N-(tert-butoxycarbonyl)-3-imidazol-1-yl-L-alanine | 122225-53-0

• 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)-3-imidazol-1-yl-L-alanine
• 英文别名: N-Boc-3-imidazol-1-yl-Ala；(2S)-3-imidazol-1-yl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 122225-53-0
• 化学式: C₁₁H₁₇N₃O₄
• 分子量: 255.274
• InChiKey: HQKMWDFFFCQCFA-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-3-imidazol-1-yl-L-alanine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 H-3-imidazol-1-yl-L-alanine amide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane
  参考文献：
  名称：

  Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides

  摘要：

  A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.

  DOI：

  10.1021/jm00056a005
• 作为产物：
  描述：

  (S)-α-Boc-氨基-β-丙内酯 、 三甲基硅咪唑 以 乙腈 为溶剂， 以55%的产率得到N-(tert-butoxycarbonyl)-3-imidazol-1-yl-L-alanine
  参考文献：
  名称：

  Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids

  摘要：

  Novel, potent small molecule motilin receptor antagonists are described. These peptidomimetic macrocycles are composed of a tripeptide cyclized backbone-to-backbone with a nonpeptidic tether and bear new unnatural amino acids containing basic side chains. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.043

文献信息

• MACROCYCLIC ANTAGONISTS OF THE MOTILIN RECEPTOR FOR TREATMENT OF GASTROINTESTINAL DYSMOTILITY DISORDERS
  申请人：Marsault Eric

  公开号：US20100093720A1

  公开（公告）日：2010-04-15

  The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.

  本发明提供了与胃动素受体及其亚型、异构体和/或变体结合和/或是功能调节剂的构象定义明确的大环化合物。这些大环化合物至少具有足够的药理特性，可用作治疗一系列疾病指示的治疗药物。特别是，这些化合物对于治疗和预防以高胃动素血症和/或胃肠道高蠕动性为特征的疾病非常有用，包括但不限于腹泻、癌症治疗相关腹泻、癌症诱导腹泻、化疗诱导腹泻、放射性肠炎、放射性腹泻、压力诱导腹泻、慢性腹泻、艾滋病相关腹泻、C. difficile相关腹泻、旅行者腹泻、移植物宿主病引起的腹泻、其他类型的腹泻、消化不良、肠易激综合征、化疗诱导的恶心和呕吐（呕吐）以及术后恶心和呕吐和功能性胃肠道疾病。此外，这些化合物对于治疗以胃或肠道吸收不良为特征的疾病和疾病也具有用途，例如短肠综合征、乳糜泻和虚弱。这些化合物还可用于治疗胃肠道炎症性疾病和疾病，如炎症性肠病、溃疡性结肠炎、克罗恩病和胰腺炎。因此，本发明还提供了治疗此类疾病的方法和包括本发明化合物的药物组合物。
• US9133235B2
  申请人：——

  公开号：US9133235B2

  公开（公告）日：2015-09-15
• [EN] MACROCYCLIC ANTAGONISTS OF THE MOTILIN RECEPTOR FOR TREATMENT OF GASTROINTESTINAL DYSMOTILITY DISORDERS<br/>[FR] ANTAGONISTES MACROCYCLIQUES DU RÉCEPTEUR DE LA MOTILINE POUR LE TRAITEMENT DE TROUBLES DE DYSMOTILITÉ GASTRO-INTESTINALE
  申请人：TRANZYME PHARMA INC

  公开号：WO2008033328A2

  公开（公告）日：2008-03-20

  [EN] The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.
  [FR] La présente invention concerne des composés macrocycliques conformationnellement définis se liant au récepteur de la motiline et/ou constituant des modulateurs fonctionnels dudit récepteur, y compris des sous-types, des isoformes et/ou des variants de ces composés. Lesdits composés macrocycliques possèdent au moins des propriétés pharmacologiques appropriées pour une utilisation comme agents thérapeutiques destinés à diverses maladies. Plus particulièrement, ces composés sont utiles pour traiter et prévenir des troubles caractérisés par une hypermotilinémie et/ou une hypermotilité gastro-intestinale, tels que, entre autres, la diarrhée, la diarrhée associée au traitement du cancer, la diarrhée induite par le cancer, la diarrhée induite par la chimiothérapie, l'entérite radique, la diarrhée induite par les radiations, la diarrhée induite par le stress, la diarrhée chronique, la diarrhée associée au SIDA, la diarrhée associée à C. difficile, la diarrhée des voyageurs, la diarrhée induite par la réaction de greffe contre hôte, d'autres types de diarrhée, la dyspepsie, le syndrome du côlon irritable, la nausée et le vomissement (émèse) induits par la chimiothérapie, ainsi que la nausée et le vomissement post-opératoires et les troubles gastro-intestinaux fonctionnels. En outre, ces composés sont utiles pour traiter des maladies et des troubles caractérisés par une absorption stomacale ou intestinale insuffisante, tels que le syndrome du grêle court, la maladie coeliaque et la cachexie. Lesdits composés sont également utiles pour traiter des maladies et des troubles inflammatoires du tractus gastro-intestinal, tels que l'affection abdominale inflammatoire, la rectocolite hémorragique, la maladie de Crohn et la pancréatite. Par conséquent, la présente invention concerne également des méthodes de traitement de ces troubles et des compositions pharmaceutiques comprenant lesdits composés.
• Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids
  作者：Eric Marsault、Kamel Benakli、Sylvie Beaubien、Carl Saint-Louis、Robert Déziel、Graeme Fraser

  DOI：10.1016/j.bmcl.2007.05.043

  日期：2007.8

  Novel, potent small molecule motilin receptor antagonists are described. These peptidomimetic macrocycles are composed of a tripeptide cyclized backbone-to-backbone with a nonpeptidic tether and bear new unnatural amino acids containing basic side chains. (c) 2007 Elsevier Ltd. All rights reserved.
• Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides
  作者：Saul H. Rosenberg、Kenneth P. Spina、Keith W. Woods、Jim Polakowski、Donald L. Martin、Zhengli Yao、Herman H. Stein、Jerome Cohen、Jennifer L. Barlow

  DOI：10.1021/jm00056a005

  日期：1993.2

  A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.