benzhydryl 7β-(2-(thien-2-yl)acetamido)-3-(hydroxymethyl)-2-cephem-4-carboxylate | 57832-67-4

• 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: benzhydryl 7β-(2-(thien-2-yl)acetamido)-3-(hydroxymethyl)-2-cephem-4-carboxylate
• 英文别名: benzhydryl 7β-[2-(thien-2-yl)acetamido]-3-(hydroxymethyl)-2-cephem-4-carboxylate；Benzhydryl 3-hydroxymethyl-7beta-(thiophen-2-yl-acetamido)-ceph-2-em-4carboxylate；benzhydryl (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate
• CAS: 57832-67-4
• 化学式: C₂₇H₂₄N₂O₅S₂
• 分子量: 520.63
• InChiKey: GOLTVERXHUZLIL-NAMMGXCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzhydryl 7β-(2-(thien-2-yl)acetamido)-3-(hydroxymethyl)-2-cephem-4-carboxylate 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 吡啶 、 2,6-二甲基吡啶 、 三乙基硅烷 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.75h， 生成 7β-(2-(thien-2-yl)acetamido)-3-<<<<(4-methylbenzoyl)hydrazino>carbonyl>oxy>methyl>-3-cephem-4-carboxylic acid 1β-sulfoxide
  参考文献：
  名称：

  Synthesis of acylhydrazido-substituted cephems. Design of cephalosporin-vinca alkaloid prodrugs: substrates for an antibody targeted enzyme

  摘要：

  Cephalosporin 20 substituted at the C-3' position with the potent oncolytic agent desacetylvinblastine hydrazide (3) was synthesized as a potential prodrug for the treatment of solid tumors. The design of this novel prodrug was based on the knowledge that hydrolysis of a cephalosporin's beta-lactam bond can result in the expulsion of the C-3' substituent. Proper selection of the linkage used to join the cephem to the vinca, e.g., 8 vs 20, provided a releasable form of the drug as well as a chemically stable prodrug. We envisioned the conversion of prodrug to free vinca to be mediated by an immunoconjugate, consisting of a beta-lactamase enzyme covalently attached to a monoclonal antibody, which has been prelocalized at the tumor. Treatment of candidate prodrugs with the P99 beta-lactamase enzyme isolated from Enterobacter cloacae 265A efficiently catalyzed their conversion to the free drug form. A study of model compounds 11 and 18 indicated that cephem 1-beta-sulfoxide 18 was a better substrate for the enzyme than its sulfide counterpart 11. This finding prompted the synthesis of cephem sulfoxide 20 which was efficiently accomplished via condensation of desacetylvinblastine hydrazide with the cephalothin derived cephem 3'-p-nitrophenyl carbonate 15.

  DOI：

  10.1021/jo00034a027
• 作为产物：
  描述：

  7-β-<2-(thien-2-yl)acetamido>-3-hydroxymethyl-2-cephem-4-carboxylic acid 、 二苯基重氮甲烷 以 丙酮 、 乙腈 为溶剂， 反应 1.0h， 以60%的产率得到benzhydryl 7β-(2-(thien-2-yl)acetamido)-3-(hydroxymethyl)-2-cephem-4-carboxylate
  参考文献：
  名称：

  Synthesis of acylhydrazido-substituted cephems. Design of cephalosporin-vinca alkaloid prodrugs: substrates for an antibody targeted enzyme

  摘要：

  Cephalosporin 20 substituted at the C-3' position with the potent oncolytic agent desacetylvinblastine hydrazide (3) was synthesized as a potential prodrug for the treatment of solid tumors. The design of this novel prodrug was based on the knowledge that hydrolysis of a cephalosporin's beta-lactam bond can result in the expulsion of the C-3' substituent. Proper selection of the linkage used to join the cephem to the vinca, e.g., 8 vs 20, provided a releasable form of the drug as well as a chemically stable prodrug. We envisioned the conversion of prodrug to free vinca to be mediated by an immunoconjugate, consisting of a beta-lactamase enzyme covalently attached to a monoclonal antibody, which has been prelocalized at the tumor. Treatment of candidate prodrugs with the P99 beta-lactamase enzyme isolated from Enterobacter cloacae 265A efficiently catalyzed their conversion to the free drug form. A study of model compounds 11 and 18 indicated that cephem 1-beta-sulfoxide 18 was a better substrate for the enzyme than its sulfide counterpart 11. This finding prompted the synthesis of cephem sulfoxide 20 which was efficiently accomplished via condensation of desacetylvinblastine hydrazide with the cephalothin derived cephem 3'-p-nitrophenyl carbonate 15.

  DOI：

  10.1021/jo00034a027

文献信息

• 7-acyl-3-(substituted carbamoyloxy) cephem compounds and process for
  申请人：Eisai Co., Ltd.

  公开号：US05604217A1

  公开（公告）日：1997-02-18

  A 7-acyl-3-substituted carbamoyloxy cephem compound represented by the following formula (1): ##STR1## wherein A means a --CH.dbd. or --N.dbd. group; R.sup.1 denotes a hydroxyl, lower alkoxyl, fluorine-substituted lower alkoxyl or protected hydroxyl group; R.sup.2 and R.sup.3 are the same or different and individually represent a lower alkyl, hydroxyl-substituted lower alkyl, a carbamoyl-substituted lower alkyl group or cyano-substituted lower alkyl group, R.sup.2 is a hydrogen atom and R.sup.3 is a lower alkoxyl or alkyl group optionally substituted by one or more halogen atoms or the group ##STR2## means a 4-6 membered heterocyclic group, which contains one nitrogen atom, or a morpholino group, said heterocyclic group or morpholino group being optionally substituted by one or more lower alkyl, hydroxyl and/or hydroxyl-substituted lower alkyl groups; and R.sup.4 denotes a carboxyl or protected carboxyl group; or a pharmaceutically acceptable salt thereof; and a process for the preparation thereof; as well as an antibacterial composition containing the above cephem compound.

  以下是式子(1)所代表的7-酰基-3-取代基氨基甲酰氧头孢菌素类化合物： ##STR1## 其中，A代表--CH.dbd.或--N.dbd.基团；R.sup.1代表羟基、低碳基氧基、氟取代的低碳基氧基或保护羟基基团；R.sup.2和R.sup.3相同或不同，分别代表低碳基、羟基取代的低碳基、氨基甲酰取代的低碳基基团或氰基取代的低碳基基团；R.sup.2为氢原子，R.sup.3为低碳基氧基或低碳基基团，可选地被一个或多个卤素原子或该基团##STR2##所取代；其中，##STR2##代表一个含有一个氮原子的4-6元杂环基团，或一个morpholino基团，所述杂环基团或morpholino基团可选地被一个或多个低碳基、羟基和/或羟基取代的低碳基基团所取代；R.sup.4代表羧基或保护羧基基团；或其药学上可接受的盐；以及含有上述头孢菌素类化合物的抗菌组合物。
• Cephalosporin type antibacterials
  申请人：Syntex (U.S.A.) Inc.

  公开号：US03983113A1

  公开（公告）日：1976-09-28

  3-[3-(1-Methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7.beta.-(.alpha.-substitu ted acetamido)-ceph-3-em-4-carboxylic acid; 7.beta.-(.alpha.-substituted acetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carb oxylic acid derivatives and salts thereof; and ester intermediates and processes for preparing such compounds. The compounds are useful as antibacterials and are active against a wide variety of gram positive and gram negative bacteria.

  3-[3-(1-甲基四唑-5-基硫)-丙-1-(t)-烯基]-7.beta.-(.alpha.-取代乙酰胺基)-头孢-3-酮-4-羧酸；7.beta.-(.alpha.-取代乙酰胺基)-3-[3-(1,2,4-三唑-5-基硫)-丙-1-(t)-烯基]-头孢-3-酮-4-羧酸衍生物及其盐；以及制备这些化合物的酯中间体和方法。这些化合物可用作抗菌剂，并对各种革兰氏阳性菌和革兰氏阴性菌具有活性。
• Cephalosporin type antibacterials having a substituted propenyl group in
  申请人：Syntex (U.S.A.) Inc.

  公开号：US04112087A1

  公开（公告）日：1978-09-05

  Compounds of the formula ##STR1## wherein R is alkyl having 1 to 4 carbon atoms, .beta.-haloethyl, allyl, propargyl, cyclopentyl or benzyl; R.sup.1 is hydrogen or an .alpha.-substituted acetamido group; R.sup.2 is hydrogen or a protecting group; and the pharmaceutically acceptable salts thereof. The 7.beta.-amino compounds are useful as intermediates for the 7.beta.-(.alpha.-substituted acetamido) compounds which are useful as antibacterials against a wide variety of gram positive and gram negative bacteria.

  化合物的公式为##STR1##其中R是具有1至4个碳原子的烷基，β-卤乙基，烯丙基，丙炔基，环戊基或苄基; R.sup.1是氢或α-取代的乙酰胺基团; R.sup.2是氢或保护基;以及其医药上可接受的盐。7β-氨基化合物可用作7β-（α-取代乙酰胺基）化合物的中间体，后者对广泛的革兰氏阳性和革兰氏阴性细菌具有抗菌作用。
• US3983113A
  申请人：——

  公开号：US3983113A

  公开（公告）日：1976-09-28
• US4049806A
  申请人：——

  公开号：US4049806A

  公开（公告）日：1977-09-20