1-chloro-3-(4-fluorophenyl)-6-fluoroindan | 344755-05-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 1-chloro-3-(4-fluorophenyl)-6-fluoroindan
• 英文别名: 1-chloro-3-(4'-fluorophenyl)-6-fluoroindane；3-chloro-5-fluoro-1-(4-fluorophenyl)-2,3-dihydro-1H-indene
• CAS: 344755-05-1
• 化学式: C₁₅H₁₁ClF₂
• 分子量: 264.702
• InChiKey: UTAHPBAXSBVJTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(1-哌嗪)-1,2-丙二醇 、 1-chloro-3-(4-fluorophenyl)-6-fluoroindan 以 丁酮 为溶剂， 反应 16.0h， 生成 3-[4-[6-fluoro-3-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]piperazin-1-yl]propane-1,2-diol
  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
• 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 为溶剂， 反应 4.17h， 生成 1-chloro-3-(4-fluorophenyl)-6-fluoroindan
  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

• Indane derivatives, pharmaceutical compositions thereof and method of
  申请人：Kefalas A/S

  公开号：US04443448A1

  公开（公告）日：1984-04-17

  The present invention relates to novel 1-piperazino-3-phenyl-indane derivatives which have pronounced psychopharmacological activity such as neuroleptic activity, analgesic activity, antidepressant activity and, at the same time, a low degree of undesired side-effects, methods for the preparation of said indane derivatives, pharmaceutical compositions containing same, and methods for the treatment of psychic disorders, such as psychoses and depressions and pain, by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings.

  本发明涉及新的1-哌嗪基-3-苯基-茚衍生物，具有明显的精神药理学活性，如神经阻滞活性、镇痛活性、抗抑郁活性，并且同时具有低程度的不良副作用，制备该茚衍生物的方法、含有该茚衍生物的制药组合物，以及通过向生物体，包括人类，施用所述衍生物之一的治疗有效量来治疗精神障碍，如精神病和抑郁症以及疼痛的方法。
• 3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake
  作者：Klaus P. Bogeso、A. Vibeke Christensen、John Hyttel、Tommy Liljefors

  DOI：10.1021/jm00150a012

  日期：1985.12

  3-phenyl-1-indanamines was synthesized and tested for potential antidepressant activity and for inhibition of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) uptake. Trans isomers were generally potent inhibitors of DA, NE, and 5-HT uptake, while cis isomers preferentially inhibited the uptake of 5-HT. The affinity for the DA-uptake site was very dependent on the aromatic substitution pattern

  合成了一系列3-苯基-1-茚满胺，并测试了其潜在的抗抑郁活性以及对多巴胺（DA），去甲肾上腺素（NE）和5-羟色胺（5-HT）吸收的抑制作用。反式异构体通常是DA，NE和5-HT吸收的有效抑制剂，而顺式异构体则优先抑制5-HT的吸收。对DA吸收位点的亲和力非常取决于芳族取代模式，其中3'，4'-二氯取代的化合物的效价最高（45）。这种取代模式也导致了对NE和5-HT摄取位点的高度亲和力，但是用其他取代模式也可以获得强大的5-HT摄取抑制活性。在5-HT摄取部位只能容纳少量胺，而在DA和NE摄取部位都可以容纳较大的胺（例如哌嗪）。观察到的构效关系是根据反式（45）和顺式（72）异构体分别与5-HT和DA重叠的结果解释的，与拟议的摄取抑制剂在摄取时的三点结合有关网站。最后，比较了3-苯基-1-茚满胺与其他新型双环儿茶酚胺和/或5-羟色胺摄取抑制剂的结构，发现它们对有效抑制DA-，NE-和/或5-HT摄取具有重要意义。
• Indane derivatives, methods of their preparation and compositions containing them
  申请人：KEFALAS A/S

  公开号：EP0035363A1

  公开（公告）日：1981-09-09

  1-Piperazino-3-phenylindane derivatives of the formula: wherein R1, R2, R3 and R4 are as defined in Claim 1, and their pharmaceutically acceptable acid addition salts. The compounds are prepared by the usual methods for analogous compounds. They have been found to have psychopharmacological and analgetic activity. Pharmaceutical compositions containing the compounds have been disclosed.

  式中 R1、R2、R3 和 R4 如权利要求 1 所定义的 1-哌嗪基-3-苯基茚满衍生物及其药学上可接受的酸加成盐。 这些化合物是用类似化合物的常规方法制备的。 它们具有精神药理学和镇痛活性。 含有这些化合物的药物组合物已被公开。
• Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity
  作者：Klaus P. Bogeso、Jorn Arnt、Kristen Frederiksen、Hans Otto Hansen、John Hyttel、Henrik Pedersen

  DOI：10.1021/jm00022a004

  日期：1995.10

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.
• BOGESO, K. P., J. MED. CHEM., 1983, 26, N 7, 935-947
  作者：BOGESO, K. P.

  DOI：——

  日期：——