alpha-氨基-3-氯-4,5-二氢-5-异恶唑乙酸 | 52583-41-2

• 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
• 中文名称: alpha-氨基-3-氯-4,5-二氢-5-异恶唑乙酸
• 中文别名: 戊搭烯,1,3a,4,6a-四氢-3,6-二苯基-,(3aR,6aR)-
• 英文名称: acivicin
• 英文别名: dl-Erythro-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid；avicidin；amino-(3-chloro-4,5-dihydro-isoxazol-5-yl)-acetic acid；α-amino-3-chloro-2-isoxazoline-5-acetic acid；2-Azaniumyl-2-(3-chloro-4,5-dihydro-1,2-oxazol-5-yl)acetate
• CAS: 52583-41-2
• 化学式: C₅H₇ClN₂O₃
• mdl: MFCD00058450
• 分子量: 178.575
• InChiKey: QAWIHIJWNYOLBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  alpha-氨基-3-氯-4,5-二氢-5-异恶唑乙酸 在 N-甲基吗啉 、 柠檬酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.75h， 生成 α-<(D-valylleucyllysyl)amino>-3-chloro-4,5-dihydro-5-isoxazoleacetic acid bis(trifluoroacetate)
  参考文献：
  名称：

  Plasmin-activated prodrugs for cancer chemotherapy. 1. Synthesis and biological activity of peptidylacivicin and peptidylphenylenediamine mustard

  摘要：

  Many tumors contain elevated levels of plasminogen activator and thus produce elevated levels of the protease plasmin in the milieu of the tumor. We have hypothesized, therefore, that it should be possible to prepare peptidyl prodrug derivatives of anticancer drugs that would be locally activated by tumor-associated plasmin. As an initial test of this hypothesis, we synthesized the peptidyl prodrugs of the anticancer drugs (alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin, AT-125) and N,N-bis(2-chloroethyl)-p-phenylenediamine (phenylenediamine mustard) by mixed anhydride coupling of the parent drug with the protected tripeptide, Boc-D-Val-Leu-Lys(Boc)-OH, followed by deprotection with trifluoroacetic acid. The prodrugs showed an increased selective in vitro cytotoxicity for Rous sarcoma virus transformed chicken embryo fibroblasts (which produce elevated levels of plasminogen activator) compared to nontransformed fibroblasts (which produce low levels of plasminogen activator). In the presence of the plasmin inhibitor, p-nitrophenyl p'-guanidinobenzoate at 2 micrograms/mL, the selectivity of the phenylenediamine mustard prodrug was reduced, but there was no effect on the cytotoxicity of the free drug. Furthermore, the prodrug analogue D-valylleucyl-D-lysylphenylenediamine mustard (in which L-Lys has been replaced by D-Lys) was inactive. Finally, the prodrug derivative of acivicin did not display selective toxicity for transformed cells when the cells were cultured in plasminogen-free medium. These results suggest that plasmin hydrolysis is necessary for the activation of the prodrugs. The prodrugs were tested in vivo for antitumor activity. The prodrug of acivicin, like acivicin itself, was inactive against the B16 melanoma, a murine tumor that produces high levels of plasminogen activator. This prodrug was active against the M5076 carcinoma, a tumor that displays only moderate levels of plasminogen activator; however, despite the fact that the prodrug was 2- to 3-fold less toxic on a molar basis than acivicin, there was no evidence of an increased therapeutic index. The prodrug of phenylenediamine mustard was also slightly less toxic than the parent drug, but again there was no evidence for an improved therapeutic index against the B16 tumor.

  DOI：

  10.1021/jm00359a003

文献信息

• Inhibitors of hepatitis C virus NS3 protease
  申请人：——

  公开号：US20020065248A1

  公开（公告）日：2002-05-30

  The present invention relates to compounds of Formula (I): 1 wherein A 1 is methylene, ethylene or propylene group and A 2 is N or CR 5 , or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HCV NS3 protease, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent.

  本发明涉及化合物的结构公式（I）：其中A1为亚甲基、乙烯基或丙烯基，A2为N或CR5，或其立体异构体形式、立体异构体混合物或药用盐形式，用作HCV NS3蛋白酶的抑制剂，以及包含相同化合物的药物组合物和诊断试剂盒，以及用于治疗病毒感染或作为测定标准或试剂的方法。
• [EN] PROTEOGLYCAN MIMETICS FOR ENHANCED WOUND HEALING, ANGIOGENESIS, AND VASCULAR REPAIR<br/>[FR] MIMÉTIQUES DE PROTÉOGLYCANE POUR UNE CICATRISATION, UNE ANGIOGENÈSE ET UNE RÉPARATION VASCULAIRE AMÉLIORÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195780A1

  公开（公告）日：2019-10-10

  The present disclosure provides pro-angiogenic proteoglycan mimetics that can provide a provisional, pro-angiogenic scaffold to support tissue regeneration while limiting systemic exposure to VEGF activity. These mimetics can protect a collagen matrix from rapid degradation, and in conjunction with EPCs promote angiogenesis in order to accelerate ischemic wound healing. For example, the provided compounds can be delivered from the end of a catheter following balloon angioplasty to coat the collagen exposed areas, prevent platelet binding and thrombosis, support capture of EPCs from blood to facilitate reendothelialization, and reduce late-lumen loss (neointimal hyperplasia).

  本公开提供了促血管生成的蛋白聚糖类似物，可以提供一个暂时的、促血管生成的支架，支持组织再生，同时限制系统暴露于VEGF活性。这些类似物可以保护胶原基质免受快速降解，并与EPCs一起促进血管生成，以加速缺血性伤口愈合。例如，所提供的化合物可以从导管的末端输送，经过球囊扩张后涂覆暴露的胶原区域，防止血小板结合和血栓形成，支持从血液中捕获EPCs以促进再内皮化，减少晚期腔隙损失（内膜增生）。
• Peptide inhibitors of hepatitis C virus NS3 protein
  申请人：——

  公开号：US20020177725A1

  公开（公告）日：2002-11-28

  This invention relates to a novel class of peptides having the Formula (I): 1 Which are useful as serine protease inhibitors, and more particularly as Hepatitis C virus(HCV) NS3 protease inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same in the treatment of HCV infection.

  本发明涉及一类新型肽的公式(I)：1，其作为丝氨酸蛋白酶抑制剂具有用途，更具体地作为丙型肝炎病毒（HCV）NS3蛋白酶抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗HCV感染的方法。
• [EN] ALPHA-KETOAMIDE INHIBITORS OF HEPATITIS C VIRUS NS3 PROTEASE<br/>[FR] INHIBITEURS D'ALPHA-CETOAMIDES DE LA PROTEASE NS3 DU VIRUS DE L'HEPATITE C
  申请人：DU PONT PHARM CO

  公开号：WO2001040262A1

  公开（公告）日：2001-06-07

  The present invention relates to ketoamide and ketoester compounds of Formula (I): where W is -NH- or -O-, or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HCV NS3 protease, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent.

  本发明涉及式(I)的酮酰胺和酮酯化合物：其中W为-NH-或-O-，或其立体异构体、立体异构体混合物或药学上可接受的盐形式，它们可用作HCV NS3蛋白酶的抑制剂，以及包含它们的制药组合物和诊断试剂盒，以及将它们用于治疗病毒感染或作为测定标准或试剂的方法。
• Alpha-4 beta-1 integrin ligands for imaging and therapy
  申请人：Lam S. Kit

  公开号：US20060019900A1

  公开（公告）日：2006-01-26

  The present invention provides α 4 β 1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.

  本发明提供了α4β1整合素配体，该配体具有高结合亲和力、特异性和稳定性。该配体包括具有n个独立选择的氨基酸的肽，其中至少一个氨基酸是非天然氨基酸或D-氨基酸，n为3到20的整数。提供了用于治疗癌症、炎症性疾病和自身免疫疾病的配体给药方法。还提供了用于在受试者中成像肿瘤、器官或组织的配体给药方法。