(S)-8-叔-丁基3-乙基2,8-二氮杂螺[4.5]癸烷-3,8-二甲酸基酯 | 1259039-30-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-8-叔-丁基3-乙基2,8-二氮杂螺[4.5]癸烷-3,8-二甲酸基酯
• 英文名称: (3S)-8-tert-butyl 3-ethyl 2,8-diazaspiro[4.5]decane-3,8-dicarboxylate
• 英文别名: 8-(tert-butyl) 3-ethyl (S)-2,8-diazaspiro[4.5]decane-3,8-dicarboxylate；8-tert-butyl 3-ethyl 2,8-diazaspiro[4.5]decane-3,8-dicarboxylate；8-tert-butyl 3-ethyl (3S)-2,8-diazaspiro[4.5]decane-3,8-dicarboxylate；(S)-8-tert-butyl 3-ethyl 2,8-diazaspiro[4.5]decane-3,8-dicarboxylate；8-O-tert-butyl 3-O-ethyl (3S)-2,8-diazaspiro[4.5]decane-3,8-dicarboxylate
• CAS: 1259039-30-9
• 化学式: C₁₆H₂₈N₂O₄
• 分子量: 312.409
• InChiKey: WXRWBESBLVCYGR-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-8-叔-丁基3-乙基2,8-二氮杂螺[4.5]癸烷-3,8-二甲酸基酯 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 lithium hydroxide monohydrate 、 5%-palladium/activated carbon 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 potassium hydrogencarbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 180.0h， 生成 (3S)-8-(2-amino-6-((1R)-2,2,2-trifluoro-1-(4-(((1,1,1,3,3,3-hexafluoro-2-methylpropan-2-yl)oxy)carbonyl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
  参考文献：
  名称：

  [EN] SPIROCYCLIC COMPOUNDS AS TRYPTOPHAN HYDROXYLASE INHIBITORS
  [FR] COMPOSÉS SPIROCYCLIQUES EN TANT QU'INHIBITEURS DE LA TRYPTOPHANE HYDROXYLASE

  摘要：

  本发明涉及一种螺环化合物，它们是色氨酸羟化酶（TPH）的抑制剂，特别是异构体1（TPH1），可用于治疗与外周血清素相关的疾病或紊乱，例如胃肠道、心血管、肺部、炎症、代谢和低骨密度疾病，以及血清素综合征和癌症。

  公开号：

  WO2015035113A1
• 作为产物：
  描述：

  2,8-二氮杂螺[4.5]癸烷-3,8-二甲酸8-叔-丁酯3-乙酯 在 sodium carbonate 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 正庚烷 、 水 为溶剂， 反应 1.75h， 生成 (S)-8-叔-丁基3-乙基2,8-二氮杂螺[4.5]癸烷-3,8-二甲酸基酯
  参考文献：
  名称：

  [EN] RESOLUTION OF OPTICALLY ACTIVE DIAZASPIRO[4.5]DECANE DERIVATIVES
  [FR] RÉSOLUTION DE DÉRIVÉS DE DIAZASPIRO [4,5] DÉCANE OPTIQUEMENT ACTIFS

  摘要：

  本发明涉及一种用于制备螺环化合物的二氮杂螺[4.5]癸烷中间体及其盐，该化合物是色氨酸羟化酶（TPH）的抑制剂，特别是TPH1。本发明还提供了制备中间体及其盐的方法。

  公开号：

  WO2018087602A1

文献信息

• COMPOUND HAVING SPIRO-BONDED CYCLIC GROUP AND USE THEREOF
  申请人：Yoshida Koji

  公开号：US20120101280A1

  公开（公告）日：2012-04-26

  The invention relates to a compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification). The compound of the present invention exhibits very low risk of side effects and also has persistent and strong antagonistic activity against CXCR4, and is therefore useful as pharmaceuticals, for example, preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or an agent for regeneration therapy.

  本发明涉及一种由式(I)表示的化合物：其盐，其N-氧化物或其溶剂化物（式中的符号如说明书所述）。本发明的化合物表现出极低的副作用风险，并且对CXCR4具有持久且强烈的拮抗活性，因此可用作药物，例如，预防和/或治疗炎症和免疫性疾病，感染（例如，HIV感染），与HIV感染相关的疾病（例如，获得性免疫缺陷综合症（艾滋病）），癌症，癌症转移，心理神经疾病和心血管疾病（例如，视网膜病），代谢性疾病，癌症性疾病或再生疗法的药剂。
• Compound having spiro-bonded cyclic group and use thereof
  申请人：Yoshida Koji

  公开号：US08476290B2

  公开（公告）日：2013-07-02

  A compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification). The compounds of the present invention exhibit very low risk of side effects and also have persistent and strong antagonistic activity against CXCR4, and are therefore useful as pharmaceuticals, for example, as a preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or as an agent for regeneration therapy.

  化合物式为（I）的化合物：其盐，其N-氧化物或其溶剂合物（式中符号如说明书所述）。本发明的化合物表现出非常低的副作用风险，同时具有持久且强烈的CXCR4拮抗活性，因此可作为药物使用，例如，作为预防和/或治疗炎症和免疫性疾病、感染（例如，HIV感染）、与HIV感染相关的疾病（例如，获得性免疫缺陷综合症（AIDS））、癌症、癌症转移、精神神经疾病和心血管疾病（例如，视网膜病变）、代谢性疾病、癌症疾病或作为再生治疗剂。
• SPIROCYCLIC COMPOUNDS AS TRYPTOPHAN HYDROXYLASE INHIBITORS
  申请人：Karos Pharmaceuticals, Inc.

  公开号：US20150080393A1

  公开（公告）日：2015-03-19

  The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.

  本发明涉及螺环化合物，它们是色氨酸羟化酶（TPH）的抑制剂，特别是isoform 1（TPH1），可用于治疗与外周血清素相关的疾病或疾病，例如胃肠道、心血管、肺部、炎症、代谢和低骨量疾病，以及血清素综合症和癌症。
• Spirocyclic compounds as tryptophan hydroxylase inhibitors
  申请人：Karos Pharmaceuticals, Inc.

  公开号：US09199994B2

  公开（公告）日：2015-12-01

  The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.

  本发明涉及螺环化合物，其是色氨酸羟化酶（TPH）的抑制剂，特别是isoform 1（TPH1），可用于治疗与外周血清素相关的疾病或疾病，例如胃肠道，心血管，肺部，炎症，代谢和低骨量疾病，以及血清素综合征和癌症。
• Discovery of spirocyclic proline tryptophan hydroxylase-1 inhibitors
  作者：Daniel R. Goldberg、Stéphane De Lombaert、Robert Aiello、Patricia Bourassa、Nicole Barucci、Qing Zhang、Vishwas Paralkar、James Valentine、William Zavadoski

  DOI：10.1016/j.bmcl.2016.01.064

  日期：2016.2

  The central role of the biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter with important cognitive and behavioral functions is well known. However, 5-HT produced in the brain only accounts for approximately 5% of the total amount of 5-HT generated in the body. At the onset of our work, it appeared that substituted phenylalanine derivatives or related aryl amino acids were required to produce potent inhibitors of TPH1, as significant losses of inhibitory activity were noted in the absence of this structural element. We disclose herein the discovery of a new class of TPH1 inhibitors that significantly lower peripherally 5-HT. (C) 2016 Elsevier Ltd. All rights reserved.