(6R,7R)-7-amino-3-[(2-diphenylmethyloxycarbonyl-5-methyl-s-triazolo[1,5-a]-pyrimidin-7-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[-4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester | 99951-25-4

• 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: (6R,7R)-7-amino-3-[(2-diphenylmethyloxycarbonyl-5-methyl-s-triazolo[1,5-a]-pyrimidin-7-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[-4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester
• 英文别名: diphenylmethyl (6R,7R)-7-amino-3-[[2-diphenylmethyloxycarbonyl-5-methyl-s-triazolo(1,5-a)pyrimidin-7-yl]thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；(6R,7R)-7-amino-3-[(2-diphenylmethyloxycarbonyl-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester；benzhydryl (6R,7R)-7-amino-3-[(2-benzhydryloxycarbonyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 99951-25-4
• 化学式: C₄₁H₃₄N₆O₅S₂
• 分子量: 754.89
• InChiKey: OLMOGSYZMLWVCS-FOEBFOTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  54
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  193
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (6R,7R)-7-amino-3-[(2-diphenylmethyloxycarbonyl-5-methyl-s-triazolo[1,5-a]-pyrimidin-7-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[-4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester 生成 benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[[2,2-dimethyl-6-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-benzodioxol-5-yl]methoxyimino]acetyl]amino]-3-[(2-benzhydryloxycarbonyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  KATO, KADZUO;MURAKAMI, NIXIRO;MOTIDZUKI, XIDEHNORI;MOTIDA, XIDEH

  摘要：

  DOI：

文献信息

• Synthesis of a Chiral α-(Aminooxy)arylacetic Ester. I. A Route through Optical Resolution of a Racemic α-(Phthalimidooxy)arylacetic Acid
  作者：Hisao Iwagami、Masakazu Nakazawa、Masanobu Yatagai、Toyoto Hijiya、Yutaka Honda、Hirokazu Naora、Takashi Ohnuki、Toshihide Yukawa

  DOI：10.1246/bcsj.63.3073

  日期：1990.11

  A synthetic route has been developed to the synthesis of a chiral O-alkyloxime (S)-16, which can be a synthetic intermediate for a potent antipsedomonal cephalosporin antibiotic M-14659 (1). The oxime moiety in (S)-16 has a chiral center at the carbon atom adjacent to the oxygen atom. We have achieved that (S)-16 can be prepared via t-butyl 2-aminooxy-2-[3,4-(isopropylidenedioxy)phenyl]acetate [(S)-15]

  已开发出合成手性 O-烷基肟 (S)-16 的合成路线，该合成路线可以是强效抗假单胞菌头孢菌素抗生素 M-14659 (1) 的合成中间体。(S)-16 中的肟部分在与氧原子相邻的碳原子处具有手性中心。我们已经实现了 (S)-16 可以通过 2-氨基氧基-2-[3,4-(异亚丙基二氧基)苯基]乙酸叔丁酯 [(S)-15] 从光学活性 α-(邻苯二甲酰亚胺氧基) 酸制备(S)-12a 使用奎宁拆分获得。已证明由 (S)-16 制备的 M-14659 完全不含其 (R)-非对映异构体。
• Optical Resolution by Preferential Crystallization of 2-(3,4-Carbonyldioxyphenyl)-2-(phthalimidooxy)acetic Acid, a Key Intermediate of Cephalosporin Antibiotic M-14659
  作者：Kimihiro Murakami、Masayuki Ohashi、Atsuo Matsunaga、Ichiro Yamamoto、Akira Tomiguchi、Hiroyuki Nohira

  DOI：10.1246/bcsj.65.3288

  日期：1992.12

  (±)-2-(3,4-Carbonyldioxyphenyl)-2-(phthalimidooxy)acetic acid [(±)-1] was efficiently resolved into a pair of optically active forms by preferential crystallization. Successive preferential crystallization of (±)-1 was experimented at 15 °C under stirring in acetone, and (+)- and (−)-1 with optical purity of 68–85% were obtained. The racemization of (−)-1 proceeded smoothly in the presence of triethylamine to give (±)-1 which was reusable for the preferential crystallization procedure. A potent antipseudomonal cephalosporin M-14659 (2) was prepared from (+)-1.

  (±)-2-(3,4-羧基二氧苯基)-2-(邻苯二甲酰胺氧基)乙酸[(±)-1]通过优先结晶高效分离为一对光学活性形式。在15°C下搅拌的条件下，在丙酮中对(±)-1进行了连续的优先结晶实验，得到了光学纯度为68–85%的(+)和(−)-1。(-)-1在三乙胺的存在下平稳地进行了外消旋化反应，生成了可重复用于优先结晶过程的(±)-1。一种有效的抗伪单胞菌头孢菌素M-14659(2)是从(+) -1制备而来的。
• Cephalosporin derivatives
  申请人：Mochida Pharmaceutical Co., Ltd.

  公开号：US04880798A1

  公开（公告）日：1989-11-14

  The present invention relates to novel cephalosporin derivatives, processes for preparing thereof, compositions for preventing and/or treating infectious diseases which comprise the novel cephalosporin derivatives as active components, and the intermediate compounds in the synthesis of cephalosporin derivatives and processes for producing thereof. The present invention is based on the selection of groups containing a condensed heterocyclic ring, particularly a triazolopyrimidine ring, as substitutents at the 3-position of the cephem skeleton, and of groups containing a carboxyl and hydroxy substituted phenylmethyloxyimino moiety, particularly a (carboxy substituted catechol)methyloxyimino moiety, as substituents at the 7-position of the cephem skeleton. The compounds of the present invention containing the aforementioned substituents have a strong antibacterial activity against Gram-negative bacteria and also against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. These compounds are extremely useful for the treatment of infectious diseases.

  本发明涉及新型头孢菌素衍生物、其制备过程、用作活性成分预防和/或治疗传染病的组合物，以及头孢菌素衍生物合成中的中间化合物和其生产过程。本发明基于在头孢菌素骨架的3位选择含有紧缩杂环环，特别是三唑嘧啶环的取代基，以及在头孢菌素骨架的7位选择含有羧基和羟基取代的苯甲氧基亚胺基团，特别是含有（羧基取代的邻苯二酚）甲氧基亚胺基团的取代基。本发明中含有上述取代基的化合物对革兰氏阴性菌和包括耐甲氧西林金黄色葡萄球菌在内的革兰氏阳性菌具有强烈的抗菌活性。这些化合物对于治疗传染病非常有用。
• [EN] CEPHALOSPORIN DERIVATIVES
  申请人：MOCHIDA PHARMACEUTICAL CO., LTD.

  公开号：WO1986005786A1

  公开（公告）日：1986-10-09

  (EN) Novel cephalosporin derivatives, processes for preparing thereof, compositions for preventing and/or treating infectious diseases which comprise the novel cephalosporin derivatives as active components, and the intermediate compounds in the synthesis of cephalosporin derivatives and processes for producing thereof. The present invention is based on the selection of groups containing a condensed heterocyclic ring, particularly a triazolopyrimidine ring or a thiadiazolopyrimidine ring, as substituents at the 3-position of the cephem skeleton, and of groups containing a catechol moiety, particularly a catechol carboxymethyloxyimino moiety or a catechol carboxyimino moiety, as substituents at the 7-position of the cephem skeleton. The compounds of the present invention containing the aforementioned substituents have a strong antibacterial activity against Gram-negative bacteria and also against Gram-positive bacteria including methicillin-resistant $i(Staphylococcus aureus). These compounds are extremely useful for the treatment of infectious diseases.(FR) Nouveaux dérivés de céphalosporine, leurs procédés de préparation, compositions permettant de prévenir et/ou de traiter des maladies infectieuses et comportant les nouveaux dérivés de céphalosporine comme constituants actifs, ainsi que composés intermédiaires dans la synthèse des dérivés de céphalosporine et leurs procédés de préparation. La présente invention est fondée sur la sélection de groupes contenant un noyau hétérocyclique condensé, notamment un noyau de triazolopyrimidine ou un noyau de thiadiazolopyrimide, sous forme de substituants en position 3 du squelette de céphème, et de groupes contenant une fraction catéchol, en particulier une partie carboxyméthyloxyimino de catéchol ou une partie carboxymino de catéchol, sous forme de substituants en position 7 du squelette du céphème. Les composés ci-décrits contenant les substituants précités possèdent une forte activité antibactérienne contre les bactéries Gram-négatives et également contre les bactéries Gram-positives y compris le staphylocoque doré résistant à la méthiciline. Ces composés sont extrêmement utiles dans le traitement des maladies infectieuses.

  (EN) 新型头孢菌素衍生物，其制备方法，包括新型头孢菌素衍生物作为活性成分的预防和/或治疗传染病的组合物，以及头孢菌素衍生物合成中的中间化合物和其制备方法。本发明基于选择包含紧缩杂环环，特别是三唑嘧啶环或噻唑嘧啶环，作为头孢菌素骨架3位的取代基，以及包含儿茶酚基，特别是儿茶酚羧甲氧基亚胺基或儿茶酚羧基亚胺基，作为头孢菌素骨架7位的取代基。本发明中含有上述取代基的化合物对革兰氏阴性菌和包括甲氧西林耐药金黄色葡萄球菌在内的革兰氏阳性菌具有强大的抗菌活性。这些化合物在治疗传染病方面非常有用。 (FR) Nouveaux dérivés de céphalosporine, leurs procédés de préparation, compositions permettant de prévenir et/ou de traiter des maladies infectieuses et comportant les nouveaux dérivés de céphalosporine comme constituants actifs, ainsi que composés intermédiaires dans la synthèse des dérivés de céphalosporine et leurs procédés de préparation. La présente invention est fondée sur la sélection de groupes contenant un noyau hétérocyclique condensé, notamment un noyau de triazolopyrimidine ou un noyau de thiadiazolopyrimide, sous forme de substituants en position 3 du squelette de céphème, et de groupes contenant une fraction catéchol, en particulier une partie carboxyméthyloxyimino de catéchol ou une partie carboxymino de catéchol, sous forme de substituants en position 7 du squelette du céphème. Les composés ci-décrits contenant les substituants précités possèdent une forte activité antibactérienne contre les bactéries Gram-négatives et également contre les bactéries Gram-positives y compris le staphylocoque doré résistant à la méthiciline. Ces composés sont extrêmement utiles dans le traitement des maladies infectieuses.
• Intermediates of cephalosporin compounds
  申请人：Mochida Pharmaceutical Co., Ltd.

  公开号：US04956474A1

  公开（公告）日：1990-09-11

  The present invention relates to novel cephalosporin derivatives, processes for preparing thereof, compositions for preventing and/or treating infectious diseases which comprise the novel cephalosporin derivatives as active components, and the intermediate compounds in the synthesis of cephalosporin derivatives and processes for producing thereof. The present invention is based on the selection of groups containing a condensed heterocyclic ring, particularly a triazolopyrimidine ring or a thiadiazolopyrimidine ring, as substituents at the 3-position of the cephem skeleton, and of groups containing a catechol moiety, particularly a catechol carboxymethyloxyimino moiety or a catechol carboxyimino moiety, as substituents at the 7-position of the cephem skeleton. The compounds of the present invention containing the aforementioned substituents have a strong antibacterial activity against Gram-negative bacteria and also against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. These compounds are extremely useful for the treatment of infectious diseases.

  本发明涉及新的头孢菌素衍生物、其制备方法、以新的头孢菌素衍生物作为活性成分的预防和/或治疗传染病的组合物，以及头孢菌素衍生物合成中的中间体和生产方法。本发明基于在头孢菌素骨架的3位选择含有紧缩杂环环，特别是三唑嘧啶环或噻唑嘧啶环的取代基，以及在头孢菌素骨架的7位选择含有儿茶酚基团，特别是儿茶酚羧甲氧基亚胺基团或儿茶酚羧基亚胺基团的取代基。本发明中含有上述取代基的化合物对革兰氏阴性菌和包括甲氧西林耐药金黄色葡萄球菌在内的革兰氏阳性菌具有强大的抗菌活性。这些化合物对于治疗传染病非常有用。