ethyl 4-(2-bromophenylamino)-4-cyano-1-piperidinecarboxylate | 240486-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 4-(2-bromophenylamino)-4-cyano-1-piperidinecarboxylate
• 英文别名: ethyl 4-[(2-bromophenyl)amino]-4-cyanopiperidine-1-carboxylate；ethyl 4-(2-bromoanilino)-4-cyanopiperidine-1-carboxylate
• CAS: 240486-10-6
• 化学式: C₁₅H₁₈BrN₃O₂
• 分子量: 352.231
• InChiKey: CPEBJKLCUQANRU-UHFFFAOYSA-N

物化性质

• 沸点：
  496.9±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(2-bromophenylamino)-4-cyano-1-piperidinecarboxylate 在 氧气 盐酸 、 三乙基硼 、 水 、 三正丁基氢锡 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 84.0h， 生成 N-(2-{[(2S)-3-({spiro[indole-2-4'-piperidin]-3(1H)-one}-1'-yl)-2-hydroxypropyl]oxy}-4-hydroxyphenyl)acetamide
  参考文献：
  名称：

  WO2008/103126

  摘要：

  公开号：
• 作为产物：
  描述：

  三甲基氰硅烷 、 N-乙氧羰基-4-哌啶酮 、 2-溴苯胺 以 溶剂黄146 为溶剂， 反应 112.0h， 以94%的产率得到ethyl 4-(2-bromophenylamino)-4-cyano-1-piperidinecarboxylate
  参考文献：
  名称：

  Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization

  摘要：

  Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R-2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R-2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2e and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.

  DOI：

  10.1021/jo970105t

文献信息

• Novel Combination of Compounds to be Used in the Treatment of Airway Diseases, Especially Chronic Obstructive Pulmonary Disease (COPD) and Asthma
  申请人：Eriksson Tomas

  公开号：US20110124613A1

  公开（公告）日：2011-05-26

  The present invention provides a pharmaceutical product comprising, in combination of, (a) a (therapeutically effective) dose of a first active ingredient, which is a compound of formula (I) or a pharmaceutically acceptable salt thereof; and (b) a (therapeutically effective) dose of a second active ingredient, which is a glucocorticoid receptor agonist; and optionally, (c) a (therapeutically effective) dose of a third active ingredient, which is a β 2 -agonist. The invention further relates to pharmaceutical compositions comprising said combination and to methods of treating treatment of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma in mammals by administrating said combination. The invention further relates to a kit comprising the combination and use of said kit in treatment of airway diseases such as COPD and asthma.

  本发明提供一种药物产品，其中包括以下组合物：(a)第一活性成分的(治疗有效)剂量，该成分是公式(I)的化合物或其药学上可接受的盐；和(b)第二活性成分的(治疗有效)剂量，该成分是糖皮质激素受体激动剂；可选的，(c)第三活性成分的(治疗有效)剂量，该成分是β2-激动剂。本发明还涉及包含该组合物的药物组合物以及通过给予该组合物治疗哺乳动物的呼吸道疾病，特别是慢性阻塞性肺疾病(COPD)和哮喘的方法。本发明还涉及一种包含该组合物的工具包以及在治疗COPD和哮喘等呼吸道疾病中使用该工具包的用途。
• NOVEL COMBINATION OF COMPOUNDS TO BE USED IN THE TREATMENT OF AIRWAY DISEASES, ESPECIALLY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ASTHMA
  申请人：AstraZeneca AB

  公开号：EP2120935A1

  公开（公告）日：2009-11-25
• [EN] NOVEL COMBINATION OF COMPOUNDS TO BE USED IN THE TREATMENT OF AIRWAY DISEASES, ESPECIALLY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ASTHMA<br/>[FR] NOUVELLE COMBINAISON DE COMPOSÉS UTILISÉS DANS LE TRAITEMENT DES MALADIES DES VOIES AÉRIENNES, EN PARTICULIER LA BRONCHOPNEUMOPATHIE CHRONIQUE OBSTRUCTIVE (COPD) ET L'ASTHME
  申请人：ASTRAZENECA AB

  公开号：WO2008103126A1

  公开（公告）日：2008-08-28

  [EN] The present invention provides a pharmaceutical product comprising, in combination of, (a) a (therapeutically effective) dose of a first active ingredient, which is a compound of formula (I) or a pharmaceutically acceptable salt thereof; and (b) a (therapeutically effective) dose of a second active ingredient, which is a glucocorticoid receptor agonist; and optionally, (c) a (therapeutically effective) dose of a third active ingredient, which is a ß₂-agonist. The invention further relates to pharmaceutical compositions comprising said combination and to methods of treating treatment of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma in mammals by administrating said combination. The invention further relates to a kit comprising the combination and use of said kit in treatment of airway diseases such as COPD and asthma.
  [FR] La présente invention concerne un produit pharmaceutique combinant (a) une dose thérapeutiquement efficace d'un premier ingrédient actif qui est un composé représenté par la formule (I) ou un sel pharmaceutiquement acceptable de celui-ci; et (b) une dose thérapeutiquement efficace d'un deuxième ingrédient actif qui est un agoniste du récepteur des glucocorticoïdes, et éventuellement (c) une dose thérapeutiquement efficace d'un troisième ingrédient actif qui est un agoniste ß₂. L'invention concerne également des compositions pharmaceutiques contenant ladite combinaison et des méthodes de traitement des maladies des voies aériennes, en particulier la bronchopneumopathie chronique obstructive (COPD) et l'asthme, chez des mammifères par administration de ladite combinaison. L'invention concerne également un kit contenant ladite combinaison et l'utilisation dudit kit dans le traitement des maladies des voies aériennes telles que la bronchopneumopathie chronique obstructive (COPD) et l'asthme.
• WO2008/103126
  申请人：——

  公开号：——

  公开（公告）日：——
• Conformational Switching and the Synthesis of Spiro[2<i>H</i>-indol]-3(1<i>H</i>)-ones by Radical Cyclization
  作者：Richard Sulsky、Jack Z. Gougoutas、John DiMarco、Scott A. Biller

  DOI：10.1021/jo970105t

  日期：1999.7.1

  Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R-2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R-2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2e and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.