(2R)-2-氨基-4-[[叔丁氧羰基]氨基]丁酸 | 114360-55-3

• 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: (2R)-2-氨基-4-[[叔丁氧羰基]氨基]丁酸
• 中文别名: (R)-2-氨基-4-(BOC-氨基)丁酸
• 英文名称: N⁵-(tert-butoxycarbonyl)-D-diaminobutanoic acid
• 英文别名: (2R)-2-azaniumyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 114360-55-3
• 化学式: C₉H₁₈N₂O₄
• 分子量: 218.253
• InChiKey: ICJFZQLAIOCZNG-ZCFIWIBFSA-N

物化性质

• 沸点：
  388.2±37.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (2R)-2-氨基-4-[[叔丁氧羰基]氨基]丁酸 在 N-甲基吗啉 、 sodium hydroxide 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 18.34h， 生成
  参考文献：
  名称：

  d-Amino Acid-Based Protein Arginine Deiminase Inhibitors: Synthesis, Pharmacokinetics, and in Cellulo Efficacy

  摘要：

  The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Because D-amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of D-amino acid analogues of our Pan-PAD inhibitor Cl-amicline, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that D-Cl-amidine and D-o-F-amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of D-Cl-amidine were moderately improved over those of L-Cl-amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.

  DOI：

  10.1021/ml300288d

文献信息

• [EN] FACTOR XIA NEW MACROCYCLE BEARING A NON-AROMATIC P2' GROUP<br/>[FR] NOUVEAU MACROCYCLE DE FACTEUR XIA PORTANT UN GROUPE P2' NON AROMATIQUE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017019821A1

  公开（公告）日：2017-02-02

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了化合物的结构式（I）：或其立体异构体、互变异构体或药学上可接受的盐，其中所有变量如本文所定义。这些化合物是选择性因子XIa抑制剂或FXIa和血浆激肽酶的双重抑制剂。本发明还涉及包含这些化合物的药物组合物以及使用它们治疗血栓栓塞和/或炎症性疾病的方法。
• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Beta-hairpin peptidomimetics
  申请人：POLYPHOR AG

  公开号：US10259847B2

  公开（公告）日：2019-04-16

  Beta-hairpin peptidomimetics of the general formula (I), cyclo[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-T1-T2], and pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  通式(I)、环[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-T1-T2]的β-发夹肽拟物化物及其药学上可接受的盐，其中 P1 至 P12、T1 和 T2 是如说明书和权利要求书中所定义的元素，具有革兰氏阴性抗菌活性，例如抑制肺炎克雷伯菌和/或鲍曼尼不动杆菌和/或大肠埃希菌等微生物的生长或杀灭它们。g. 抑制肺炎克雷伯氏菌和/或鲍曼不动杆菌和/或大肠埃希氏菌等微生物的生长或将其杀死。它们可用作治疗或预防感染的药物，或用作食品、化妆品、药品或其他含营养物质的消毒剂。这些拟肽物可通过基于固相和溶相混合合成策略的工艺制造。
• β-hairpin peptidomimetics
  申请人：POLYPHOR AG

  公开号：US10654897B2

  公开（公告）日：2020-05-19

  Beta-hairpin peptidomimetics of the general formula (I), cyclo[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-T1-T2] and pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have Gramnegative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  通式(I)、环[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-T1-T2]的β-发夹肽拟物化物及其药学上可接受的盐，其中 P1 至 P12、T1 和 T2 是如说明书和权利要求书中所定义的元素，具有革兰氏阴性抗菌活性，例如抑制肺炎克雷伯菌和/或鲍曼尼不动杆菌和/或大肠埃希菌等微生物的生长或杀灭这些微生物。g. 抑制肺炎克雷伯氏菌和/或鲍曼不动杆菌和/或大肠埃希氏菌等微生物的生长或将其杀死。它们可用作治疗或预防感染的药物，或用作食品、化妆品、药品或其他含营养物质的消毒剂。这些拟肽物可通过基于固相和溶相混合合成策略的工艺制造。
• Factor XIa macrocycle inhibitors bearing a non-aromatic P2' group
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10676477B2

  公开（公告）日：2020-06-09

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了式(I)化合物：或其立体异构体、同系物或药学上可接受的盐，其中所有变量如本文所定义。这些化合物是选择性因子 XIa 抑制剂或 FXIa 和血浆球蛋白的双重抑制剂。本发明还涉及包含这些化合物的药物组合物以及使用这些化合物治疗血栓栓塞性和/或炎症性疾病的方法。