7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid sulfone tert-butyl ester | 136120-41-7

• 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: 7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid sulfone tert-butyl ester
• 英文别名: 7α-chlorodeacetoxycephalosporanic acid sulfone tert-butyl ester；tert-butyl 7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylate；tert-butyl 7α-chloro-3-methyl-3-cephem-4-carboxylate 1,1-dioxide；t-Butyl 7alpha-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylate；tert-butyl (6R,7S)-7-chloro-3-methyl-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 136120-41-7
• 化学式: C₁₂H₁₆ClNO₅S
• 分子量: 321.782
• InChiKey: FCQHUUQODDPYKY-OIBJUYFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid sulfone tert-butyl ester 在 N-溴代丁二酰亚胺(NBS) 、 水 、 三乙胺 作用下， 生成 tert-butyl ester of 7α-chloro-3-(4-nitrophenoxycarbonyloxy)methylceph-3-em-4-carbonic acid sulfone
  参考文献：
  名称：

  Doxorubicin prodrug on the basis of tert -butyl cephalosporanate sulfones

  摘要：

  Doxorubicin-cephalosporin prodrug adapted to the development of elastases for the liberation of parent drug was synthesized on the basis of cephalosporanate sulfone esters. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.071
• 作为产物：
  描述：

  7-氨基-3-甲基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-甲酸 在 盐酸 、 Oxone 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 丙酮 为溶剂， 反应 6.42h， 生成 7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid sulfone tert-butyl ester
  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

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.
• Synthesis and evaluation of dual action cephalosporins as elastase inhibitors
  作者：Grigory Veinberg、Irina Shestakova、Larisa Petrulanis、Nora Grigan、Dan Musel、Dairis Zeile、Iveta Kanepe、Ilona Domrachova、Ivars Kalvinsh、Andris Strakovs、Edmunds Lukevics

  DOI：10.1016/s0960-894x(97)00104-2

  日期：1997.1

  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.
• Synthesis and anticancer properties of 7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid esters
  作者：M. Vorona、G. Veinberg、I. Shestakova、I. Kanepe、I. Potorochina、K. Dikovskaya、R. Bokaldere、M. Petrova、E. Liepinsh、E. Lukevics

  DOI：10.1007/s10593-007-0033-x

  日期：2007.2
• Bromination of tert-Butyl Esters of 7α-Chloro and 7-Alkylidenedeacetoxycephalosporanic Acid Sulfones
  作者：M. Vorona、G. Veinberg、I. Turovskis、E. Lukevics

  DOI：10.1007/s10593-005-0199-z

  日期：2005.5
• Synthesis and structural modification of tert-butyl ester of 7α-chloro-2-(N,N-dimethylaminomethylene)-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid
  作者：M. Vorona、I. Potoročina、G. Veinberg、I. Shestakova、I. Kanepe、M. Petrova、E. Liepinsh、E. Lukevics

  DOI：10.1007/s10593-007-0101-2

  日期：2007.5