Lu 23-086 | 106516-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: Lu 23-086
• 英文别名: 1-[2-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-2-imidazolidinone；des-chloro sertindole；1-(4'-Fluorophenyl)-3-(1-(2-imidazolidinon-1-ylethyl)-4-piperidyl)-1H-indole；1-(4-Fluorophenyl)-3-[1-[2-(2-oxo-1-imidazolidinyl)ethyl]-4-piperidinyl]-1H-indole；1-[2-[4-[1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]imidazolidin-2-one
• CAS: 106516-21-6
• 化学式: C₂₄H₂₇FN₄O
• 分子量: 406.503
• InChiKey: QPOLRENOYJQNEP-UHFFFAOYSA-N

物化性质

• 沸点：
  569.3±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Lu 23-086 在 sodium cyanoborohydride 、 溶剂黄146 、 三氟乙酸 作用下， 生成 1-(2-{4-[1-(4-Fluoro-phenyl)-2,3-dihydro-1H-indol-3-yl]-piperidin-1-yl}-ethyl)-imidazolidin-2-one
  参考文献：
  名称：

  Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches

  摘要：

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00196-3
• 作为产物：
  描述：

  对溴氟苯 在 platinum on activated charcoal 盐酸 、 copper bronze 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 、 potassium iodide 、 copper(I) bromide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 Lu 23-086
  参考文献：
  名称：

  Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches

  摘要：

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00196-3

文献信息

• Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles
  作者：Jens Perregaard、Joern Arnt、Klaus P. Boegesoe、John Hyttel、Connie Sanchez

  DOI：10.1021/jm00084a014

  日期：1992.3

  antagonism. Piperazinyl and tetrahydropyridyl indoles were cataleptogenic, while piperidyl substituted indoles surprisingly were found to be noncataleptogenic or only weakly cataleptogenic. Noncataleptogenic piperidyl derivatives also failed to block dopaminergic-mediated stereotypies, that is methyl phenidate-induced gnawing behavior in mice. These profiles resemble that of the atypical neuroleptic clozapine

  合成了一系列在3-位被1-哌嗪基，1,2,3,6-四氢-4-吡啶基和4-哌啶基取代的1-（4-氟苯基）-1H-吲哚。在所有三个亚系列中，在配体结合研究中发现了有效的多巴胺D-2和5-羟色胺5-HT2受体亲和力。作为对中枢5-HT 2受体拮抗作用的量度，大多数衍生物抑制了奎帕嗪诱导的大鼠头部抽搐。哌嗪基和四氢吡啶基吲哚是致肽原的，而哌啶基取代的吲哚令人惊讶地被发现是非致肽原的或仅是弱致肽原的。非致死因的哌啶基衍生物也未能阻止多巴胺能介导的定型观念，即哌醋甲酯诱导的小鼠行为。这些特征类似于非典型的精神抑制药氯氮平的特征。为了避免僵直，发现1-乙基-2-咪唑啉酮是碱性氮原子的最佳取代基。非典型的抗精神病药1- [2- [4- [5-氯-1-（4-氟苯基）-1H-吲哚-3-基] -1-哌啶基]乙基] -2-咪唑啉酮（sertindole，化合物14c）为这些结构/活性研究的结果，选择了进一步开发。
• Identification and synthesis of impurities formed during sertindole preparation
  作者：I V Sunil Kumar、G S R Anjaneyulu、V Hima Bindu

  DOI：10.3762/bjoc.7.5

  日期：——

  Sertindole (1), an atypical anti-psychotic drug is used for the treatment of schizophrenia. During the laboratory optimization and later during its bulk synthesis the formation of various impurities was observed. The impurities formed were monitored and their structures were tentatively assigned on the basis of their fragmentation patterns in LC-MS. Most of the impurities were synthesized and their assigned constitutions confirmed by co-injection in HPLC. We describe herein the formation, synthesis and characterization of these impurities. Our study will be of immense help to others to obtain chemically pure sertindole.

  Sertindole（1），一种非典型抗精神病药物，用于治疗精神分裂症。在实验室优化和后来的批量合成过程中，观察到了各种杂质的形成。这些杂质的形成得到了监测，并根据它们在LC-MS中的碎片图谱初步确定了它们的结构。大多数杂质已经合成，并通过HPLC共注射确认了它们的构成。我们在此描述了这些杂质的形成、合成和表征。我们的研究将对他人获得化学纯净的Sertindole有巨大的帮助。
• Veronica plant named ‘Allvjewel’
  申请人：van den Hoogen Wilhelmus T. J.

  公开号：USPP034299P2

  公开（公告）日：2022-06-07

  A new and distinct cultivar of Veronica plant named ‘Allvjewel’, characterized by its upright plant habit with relatively long stems; dark green-colored leaves; freely flowering habit; dense and relatively long inflorescences with numerous white-colored flowers; and good performance as a garden plant and as a cut flower.

  一种新的、独特的婆婆纳花品种，命名为“Allvjewel”，其特征为：直立的植株习性，相对较长的茎；深绿色的叶子；自由开花的习性；密集而相对较长的花序，有许多白色的花朵；在花园植物和切花方面表现良好。
• 1-(4'-fluorophenyl)-3,5-substituted indoles useful in the treatment of
  申请人：H. Lundbeck A/S

  公开号：US04710500A1

  公开（公告）日：1987-12-01

  The present invention relates to novel indole derivatives which have interesting pharmacodynamic effects indicating pronounced activity in the treatment of psychic disorders, especially psychoses and, at the same time, a low degree of undesired side effects. Moreover, the invention relates to methods for the preparation of said indole derivatives, pharmaceutical compositions containing same, and methods for the treatment of psychic disorders, especially psychoses, by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings. The novel indole derivatives of the present invention are represented by the following formula: ##STR1## wherein R is phenyl, optionally substituted with halogen, lower alkyl or trifluoromethyl, or a hetero aromatic group, such as 2-thienyl, 3-thienyl, 2-furoyl, 3-furoyl, 2-thiazol, 2-oxazol, 2-imidazole, 2-pyridyl, 3-pyridyl or 4-pyridyl; R.sup.1 is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, lower alkylthio, trifluoromethyl, lower alkylsulfonyl, amino, lower alkylamino or lower di-alkylamino; "A" is nitrogen or carbon, and the dotted line indicates--when A is carbon--an optional bond; R.sup.2 is hydrogen, cycloalkyl, lower alkyl or lower alkenyl, optionally substituted with one or two hydroxy groups, any hydroxy group present being optionally esterified with an aliphatic carboxylic acid radical having from two to twenty-four carbon atoms inclusive, or R.sup.2 is the group ##STR2## wherein "n" is an integer of 2-6; X is oxygen or sulfur, or >C.dbd.X may constitute the group >CH.dbd. when Y is .dbd.N-- or .dbd.CH--; Y is oxygen, sulfur, CH.sub.2 or N R.sup.3, where R.sup.3 is hydrogen or lower alkyl, lower alkenyl or a cycloalkylmethyl group, said "cycloalkyl" having from three to six carbon atoms inclusive; Z is --(CH.sub.2).sub.m --, "m" being 2 or 3, or Z is --CH.dbd.CH-- or 1,2-phenylene optionally substituted with halogen or trifluoromethyl, or Z is --CO(or S)CH.sub.2 --; U is nitrogen or carbon, provided that when R.sup.1 is chloro, A is nitrogen and R.sup.2 is methyl or cyclohexyl, R may not be phenyl; as well as their pharmaceutically acceptable acid addition salts.

  本发明涉及新型吲哚衍生物，具有有趣的药效学效果，表明其在治疗精神障碍，特别是精神病方面具有显著的活性，同时副作用较低。此外，本发明还涉及制备所述吲哚衍生物的方法，含有相同成分的药物组合物以及通过向生物体，包括人类，给予所述衍生物的治疗有效量的方法来治疗精神障碍，特别是精神病。本发明的新型吲哚衍生物由以下公式表示：##STR1##其中R是苯基，可选地被卤素，低烷基或三氟甲基取代，或者是杂芳基，例如2-噻吩基，3-噻吩基，2-呋喃酰基，3-呋喃酰基，2-噻唑基，2-噁唑基，2-咪唑基，2-吡啶基，3-吡啶基或4-吡啶基；R.sup.1是氢，卤素，低烷基，低烷氧基，羟基，氰基，硝基，低烷基硫基，三氟甲基，低烷基磺酰基，氨基，低烷基氨基或低二烷基氨基；“A”是氮或碳，虚线表示--当A是碳时--可选键；R.sup.2是氢，环烷基，低烷基或低烯基，可选地取代一个或两个羟基，任何存在的羟基可选择酯化为具有从2到24个碳原子的脂肪族羧酸基，或者R.sup.2是以下基团##STR2##其中“n”是2-6的整数；X是氧或硫，或>C.dbd.X可以构成>CH.dbd.当Y是.dbd.N--或.dbd.CH--时；Y是氧，硫，CH.sub.2或NR.sup.3，其中R.sup.3是氢或低烷基，低烯基或环烷基甲基基团，所述“环烷基”具有三到六个碳原子；Z是--(CH.sub.2).sub.m --，“m”为2或3，或Z是--CH.dbd.CH--或1,2-苯基可选地被卤素或三氟甲基取代，或Z是--CO（或S）CH.sub.2--；U是氮或碳，条件是当R.sup.1是氯，A是氮，R.sup.2是甲基或环己基时，R可能不是苯基；以及它们的药物可接受的酸盐。
• [EN] TREATMENT OF ADDICTION TO DRUGS AND SUBSTANCES OF ABUSE
  申请人：H. LUNDBECK A/S

  公开号：WO1992015302A1

  公开（公告）日：1992-09-17

  (EN) 1-Aryl-3-(4-piperidyl)-indole derivatives having general formula (I), wherein R1 is hydrogen, halogen, alkyl, alkoxy, hydroxy, cyano, nitro, alkylthio, trifluoromethyl, trifluoromethylthio, alkylsulfonyl, amino, alkylamino or dialkylamino; R is optionally substituted phenyl or a heteroaromatic group; and R2 is hydrogen, cycloalkyl, alkyl or alkenyl, optionally substituted with one or two hydroxy groups, or R2 is a group of formula (IV), wherein n is an integer of from 2-6; W is O, S or N-R3, wherein R3 is H, alkyl or cycloalkyl; U is N or CH, Z is -(CH2)m-, m being 2 or 3, or Z is -CH=CH-, 1,2-phenylene, or -COCH2- or -CSCH2-; V is O, S, CH2, or NR4, wherein R4 is hydrogen, optionally hydroxy substituted alkyl, alkenyl or cycloalkylmethyl; are useful in alleviating, relieving or suppressing withdrawal or abstinence symptoms or suppressing the dependency of a drug or a substance of abuse.(FR) On décrit des dérivés de 1-aryl-3-(4-pipéridyl)-indole de formule générale (I) dans laquelle R1 représente hydrogène, halogène, alkyle, alcoxy, hydroxy, cyano, nitro, alkylthio, trifluorométhyle, trifluorométhylthio, alkylsulfonyle, amino, alkylamino ou dialkylamino; R représente éventuellement phényle substitué ou un groupe hétéroaromatique; et R2 représente hydrogène, cycloalkyle, alkyle ou alcényle, éventuellement substitués par un ou deux groupes hydroxy, ou bien R2 représente un groupe de formule (IV) dans laquelle n est un nombre entier compris entre 2 et 6; W est O, S ou N-R3, où R3 représente H, alkyle ou cycloalkyle, U représente N ou CH; Z est -(CH2)m-, m étant 2 ou 3, ou bien Z représente -CH=CH-, 1,2-phénylène, ou -COCH2- ou -CSCH2-; V est O, S, CH2, ou NR4, où R4 est hydrogène, alkyle, alcényle ou cycloalkylméthyle éventuellement substitués par hydroxy. Lesdits dérivés sont utiles pour atténuer, calmer ou supprimer les symptômes de retrait ou d'abstinence, ou pour supprimer la dépendance d'une drogue ou d'une substance toxique.

  具有通用式(I)的1-aryl-3-(4-piperidyl)-indole衍生物，其中R₁表示氢、卤素、烷基、羟基、羟基、羰基、硝基、烷基硫基、 trifluoromethyl、trifluoromethyl硫基、烷基硫酸基、氨基、烷基氨基或二甲基氨基；R可为可选取代的苯基或杂环基团；R₂为氢、环烷基、烷基或烯基，可被一个或两个羟基取代，或有公式(IV)的R₂，其中n为2至6之间的整数；W为O、S或N-R3，其中R3为H、烷基或环烷基；U为N或CH；Z为-(CH2)m-，m为2或3，或为-CH=CH-、1,2-苯二烯-、-CO -或-C S -；V为O、S、CH₂或NR4，其中R4为氢或可被羟基取代的烷基、烯基或环烷基甲基。这些衍生物可用于减轻、缓解或抑制Withdrawal、放走或放弃症状、减弱或抑制依赖性药物或珍稀物质。