1-chloro-4-(4-flurophenyl)indan | 104087-10-7

• 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-4-(4-flurophenyl)indan
• 英文别名: 3-(4-fluorophenyl)-1-chloroindan；1-chloro-3-(4-fluorophenyl)-2,3-dihydro-1H-indene
• CAS: 104087-10-7
• 化学式: C₁₅H₁₂ClF
• 分子量: 246.712
• InChiKey: WIDZVWULMHICJQ-UHFFFAOYSA-N

物化性质

• 沸点：
  339.5±42.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  17
• 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：
  1

反应信息

• 作为反应物：
  描述：

  1-chloro-4-(4-flurophenyl)indan 在 potassium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 19.0h， 生成 茚达酮
  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-(4-氟苯基)茚满-1-酮 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.5h， 生成 1-chloro-4-(4-flurophenyl)indan
  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

• 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。
• 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公式的吲哚衍生物：##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)烯丙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，可选择地取代卤素或三氟甲基，或Z=1,2--C.sub.6 H.sub.4 CO--（形成喹唑啉酮或-硫酮环系统）。U = N或C。每种化合物存在为几何异构体和每个异构体都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，公式I化合物的药学上可接受的酸加合盐也在本发明的范围内。含有公式I化合物或其盐作为活性成分的药物组合物以及通过向生物体，包括人类，中投与公式I化合物之一的治疗活性量的方法，用于治疗高血压和其他心血管疾病以及焦虑也在本发明的范围内。
• 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。
• 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：——