(3R)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione | 1280013-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: (3R)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione
• CAS: 1280013-74-2
• 化学式: C₁₉H₃₃N₃O₃
• 分子量: 351.489
• InChiKey: PXMLKFYDCZDVBK-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  81.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione 在 盐酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-(((3R)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl)methyl)phenoxy]benzoic acid hydrochloride
  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)-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 COMPRISING COMBINATION OF TRIAZASPIRO 5,5 U NDECANE DERIVATIVE WITH CYTOCHROME P450 ISOZYME 3A4 INHIBITOR AND/OR P−GLYCOPROTEIN INHIBITOR
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1438962A1

  公开（公告）日：2004-07-21

  A pharmaceutical composition which comprises a combination of a triazaspiro[5.5]undecane derivative of the formula (I): (wherein all the symbols have the same meanings as defined hereinafter), a quaternary ammonium salt thereof, or an N-oxide thereof, or a non-toxic salt thereof with at least one cytochrome P450 isozyme 3A4 inhibitor and/or at least one P-glycoprotein inhibitor. As a result the pharmaceutical composition comprising the above-described combination, bioavailability of the compound of the formula (I) is enhanced and is able to be effectively utilized as an oral agent in the treatment of various diseases.

  一种药物组合物，它由式（I）的三氮杂螺[5.5]十一烷衍生物、其季铵盐、或其 N-氧化物、或其无毒盐与至少一种抗氧化剂结合而成： (其中所有符号的含义与下文所定义的相同）、其季铵盐或其 N-氧化物或其无毒盐与至少一种细胞色素 P450 同工酶 3A4 抑制剂和/或至少一种 P 糖蛋白抑制剂的组合。因此，由上述组合物组成的药物组合物可提高式（I）化合物的生物利用度，并能有效地用作治疗各种疾病的口服药物。
• 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。
• 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
• US7119091B2
  申请人：——

  公开号：US7119091B2

  公开（公告）日：2006-10-10
• US7285552B2
  申请人：——

  公开号：US7285552B2

  公开（公告）日：2007-10-23