N-tert-butoxycarbonyl-β-(R)-hydroxy-D-leucine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-tert-butoxycarbonyl-β-(R)-hydroxy-D-leucine
• 英文别名: (2R,3R)-2-(t-butoxycarbonylamino)-3-hydroxy-4-methylpentanoic acid；(2R*, 3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid；(2R,3R)-3-hydroxy-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid
• 化学式: C₁₁H₂₁NO₅
• 分子量: 247.291
• InChiKey: ISRKGGQOVLQWDW-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-β-(R)-hydroxy-D-leucine 在 盐酸 、 溶剂黄146 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane
  参考文献：
  名称：

  Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.10.084
• 作为产物：
  描述：

  methyl 4-methyl-2-pentenoate 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 、 20 % Pd(OH)2/C 、 titanium(IV) isopropoxide 、 氢气 、 三氧化硫吡啶 、 二异丁基氢化铝 、 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 17.0h， 生成 N-tert-butoxycarbonyl-β-(R)-hydroxy-D-leucine
  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

• Synthesis, Structure-Activity, and Structure-Stability Relationships of 2-Substituted-<i>N</i>-(4-oxo-3-oxetanyl)<i>N</i>-Acylethanolamine Acid Amidase (NAAA) Inhibitors
  作者：Romina Vitale、Giuliana Ottonello、Rita Petracca、Sine Mandrup Bertozzi、Stefano Ponzano、Andrea Armirotti、Anna Berteotti、Mauro Dionisi、Andrea Cavalli、Daniele Piomelli、Tiziano Bandiera、Fabio Bertozzi

  DOI：10.1002/cmdc.201300416

  日期：2014.2

  peroxisome proliferator‐activated receptor‐α (PPAR‐α). Compounds that feature an α‐amino‐β‐lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti‐inflammatory effects that are mediated through FAE‐dependent activation of PPAR‐α. We synthesized and tested a series of racemic, diastereomerically pure β‐substituted α‐amino‐β‐lactones, as either carbamate

  ñ‐酰基乙醇胺酸酰胺酶（NAAA）是一种半胱氨酸酰胺酶，可优先水解饱和或单不饱和脂肪酸乙醇酰胺（FAE），例如棕榈酰乙醇酰胺（PEA）和油酰基乙醇酰胺（OEA），它们是核过氧化物酶体增殖物激活的受体α（ PPAR-α）。具有α-氨基-β-内酯环的化合物已被确认为有效的和选择性的NAAA抑制剂，并显示出通过FAE依赖的PPAR-α激活介导的显着抗炎作用。我们合成并测试了一系列外消旋，非对映体纯的β-取代的α-氨基-β-内酯，分别为氨基甲酸酯或酰胺衍生物，研究了β取代基变化后的结构-活性和结构-稳定性关系（SAR和SSR）。尺寸，α-和β-位的相对立体化学，以及α-氨基官能团。取代的氨基甲酸酯衍生物比酰胺类似物具有更高的活性和稳定性，其中为了稳定性，通常优选顺式构型。β位的空间体积增加会对NAAA抑制力产生负面影响，同时改善化学和血浆稳定性。
• 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。
• 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。
• 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。
• 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。