3α-((10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)oxy)-8-methyl-8-azabicyclo[3.2.1]octane

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 3α-((10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)oxy)-8-methyl-8-azabicyclo[3.2.1]octane
• 英文别名: deptropine
• 化学式: C₂₃H₂₇NO
• 分子量: 333.473
• InChiKey: ZWPODSUQWXAZNC-PMOLBWCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.52
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  12.47
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3α-((10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)oxy)-8-methyl-8-azabicyclo[3.2.1]octane 在 potassium permanganate 、 O-(benzotriazol-1-yl )-N,N,N' ,N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 potassium hydroxide 作用下， 以 吡啶 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 1-(3α-((10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)oxy)-8-azabicyclo[3.2.1]octan-8-yl)-2-hydroxy-2-phenylethanone
  参考文献：
  名称：

  Structure-based design, synthesis and structure–activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein

  摘要：

  Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the alpha 7 and alpha 4 beta 2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.008
• 作为产物：
  描述：

  二苯并环庚烯酮基氯 、 3-tropanol 以 甲苯 为溶剂， 生成 3α-((10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)oxy)-8-methyl-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Structure-based design, synthesis and structure–activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein

  摘要：

  Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the alpha 7 and alpha 4 beta 2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.008

文献信息

• SUBSTITUTED INDOLES
  申请人：Gant Thomas G.

  公开号：US20090191183A1

  公开（公告）日：2009-07-30

  Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了Formula I的替代吲哚半胱氨酸白三烯受体调节剂，其制备方法，药物组合物以及使用方法。
• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• [EN] COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'ADMINISTRER DES AGENTS THÉRAPEUTIQUES
  申请人：MODERNATX INC

  公开号：WO2017099823A1

  公开（公告）日：2017-06-15

  This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

  这项披露提供了改进的基于脂质的组合物，包括脂质纳米粒子组合物，以及它们用于体内传递药剂的方法，包括核酸和蛋白质。这些组合物不受加速血清清除的影响，并且它们在体内具有改进的毒性特性。
• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143143A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。