N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]-2-{6-oxo-2-phenyl-5-[(phenylmethoxy)carbamido]hydropyrimidinyl}acetamide | 293329-65-4

• 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: N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]-2-{6-oxo-2-phenyl-5-[(phenylmethoxy)carbamido]hydropyrimidinyl}acetamide
• 英文别名: N-((1RS)-1-(2-t-butyl-1,3,4-oxadiazol-5-ylcarbonyl)-2-methylpropyl)-2-(5-benzyloxycarbonylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)acetamide；benzyl N-[1-[2-[[1-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]-6-oxo-2-phenylpyrimidin-5-yl]carbamate
• CAS: 293329-65-4
• 化学式: C₃₁H₃₄N₆O₆
• 分子量: 586.648
• InChiKey: KPWLAZHDXRZIGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]-2-{6-oxo-2-phenyl-5-[(phenylmethoxy)carbamido]hydropyrimidinyl}acetamide 在 palladium-carbon 作用下， 以 甲醇 、 水 为溶剂， 生成 5-氨基-N-[1-[[5-(1,1-二甲基乙基)-1,3,4-恶二唑-2-基]羰基]-2-甲基丙基]-6-氧-2-苯基-1(6H)-嘧啶乙酰胺
  参考文献：
  名称：

  1,3,4-oxadiazole derivatives and process for producing the same

  摘要：

  氧代唑衍生物由以下公式（I）表示：（其中R1代表氢原子或氨基保护基团；R2、R3和R4分别表示烷基基团、环烷基基团、苯基基团（可能被取代），或3,4-亚甲二氧基苯基基团，或R3和R4一起表示C2-6烷基基团），制备该衍生物的方法，以及使用上述衍生物制备由以下公式（II）表示的氧代唑衍生物的方法：（其中所有符号的含义与上述描述相同）。根据本发明，通过较少的步骤以高产率生产由公式（II）表示的化合物。

  公开号：

  US06534658B1
• 作为产物：
  描述：

  {(S)-1-[(5-tert-Butyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 草酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]-2-{6-oxo-2-phenyl-5-[(phenylmethoxy)carbamido]hydropyrimidinyl}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

文献信息

• 1,3,4-Oxadiazole derivatives and process for producing the same
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20030153758A1

  公开（公告）日：2003-08-14

  Oxadiazole derivatives represented by formula (I): 1 (wherein R 1 represents a hydrogen atom or an amino-protective group; R 2 , R 3 , and R 4 each independently represents an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, or a 3,4-methylenedioxyphenyl group, or R 3 and R 4 are taken together to represent a C 2-6 alkylene group), a process of producing the same, and a process for producing oxadiazole derivatives represented by formula (II): 2 (wherein all symbols have the same meanings as described above) using the above derivative. According to the invention, the compound represented by formula (II) is produced through fewer steps in a high yield.

  公式（I）表示的Oxadiazole衍生物：1（其中R1表示氢原子或氨基保护基；R2、R3和R4各自独立地表示烷基、环烷基、苯基（可能被取代）或3,4-亚甲二氧基苯基，或R3和R4一起表示C2-6烷基），制备该化合物的过程以及使用上述衍生物制备公式（II）表示的Oxadiazole衍生物的过程：2（其中所有符号的含义与上述相同）。根据本发明，在高收率下通过较少的步骤制备出公式（II）表示的化合物。
• 1,3,4-OXADIAZOLE DERIVATIVES AND PROCESS FOR PRODUCING THE SAME
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1162199A1

  公开（公告）日：2001-12-12

  Oxadiazole derivatives represented by formula (I): (wherein R1 represents a hydrogen atom or an amino-protective group; R2, R3, and R4 each independently represents an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, or a 3,4-methylenedioxyphenyl group, or R3 and R4 are taken together to represent a C2-6 alkylene group), a process of producing the same, and a process for producing oxadiazole derivatives represented by formula (II): (wherein all symbols have the same meanings as described above) using the above derivative. According to the invention, the compound represented by formula (II) is produced through fewer steps in a high yield.

  式 (I) 所代表的噁二唑衍生物： (其中R1代表氢原子或氨基保护基；R2、R3和R4各自独立地代表烷基、环烷基、可被取代的苯基或3，4-亚甲基二氧苯基，或R3和R4合起来代表C2-6亚烷基）的噁二唑衍生物，以及利用上述衍生物生产由式（II）代表的噁二唑衍生物的工艺： (其中所有符号的含义与上述相同）使用上述衍生物的工艺。 根据本发明，式（II）代表的化合物的生产步骤较少，产率较高。
• US6534658B1
  申请人：——

  公开号：US6534658B1

  公开（公告）日：2003-03-18
• Development of Orally Active Nonpeptidic Inhibitors of Human Neutrophil Elastase
  作者：Kazuyuki Ohmoto、Tetsuya Yamamoto、Motohiro Okuma、Toshihide Horiuchi、Hirotoshi Imanishi、Yoshihiko Odagaki、Kazuhito Kawabata、Tomohiko Sekioka、Yasushi Hirota、Shozo Matsuoka、Hisao Nakai、Masaaki Toda、John C. Cheronis、Lyle W. Spruce、Albert Gyorkos、Maciej Wieczorek

  DOI：10.1021/jm000410y

  日期：2001.4.1

  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.
• 1,3,4-oxadiazole derivatives and process for producing the same
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06534658B1

  公开（公告）日：2003-03-18

  Oxadiazole derivatives represented by formula (I): (wherein R1 represents a hydrogen atom or an amino-protective group; R2, R3, and R4 each independently represents an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, or a 3,4-methylenedioxyphenyl group, or R3 and R4 are taken together to represent a C2-6 alkylene group), a process of producing the same, and a process for producing oxadiazole derivatives represented by formula (II): (wherein all symbols have the same meanings as described above) using the above derivative. According to the invention, the compound represented by formula (II) is produced through fewer steps in a high yield.

  氧代唑衍生物由以下公式（I）表示：（其中R1代表氢原子或氨基保护基团；R2、R3和R4分别表示烷基基团、环烷基基团、苯基基团（可能被取代），或3,4-亚甲二氧基苯基基团，或R3和R4一起表示C2-6烷基基团），制备该衍生物的方法，以及使用上述衍生物制备由以下公式（II）表示的氧代唑衍生物的方法：（其中所有符号的含义与上述描述相同）。根据本发明，通过较少的步骤以高产率生产由公式（II）表示的化合物。