(2R)-5-amino-2-benzamidopentanoic acid | 904841-07-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R)-5-amino-2-benzamidopentanoic acid
• CAS: 904841-07-2
• 化学式: C₁₂H₁₆N₂O₃
• 分子量: 236.271
• InChiKey: PKONOCQSEOHHJW-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-5-amino-2-benzamidopentanoic acid 、 2-氯-1-乙氧基乙胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (2R)-5-[(1-amino-2-chloroethylidene)amino]-2-benzamidopentanoic acid
  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
• 作为产物：
  描述：

  苯甲酰氯 在 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醚 为溶剂， 反应 19.17h， 生成 (2R)-5-amino-2-benzamidopentanoic acid
  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

• SYNTHESIS AND USE OF NOVEL INHIBITORS AND INACTIVATORS OF PROTEIN ARGININE DEIMINASES
  申请人：Thompson Paul Ryan

  公开号：US20090306153A1

  公开（公告）日：2009-12-10

  In one embodiment of the present disclosure, an inactivator of protein arginine deiminase 4 is disclosed. The inactivator includes: (I) and x includes F; Cl, and H, y includes OH and NH 2 , R includes H, an alkyl group, an alkenyl group, an alknyl group, and n is greater than 0.

  在本公开的一种实施例中，揭示了一种蛋白质精氨酸脱亚胺酶4的失活剂。该失活剂包括：（I）和x包括F、Cl和H，y包括OH和NH2，R包括H、烷基、烯基、炔基，n大于0。
• Composition containing a penem or carbapenem antibiotic
  申请人：SANKYO COMPANY LIMITED

  公开号：EP0178911A2

  公开（公告）日：1986-04-23

  57 Administration of an N-acylated amino acid (ornithine, lysine, phenylglycine or phenylalanine) in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. A pharmaceutical composition may be prepared simply by mixing the two components.

  57 将 N-酰化氨基酸（鸟氨酸、赖氨酸、苯甘氨酸或苯丙氨酸）与培南类或碳青霉烯类抗生素联合给药，可缓解或消除与单独给药抗生素相关的肾脏问题。 氨基酸和抗生素可一起配制成组合物，也可同时或依次单独给药。 只需将两种成分混合即可制备成药物组合物。
• US4757066A
  申请人：——

  公开号：US4757066A

  公开（公告）日：1988-07-12
• US7964636B2
  申请人：——

  公开号：US7964636B2

  公开（公告）日：2011-06-21
• [EN] SYNTHESIS AND USE OF NOVEL INHIBITORS AND INACTIVATORS OF PROTEIN ARGININE DEIMINASES<br/>[FR] SYNTHESE ET UTILISATION DE NOUVEAUX INHIBITEURS ET INACTIVATEURS DE PROTEINES ARGININE DEIMINASES
  申请人：UNIV SOUTH CAROLINA

  公开号：WO2007056389A2

  公开（公告）日：2007-05-18

  [EN] In one embodiment of the present disclosure, an inactivator of protein arginine deiminase 4 is disclosed. The inactivator includes: (I) and x includes F, Cl, and H, y includes OH and NH₂, R includes H, an alkyl group, an alkenyl group, an alknyl group, and n is greater than 0.
  [FR] Cette invention concerne, dans un mode de réalisation, un inactivateur de protéine arginine déiminase 4. L'inactivateur comprend le composé représenté par la formule (I) dans laquelle x désigne F, Cl et H, y désigne OH et NH₂, R désigne H, un groupe alkyle, un groupe alcényle, un groupe alknyl et n est supérieur à 0.