2-甲基-2-丙基5-氨基-2-羟基苯甲酸酯 | 155388-93-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-甲基-2-丙基5-氨基-2-羟基苯甲酸酯
• 英文名称: 5-aminosalicylic acid tert-butyl ester
• 英文别名: tert-butyl 5-aminosalicylate；5-aminosalicylic tert-butyl ester；Tert-butyl 5-amino-2-hydroxybenzoate
• CAS: 155388-93-5
• 化学式: C₁₁H₁₅NO₃
• mdl: MFCD12766677
• 分子量: 209.245
• InChiKey: LLDXDSXJOWWPME-UHFFFAOYSA-N

物化性质

• 熔点：
  49 °C
• 沸点：
  340.0±27.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基5-氨基-2-羟基苯甲酸酯 在 偶氮二甲酸二异丙酯 、 溶剂黄146 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Azo-reductase activated budesodine prodrugs for colon targeting

  摘要：

  Budesodine is a synthetic glurocorticoid that undergoes substantial first pass metabolism, limiting systemic exposure. Its use in treatment of inflammatory bowel disease would benefit from a targeting strategy that could lead to a local topical effect, improving safety and increasing anti-inflammatory efficacy. A two-step prodrug strategy involving azoreduction/cyclization that we developed previously for prednisolone is here applied with some variations to budesonide. The budesodine prodrugs were tested using an in vitro azoreductase assay simulating human colonic microflora. The kinetics of amino steroid ester cyclization and its pH dependence was also evaluated. The stability of the prodrugs systems in simulated human duodenal and gastric fluid was evaluated to determine the likelihood of intact intestinal transit. The propionic acid derived prodrug 3 undergoes rapid activation by Clostridium perfingens and its putative reduction product cyclizes with acceptable rapidity when synthesized independently. These properties of 3 suggest that it has potential in management of ulcerative colitis. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.006
• 作为产物：
  描述：

  5-硝基水杨酸 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 52.0h， 生成 2-甲基-2-丙基5-氨基-2-羟基苯甲酸酯
  参考文献：
  名称：

  Structure-Activity Relationships in a Series of 5-[(2,5-Dihydroxybenzyl)amino]salicylate Inhibitors of EGF-Receptor-Associated Tyrosine Kinase: Importance of Additional Hydrophobic Aromatic Interactions

  摘要：

  Potent inhibitors of EGF-dependent protein tyrosine kinase (PTK) activity were synthesized in a series of 5-[(2,5-dihydroxybenzyl)amino]salicylates. Several of these compounds inhibited EGF-dependent DNA synthesis in ER 22 cells with IC50 < 1 muM. In this series of PTK inhibitors, the role of the salicylate moiety as a potential divalent ion chelator was tested and found to be nonessential in all cases. The length and ramification of the substituting carboxyl group were investigated to improve cellular bioavailability, and this analysis provided compounds with increased inhibitory effect on EGF-induced DNA synthesis. Salicylates esterified with long hydrophobic chains were shown to be noncompetitive inhibitors of ATP, in contrast to the free acid and methyl salicylate. Moreover, all the tested inhibitors were shown to be noncompetitive inhibitors of the peptide substrate. Structure-activity relationships allowed us to suspect a hydrophobic pocket in the tyrosine kinase domain, preferentially interacting with aromatic rings. Finally, the selectivity of the best inhibitors was tested against other kinases, and they were found to be selective for tyrosine kinase. They were also shown to be good inhibitors of EGF-receptor autophosphorylation.

  DOI：

  10.1021/jm00032a020

文献信息

• [EN] TARGETING DIAZO PRODRUGS FOR THE TREATMENT OF GASTROINTESTINAL DISEASES<br/>[FR] CIBLAGE DE PROMÉDICAMENTS DIAZO POUR LE TRAITEMENT DE MALADIES GASTRO-INTESTINALES
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2009003970A1

  公开（公告）日：2009-01-08

  Provided herein are compounds, compositions and methods for decreasing NFkB DNA-binding activity in a patient comprising administering of a therapeutically effective amount of a compound or composition of the application to the patient to reduce, alleviate or treat various gastrointestinal diseases, such as inflammatory bowel disease (IBD).

  本文提供了一种减少患者NFkB DNA结合活性的化合物、组合物和方法，包括向患者施用本申请的化合物或组合物的治疗有效量，以减少、缓解或治疗各种胃肠疾病，如炎症性肠病（IBD）。
• Discovery and structure–activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors
  作者：Hidenobu Murafuji、Hiroki Sakai、Megumi Goto、Seiichi Imajo、Hajime Sugawara、Tsuyoshi Muto

  DOI：10.1016/j.bmcl.2017.10.030

  日期：2017.12

  discovered as a novel human kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme, SCCE) inhibitor, and its derivatives were synthesized and evaluated. Structure–activity relationship studies of the amidoxime unit and benzoic acid part of this new scaffold led to the identification of 25 and 34, which were more potent than the hit compound, 1. The X-ray co-crystal structure of compound 25 and human KLK7

  发现了由1,3,6-三取代的1,4-二氮杂-7-one组成的化合物1作为新型人激肽释放酶7（KLK7，角质层糜蛋白酶，SCCE）抑制剂，并对其衍生物进行合成和评估。对这种新型支架的mid胺肟单元和苯甲酸部分的结构-活性关系的研究导致鉴定出25和34，它们比命中化合物1更有效。化合物25和人KLK7的X射线共晶体结构揭示了特征相互作用，并能解释结构与活性之间的关系。
• Design, Synthesis, and Pharmacological Effects of a Cyclization-Activated Steroid Prodrug for Colon Targeting in Inflammatory Bowel Disease
  作者：Juan F. Márquez Ruiz、Gabor Radics、Henry Windle、Hugo O. Serra、Ana Luísa Simplício、Kinga Kedziora、Padraic G. Fallon、Dermot P. Kelleher、John F. Gilmer

  DOI：10.1021/jm8016317

  日期：2009.5.28

  colon causing severe systemic side effects. We report here on a novel prodrug approach to targeting corticosteroids to the colon. The design involves attaching a 21-ester group that suppresses absorption during transit to the colon. The prodrug is designed to be primed by colonic microflora liberating an amino ester that cyclizes releasing the steroid. One of the prodrugs 5b was as efficacious as prednisolone

  糖皮质激素用于治疗炎性肠病。其使用的限制是它们在到达结肠之前会先从GIT吸收，从而引起严重的全身性副作用。我们在这里报告了一种针对皮质类固醇靶向结肠的新型前药方法。该设计涉及连接一个21酯基团，该基团在转移到结肠的过程中会抑制吸收。前药被设计成通过结肠微生物区系释放，释放出环化释放类固醇的氨基酯。在鼠DSS模型中，前药5b之一与泼尼松龙一样有效，但是没有引起胸腺萎缩，胸腺萎缩是全身性类固醇作用的标志。
• Targeting Prodrugs for the Treatment of Gastrointestinal Diseases
  申请人：Gilmer John Francis

  公开号：US20090082314A1

  公开（公告）日：2009-03-26

  Provided herein are compounds, compositions and methods for decreasing NFκB DNA-binding activity in a patient comprising administering of a therapeutically effective amount of a compound or composition of the application to the patient to reduce, alleviate or treat various gastrointestinal diseases, such as inflammatory bowel disease (IBD).

  本文提供了一种降低患者NFκB DNA结合活性的化合物、组合物和方法，包括将本申请的化合物或组合物以治疗有效量的方式给予患者，以减轻、缓解或治疗各种胃肠道疾病，如炎症性肠病（IBD）。
• 一种JAK激酶抑制剂的前药
  申请人：[en]E-NITIATE BIOPHARMACEUTICALS (HANGZHOU) CO., LTD;[zh]启元生物（杭州）有限公司

  公开号：WO2024041586A1

  公开（公告）日：2024-02-29

  本发明涉及含JAK抑制剂的前药、组合物及其应用。特别地，本发明涉及式 (II) 所示的化合物、含有本发明化合物的药物组合物，及其作为JAK抑制剂前药在治疗炎症性疾病和肿瘤相关疾病中的用途。