(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-phenylmethyl-1,4,9-triazaspiro[5.5]undecane | 676449-46-0

• 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)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-phenylmethyl-1,4,9-triazaspiro[5.5]undecane
• 英文别名: (3R)-1-Butyl-2,5-dioxo-3-[(1R)-1-hydroxy-1-cyclohexylmethyl]-9-benzyl-1,4,9-triazaspiro[5.5]undecane methanesulfonate；(3R)-9-benzyl-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione
• CAS: 676449-46-0
• 化学式: C₂₆H₃₉N₃O₃
• 分子量: 441.614
• InChiKey: GHYDDSRHCRKPCJ-DHIUTWEWSA-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)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-phenylmethyl-1,4,9-triazaspiro[5.5]undecane 生成 (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride
  参考文献：
  名称：

  Triazaspiro[5.5]undecane derivative and pharmaceutical composition comprising the same as active ingredient

  摘要：

  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为公式（II）或公式（III）; R2为烷基或炔基等; R3，R4为H，（取代的）烷基等，或R3和R4结合形成公式（IV）; R5为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。

  公开号：

  US07262193B2
• 作为产物：
  描述：

  3-cyclohexylacrylic acid 在 叔丁基过氧化氢 、 sodium hypochlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 D-(-)-酒石酸二乙酯 、 硫酸 、 20 % Pd(OH)2/C 、 titanium(IV) isopropoxide 、 氢气 、 三氧化硫吡啶 、 二异丁基氢化铝 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正辛烷 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 34.0h， 生成 (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-phenylmethyl-1,4,9-triazaspiro[5.5]undecane
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.05.022

文献信息

• 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。
• 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。
• EP1541574
  申请人：——

  公开号：——

  公开（公告）日：——
• Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite
  作者：Rena Nishizawa、Toshihiko Nishiyama、Katsuya Hisaichi、Naoki Matsunaga、Chiaki Minamoto、Hiromu Habashita、Yoshikazu Takaoka、Masaaki Toda、Shiro Shibayama、Hideaki Tada、Kenji Sagawa、Daikichi Fukushima、Kenji Maeda、Hiroaki Mitsuya

  DOI：10.1016/j.bmcl.2006.10.084

  日期：2007.2

  Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from beta-substituted (2R,3R)-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1 alpha to human CCR5, compared with the non-hydroxylated derivatives and the other isomers. (c) 2006 Elsevier Ltd. All rights reserved.
• EP1541573
  申请人：——

  公开号：——

  公开（公告）日：——