity and metabolically more stable than FK788. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.033
• 作为产物：
  描述：

  4,4'-二氟二苯胺 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 (2R)-2-{[N,N-di(4-flurophenyl)carbamoyloxy]methyl}-5-[(ethoxycarbonyl)methoxy]-2-hydroxy-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  Metabolism investigation leading to novel drug design 2: Orally active prostacyclin mimetics. Part 5

  摘要：

  A metabolism study of FK788 (2) led to the discovery of new diphenylcarbamoyl derivatives as prostacyclin mimetics without the PG skeleton. We designed and evaluated PGI(2) mimetics based on blocking the main metabolic pathway of FK788. The new compound 7c was found to be equipotent to FK788 towards PGI(2) agonist activity and metabolically more stable than FK788. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.033

文献信息

• Naphthalene derivatives
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06303649B1

  公开（公告）日：2001-10-16

  A compound of formula (I), wherein R1 is carboxy or protected carboxy, R2 and R3 are each independently hydrogen, hydroxy, or protected hydroxy, R4 is hydrogen or halogen, R5 is aryl substituted with halogen, amino, hydroxy or protected hydroxy, R6 is aryl optionally substituted with halogen, amino, hydroxy or protected hydroxy, A1 and A2 are each independently lower alkylene, and (II) is (III), (IV), (V) or (VI) or its salt, process for preparing it, a pharmaceutical composition including it, and a use thereof.

  式(I)的化合物，其中R1是羧基或保护羧基，R2和R3分别独立地是氢、羟基或保护羟基，R4是氢或卤素，R5是芳基，其上取代有卤素、氨基、羟基或保护羟基，R6是芳基，可选地取代有卤素、氨基、羟基或保护羟基，A1和A2分别独立地是较低的烷基，(II)是(III)、(IV)、(V)或(VI)或其盐，制备方法，包括它的药物组合物，及其用途。
• NAPHTHALENE DERIVATIVES
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP1042277A1

  公开（公告）日：2000-10-11
• US6303649B1
  申请人：——

  公开号：US6303649B1

  公开（公告）日：2001-10-16
• [EN] NAPHTHALENE DERIVATIVES<br/>[FR] DERIVES DE NAPHTALENE
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1999032435A1

  公开（公告）日：1999-07-01

  (EN) A compound of formula (I), wherein R1 is carboxy or protected carboxy, R2 and R3 are each independently hydrogen, hydroxy, or protected hydroxy, R4 is hydrogen or halogen, R5 is aryl substituted with halogen, amino, hydroxy or protected hydroxy, R6 is aryl optionally substituted with halogen, amino, hydroxy or protected hydroxy, A1 and A2 are each independently lower alkylene, and (II) is (III), (IV), (V) or (VI) or its salt, process for preparing it, a pharmaceutical composition including it, and a use thereof.(FR) L'invention concerne un composé qui correspond à la formule suivante: (I) dans laquelle R1 est carboxy ou carboxy protégé; R2 et R3 sont chacun indépendamment hydrogène, hydroxy ou hydroxy protégé; R4 est hydrogène ou halogène; R5 est aryle substitué avec halogène, amino, hydroxy ou hydroxy protégé; R6 est aryle éventuellement substitué avec halogène, amino, hydroxy ou hydroxy protégé; A1 et A2 sont chacun indépendamment alkylène inférieur et (II) est (III), (IV), (V) ou (VI), ainsi qu'un sel de ce composé, un procédé de fabrication correspondant, une composition pharmaceutique comprenant ce composé et son utilisation.
• Metabolism investigation leading to novel drug design 2: Orally active prostacyclin mimetics. Part 5
  作者：Fujiko Takamura、Akira Tanaka、Hisashi Takasugi、Kiyoshi Taniguchi、Mie Nishio、Jiro Seki、Kouji Hattori

  DOI：10.1016/j.bmcl.2006.06.033

  日期：2006.9

  A metabolism study of FK788 (2) led to the discovery of new diphenylcarbamoyl derivatives as prostacyclin mimetics without the PG skeleton. We designed and evaluated PGI(2) mimetics based on blocking the main metabolic pathway of FK788. The new compound 7c was found to be equipotent to FK788 towards PGI(2) agonist activity and metabolically more stable than FK788. (c) 2006 Elsevier Ltd. All rights reserved.