1'-benzyl-4-(2-methoxyethoxy)-4'-methyl-[1,4']bipiperidinyl | 470690-01-8

• 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: 1'-benzyl-4-(2-methoxyethoxy)-4'-methyl-[1,4']bipiperidinyl
• 英文别名: 8-(1-Benzyl-4-methyl-piperidin-4-yl)-1,4-dioxa-8-aza-spiro[4.5]decane；8-(1-benzyl-4-methylpiperidin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• CAS: 470690-01-8
• 化学式: C₂₀H₃₀N₂O₂
• 分子量: 330.47
• InChiKey: PWQVPTZORSSXPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1'-benzyl-4-(2-methoxyethoxy)-4'-methyl-[1,4']bipiperidinyl 在 palladium dihydroxide 盐酸 、 甲酸铵 、 三乙酰氧基硼氢化钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.25h， 生成 (2,6-dimethyl-phenyl)-(4'-methyl-4-phenylamino-[1,4']bipiperidinyl-1'-yl)-methanone
  参考文献：
  名称：

  Orally Bioavailable Competitive CCR5 Antagonists

  摘要：

  The chemokine receptor CCR5 plays an important role in inflammatory and autoimmune disorders as well as in transplant rejection by affecting the trafficking of effector T cells and monocytes to diseased tissues. Antagonists of CCR5 are believed to be of potential therapeutic value for the disorders mentioned above and HIV infection. Here we report on the structure-activity relationship of a new series of highly potent and selective competitive CCR5 antagonists. While all compounds tested were inactive on rodent CCR5, this series includes compounds that cross-react with the cynomolgus monkey (cyno) receptor. One of these compounds, i.e., 26n, has good PK properties in cynos, and its overall favorable profile makes it a promising candidate for in vivo profiling in transplantation and other disease models.

  DOI：

  10.1021/jm031046g
• 作为产物：
  描述：

  4-哌啶酮缩乙二醇 在 titanium(IV) isopropylate 作用下， 以 四氢呋喃 、 乙醚 、 1,2-二氯乙烷 为溶剂， 反应 35.0h， 生成 1'-benzyl-4-(2-methoxyethoxy)-4'-methyl-[1,4']bipiperidinyl
  参考文献：
  名称：

  Orally Bioavailable Competitive CCR5 Antagonists

  摘要：

  The chemokine receptor CCR5 plays an important role in inflammatory and autoimmune disorders as well as in transplant rejection by affecting the trafficking of effector T cells and monocytes to diseased tissues. Antagonists of CCR5 are believed to be of potential therapeutic value for the disorders mentioned above and HIV infection. Here we report on the structure-activity relationship of a new series of highly potent and selective competitive CCR5 antagonists. While all compounds tested were inactive on rodent CCR5, this series includes compounds that cross-react with the cynomolgus monkey (cyno) receptor. One of these compounds, i.e., 26n, has good PK properties in cynos, and its overall favorable profile makes it a promising candidate for in vivo profiling in transplantation and other disease models.

  DOI：

  10.1021/jm031046g

文献信息

• [EN] BIPIPERIDINYL-DERIVATIVES AND THEIR USE AS CHEMOKINE RECEPTORS INHIBITORS<br/>[FR] DERIVES BIPIPERIDINYLE ET LEUR UTILISATION COMME INHIBITEURS DES RECEPTEURS DE CHEMOKINE
  申请人：NOVARTIS AG

  公开号：WO2002081449A1

  公开（公告）日：2002-10-17

  Piperidine derivatives of formula (I) as disclosed in the specification have interesting pharmaceutical properties e.g. as CCR5 inhibitors.

  规范中披露的式（I）的哌啶衍生物具有有趣的药理特性，例如作为CCR5抑制剂。
• Triazaspiro[5.5]undecane derivatives and drugs comprising the same as the active ingredient
  申请人：Takaoka Yoshikazu

  公开号：US20050267114A1

  公开（公告）日：2005-12-01

  Compounds represented by formula (I) (wherein all of the symbols have the same meanings as defined in specification.), quaternary ammonium salts thereof, N-oxides thereof or salts thereof. The compounds represented by formula (I) are used for prevention and/or treatment of various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, chronic rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis and the like), immunologic diseases (autoimmune diseases, transplant rejection, immunosuppression, psoriasis, multiple sclerosis and the like), human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, nettle rash, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis and the like), ischemia-reperfusion injury, acute respiratory distress syndrome, shock accompanied by bacterial infection, diabetes mellitus, or metastasis and the like.

  化合物的化学式为(I)（其中所有符号的含义与规范中定义的相同），以及其季铵盐、N-氧化物或盐。式(I)所代表的化合物用于预防和/或治疗各种炎症性疾病（哮喘、肾炎、肾病、肝炎、关节炎、慢性类风湿性关节炎、鼻炎、结膜炎、溃疡性结肠炎等）、免疫性疾病（自身免疫疾病、移植排斥、免疫抑制、银屑病、多发性硬化症等）、人类免疫缺陷病毒（获得性免疫缺陷综合症等）、过敏性疾病（特应性皮炎、荨麻疹、过敏性支气管肺曲霉病、过敏性嗜酸性胃肠炎等）、缺血再灌注损伤、急性呼吸窘迫综合症、伴有细菌感染的休克、糖尿病或转移等。
• Bipiperidinyl-derivatives and their use as chemokine receptors inhibitors
  申请人：——

  公开号：US20040142920A1

  公开（公告）日：2004-07-22

  Piperidine derivatives of formula (I) as disclosed in the specification have interesting pharmaceutical properties e.g. as CCR5 inhibitors.

  在说明书中公开的式(I)的吡啶衍生物具有有趣的药理特性，例如作为CCR5抑制剂。
• Piperdine Derivatives as CCR5 Inhibitors
  申请人：ALBERT Rainer

  公开号：US20080249111A1

  公开（公告）日：2008-10-09

  Disclosed are compounds of formula I: wherein R 1 , R 2 , R 3 and X are as defined herein, in free or salt form, which are useful as CCR5 inhibitors, e.g. in the prevention or treatment of disorders mediated by interactions between chemokine receptors and their ligands.

  揭示了式I的化合物：其中R1、R2、R3和X如此定义，以自由或盐形式存在，它们可用作CCR5抑制剂，例如在预防或治疗由趋化因子受体与其配体之间相互作用介导的疾病中。
• TRIAZASPIRO 5.5 UNDECANE DERIVATIVES AND DRUGS COMPRISI NG THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1541574A1

  公开（公告）日：2005-06-15

  Compounds represented by formula (I) (wherein all of the symbols have the same meanings as defined in specification.), quaternary ammonium salts thereof, N-oxides thereof or salts thereof. The compounds represented by formula (I) are used for prevention and/or treatment of various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, chronic rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis and the like), immunologic diseases (autoimmune diseases, transplant rejection, immunosuppression, psoriasis, multiple sclerosis and the like), human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, nettle rash, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis and the like), ischemia-reperfusion injury, acute respiratory distress syndrome, shock accompanied by bacterial infection, diabetes mellitus, or metastasis and the like.

  式 (I) 所代表的化合物（其中所有符号的含义与说明书中的定义相同。 (其中所有符号的含义与说明书中定义的相同）、其季铵盐、其 N-氧化物或其盐。式 (I) 所代表的化合物可用于预防和/或治疗各种炎症性疾病（哮喘、肾炎、肾病、肝炎、关节炎、慢性类风湿性关节炎、鼻炎、结膜炎、溃疡性结肠炎等）、免疫性疾病（自身免疫性疾病、移植排斥、免疫抑制、牛皮癣、多发性硬化等）、人类免疫缺陷病毒（获得性免疫缺陷综合征等）、过敏性疾病（特应性皮炎、荨麻疹、过敏性支气管肺曲霉病、过敏性嗜酸性粒细胞性胃肠炎等）、缺血再灌注损伤、急性呼吸窘迫综合征、细菌感染引起的休克、糖尿病或转移等。