4-(4-(((S)-1-butyl-3-((S)-cyclohexyl(hydroxy)methyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl)methyl)phenoxy)benzoic acid hydrochloride

• 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: 4-(4-(((S)-1-butyl-3-((S)-cyclohexyl(hydroxy)methyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl)methyl)phenoxy)benzoic acid hydrochloride
• 英文别名: 4-[4-[[(3S)-1-butyl-3-[(S)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid
• 化学式: C₃₃H₄₃N₃O₆
• 分子量: 577.721
• InChiKey: GWNOTCOIYUNTQP-VMPREFPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-(((S)-1-butyl-3-((S)-cyclohexyl(hydroxy)methyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl)methyl)phenoxy)benzoic acid hydrochloride 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 4-[4-(((3S)-1-butyl-3-[(R)-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 、 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 L-(+)-酒石酸二乙酯 、 过氧化氢异丙苯 、 硫酸 、 20 % Pd(OH)2/C 、 氢气 、 三氧化硫吡啶 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 溶剂黄146 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 4-(4-(((S)-1-butyl-3-((S)-cyclohexyl(hydroxy)methyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-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

文献信息

• Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient
  申请人：——

  公开号：US20040082584A1

  公开（公告）日：2004-04-29

  Triazaspiro[5.5]undecane derivatives of the formula (I), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as active ingredients (wherein R 1 is formula (II) or formula (III); R 2 is alkyl or alkynyl etc.; R 3 , R 4 is H, (substituted) alkyl etc., or R 3 and R 4 together to form formula (IV); R 5 is H or alkyl). 1 Therefore 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.

  化合物的公式（I）是Triazaspiro[5.5]十一烷衍生物，其季铵盐，N-氧化物，非毒性盐，或以其为活性成分的制药组合物（其中R1是公式（II）或公式（III）; R2是烷基或烷炔基等; R3，R4是H，（取代）烷基等，或R3和R4一起形成公式（IV）; R5是H或烷基）。因此，公式（I）的化合物调节趋化因子/趋化因子受体的作用，它们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 derivative and pharmaceutical composition comprising the same as active ingredient
  申请人：Habashita Hiromu

  公开号：US20050215557A1

  公开（公告）日：2005-09-29

  Triazaspiro[5.5]undecane derivatives of the formula (I), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as active ingredients (wherein R 1 is formula (II) or formula (III); R 2 is alkyl or alkynyl etc.; R 3 , R 4 is H, (substituted) alkyl etc., or R 3 and R 4 together to form formula (IV); R 5 is H or alkyl). Therefore 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.

  公式（I）的Triazaspiro [5.5] undecane衍生物，其季铵盐，N-氧化物，非毒性盐或包含它们的制药组合物作为活性成分（其中R1是公式（II）或公式（III）; R2是烷基或烷炔基等; R3，R4是H，（取代）烷基等，或R3和R4一起形成公式（IV）; R5是H或烷基）。因此，公式（I）的化合物调节趋化因子/趋化因子受体的效应，它们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：EP1378510A1

  公开（公告）日：2004-01-07

  Triazaspiro[5.5]undecane derivatives of the formula (I), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as active ingredients (wherein R1 is formula (II) or formula (III); R2 is alkyl or alkynyl etc.; R3, R4 is H, (substituted) alkyl etc., or R3 and R4 together to form formula (IV); R5 is H or alkyl). Therefore 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.

  作为活性成分的式(I)的三氮杂螺[5.5]十一烷衍生物、其季铵盐、其N-氧化物、其无毒盐或由其组成的药物组合物（其中R1为式(II)或式(III)；R2为烷基或炔基等；R3、R4为H、（取代的）烷基等，或R3和R4共同组成式(IV)；R5为H或烷基）。 因此，式（I）化合物可调节趋化因子/趋化因子受体的作用，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。
• 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 pharmaceutical composition comprising the same as active ingredient
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1619194A2

  公开（公告）日：2006-01-25

  Triazaspiro[5.5]undecane derivatives of the formula (I), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as active ingredients (wherein R1 is formula (II) or formula (III); R2 is alkyl or alkynyl etc.; R3, R4 is H, (substituted) alkyl etc., or R3 and R4 together to form formula (IV); R5 is H or alkyl). Therefore 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.

  作为活性成分的式(I)的三氮杂螺[5.5]十一烷衍生物、其季铵盐、其N-氧化物、其无毒盐或由其组成的药物组合物（其中R1为式(II)或式(III)；R2为烷基或炔基等；R3、R4为H、（取代的）烷基等，或R3和R4共同组成式(IV)；R5为H或烷基）。 因此，式（I）化合物可调节趋化因子/趋化因子受体的作用，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。