diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate | 163009-57-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate
• 英文别名: benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(1-tritylpyrazol-4-yl)methylsulfanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 163009-57-2
• 化学式: C₄₉H₄₁N₇O₅S₃
• 分子量: 904.106
• InChiKey: FQCCFXDEGQICAT-FVBDHWPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  64
• 可旋转键数：
  16
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  233
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 、 苯甲醚 为溶剂， 反应 1.5h， 以63%的产率得到7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)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：

  7β-amino-3-methanesulfonyloxycephem 在 苯磺酰胺 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate
  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

文献信息

• [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。
• Cephem compounds
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06468995B1

  公开（公告）日：2002-10-22

  A compound of the formula: wherein R1 is amino or protected amino; R2 is hydrogen, lower alkyl or hydroxy protective group; R3 is carboxy or protected carboxy; R4 is an unsubstituted 5, 6 or 7-membered heteromonocyclic group containing two nitrogen atoms as heteroatoms, and which optionally further contains one oxygen or sulfur atom; or R4 is said 5, 6 or 7-membered heteromonocyclic group substituted by 1 to 4 groups selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, cyclo(lower)alkyl, cyclo(lower)alkenyl, halogen, amino, protected amino, protected hydroxy, cyano, nitro, carboxy, hydroxy(lower)alkyl, amino(lower)alkyl, and carbamoyloxy; and n is 1 or 2.

  该化合物的公式为：其中R1是氨基或保护氨基；R2是氢、低级烷基或羟基保护基；R3是羧基或保护羧基；R4是未取代的含有两个氮原子作为杂原子的5、6或7元杂单环族，可选地进一步含有一个氧或硫原子；或者R4是该5、6或7元杂单环族中的1至4个基团所取代，所述基团选自低级烷基、低级烷氧基、低级烷基硫基、低级烷基氨基、环(低级)烷基、环(低级)烯基、卤素、氨基、保护氨基、保护羟基、氰基、硝基、羧基、羟基(低级)烷基、氨基(低级)烷基和氨基甲酰氧基；n为1或2。
• NEW CEPHEM COMPOUNDS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0667868A1

  公开（公告）日：1995-08-23
• CEPHEM COMPOUNDS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0667868B1

  公开（公告）日：2002-05-15
• US6468995B1
  申请人：——

  公开号：US6468995B1

  公开（公告）日：2002-10-22