(3R)-9-benzyl-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione | 1280013-68-4

• 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: (3R)-9-benzyl-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione
• CAS: 1280013-68-4
• 化学式: C₂₆H₃₉N₃O₃
• 分子量: 441.614
• InChiKey: GHYDDSRHCRKPCJ-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-9-benzyl-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione 在 20 % Pd(OH)2/C 、 氢气 、 盐酸 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 生成 (3R)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione
  参考文献：
  名称：

  Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate

  摘要：

  Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.109
• 作为产物：
  描述：

  3-cyclohexylacrylic acid 在 titanium(IV) isopropylate 、 盐酸 、 Jones reagent 、 L-(+)-酒石酸二乙酯 、 过氧化氢异丙苯 、 硫酸 、 20 % Pd(OH)2/C 、 氢气 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 生成 (3R)-9-benzyl-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione
  参考文献：
  名称：

  Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate

  摘要：

  Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.109

文献信息

• Drugs containing triazaspiro[5.5]undecane derivatives as the active ingredient
  申请人：——

  公开号：US20040106619A1

  公开（公告）日：2004-06-03

  A pharmaceutical composition for prevention and/or treatment for HIV infection or AIDS induced by the infection which comprises, as an active ingredient, a triazaspiro[5.5]undecane derivative, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof, and if necessary, it may be combined with at least one member of other agents for prevention and/or treatment for HIV infection (wherein all symbols are as defined in the specification.). 1 The triazaspiro[5.5]undecane derivatives, the quaternary ammonium salts thereof or the N-oxides thereof, or the non-toxic salts thereof are useful in preventing and/or treating HIV infection and AIDS induced by the infection.

  一种用于预防和/或治疗由HIV感染引起的艾滋病的药物组合物，其作为活性成分包括三氮杂螺[5.5]十一烷衍生物、其季铵盐、其N-氧化物或其非毒性盐，如有必要，还可以与其他预防和/或治疗HIV感染的药物组合使用（其中所有符号均如规范中定义） 。1三氮杂螺[5.5]十一烷衍生物、其季铵盐或其N-氧化物，或其非毒性盐在预防和/或治疗HIV感染和由该感染引起的艾滋病中有用。
• DRUGS CONTAINING TRIAZASPIRO 5.5]UNDECANE DERIVATIVES AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1378509A1

  公开（公告）日：2004-01-07

  A pharmaceutical composition for prevention and/or treatment for HIV infection or AIDS induced by the infection which comprises, as an active ingredient, a triazaspiro[5.5]undecane derivative, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof, and if necessary, it may be combined with at least one member of other agents for prevention and/or treatment for HIV infection (wherein all symbols are as defined in the specification.). The triazaspiro[5.5]undecane derivatives, the quatemary ammonium salts thereof or the N-oxides thereof, or the non-toxic salts thereof are useful in preventing and/or treating HIV infection and AIDS induced by the infection.

  一种用于预防和/或治疗HIV感染或由该感染诱发的艾滋病的药物组合物，作为活性成分，它包括一种三氮杂螺[5.5]十一烷衍生物、其季铵盐、其N-氧化物或其无毒盐，必要时，它可与至少一种用于预防和/或治疗HIV感染的其他制剂成员结合使用（其中所有符号如说明书中所定义。） 三氮杂螺[5.5]十一烷衍生物、其藜芦铵盐或其N-氧化物或其无毒盐可用于预防和/或治疗HIV感染和由感染诱发的艾滋病。
• Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient
  申请人：——

  公开号：US20040097511A1

  公开（公告）日：2004-05-20

  Triazaspiro[5.5]undecane derivatives, quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as an active ingredient. 1 So the compounds of the formula (I) regulate the effect of chemokine/chemokine receptor, they are used for prevention and treatment of various inflammatory diseases, asthma, atopic dermatitis, urticaria, allergic diseases, nephritis, nephropathy, hepatitis, arthritis or rheumatoid arthritis etc.

  作为活性成分的三氮杂螺[5.5]十一烷衍生物、其季铵盐、其 N-氧化物、其无毒盐或包含它们的药物组合物。 1 因此，式（I）化合物具有调节趋化因子/趋化因子受体的作用，可用于预防和治疗各种炎症性疾病、哮喘、特应性皮炎、荨麻疹、过敏性疾病、肾炎、肾病、肝炎、关节炎或类风湿性关节炎等。
• Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A highly potent orally available CCR5 selective antagonist
  作者：Rena Nishizawa、Toshihiko Nishiyama、Katsuya Hisaichi、Chiaki Minamoto、Masayuki Murota、Yoshikazu Takaoka、Hisao Nakai、Hideaki Tada、Kenji Sagawa、Shiro Shibayama、Daikichi Fukushima、Kenji Maeda、Hiroaki Mitsuya

  DOI：10.1016/j.bmc.2011.05.022

  日期：2011.7

  Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. (C) 2011 Elsevier Ltd. All rights reserved.
• TRIAZASPIRO 5.5]UNDECANE DERIVATIVES AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1236726B1

  公开（公告）日：2004-12-01