tert-butyl 3-(acetoxymethyl)-7α-methoxy-4-methyl-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylate | 108052-80-8

• 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: tert-butyl 3-(acetoxymethyl)-7α-methoxy-4-methyl-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylate
• 英文别名: tert-butyl (6R,7S)-3-(acetyloxymethyl)-7-methoxy-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 108052-80-8
• 化学式: C₁₆H₂₃NO₆S
• 分子量: 357.428
• InChiKey: GKNDZJVOGKCFRK-GWLKJFNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(acetoxymethyl)-7α-methoxy-4-methyl-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylate 在 苯甲醚 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 [((6R,7S)-3-Acetoxymethyl-7-methoxy-4-methyl-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-acetic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of human leukocyte elastase. 4. Selection of a substituted cephalosporin (L-658,758) as a topical aerosol

  摘要：

  Human leukocyte elastase (HLE) is a serine protease which has been implicated as a causative agent in several pulmonary diseases. The continued modification of our previously reported cephalosporin-based HLE inhibitors has led to the identification of a series of C-2 amides with potent, topical activity in an in vivo hamster lung hemorrhage model. While the most potent in vitro HLE inhibition had previously been obtained with lipophilic ester derivatives, it was found that the less active, but more polar and stable, amide derivatives were much more effective in vivo. The development of the structure-activity relations for optimization of these activities is discussed. These results led to the selection of 3-(acetoxymethyl)-2-[(2(S)-carboxypyrrolidino)carbonyl]-7alpha-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene 5,5-dioxide (3, L-658,758) as a selective, potent, time-dependent HLE inhibitor suitable for formulation as a topical aerosol drug for possible clinical use.

  DOI：

  10.1021/jm00099a002
• 作为产物：
  描述：

  tert-butyl (5S,6R,7S)-3-(acetyloxymethyl)-7-methoxy-4-methyl-5,8-dioxo-5λ4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 生成 tert-butyl 3-(acetoxymethyl)-7α-methoxy-4-methyl-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylate
  参考文献：
  名称：

  DOHERTY, JAMES B.;HAGMANN, WILLIAM K.;FINKE, PAUL E.;SHAH, SHRENIK K.

  摘要：

  DOI：

文献信息

• Tetrazolyl derivatives of beta-lactams useful as elastase inhibitors
  申请人：Merck & Co., Inc.

  公开号：EP0207447A2

  公开（公告）日：1987-01-07

  Tetrazolyl derivatives of β-lactams are found to be potent elsstase inhibitors and thereby useful anti-inflammatory/antidegenerative agents. Those compounds have the structural formula: wherein T is or wherein n is an integer of 0 to 2; M is, e.g., trifluoromethyl; chloro or fluoro; or -CH2A wherein A represents: (a) Ra-CO-O-; (b) R.HN-CO-O-; (c) RaO-CO-CH2NH-CO-O-; or (d) Ra-S-; R' is, e.g., (1) C1-6alkyl; (2) hydroxy; (3) ORa where R. is (a) C1-6alkyl; (b) -C6H5; (c) -CN2C6H5; (d) -CH2CH2C6N5; (e) , where Rh represents hydrogen, C1-6alkyl, phenyl, benzyl, or C1-6alkylamino; or (4) fluoro or chloro; (5) halo; (6) -SO2Rh; (7) phenyl; or (8) haloC1-6alkyl-CO-NH-; R2 is H; -O-C1-6 alkyl; halo; or C1-6 alkyl; Q' and Q2 independently are, e.g., (1) hydrogen; (2) methyl, ethyl or i-or n-propyl; (3) methylene; (4) phenylthiomethyl or phenyl sulfonylmethyl; (5) benzyl of formula wherein X, and X2 independently are H, OCH3, -COOH, C1- 6alkyl, -COOC1-6-alkyl, -CH2COOH, or CH2COOC1-6-alkyl; or (6) -CH2-CO-ORh; and R is Ra.

  发现β-内酰胺的四唑基衍生物是强效的elsstase抑制剂，因此是有用的抗炎/抗退行性药物。 这些化合物的结构式如下 其中 T 是 或 其中 n 为 0 至 2 的整数；M 为三氟甲基；氯或氟；或 - A，其中 A 代表： (a) Ra-CO-O-； (b) R.HN-CO-O-； (c) RaO-CO- NH-CO-O-；或 (d) Ra-S-； R'是，例如 (1) C1-6 烷基 (2) 羟基 (3) ORa，其中 R. 是 (a) C1-6 烷基 (b) -C6H5 (c) -CN2 (d) - C6N5 (e) 其中 Rh 代表氢、C1-6烷基、苯基、苄基或 C1-6 烷基氨基；或 (4) 氟或氯 (5) 卤代 (6) -SO2Rh (7) 苯基；或 (8) 卤代 C1-6 烷基-CO-NH-； R2 是 H；-O-C1-6 烷基；卤代；或 C1-6 烷基； Q' 和 Q2 独立地是，例如 (1) 氢 (2) 甲基、乙基或 i 或 n-丙基 (3) 亚甲基 (4) 苯硫基甲基或苯磺酰甲基 (5) 式中的苄基 其中 X 和 X2 独立地为 H、OCH3、-COOH、C1-6-烷基、-COOC1-6-烷基、- COOH 或 COOC1-6-烷基；或 (6) -CH2-CO-ORh；且 R 为 Ra。
• US4699904A
  申请人：——

  公开号：US4699904A

  公开（公告）日：1987-10-13
• US4845088A
  申请人：——

  公开号：US4845088A

  公开（公告）日：1989-07-04