(2-{[(2S)-3-(5-chloro-1'H,3H-spiro[1-benzofuran-2,4'-piperidin]-1'-yl)-2-hydroxypropyl]oxy}-4-fluorophenyl)methanesulfonic acid | 1050595-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (2-{[(2S)-3-(5-chloro-1'H,3H-spiro[1-benzofuran-2,4'-piperidin]-1'-yl)-2-hydroxypropyl]oxy}-4-fluorophenyl)methanesulfonic acid
• 英文别名: [2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-4-fluorophenyl]methanesulfonic acid
• CAS: 1050595-98-6
• 化学式: C₂₂H₂₅ClFNO₆S
• 分子量: 485.961
• InChiKey: VWXDIOCVQHZYHB-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-羟基-4-氟苯甲醇 在 四氯化碳 、 caesium carbonate 、 三苯基膦 、 sodium sulfite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.0h， 生成 (2-{[(2S)-3-(5-chloro-1'H,3H-spiro[1-benzofuran-2,4'-piperidin]-1'-yl)-2-hydroxypropyl]oxy}-4-fluorophenyl)methanesulfonic acid
  参考文献：
  名称：

  WO2008/103126

  摘要：

  公开号：

文献信息

• New Combination 665
  申请人：Cadogan Elaine Bridget

  公开号：US20080242649A1

  公开（公告）日：2008-10-02

  The invention provides a pharmaceutical product comprising a first active ingredient which is N—[2-(Diethylamino)ethyl]-N-(2-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-naphthyl)ethoxy]propanamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DP1 antagonist; an Histone Deacetylase Inducer; an IKK2 inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; an MPO inhibitor; a muscarinic antagonist which is Aclidinium bromide, Glycopyrrolate, Oxitropium bromide, Pirenzepine, telenzepine, Tiotropium bromide, 3(R)—(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide, 3(R)—1-phenethyl-3-(9H-xanthene-9-carbonyloxy)-1-azoniabicyclo[2.2.2]octane bromide or (3R)—3-[(2S)—2-cyclopentyl-2-hydroxy-2-thien-2-ylacetoxy]-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]actane bromide; a p38 inhibitor; a PDE inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

  本发明提供了一种药物产品，其中包括第一活性成分，该成分为N-[2-(二乙氨基)乙基]-N-(2-[2-(4-羟基-2-氧代-2,3-二氢-1,3-苯并噻唑-7-基)乙基]氨基}乙基)-3-[2-(1-萘基)乙氧基]丙酰胺或其盐，并且包括第二活性成分，所述第二活性成分选自：非类固醇糖皮质激素受体（GR受体）激动剂；抗氧化剂；CCR1拮抗剂；趋化因子拮抗剂（非CCR1）；皮质类固醇；CRTh2拮抗剂；DP1拮抗剂；组蛋白去乙酰化酶诱导剂；IKK2抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MPO抑制剂；Aclidinium溴化物、Glycopyrrolate、Oxitropium溴化物、Pirenzepine、telenzepine、Tiotropium溴化物、3(R)-（2-羟基-2,2-二硫基-2-乙酰氧基）-1-(3-苯氧基丙基)-1-氮杂双环[2.2.2]辛烷溴化物、3(R)-1-苯乙基-3-(9H-黄酮-9-羧酰氧基)-1-氮杂双环[2.2.2]辛烷溴化物或（3R）-3-[(2S)-2-环戊基-2-羟基-2-噻唑基乙氧基]-1-(2-苯氧基乙基)-1-氮杂双环[2.2.2]辛烷溴化物；p38抑制剂；PDE抑制剂；PPARγ激动剂；蛋白酶抑制剂；他汀类药物；血栓素拮抗剂；血管扩张剂；或ENAC阻滞剂（上皮钠通道阻滞剂），以及其在呼吸系统疾病治疗中的应用。
• Combinations of Beta-2-Adrenoceptor Agonistic Benzothiazolone
  申请人：Cadogan Elaine Bridget

  公开号：US20100029732A1

  公开（公告）日：2010-02-04

  The invention provides a pharmaceutical product comprising a first active ingredient which is N-[2-(Diethylamino)ethyl]-N-(2-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-naphthyl)ethoxy]propan amide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor)=Agonist; an antioxidant; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DP1 antagonist; an Histone Deacetylase Inducer; an IKK2 inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; an MPO inhibitor; a muscarinic antagonist which is Aclidinium bromide, Glycopyrrolate, Oxitropium bromide, Pirenzepine, telenzepine, Tiotropium bromide, 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azo-niabicyclo[2.2.2]octane bromide, 3(R)- 1 -phenethyl-3-(9H-xanthene-9-carbonyloxy)-1-azoniabicyclo[2.2.2]octane bromide or (3R)-3-[(2S)-2-cyclopentyl-2-hydroxy-2-thien-2-ylacetoxy]-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]actane bromide; a p38 inhibitor; a PDE inhibitor; a PPARy agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

  该发明提供了一种药物产品，包括第一活性成分为N-[2-(二乙氨基)乙基]-N-(2-[2-(4-羟基-2-氧代-2,3-二氢-1,3-苯并噻唑-7-基)乙基]氨基}乙基)-3-[2-(1-萘基)乙氧基]丙酰胺或其盐，和第二活性成分从以下中选择：非甾体型糖皮质激素受体（GR受体）=激动剂；抗氧化剂；CCR1拮抗剂；趋化因子拮抗剂（非CCR1）；类固醇；CRTh2拮抗剂；DP1拮抗剂；组蛋白去乙酰化酶诱导剂；IKK2抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MPO抑制剂；Aclidinium溴化物，Glycopyrrolate，Oxitropium溴化物，Pirenzepine，telenzepine，Tiotropium溴化物，3(R)-(2-羟基-2,2-二噻吩-2-乙氧基)-1-(3-苯氧基丙基)-1-氮杂双环[2.2.2]辛烷溴化物，3(R)-1-苯乙基-3-(9H-黄酮-9-羰基氧基)-1-氮杂双环[2.2.2]辛烷溴化物或(3R)-3-[(2S)-2-环戊基-2-羟基-2-噻吩-2-乙氧基]-1-(2-苯氧基乙基)-1-氮杂双环[2.2.2]辛烷溴化物；p38抑制剂；PDE抑制剂；PPARy激动剂；蛋白酶抑制剂；他汀类药物；血栓素受体拮抗剂；血管扩张剂；或ENAC阻滞剂（上皮钠通道阻滞剂），以及其在呼吸道疾病治疗中的应用。
• COMBINATION 408
  申请人：Connolly Stephen

  公开号：US20100144606A1

  公开（公告）日：2010-06-10

  The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclohexyl-N 3 -[2-(3-fluorophenyl)ethyl]-N-(2-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-β-alaninamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DP1 antagonist; an Histone Deacetylase Inducer; an IKK2 inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; an MPO inhibitor; a muscarinic antagonist; a p38 inhibitor; a PDE inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease (for example chronic obstructive pulmonary disease (COPD) or asthma); to certain salts of N-Cyclohexyl-N 3 -[2-(3-fluorophenyl)ethyl]-N-(2-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-β-alaninamide and to an intermediate useful in the manufacture of this pharmaceutically active substance and salts thereof.

  本发明提供了一种药物产品、试剂盒或组合物，包括第一活性成分，该成分为N-环己基-N3-[2-(3-氟苯基)乙基]-N-(2-[2-(4-羟基-2-氧代-2,3-二氢-1,3-苯并噻唑-7-基)乙基]氨基}乙基)-β-丙氨酰胺或其盐，以及第二活性成分，所述第二活性成分选自：非类固醇糖皮质激素受体（GR受体）激动剂；抗氧化剂；CCR1拮抗剂；趋化因子拮抗剂（不包括CCR1）；皮质类固醇；CRTh2拮抗剂；DP1拮抗剂；组蛋白脱乙酰化酶诱导剂；IKK2抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MPO抑制剂；毒蕈碱受体拮抗剂；p38抑制剂；PDE抑制剂；PPARγ激动剂；蛋白酶抑制剂；他汀类药物；血栓素受体拮抗剂；血管扩张剂；或者ENAC阻滞剂（上皮钠通道阻滞剂）。该药物产品、试剂盒或组合物用于治疗呼吸系统疾病（例如慢性阻塞性肺疾病（COPD）或哮喘），以及N-环己基-N3-[2-(3-氟苯基)乙基]-N-(2-[2-(4-羟基-2-氧代-2,3-二氢-1,3-苯并噻唑-7-基)乙基]氨基}乙基)-β-丙氨酰胺的某些盐和用于制造该药物活性物质及其盐的中间体。
• 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。
• Combination of beta-adrenoceptor agonist and corticosteroid
  申请人：AstraZeneca AB

  公开号：EP2364704A1

  公开（公告）日：2011-09-14

  The invention provides a pharmaceutical product comprising a first active ingredient which is N-[2-(Diethylamino)ethyl]-N-(2-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-naphthyl)ethoxy]propanamide or a salt thereof, and a second active ingredient which is a corticosteroid.

  本发明提供了一种药物产品，其第一种活性成分是 N-[2-(二乙基氨基)乙基]-N-(2-[2-(4-羟基-2-氧代-2,3-二氢-1,3-苯并噻唑-7-基)乙基]氨基}乙基)-3-[2-(1-萘基)乙氧基]丙酰胺或其盐，第二种活性成分是皮质类固醇。