5,6-diethylindan-1,2-dione 2-oxime | 312753-52-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5,6-diethylindan-1,2-dione 2-oxime
• 英文别名: 5,6-Diethyl-indan-1,2-dione 2-oxime；5,6-diethyl-2-hydroxyimino-3H-inden-1-one
• CAS: 312753-52-9
• 化学式: C₁₃H₁₅NO₂
• 分子量: 217.268
• InChiKey: YIJFICBDKBCFAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-diethylindan-1,2-dione 2-oxime 在 硫酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 19.0~22.0 ℃ 、400.01 kPa 条件下， 反应 48.0h， 生成 2-氨基-5,6-二乙基茚烷
  参考文献：
  名称：

  The Identification of Indacaterol as an Ultralong-Acting Inhaled β₂-Adrenoceptor Agonist

  摘要：

  Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.

  DOI：

  10.1021/jm100068m
• 作为产物：
  描述：

  5,6-diethylindan-1-one 生成 5,6-diethylindan-1,2-dione 2-oxime
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING 5-'(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL!-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALT, USEFUL AS AN ADRENOCEPTOR AGONIST
  [FR] PROCEDE DE PREPARATION D'UN SEL DE 5-[(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE, UTILISE EN TANT QU'AGONISTE D'UN ADRENO-RECEPTEUR

  摘要：

  一种制备5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮盐的方法。该方法涉及形成5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-取代氧基-(1H)-喹啉-2-酮（V）的酸盐，并将酸盐转化为5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮（VI）的盐，而无需分离5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮的自由碱。公式（A）；（V）：R = 保护基，（VI）：R = H。

  公开号：

  WO2004076422A1

文献信息

• [EN] BETA2-ADRENOCEPTOR AGONISTS<br/>[FR] AGONISTES DU RECEPTEUR BETA 2-ADRENERGIQUE
  申请人：NOVARTIS AG

  公开号：WO2000075114A1

  公开（公告）日：2000-12-14

  Compounds of formula (I) in free or salt or solvate form, where Ar is a group of formula (II) Y is carbon or nitrogen and R?1, R2, R3, R4, R5, R6, R7, R8, R9, R10¿, X, n, p, q and r are as defined in the specification, their preparation and their use as pharmaceuticals, particularly for the treatment of obstructive or inflammatory airways diseases. The compounds of formula (I) in free, salt or solvate form, have β2-adrenoreceptor agonist activity.

  公式（I）的化合物，其自由形式、盐形式或溶剂化合物形式中，其中Ar是公式（II）的基团，Y是碳或氮，R?1，R2，R3，R4，R5，R6，R7，R8，R9，R10，X，n，p，q和r如规范所定义，它们的制备以及它们作为药物的用途，特别是用于治疗阻塞性或炎性呼吸道疾病。公式（I）的化合物在自由、盐或溶剂化合物形式中具有β2-肾上腺素受体激动剂活性。
• [EN] PROCESS FOR PREPARING 5-'(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL!-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALT, USEFUL AS AN ADRENOCEPTOR AGONIST<br/>[FR] PROCEDE DE PREPARATION D'UN SEL DE 5-[(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE, UTILISE EN TANT QU'AGONISTE D'UN ADRENO-RECEPTEUR
  申请人：NOVARTIS AG

  公开号：WO2004076422A1

  公开（公告）日：2004-09-10

  A process for preparing 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one salt. The process involves forming an acid salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-substituted oxy-(1 H)-quinolin-2-one (V); and converting the acid salt to a salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one (VI) without isolating the free base of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one. Formula (A); (V): R = a protecting group, (VI): R = H.

  一种制备5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮盐的方法。该方法涉及形成5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-取代氧基-(1H)-喹啉-2-酮（V）的酸盐，并将酸盐转化为5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮（VI）的盐，而无需分离5-[(R)-2-(5,6-二乙基-茚-2-基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮的自由碱。公式（A）；（V）：R = 保护基，（VI）：R = H。
• Mixtures or Organic Compounds for the Treatment of Airway Diseases
  申请人：Cuenoud Bernard

  公开号：US20120108555A1

  公开（公告）日：2012-05-03

  A medicament comprising, separately or together, (A) a compound of formula (I) in free or pharmaceutically acceptable salt or solvate form and (B) a corticosteroid, for simultaneous, sequential or separate administration in the treatment of an inflammatory or obstructive airways disease, the molar ratio of (A) to (B) being from 100:1 to 1:300.

  一种药物，包括（A）式（I）的化合物，以自由或药学上可接受的盐或溶剂形式分别或共同使用，以及（B）皮质类固醇，用于治疗炎症或阻塞性呼吸道疾病的同时、顺序或分别给药，（A）与（B）的摩尔比为100：1至1：300。
• The Identification of Indacaterol as an Ultralong-Acting Inhaled β₂-Adrenoceptor Agonist
  作者：François Baur、David Beattie、David Beer、David Bentley、Michelle Bradley、Ian Bruce、Steven J. Charlton、Bernard Cuenoud、Roland Ernst、Robin A. Fairhurst、Bernard Faller、David Farr、Thomas Keller、John R. Fozard、Joe Fullerton、Sheila Garman、Julia Hatto、Claire Hayden、Handan He、Colin Howes、Diana Janus、Zhengjin Jiang、Christine Lewis、Frederique Loeuillet-Ritzler、Heinz Moser、John Reilly、Alan Steward、David Sykes、Lauren Tedaldi、Alexandre Trifilieff、Morris Tweed、Simon Watson、Elke Wissler、Daniel Wyss

  DOI：10.1021/jm100068m

  日期：2010.5.13

  Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.