tert-butyl 3-bromomethyl-7α-methoxy-3-cephem-4-carboxylate 1,1-dioxide | 165533-77-7

• 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-bromomethyl-7α-methoxy-3-cephem-4-carboxylate 1,1-dioxide
• CAS: 165533-77-7
• 化学式: C₁₃H₁₈BrNO₆S
• 分子量: 396.259
• InChiKey: BCCGBJGMXUFCMU-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.59
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  89.98
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-bromomethyl-7α-methoxy-3-cephem-4-carboxylate 1,1-dioxide 在 吡啶 、 苯甲醚 、 三乙胺 、 三氟乙酸 、 H-pEEDSG-OH 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.75h， 生成 (S)-2-<(benzhydryloxy)carbonyl>-2-<(tert-butoxycarbonyl)amino>ethyl 7α-methoxy-3-<<(1-methyl-1,2,3,4-tetrazol-5-yl)thi>methyl>-3-cephem-4-thiolcarboxylate 1,1-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of new elastase inhibitors. I. 1,1-Dioxocephem-4-thiolesters

  摘要：

  Several 7alpha-chloro and 7alpha-methoxy cephalosporin thiolester sulphones variously substituted at the C-3' position were synthesized from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA). The compounds are time-dependent inhibitors of human leukocyte elastase (HLE) with effective K(i) ranging from micro- to nanomolar values, and second order rate constant reaching 10(6) M-1s-1; they also inhibit porcine pancreatic elastase with similar, though not identical efficiency. Compared to the corresponding cephem esters, the thiolesters of the 7-Cl series inhibit HLE up to 10 times as fast. Complete enzyme inactivation is achieved when a leaving group at C-3' (OAc or S-Het) is present, at the expense however of stability towards hydrolytic beta-lactam cleavage. In the 7-OMe series the thiolester compounds are far more stable and retain good efficiency for irreversible enzyme inhibition, superior to that displayed by the corresponding ester compounds. Three representative compounds (including one ester and two thiolesters) are shown to be effective inhibitors of HLE in the presence of insoluble elastin.

  DOI：

  10.1016/0223-5234(92)90019-w
• 作为产物：
  描述：

  7-diazodesacetoxycephalosporanic acid tert-butyl ester sulfone 在 N-溴代丁二酰亚胺(NBS) 、 三氟化硼乙醚 作用下， 以 苯 为溶剂， 反应 24.5h， 生成 tert-butyl 3-bromomethyl-7α-methoxy-3-cephem-4-carboxylate 1,1-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of dual action cephalosporins as elastase inhibitors

  摘要：

  tert-Butyl 7 alpha-chloro- and 7 alpha-methoxycephalosporanate 1,1-dioxides containing Aspirin and Diclofenac in their 3-acyloxymethyl moiety were synthesized. These dual action cephalosporins have been found to be potent elastase inhibitors and stimulators of NO biosynthesis in macrophages. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00104-2

文献信息

• New biological properties of tert-butyl cephalosporanate sulfones
  作者：Grigory Veinberg、Irina Shestakova、Nora Grigan、Dan Musel、Iveta Kanepe、Ilona Domrachova、Vera Grigoryeva、Olga Zharkova、Ivars Turovskis、Ivars Kalvinsh、Andris Strakovs、Edmunds Lukevics

  DOI：10.1016/s0223-5234(99)80027-0

  日期：1998.10

  tert-Butyl cephalosporanate I,l-dioxides variously substituted in positions 7 and 3 were obtained from 7-aminodeacetoxycephalosporanic acid (7-ADCA) and 7-aminocephalosporanic acid (7 ACA). It was found that the cephalosporins containing Aspirin and Diclofenac in a prodrug form in their 3-acyloxymethyl moiety release them after hydrolytic splitting of the beta-lactam ring. They also demonstrated high efficacy as elastase inhibitors. Two of them stimulated the biosynthesis of nitric oxide in RAW 264.7 macrophages cells. The same effect observed in tumor and normal cells in the presence of cephalosporins was accompanied by cytotoxic effect in vitro. (C) Elsevier, Paris.