(6R,7R)-3-[(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoyloxymethyl]-5,8-dioxo-7-(2-phenoxy-acetylamino)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 370578-75-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (6R,7R)-3-[(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoyloxymethyl]-5,8-dioxo-7-(2-phenoxy-acetylamino)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 英文别名: (6R,7R)-3-[[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoyl]oxymethyl]-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid；(6R,7R)-3-[[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoyl]oxymethyl]-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5λ4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 370578-75-9
• 化学式: C₃₆H₄₂N₂O₈S
• 分子量: 662.804
• InChiKey: CVHSCWJAZRJAII-ACMVLVGNSA-N

物化性质

• 沸点：
  936.1±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  47
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (6R,7R)-3-[(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoyloxymethyl]-5,8-dioxo-7-(2-phenoxy-acetylamino)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 phosphate buffer 、 β-lactamase from Escherichia coli 27C7 作用下， 以 二甲基亚砜 为溶剂， 生成 维A酸
  参考文献：
  名称：

  Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate

  摘要：

  Two novel series of all-trans-beta -retinoic acid derivatives were synthesized and found to possess anticancer activity. The first series, cephalosporin 3 ' -retinoic esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta -retinoic acid (2) with cephalosporins 4 and 5. The second series, 7-(retinamido)cephalosporins 11 and 12, were synthesized, respectively, by the condensation of 2 with cephalosporins 9 and 10. These four heretofore undescribed compounds 6, 7, 11, and 12 showed inhibitory activity against murine leukemias (L1210 and P388), sarcoma 180, breast carcinoma (MCF7), and human T-lymphocytes (Molt4/C8 and CEM/0). They also inhibited squamous metaplasia and keratinization in tracheal or.-an cultures derived from vitamin-A-deficient hamsters. Moreover, cephalosporin 3 ' -retinoic ester 7 exhibited enhanced activity against keratinization with ED50 = 3.91 x 10(-11) M in the presence of a beta -lactamase from Staphylococcus aureus 95. A tumor targeting fusion protein (dsFv3-beta -lactamase) was also used in conjunction with cephem-based retinoid 7 and the potency of 7 toward L1210, P388, and MCF7 was found to approach that of the free retinoic acid (2). In the presence of dsFv3-beta -lactamase, tumor cells were found to be much more susceptible to retinoid 7 than normal human embryonic lung cells. These notions provide a new approach to the use of beta -retinoic acid for antitumor therapy. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00127-4
• 作为产物：
  描述：

  维A酸 、 (6R,7R)-3-Iodomethyl-8-oxo-7-(2-phenoxy-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester 在 三甲基溴硅烷 、 间氯过氧苯甲酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 以40%的产率得到(6R,7R)-3-[(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoyloxymethyl]-5,8-dioxo-7-(2-phenoxy-acetylamino)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate

  摘要：

  Two novel series of all-trans-beta -retinoic acid derivatives were synthesized and found to possess anticancer activity. The first series, cephalosporin 3 ' -retinoic esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta -retinoic acid (2) with cephalosporins 4 and 5. The second series, 7-(retinamido)cephalosporins 11 and 12, were synthesized, respectively, by the condensation of 2 with cephalosporins 9 and 10. These four heretofore undescribed compounds 6, 7, 11, and 12 showed inhibitory activity against murine leukemias (L1210 and P388), sarcoma 180, breast carcinoma (MCF7), and human T-lymphocytes (Molt4/C8 and CEM/0). They also inhibited squamous metaplasia and keratinization in tracheal or.-an cultures derived from vitamin-A-deficient hamsters. Moreover, cephalosporin 3 ' -retinoic ester 7 exhibited enhanced activity against keratinization with ED50 = 3.91 x 10(-11) M in the presence of a beta -lactamase from Staphylococcus aureus 95. A tumor targeting fusion protein (dsFv3-beta -lactamase) was also used in conjunction with cephem-based retinoid 7 and the potency of 7 toward L1210, P388, and MCF7 was found to approach that of the free retinoic acid (2). In the presence of dsFv3-beta -lactamase, tumor cells were found to be much more susceptible to retinoid 7 than normal human embryonic lung cells. These notions provide a new approach to the use of beta -retinoic acid for antitumor therapy. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00127-4

文献信息

• Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate
  作者：Gholam H. Hakimelahi、Tai Wei Ly、Sheng-Fa Yu、Maryam Zakerinia、Ali Khalafi-Nezhad、Mohammad N. Soltani、Mohsen N. Gorgani、Azra R. Chadegani、Ali A. Moosavi-Movahedi

  DOI：10.1016/s0968-0896(01)00127-4

  日期：2001.8

  Two novel series of all-trans-beta -retinoic acid derivatives were synthesized and found to possess anticancer activity. The first series, cephalosporin 3 ' -retinoic esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta -retinoic acid (2) with cephalosporins 4 and 5. The second series, 7-(retinamido)cephalosporins 11 and 12, were synthesized, respectively, by the condensation of 2 with cephalosporins 9 and 10. These four heretofore undescribed compounds 6, 7, 11, and 12 showed inhibitory activity against murine leukemias (L1210 and P388), sarcoma 180, breast carcinoma (MCF7), and human T-lymphocytes (Molt4/C8 and CEM/0). They also inhibited squamous metaplasia and keratinization in tracheal or.-an cultures derived from vitamin-A-deficient hamsters. Moreover, cephalosporin 3 ' -retinoic ester 7 exhibited enhanced activity against keratinization with ED50 = 3.91 x 10(-11) M in the presence of a beta -lactamase from Staphylococcus aureus 95. A tumor targeting fusion protein (dsFv3-beta -lactamase) was also used in conjunction with cephem-based retinoid 7 and the potency of 7 toward L1210, P388, and MCF7 was found to approach that of the free retinoic acid (2). In the presence of dsFv3-beta -lactamase, tumor cells were found to be much more susceptible to retinoid 7 than normal human embryonic lung cells. These notions provide a new approach to the use of beta -retinoic acid for antitumor therapy. (C) 2001 Elsevier Science Ltd. All rights reserved.