trans-4-<3-(4-fluorophenyl)-6-fluoro-1-indanyl>-1-piperazineethanol | 80273-31-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: trans-4-<3-(4-fluorophenyl)-6-fluoro-1-indanyl>-1-piperazineethanol
• 英文别名: trans-4-[3-(4-Fluorophenyl)-6-fluoro-indan-1-yl]-1-piperazineethanol；2-[4-[(1R,3S)-6-fluoro-3-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]piperazin-1-yl]ethanol
• CAS: 80273-31-0
• 化学式: C₂₁H₂₄F₂N₂O
• 分子量: 358.431
• InChiKey: KHGDILJGZLKKBP-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-4-<3-(4-fluorophenyl)-6-fluoro-1-indanyl>-1-piperazineethanol 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 3.0h， 生成 trans-1-<2-<(2-aminoethyl)amino>ethyl>-4-<3-(4-fluorophenyl)-6-fluoro-1-indanyl>piperazine
  参考文献：
  名称：

  在一系列具有有效的5-HT2-拮抗活性的1-哌嗪子-3-苯基茚满中的降压活性。

  摘要：

  合成了一系列反式-1-哌嗪子-3-苯基茚满，其目的是用周围的5-羟基色胺（5-HT2）拮抗作用来取代它们建立的抗精神病药。在茚满环中具有未取代或氟取代的6-位并且具有通过乙烯链连接至哌嗪环的五元或六元杂环的化合物，满足了该目的。一些化合物在有意识的，自发性高血压大鼠（SHR）中具有有效的降压活性。在成髓大鼠中，它们拮抗5-HT诱导的升压作用，其剂量比拮抗去氧肾上腺素的升压作用所需的剂量低100-1000倍。该作用是立体选择性的，并且与具有1R，3S绝对构型的对映异构体有关。1S，3R对映体在体外抑制多巴胺和去甲肾上腺素的摄取。降压活性最好的化合物是（+）-（1R，3S）-1- [2- [4- [3-（4-氟苯基）-1-茚满基] -1-哌嗪基]乙基] -2-咪唑啉酮（Lu 21-098，irindalone）。它的药理特性与标准化合物酮色林相似。酮色林和伊立酮之间存在紧密的结构对应关系，这种

  DOI：

  10.1021/jm00120a003
• 作为产物：
  描述：

  3,3-bis(4-fluorophenyl)-propanoic acid 在 sodium hydroxide 、 氯化亚砜 、 PPA 、 Polyphosphoric acid (PPA) 、 双氧水 、 potassium tri-sec-butyl-borohydride 作用下， 以 甲苯 、 丁酮 为溶剂， 反应 20.17h， 生成 trans-4-<3-(4-fluorophenyl)-6-fluoro-1-indanyl>-1-piperazineethanol
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002

文献信息

• Antihypertensive fluorophenylindanyl imidazolidinoneethylpiperazines
  申请人：H. Lundbeck A/S

  公开号：US04684650A1

  公开（公告）日：1987-08-04

  The present invention relates to indane derivatives with the following formula: ##STR1## wherein R.sub.1 is H, Halogen, an alkyl group having from one to three carbon atoms inclusive, methoxy, a methylthio-group, or a trifluoromethyl group, n is 2-4 X is O or S, Y is O, CH.sub.2 or N--R.sub.2, where R.sub.2 is hydrogen or an (1-6 C) alkyl, (2-6 C) alkenyl or cycloalkyl-methyl group having from three to six carbon atoms, Z is --(CH.sub.2).sub.n --, n is 2 or 3 or Z is 1,2-phenylene optionally substituted with halogen or trifluoromethyl or Z=1,2--C.sub.6 H.sub.4 CO-- (to form a quinazolidinone or -thione ring system). U=N or C. Each compound exists as geometric isomers and each of these as a pair of optical isomers; and the separation and isolation of these are also within the scope of the invention. Moreover, pharmaceutically acceptable acid addition salts of the compounds of Formula I are within the scope of the present invention. Pharmaceutical compositions containing a compound of Formula I or a salt thereof as an active ingredient, and methods for the treatment of hypertension and other cardiovascular diseases as well as anxiety, by administration of a therapeutically active amount of one of the compounds of Formula I to a living animal body, including human beings, fall within the scope of the present invention.

  本发明涉及具有以下式的茚烷衍生物：##STR1##其中R.sub.1为H，卤素，具有1至3个碳原子的烷基，甲氧基，甲基硫基，或三氟甲基基团，n为2-4，X为O或S，Y为O，CH.sub.2或N--R.sub.2，其中R.sub.2为氢或具有3至6个碳原子的(1-6 C)烷基，(2-6 C)烯基或环烷基甲基基团，Z为--(CH.sub.2) .sub.n--，n为2或3或Z为1,2-苯基，可选择卤素或三氟甲基取代或Z=1,2--C.sub.6 H.sub.4 CO--（以形成喹唑啉酮或-硫酮环系）。U=N或C。每种化合物均存在几何异构体，每种化合物均存在一对光学异构体; 分离和分离这些也在本发明的范围内。此外，本发明的范围还包括化合物的药学上可接受的酸加成盐。含有式I化合物或其盐作为活性成分的药物组合物，以及通过向活体动物体，包括人类，投与式I化合物之一的治疗性有效量的方法，用于治疗高血压和其他心血管疾病以及焦虑症，也属于本发明的范围。
• Indane derivatives and methods of preparation and treatment
  申请人：H. LUNDBECK A/S

  公开号：EP0183349A1

  公开（公告）日：1986-06-04

  Indane derivatives with the formula: wherein R1 is H, Halogen, an alkyl group having from one to three carbon atoms inclusive, methoxy, a methylthio-group, or a trifluoromethyl group, n is 2-4, X is O or S, Y is 0, CH2 or N-R2, where R2 is hydrogen or an (1-6 C) alkyl, (1-6 C) alkenyl or cycloalkyl-methyl group having from three to six carbon atoms, Z is -(Ch2)n-, n is 2 or 3 or Z is 1,2-phenylene optionally substituted with halogen or trifluoromethyl or Z = 1,2-C6H4CO- (to form a quinazolidinone or -thione ring system). U = N or C, geometric isomers thereof as well as pharmaceutically acceptable acid addition salts are potent 5-HT2 antagonists useful in the treatment of cardiovascular diseases including hypertension and anxiety. Methods for the preparation of said compounds are also described.

  式中的茚满衍生物： 其中 R1 是 H、卤素、含 1 至 3 个碳原子的烷基、甲氧基、甲硫基或三氟甲基、 n 为 2-4、 X 是 O 或 S、 Y 是 0、CH2 或 N-R2，其中 R2 是氢或 (1-6 C) 烷基、 (1-6C)烯基或环烷基甲基，具有 3 至 6 个碳原子。 至六个碳原子的 (1-6 C) 烷基、(1-6 C) 烯基或环烷基甲基、 Z 是-(Ch2)n-，n 是 2 或 3，或 Z 是被卤素或三氟甲基任选取代的 1,2-亚苯基。 或 Z = 1,2-C6H4CO-（形成喹唑啉酮或硫酮环系）。 U = N 或 C、 其几何异构体以及药学上可接受的酸加成盐是强效的 5-HT2 拮抗剂，可用于治疗心血管疾病，包括高血压和焦虑症。 还描述了制备上述化合物的方法。
• US4684650A
  申请人：——

  公开号：US4684650A

  公开（公告）日：1987-08-04
• Antihypertensive activity in a series of 1-piperazino-3-phenylindans with potent 5-HT2-antagonistic activity
  作者：Klaus P. Boegesoe、Joern Arnt、Vita Boeck、A. Vibeke Christensen、John Hyttel、Klaus Gundertofte Jensen

  DOI：10.1021/jm00120a003

  日期：1988.12

  enantiomers with 1R,3S absolute configuration. 1S,3R enantiomers inhibited the uptake of dopamine and norepinephrine in vitro. The compound with the best antihypertensive activity was (+)-(1R,3S)-1-[2-[4-[3-(4-fluorophenyl)-1-indanyl]-1- piperazinyl]ethyl]-2-imidazolidinone (Lu 21-098, irindalone). Its pharmacological profile resembled that of the standard compound ketanserin. There was a close structural

  合成了一系列反式-1-哌嗪子-3-苯基茚满，其目的是用周围的5-羟基色胺（5-HT2）拮抗作用来取代它们建立的抗精神病药。在茚满环中具有未取代或氟取代的6-位并且具有通过乙烯链连接至哌嗪环的五元或六元杂环的化合物，满足了该目的。一些化合物在有意识的，自发性高血压大鼠（SHR）中具有有效的降压活性。在成髓大鼠中，它们拮抗5-HT诱导的升压作用，其剂量比拮抗去氧肾上腺素的升压作用所需的剂量低100-1000倍。该作用是立体选择性的，并且与具有1R，3S绝对构型的对映异构体有关。1S，3R对映体在体外抑制多巴胺和去甲肾上腺素的摄取。降压活性最好的化合物是（+）-（1R，3S）-1- [2- [4- [3-（4-氟苯基）-1-茚满基] -1-哌嗪基]乙基] -2-咪唑啉酮（Lu 21-098，irindalone）。它的药理特性与标准化合物酮色林相似。酮色林和伊立酮之间存在紧密的结构对应关系，这种
• Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans
  作者：Klaus P. Boegesoe

  DOI：10.1021/jm00361a002

  日期：1983.7

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.