1-tert-butoxycarbonyl-4-hydroxymethylimidazole | 120277-88-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-tert-butoxycarbonyl-4-hydroxymethylimidazole
• 英文别名: tert-butyl 5-(hydroxymethyl)-1H-imidazole-1-carboxylate；t-butyl 5-hydroxymethylimidazole-1-carboxylate；1,1-dimethylethyl 5-(hydroxymethyl)-1H-imidazole-1-carboxylate；tert-butyl 5-(hydroxymethyl)imidazole-1-carboxylate
• CAS: 120277-88-5
• 化学式: C₉H₁₄N₂O₃
• 分子量: 198.222
• InChiKey: ZXWOZMITYKMVLN-UHFFFAOYSA-N

物化性质

• 沸点：
  336.5±34.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-tert-butoxycarbonyl-4-hydroxymethylimidazole 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 tert-butyl 5-((5S,8R,11R)-8,11-dibenzyl-5-isopropyl-1-(2-isopropylthiazol-4-yl)-2-methyl -3,6,13-trioxo-14-oxa-2,4,7,12-tetraazapentadecan-15-yl)-1H-imidazole-1-carboxylate
  参考文献：
  名称：

  Pyridine-Substituted Desoxyritonavir Is a More Potent Inhibitor of Cytochrome P450 3A4 than Ritonavir

  摘要：

  Utilization of the cytochrome P450 3A4 (CYP3A4) inhibitor ritonavir as a pharmacoenhancer for anti-HIV drugs revolutionized the treatment of HIV infection. However, owing to ritonavir-related complications, there is a need for development of new CYP3A4 inhibitors with improved pharmacochemical properties, which requires a full understanding of the CYP3A4 inactivation mechanisms and the unraveling of possible inhibitor binding modes. We investigated the mechanism of CYP3A4 interaction with three desoxyritonavir analogues, containing the heme-ligating imidazole, oxazole, or pyridine group instead of the thiazole moiety (compounds 1, 2, and 3, respectively). Our data show that compound 3 is superior to ritonavir in terms of binding affinity and inhibitory potency owing to greater flexibility and the ability to adopt a conformation that minimizes steric clashing and optimizes protein-ligand interactions. Additionally, Ser119 was identified as a key residue assisting binding of ritonavir-like inhibitors, which emphasizes the importance of polar interactions in the CYP3A4-ligand association.

  DOI：

  10.1021/jm400288z
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 4-羟甲基咪唑盐酸盐 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到1-tert-butoxycarbonyl-4-hydroxymethylimidazole
  参考文献：
  名称：

  Design and Synthesis of Peptidomimetic Protein Farnesyltransferase Inhibitors as Anti-Trypanosoma brucei Agents

  摘要：

  On the basis of the structure of the CVIM tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against Trypanosoma brucel protein farnesyltransferase (TbPFT) was evaluated. Peptidomimetics where the 5-position of the imidazole ring was linked to the hydrophobic scaffold showed over 70% inhibition activity at 50 nM in the enzyme assay, whereas the corresponding C-4 regioisomers were less potent. The ester prodrug 23 was found to be a potent inhibitor against cultured Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense cells with ED50 values of 0.025 and 0.0026 muM, respectively. Furthermore introducing a second imidazole group into 23 led to 31, which showed the highest inhibition activity against the parasite with an ED50 of 0.0015 muM. The potency of the TbPFT inhibitors and the cytotoxicity of the corresponding esters to T. brucei cells were shown to be highly correlated. These studies validate TbPFT as a target for the development of novel therapeutics against African sleeping sickness.

  DOI：

  10.1021/jm030236o

文献信息

• Chemical Compounds
  申请人：Turnbull Philip Stewart

  公开号：US20090170907A1

  公开（公告）日：2009-07-02

  This invention relates to non-steroidal compounds that are modulators of androgen, glucocorticoid, mineralocorticoid, and progesterone receptors, and also to the methods for the making and use of such compounds.

  这项发明涉及非甾体化合物，它们是雄激素、糖皮质激素、矿质皮质激素和孕激素受体的调节剂，以及这些化合物的制备和使用方法。
• NUCLEAR TRANSPORT MODULATORS AND USES THEREOF
  申请人：Shacham Sharon

  公开号：US20110275607A1

  公开（公告）日：2011-11-10

  The invention generally relates to the field of nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to new substituted-heterocyclic azole compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, pulmonary fibrosis, hepatic fibrosis, glomerulonephritis, and other renal disorders, and for the treatment of viral infections (both acute and chronic).

  本发明通常涉及核运输调节剂领域，例如CRM1抑制剂，更具体地涉及新的取代杂环唑类化合物，这些化合物的合成和使用以及它们的制药组合物，例如在治疗、调节和/或预防与CRM1活性相关的生理状况方面的用途，例如治疗癌症和其他肿瘤性疾病、炎症性疾病、异常组织生长和纤维化疾病，包括心肌病、肺纤维化、肝纤维化、肾小球肾炎和其他肾脏疾病，以及治疗病毒感染（急性和慢性）。
• Therapeutic preparations
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0284174A1

  公开（公告）日：1988-09-28

  The invention concerns pharmaceutical compositions containing a 1,2-dihydro-3H-indazol-3-one derivative of the formula I wherein Ra is hydrogen, halogeno, nitro, hydroxy, (2-6C)alkanoyloxy, (1-6C)alkyl, (1-6C)alkoxy, fluoro-(1-4C)alkyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-4C)alkyl]amino, (2-6C)alkanoylamino or hydroxy-­(1-6C)alkyl; Rb is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy; and Y is a group of the formula -A¹-X-A²-Q in which A¹ is (1-6C)alkylene, (3-6C)alkenylene, (3-6C)alkynylene or cyclo(3-6C)alkylene, or A¹ is phenylene; X is oxy, thio, sulphinyl, sulphonyl, imino, (1-­6C)alkylimino, (1-6C)alkanoylimino, iminocarbonyl or phenylene, or X is a direct link to A²; A² is (1-6C)alkylene, (3-6C)alkenylene or (3-­6C)alkynylene or A² is cyclo(3-6C)alkylene or is a direct link to Q, or the group A¹-X-A² is a direct link to Q; or Y is (2-10)alkyl, (3-­10C)alkenyl or (3-6C)alkynyl; and Q is aryl or heteroaryl. The invention also provides novel 1,2-dihydro-3H-indazol-3-­ones, processes for their production and the use of 1,2-dihydro-3H-­indazol-3-one for the manufacture of medicaments for the treatment of various allergic and inflammatory diseases.

  本发明涉及含有式 I 的 1,2-二氢-3H-吲唑-3-酮衍生物的药物组合物 其中Ra是氢、卤素、硝基、羟基、(2-6C)烷酰氧基、(1-6C)烷基、(1-6C)烷氧基、氟-(1-4C)烷基、(2-6C)烷酰基、氨基、(1-6C)烷基氨基、二[(1-4C)烷基]氨基、(2-6C)烷酰氨基或羟基-(1-6C)烷基；Rb 是氢、卤素、(1-6C)烷基或 (1-6C)烷氧基；以及 Y 是式 -A¹-X-A²-Q 的基团，其中 A¹ 是 (1-6C)亚烷基、(3-6C)烯基、(3-6C)炔基或环(3-6C)亚烷基，或 A¹ 是亚苯基；X 是氧基、硫代、亚砜基、磺酰基、亚氨基、(1-6C)烷基亚氨基、(1-6C)烷酰亚氨基、亚氨基羰基或亚苯基，或 X 是与 A² 的直接连接；A²是(1-6C)亚烷基、(3-6C)亚烯基或(3-6C)亚炔基，或A²是环(3-6C)亚烷基，或与Q直接相连，或基团A¹-X-A²与Q直接相连；或Y是(2-10)烷基、(3-10C)亚烯基或(3-6C)亚炔基；且Q是芳基或杂芳基。 本发明还提供了新型 1,2-二氢-3H-吲唑-3-酮、其生产工艺以及 1,2-二氢-3H-吲唑-3-酮用于制造治疗各种过敏性和炎症性疾病的药物。
• NOVEL CYCLIC DEPSIPEPTIDE PF1022 DERIVATIVES
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP0903347A1

  公开（公告）日：1999-03-24

  Novel derivatives of PF1022 substance, which are cyclodepsipeptides represented by the general formula (I) shown below or their salts are useful as anthelmintic agent for prevention or treatment of parasitic infections.

  PF1022 物质的新型衍生物是由下图所示通式 (I) 表示的环十二肽或其盐类，可用作预防或治疗寄生虫感染的驱虫药。
• [EN] NUCLEAR TRANSPORT MODULATIORS AND USES THEREOF<br/>[FR] MODULATEURS DE TRANSPORT NUCLÉAIRE ET LEURS UTILISATIONS
  申请人：KARYOPHARM THERAPEUTICS INC

  公开号：WO2011109799A8

  公开（公告）日：2011-12-22