[2-(4-Fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-acetic acid | 251958-54-0

• 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
• 英文名称: [2-(4-Fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-acetic acid
• 英文别名: [6-Oxo-2-(4-fluorophenyl)1,6-dihydro-1-pyrimidinyl]acetic acid；2-[2-(4-fluorophenyl)-6-oxopyrimidin-1-yl]acetic acid
• CAS: 251958-54-0
• 化学式: C₁₂H₉FN₂O₃
• 分子量: 248.213
• InChiKey: WQLVPGOJKYLKOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(4-Fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-acetic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 2-[6-oxo-2-(4-fluorophenyl)-1,6-dihydro-1-pyrimidinyl]-N-[(1S)-1-[[5-(1-methylcyclopropyl)-1,3,4-oxadiazole-2-yl]carbonyl]-2-methylpropyl]acetamide
  参考文献：
  名称：

  Development of Orally Active Nonpeptidic Inhibitors of Human Neutrophil Elastase

  摘要：

  5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha -keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-1(F), 11d,e,k(H), ald,e,k(F), and ald,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

  DOI：

  10.1021/jm000410y
• 作为产物：
  描述：

  N-(2,2-dimethoxyethyl)-4-(fluorophenyl)carboxamidine 在 盐酸 、 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 生成 [2-(4-Fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-acetic acid
  参考文献：
  名称：

  Development of Orally Active Nonpeptidic Inhibitors of Human Neutrophil Elastase

  摘要：

  5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha -keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-1(F), 11d,e,k(H), ald,e,k(F), and ald,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

  DOI：

  10.1021/jm000410y

文献信息

• Peptoid and nonpeptoid containing alpha-keto oxadiazoles as serine protease inhibitors
  申请人：——

  公开号：US20020010315A1

  公开（公告）日：2002-01-24

  The present invention relates to certain substituted oxadiazole peptoids and nonpeptoids useful as inhibitors of serine proteases, especially human neutophil elastase (HNE). Compounds of the present invention are useful for the treatment or amelioration of symptoms of adult respiratory distress syndrome, septic shock, and multiple organ failure. Processes mediated by HNE are also implicated in conditions such as arthritis, periodontal disease, glomerulonephritis, and cystic fibrosis.

  本发明涉及某些取代噁唑肽和非肽类化合物，其可用作丝氨酸蛋白酶抑制剂，特别是人类中性粒细胞弹性蛋白酶（HNE）的抑制剂。本发明化合物可用于治疗或缓解成人呼吸窘迫综合症、脓毒症休克和多器官衰竭的症状。由HNE介导的过程也与关节炎、牙周病、肾小球肾炎和囊性纤维化等疾病有关。
• Serine protease inhibitors
  申请人：Cortech Inc.

  公开号：US06001814A1

  公开（公告）日：1999-12-14

  The present invention relates to certain substituted oxadiazole nonpeptides, which are useful as inhibitors of human neutrophil elastase (HNE) for the treatment of HNE-mediated processes implicated in conditions such as adult respiratory distress syndrome, septic shock and multiple organ failure. A series of studies also have indicated the involvement HNE in myocardial ischemia-reperfusion injury, emphysema. HNE-mediated processes are implicated in other conditions such as arthritis, periodontal disease, glomerulonephritis, dermatitis, psoriasis, cystic fibrosis, chronic bronchitis, atherosclerosis, Alzheimer's disease, organ transplantation, corneal ulcers, and invasion behavior of malignant tumors.

  本发明涉及某些取代的噁唑烷基非肽类化合物，其可用作人类中性粒细胞弹性蛋白酶（HNE）的抑制剂，用于治疗与HNE介导的过程有关的疾病，如成人呼吸窘迫综合征、脓毒症休克和多器官功能衰竭。一系列研究还表明HNE参与了心肌缺血再灌注损伤、肺气肿等疾病。HNE介导的过程还与其他疾病有关，如关节炎、牙周病、肾小球肾炎、皮炎、银屑病、囊性纤维化、慢性支气管炎、动脉粥样硬化、阿尔茨海默病、器官移植、角膜溃疡和恶性肿瘤的侵袭行为。
• US6001814A
  申请人：——

  公开号：US6001814A

  公开（公告）日：1999-12-14
• US6255453B1
  申请人：——

  公开号：US6255453B1

  公开（公告）日：2001-07-03
• US6548638B2
  申请人：——

  公开号：US6548638B2

  公开（公告）日：2003-04-15