7β-amino-3-methanesulfonyloxycephem | 74704-03-3

• 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: 7β-amino-3-methanesulfonyloxycephem
• 英文别名: diphenylmethyl 7β-amino-3-methanesulfonyloxy-3-cephem-4-carboxylate；benzhydryl 7β-methanesulfonyloxy-3-cephem-4-carboxylate；benzhydryl (6R,7R)-7-amino-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 74704-03-3
• 化学式: C₂₁H₂₀N₂O₆S₂
• 分子量: 460.532
• InChiKey: BKABXCICWBLURM-OXQOHEQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7β-amino-3-methanesulfonyloxycephem 在 苯磺酰胺 、 sodium hydrogensulfide 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 苯甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(ethoxyimino)acetamido]-3-[(4-pyrazolyl)methylthio]-3-cephem-4-carboxylic acid
  参考文献：
  名称：

  Orally Active Cephalosporins. Part 4: Synthesis, Structure–Activity Relationships and Oral Absorption of Novel 3-(4-Pyrazolylmethylthio)cephalosporins with Various C-7 Side Chains

  摘要：

  A series of 3-(4-pyrazolylmethylthio)cephalosporins with various C-7 side chains was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity against Haemophilus influenzae was markedly increased by the C-7 oxime moiety. Deamination at the 2 position of, or introduction of a substituent such as halogen or methyl to, the 5 position of the (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) moiety improved oral absorption. Among these compounds, FR192752 (40a) having a (Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-hydroxyiminoacetam do moiety, showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including H. influenzae and penicillin G-resistant Streptococcus pneumoniae (PRSP). Further, it showed higher oral absorption than CFDN and FK041. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00416-3
• 作为产物：
  描述：

  diphenylmethyl 7β-formamido-3-methanesulfonyloxy-3-cephem-4-carboxylate 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.5h， 以27%的产率得到7β-amino-3-methanesulfonyloxycephem
  参考文献：
  名称：

  studies on anti-helicobacter pylori agents. part 2: new cephem derivatives

  摘要：

  The synthesis and optimization of the anti-Helicobacter pylori activity of a novel series of cephem derivatives are described. Introduction of thio-heterocyclic groups containing N- and S-atoms to the 3-position and phenyl or thienyl acetamido groups to the 7-position of the cephem nucleus dramatically improved the activity. From this series of derivatives, compound 13i was Found to have extremely potent in vitro anti-H. pylori activity, superior therapeutic efficacy compared to AMPC and CAM, no cross-resistance between CAM or MNZ and low potential for causing diarrhea due to instability to beta-lactamase. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00163-2

文献信息

• [EN] CEPHEM COMPOUNDS AND PHARMACEUTICAL USE THEREOF<br/>[FR] COMPOSES DE CEPHEME ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1996017850A1

  公开（公告）日：1996-06-13

  (EN) This invention relates to a new use of a cephem compound of formula (I), wherein R1 is aryl(lower)alkyl which may have one or more suitable substituent(s), arylthio(lower)alkyl, lower alkenylthio(lower)alkyl which may have one or more suitable substituent(s), or a group of the formula: R4-A- or R4-S-A- in which R4 is heterocyclic group which may have one or more suitable substituent(s), and A is lower alkylene which may have one or more suitable substituent(s) or lower alkenylene, R2 is heterocyclic group which may have one or more suitable substituent(s), or heterocyclic(lower)-alkyl and R3 is carboxy or protected carboxy, and a pharmaceutically acceptable salt thereof, which have antimicrobial activity against $i(Helicobacter pylori), and are useful as anti-$i(Helicobacter pylori) agents, anti-gastritis agents, antiulcer agents and anticancer agents.(FR) La présente invention concerne une nouvelle utilisation d'un composé de céphème de formule (I) dans laquelle R1 est aryle alkyle(inférieur) pouvant posséder un ou plusieurs substituants appropriés, arylthio alkyle (inférieur), alcénylthio inférieur alkyle (inférieur) pouvant posséder un ou plusieurs substituants appropriés, ou bien un groupe de la formule R4-A- ou R4-S-A- dans laquelle R4 est un groupe hétérocyclique pouvant posséder un ou plusieurs substituants appropriés, et A est alkylène inférieur pouvant posséder un ou plusieurs substituants appropriés ou bien alcénylène inférieur, R2 est un groupe hétérocyclique pouvant posséder un ou plusieurs substituants appropriés, ou bien alkyle (inférieur) hétérocyclique et R3 est carboxy ou carboxy protégé, et son sel pharmaceutiquement acceptable, qui présentent une activité antimicrobienne contre $i(Helicobacter pylori), et sont utiles comme agents anti-$i(Helicobacter pylori), agents anti-gastrite, agents antiulcéreux et agents anticancéreux.

  本发明涉及一种新的使用方法，使用式(I)的头孢菌素化合物，其中R1是芳基（较低）烷基，可以具有一个或多个适当的取代基，芳硫（较低）烷基，较低烯基硫（较低）烷基，可以具有一个或多个适当的取代基，或者是公式R4-A-或R4-S-A-的基团，其中R4是杂环基团，可以具有一个或多个适当的取代基，A是较低烷基，可以具有一个或多个适当的取代基，或者是较低烯基，R2是杂环基团，可以具有一个或多个适当的取代基，或者是杂环（较低）烷基，R3是羧基或保护羧基，以及其药学上可接受的盐，具有抗菌活性，可用作抗$ i（幽门螺杆菌）剂，抗胃炎剂，抗溃疡剂和抗癌剂。
• [EN] NEW CEPHEM COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES DE CEPHEME
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1995007283A1

  公开（公告）日：1995-03-16

  (EN) New cephem compounds of formula (I), wherein R1 is amino or protected amino, R2 is hydrogen, lower alkyl or hydroxy protective group, R3 is carboxy or protected carboxy, R4 is 3-pyridyl, 4-pyridyl or optionally substituted heteromonocyclic group containing two nitrogen atoms as hetero atoms, and which may also contain one oxygen or sulfur atom, and n is 0, 1 or 2, provided that when R2 is lower alkyl, then n is 1 or 2 and R4 is optionally substituted heteromonocyclic group containing two nitrogen atoms as hetero atoms, and which may also contain one oxygen or sulfur atom, and pharmaceutically acceptable salts thereof which are useful as a medicament.(FR) L'invention porte sur des nouveaux composés céphème représentés par la formule suivante: (I) dans laquelle R1 représente amino ou amino protégé, R2 représente hydrogène, alkyle inférieur ou un groupe protecteur hydroxy, R3 représente carboxy ou carboxy protégé, R4 représente 3-pyridyle, 4-pyridyle ou un groupe hétéromonocyclique éventuellement substitué contenant deux atomes d'azote en tant qu'hétéroatomes et pouvant également contenir un atome d'oxygène ou de soufre, et n correspond à 0, 1 ou 2, à condition que, lorsque R2 représente alkyle inférieur, n corresponde à 1 ou 2, et R4 représente un groupe hétéromonocyclique contenant deux atomes d'azote en tant qu'hétéroatomes et pouvant également contenir un atome d'oxygène ou de soufre. L'invention se rapporte également à des sels pharmaceutiquement acceptables desdits composés pouvant être utilisés en tant que médicament.

  新的头孢菌素化合物的化学式为（I），其中R1为氨基或保护的氨基，R2为氢、低碳基或羟基保护基，R3为羧基或保护的羧基，R4为3-吡啶基、4-吡啶基或可选取代的含有两个氮原子作为杂原子的杂单环族基，且可能还包含一个氧或硫原子，n为0、1或2，但当R2为低碳基时，n为1或2，且R4为可选取代的含有两个氮原子作为杂原子的杂单环族基，且可能还包含一个氧或硫原子。这些化合物的药物可接受的盐可用作药物。
• FK041, a Novel Orally Active Cephalosporin: Synthesis and Biological Properties.
  作者：HIROFUMI YAMAMOTO、KOHJI KAWABATA、SHUICHI TAWARA、HISASHI TAKASUGI、HIROKAZU TANAKA

  DOI：10.7164/antibiotics.51.683

  日期：——
• Orally active cephalosporins. Part 2: Synthesis, structure–activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain
  作者：Hirofumi Yamamoto、Takeshi Terasawa、Ayako Nakamura、Kohji Kawabata、Kazuo Sakane、Satoru Matsumoto、Yoshimi Matsumoto、Shuichi Tawara

  DOI：10.1016/s0968-0896(00)00021-3

  日期：2000.5

  A series of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Journal of Antibiotics. 1998, 51, 683-687
  作者：

  DOI：——

  日期：——