[t-butoxycarbonylimino-(4-but-3-ynyl-piperazin-1-yl)methyl]carbamic acid t-butyl ester | 1243153-81-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [t-butoxycarbonylimino-(4-but-3-ynyl-piperazin-1-yl)methyl]carbamic acid t-butyl ester
• 英文别名: [tert-butoxycarbonylimino-(4-but-3-ynyl-piperazin-1-yl)-methyl]-carbamic acid tert-butyl ester；tert-butyl (NZ)-N-[(4-but-3-ynylpiperazin-1-yl)-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate
• CAS: 1243153-81-2
• 化学式: C₁₉H₃₂N₄O₄
• 分子量: 380.487
• InChiKey: WJSAIIDIJFORAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  83.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(azidoacetyl)-L-phenylalanine methyl ester 、 [t-butoxycarbonylimino-(4-but-3-ynyl-piperazin-1-yl)methyl]carbamic acid t-butyl ester 在 copper diacetate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 48.0h， 以65%的产率得到methyl (3S)-3-[[2-[4-[2-[4-[(Z)-N,N'-bis[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]piperazin-1-yl]ethyl]triazol-1-yl]acetyl]amino]-3-phenylpropanoate
  参考文献：
  名称：

  Click-Chemistry-Derived Triazole Ligands of Arginine−Glycine−Aspartate (RGD) Integrins with a Broad Capacity To Inhibit Adhesion of Melanoma Cells and Both in Vitro and in Vivo Angiogenesis

  摘要：

  A click chemistry approach was applied for the discovery of triazole-based arginine-glycine-aspartate (RGD) mimetics by Cu(1)-catalyzed 1,3-dipolar alkyne azide coupling reaction, which showed binding all properties toward alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed compound 18 capable of binding alpha(v)beta(3) integrin with nanomolar affinity according, to a two-sites model, and molecular modeling studies revealed a peculiar pi-stacking interaction between the triazole ring and Tyr178 side chain. Accordingly, compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to RGD-containing proteins of the extracellular matrix, such as vitronectin, fibronectin, and osteopontin. and also angiogenesis in in vitro and in vivo experimental models. The relevant biological effects exerted by compound 18 suggest its potential application as an antiangiogenic agent in the diagnosis and therapy of tumors where alpha(v)beta(3) integrin expression is up-regulated.

  DOI：

  10.1021/jm100754z
• 作为产物：
  描述：

  tert-butyl 4-(but-3-yn-1-yl)piperazine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 [t-butoxycarbonylimino-(4-but-3-ynyl-piperazin-1-yl)methyl]carbamic acid t-butyl ester
  参考文献：
  名称：

  [EN] 1,2,3-TRIAZOLE-BASED PEPTIDOMIMETIC INTEGRIN INHIBITORS FOR THE DIAGNOSIS AND THERAPY OF TUMORS
  [FR] INHIBITEURS PEPTIDOMIMÉTIQUES DE L'INTÉGRINE À BASE DE 1,2,3 TRIAZOLE POUR LE DIAGNOSTIC ET LE TRAITEMENT DE TUMEURS

  摘要：

  本发明涉及具有1,2,3-三唑环的化合物领域，其化学式为(I)，并具有胍基和羧基或其同系物，通过Cu催化的“点击化学”制备，用于在血管生成受损的病理情况中的医疗诊断用途，例如肿瘤来源的病理条件、肿瘤转移、骨质疏松症和类风湿性关节炎。

  公开号：

  WO2011098603A1

文献信息

• [EN] 1,2,3-TRIAZOLE-BASED PEPTIDOMIMETIC INTEGRIN INHIBITORS FOR THE DIAGNOSIS AND THERAPY OF TUMORS<br/>[FR] INHIBITEURS PEPTIDOMIMÉTIQUES DE L'INTÉGRINE À BASE DE 1,2,3 TRIAZOLE POUR LE DIAGNOSTIC ET LE TRAITEMENT DE TUMEURS
  申请人：UNIV FIRENZE

  公开号：WO2011098603A1

  公开（公告）日：2011-08-18

  The present invention refers to the field of chemical compounds bearing a 1,2,3-triazole ring of formula (I) and possessing guanidino and carboxylic groups or their isosteres, their preparation by Cu-catalyzed "click-chemistry", and medical - diagnostic use in pathologies where angiogenesis is altered, for example pathologic conditions of tumor origin, tumor metastasis, osteoporosis, and rheumatoid arthritis.

  本发明涉及具有1,2,3-三唑环的化合物领域，其化学式为(I)，并具有胍基和羧基或其同系物，通过Cu催化的“点击化学”制备，用于在血管生成受损的病理情况中的医疗诊断用途，例如肿瘤来源的病理条件、肿瘤转移、骨质疏松症和类风湿性关节炎。
• Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors
  作者：Andrea Trabocchi、Nicolino Pala、Ilga Krimmelbein、Gloria Menchi、Antonio Guarna、Mario Sechi、Tobias Dreker、Andrea Scozzafava、Claudiu T. Supuran、Fabrizio Carta

  DOI：10.3109/14756366.2014.947976

  日期：2015.5.4

  The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyses the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Creutzfeldt-Jacob's disease and cancer. In this study, we report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the beta-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study.
• US8809338B2
  申请人：——

  公开号：US8809338B2

  公开（公告）日：2014-08-19
• Click-Chemistry-Derived Triazole Ligands of Arginine−Glycine−Aspartate (RGD) Integrins with a Broad Capacity To Inhibit Adhesion of Melanoma Cells and Both in Vitro and in Vivo Angiogenesis
  作者：Andrea Trabocchi、Gloria Menchi、Nicoletta Cini、Francesca Bianchini、Silvia Raspanti、Anna Bottoncetti、Alberto Pupi、Lido Calorini、Antonio Guarna

  DOI：10.1021/jm100754z

  日期：2010.10.14

  A click chemistry approach was applied for the discovery of triazole-based arginine-glycine-aspartate (RGD) mimetics by Cu(1)-catalyzed 1,3-dipolar alkyne azide coupling reaction, which showed binding all properties toward alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed compound 18 capable of binding alpha(v)beta(3) integrin with nanomolar affinity according, to a two-sites model, and molecular modeling studies revealed a peculiar pi-stacking interaction between the triazole ring and Tyr178 side chain. Accordingly, compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to RGD-containing proteins of the extracellular matrix, such as vitronectin, fibronectin, and osteopontin. and also angiogenesis in in vitro and in vivo experimental models. The relevant biological effects exerted by compound 18 suggest its potential application as an antiangiogenic agent in the diagnosis and therapy of tumors where alpha(v)beta(3) integrin expression is up-regulated.
• 1,2,3-TRIAZOLE-BASED PEPTIDOMIMETIC INTEGRIN INHIBITORS FOR THE DIAGNOSIS AND THERAPY OF TUMORS
  申请人：Guarna Antonio

  公开号：US20130040964A1

  公开（公告）日：2013-02-14

  The present invention refers to the field of chemical compounds bearing a 1,2,3-triazole ring of formula (I) and possessing guanidino and carboxylic groups or their isosteres, their preparation by Cu-catalyzed “click-chemistry”, and medical-diagnostic use in pathologies where angiogenesis is altered, for example pathologic conditions of tumor origin, tumor metastasis, osteoporosis, and rheumatoid arthritis.

  本发明涉及具有化学化合物的领域，其具有1,2,3-三唑环的结构（I）并且具有胍基和羧基或其同分异构体，通过铜催化的“点击化学”方法制备这些化合物，并在血管生成异常的病理学中进行医学诊断使用，例如肿瘤起源的病理性状况、肿瘤转移、骨质疏松症和类风湿性关节炎。