(+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol | 1097633-66-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: (+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol
• 英文别名: (9S,10R)-6-fluoro-10-prop-2-enyltricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaen-9-ol
• CAS: 1097633-66-3
• 化学式: C₁₈H₁₇FO
• 分子量: 268.331
• InChiKey: QBMWHNWHBZAXHE-AEFFLSMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol 、 乙酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以89%的产率得到(10S*,11R*)-11-allyl-8-fluoro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl acetate
  参考文献：
  名称：

  WO2006/125812

  摘要：

  公开号：
• 作为产物：
  描述：

  烯丙基溴化镁 、 3-fluoro-6,10b-dihydro-1aH-dibenz-[3,4:6,7]cyclohepta[1,2-b]oxirene 在 氮 、 ice 、 氯化铵 、 乙酸乙酯 、 silica gel 、 (+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol 、 (trans)-2-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo[a,d]cyclohepten-10-ol 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以yielding 4.79 g (36%) of (±)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclohepten-10-ol (intermediate 3) and 2.52 g (19%) of (trans)-2-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo[a,d]cyclohepten-10-ol (intermediate 4)的产率得到(+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol
  参考文献：
  名称：

  Halogen substituted tetracyclic tetrahydrofuran derivatives

  摘要：

  本发明涉及式（I）的化合物，其N-氧化物形式，药学上可接受的加合物盐和立体化学异构体形式，其中n为零，1，2，3，4，5或6; X为CH2或O; R1和R2各自独立地为氢，C1-6烷基，C1-6烷基羰基，卤甲基羰基或C1-6烷基取代的羟基，C1-6烷氧基，羧基，C1-6烷基羰氧基，C1-6烷氧羰基或芳基; 或R1和R2与它们所连接的氮原子一起可以形成吗啡啶环或可选取代的杂环; R3和R4都是卤素; 或者R3是卤素而R4是氢; 或者R3是氢而R4是卤素; 芳基是苯基或取代有1、2或3个来自卤素、羟基、C1-6烷基和卤甲基的取代基的苯基。式（I）的化合物可用作治疗剂。

  公开号：

  US06699858B2
• 作为试剂：
  描述：

  烯丙基溴化镁 、 3-fluoro-6,10b-dihydro-1aH-dibenz-[3,4:6,7]cyclohepta[1,2-b]oxirene 在 氮 、 ice 、 氯化铵 、 乙酸乙酯 、 silica gel 、 (+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol 、 (trans)-2-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo[a,d]cyclohepten-10-ol 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以yielding 4.79 g (36%) of (±)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclohepten-10-ol (intermediate 3) and 2.52 g (19%) of (trans)-2-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo[a,d]cyclohepten-10-ol (intermediate 4)的产率得到(+/-)-trans-8-fluoro-10,11-dihydro-11-(2-propenyl)-5H-dibenzo [a,d]cyclo-hepten-10-ol
  参考文献：
  名称：

  Halogen substituted tetracyclic tetrahydrofuran derivatives

  摘要：

  本发明涉及式（I）的化合物，其N-氧化物形式，药学上可接受的加合物盐以及立体化学异构体形式，其中n为0、1、2、3、4、5或6；X为CH2或O；R1和R2各自独立地为氢、C1-6烷基、C1-6烷基羰基、卤甲基羰基或C1-6烷基取代的羟基、C1-6烷氧基、羧基、C1-6烷基羰氧基、C1-6烷氧基羰基或芳基；或者R1和R2与它们所连接的氮原子一起可以形成吗啡啶环或可选地取代的杂环；R3和R4均为卤素；或R3为卤素且R4为氢；或R3为氢且R4为卤素；芳基为苯基或取代有1、2或3个来自卤素、羟基、C1-6烷基和卤甲基的取代基。式（I）的化合物可用作治疗剂。

  公开号：

  US06511976B1

文献信息

• Novel mandelates salts of substituted tetracyclic tetrahydrofuran derivatives
  申请人：Medaer Bart Petrus Anna Maria Jozef

  公开号：US20050085533A1

  公开（公告）日：2005-04-21

  The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R 1 and R 2 each independently are hydrogen or C 1-6 alkyl and R 3 and R 4 each independently are hydrogen or halogen. In the foregoing definitions C 1-6 alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media. Also disclosed are pharmaceutical compositions comprising mandelate salts according to the invention, mandelate salts according to the invention for use as a medicine, a process for preparing the mandelate salts according to the invention and the use of the mandelate salts and pharmaceutical compositions comprising mandelate salts according to the invention for the treatment or the prevention of CNS disorders, cardiovascular disorders and gastrointestinal disorders.

  本发明的对象是一种按照公式（I）定义的取代四环四氢呋喃衍生物的新型曼德酸盐，其中N-氧化物形式和立体化学异构体形式，其中R1和R2各自独立地为氢或C1-6烷基，R3和R4各自独立地为氢或卤素。在上述定义中，C1-6烷基定义为具有1至6个碳原子的直链和支链饱和碳氢基基团，例如甲基，乙基，丙基，丁基，1-甲基丙基，1,1-二甲基乙基，戊基或己基。新型曼德酸盐不敏感于光，并且比先前的盐在室温，升高温度和相对高湿度以及在水介质中更加稳定。还披露了包括根据本发明的曼德酸盐的制药组合物，根据本发明的曼德酸盐作为药物的用途，制备根据本发明的曼德酸盐的过程以及用于治疗或预防中枢神经系统疾病，心血管疾病和胃肠疾病的曼德酸盐和包含曼德酸盐的制药组合物的用途。
• Mandelates salts of substituted tetracyclic tetrahydrofuran derivatives
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US07317115B2

  公开（公告）日：2008-01-08

  The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen or C1-6alkyl and R3 and R4 each independently are hydrogen or halogen. In the foregoing definitions C1-6alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media. Also disclosed are pharmaceutical compositions comprising mandelate salts according to the invention, mandelate salts according to the invention for use as a medicine, a process for preparing the mandelate salts according to the invention and the use of the mandelate salts and pharmaceutical compositions comprising mandelate salts according to the invention for the treatment or the prevention of CNS disorders, cardiovascular disorders and gastrointestinal disorders.

  本发明的对象是一种新型替代四环四氢呋喃衍生物的曼德酸盐，其化学式为（I），其中N-氧化物形式和立体化学异构体形式，其中R1和R2各自独立地为氢或C1-6烷基，R3和R4各自独立地为氢或卤素。在上述定义中，C1-6烷基定义为直链和支链饱和碳氢基团，其具有1至6个碳原子，例如，甲基，乙基，丙基，丁基，1-甲基丙基，1,1-二甲基乙基，戊基或己基。新型曼德酸盐不敏感于光，并且比室温下的现有盐稳定得多，在升高温度和相对高湿度以及水介质中也是如此。还公开了包括本发明的曼德酸盐的制药组合物，用于药物的曼德酸盐，制备本发明的曼德酸盐的过程以及用于治疗或预防中枢神经系统疾病，心血管疾病和胃肠疾病的曼德酸盐和包括曼德酸盐的制药组合物的用途。
• NOVEL SUBSTITUTED TETRACYCLIC TETRAHYDROFURAN, PYRROLIDINE AND TETRAHYDROTHIOPHENE DERIVATIVES
  申请人：CID-NÚÑEZ José Maria

  公开号：US20100331325A1

  公开（公告）日：2010-12-30

  This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT 2A and 5-HT 2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

  本发明涉及一种新型取代四环四氢呋喃、吡咯烷和四氢噻吩衍生物，具有与血清素受体结合亲和力，特别是5-HT2A和5-HT2C受体，以及多巴胺受体，特别是多巴胺D2受体和去甲肾上腺再摄取抑制性能，制备了包括本发明化合物的药物组合物，其用途作为药物，特别是用于预防和/或治疗一系列精神和神经系统疾病，特别是某些精神病、心血管和胃动力障碍，以及它们的生产过程。本发明的化合物可以用通式（I）表示，并包括其药学上可接受的酸或碱盐，其立体化学异构体形式，其N-氧化物形式和其前药，其中所有取代基如权利要求1所定义。
• Novel Substituted Tetracyclic Tetahydrofuran, Pyrrolidine And Tetrahydrothiophene Derivatives
  申请人：Cid-Nunez Jose Maria

  公开号：US20080287450A1

  公开（公告）日：2008-11-20

  This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT 2A and 5-HT 2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.
• US7799785B2
  申请人：——

  公开号：US7799785B2

  公开（公告）日：2010-09-21