(Z)-2-Hydroxyimino-2-(2-triphenylmethylaminothiazol-4-yl)-acetic acid | 68672-45-7

• 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: (Z)-2-Hydroxyimino-2-(2-triphenylmethylaminothiazol-4-yl)-acetic acid
• 英文别名: 2-(Z)-(Hydroxyimino)-2-<2-<(triphenylmethyl)amino>thiazol-4-yl>acetic acid；2-(2-triphenylmethylamino-4-thiazolyl)-2-(Z-hydroxyimino)acetic acid；(Z)-2-Hydroxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid；(Z)-2-(2-tritylaminothiazol-4-yl)-2-hydroxyiminoacetic acid；(Z)-2-hydroxyimino-2-(2-tritylamino-4-thiazolyl)acetic acid；2-(2-tritylamino-4-thiazolyl)-2-(hydroxyimino)-acetic acid；(2Z)-2-hydroxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid
• CAS: 68672-45-7
• 化学式: C₂₄H₁₉N₃O₃S
• 分子量: 429.499
• InChiKey: LOHLGUGGIGMESE-MEFGMAGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-2-Hydroxyimino-2-(2-triphenylmethylaminothiazol-4-yl)-acetic acid 在 盐酸 、 对甲苯磺酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 8.0h， 生成 sel de diethylammonium de l'acide (acetoxy methyl)-3(<<<(dimethyl-1,1 ethoxy)-2 oxo-2 ethoxy>imino-2 Z (tritylamino-2 thiazolyl-4)-2>-acetyl>-amino)-7 β cepheme-3 carboxylique-4
  参考文献：
  名称：

  Bucourt; Heymes; Perronnet, European Journal of Medicinal Chemistry, 1981, vol. 16, # 4, p. 307 - 316

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl (Z)-2-hydroxyimino-2-(2-triphenylmethylaminothiazol-4-yl)acetate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 (Z)-2-Hydroxyimino-2-(2-triphenylmethylaminothiazol-4-yl)-acetic acid
  参考文献：
  名称：

  头孢菌素一CHAINES氨基-2-噻唑基-4- acetyles：影响德拉存在等德拉配置D'未GROUPE氧亚氨基1河畔L'激活Google antibacterienne

  摘要：

  描述了具有反（E）和顺（Z）构型的2-（2-氨基-4-噻唑基）2-（羟基或烷氧基）-亚氨基乙酸衍生物的合成。通过这些化合物，已经实现了7β-氨基头孢烷酸（7-ACA）的氨基的酰化。这两个由此带来的一系列的头孢derivatives-防和顺式相对于它们的抗菌活性-are明显不同。一些合成化合物具有迄今为止所观察到的最高的抗菌活性。

  DOI：

  10.1016/0040-4020(78)89034-6

文献信息

• Aminothiazole substituted penicillins and antibacterial compositions
  申请人：Beecham Group P.L.C.

  公开号：US04816452A1

  公开（公告）日：1989-03-28

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt or in-vivo hydrolysable ester thereof: ##STR1## wherein R.sup.1 is hydrogen or an amino protecting group and R is substituted methyl; optionally substituted C.sub.2-12 alkyl, alkenyl or alkynyl; carbocyclyl; aryl or heterocyclyl. These compounds have antibacterial properties, and therefore are of use in the treatment of bacterial infections in humans and animals caused by a wide range of organisms.

  本发明提供了一种化合物，其化学式为(I)或其药用可接受的盐或体内可水解酯：其中R.sup.1为氢或氨基保护基，R为取代甲基；可选择取代的C.sub.2-12烷基、烯基或炔基；碳环基；芳基或杂环基。这些化合物具有抗菌性能，因此可用于治疗人类和动物因多种微生物引起的细菌感染。
• CEPHALOSPORIN DERIVATIVE
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0691343A1

  公开（公告）日：1996-01-10

  A cephalosporin derivative represented by general formula (I) or a salt thereof, wherein R¹ represents hydrogen, lower alkenyl, lower alkynyl, cycloalkyl, hydroxyl-protecting group, or (un)substituted lower alkyl; R² represents hydrogen, ester residue, or negative charge; R³ represents either (1) a group represented by general formula (a), wherein R⁴ and R⁵ represent each independently lower alkoxy or (un)substituted amino, or R⁴ and R⁵ may be combined together with the neighboring tetrahydropyridazine ring to form an (un)substituted fused 5- or 6-membered ring, or (2) a group represented by general formula (b) or (c), wherein R⁶ and R⁷ represent each independently hydrogen, halogen, amino, azido, carbamoyl, lower alkyl which may be substituted by amino, azido, carbamoyl or halogen, carbamoyl, or (un)substituted 5- or 6-membered heterocyclic group (provided the nitrogen atom of the heterocycle may be substituted to form a quaternary amine); X represents methine (-CH=) or nitrogen; and ring A represents a 4- to 5-membered nitrogenous heterocycle which may contain oxygen.

  由一般式(I)表示的头孢菌素衍生物或其盐，其中R¹代表氢、较低的烯基、较低的炔基、环烷基、羟基保护基团，或(未)取代的较低烷基；R²代表氢、酯残基或负电荷；R³表示(1)由一般式(a)表示的基团，其中R⁴和R⁵各自独立地代表较低的烷氧基或(未)取代的氨基，或R⁴和R⁵可以与相邻的四氢吡啶环结合在一起形成(未)取代的融合的5-或6-成员环，或(2)由一般式(b)或(c)表示的基团，其中R⁶和R⁷各自独立地代表氢、卤素、氨基、叠氮基、氨甲酰基、可能被氨基、叠氮基、氨甲酰基或卤素取代的较低烷基，氨甲酰基，或(未)取代的5-或6-成员杂环基团(假设杂环的氮原子可能被取代以形成季铵胺)；X代表亚甲基(-CH=)或氮；环A代表可能含氧的4-至5-成员氮杂环。
• Novel cephalosporin compounds
  申请人：LUCKY LTD.

  公开号：EP0604920A1

  公开（公告）日：1994-07-06

  The present invention relates to novel cephalosporin compounds, pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates and isomers thereof which possess potent and broad antibacterial activities. The compounds of the present invention have a (4-amino-1-substituted-alkapyrimidinium-4-yl)thiomethyl group in 3-position of the cephem nucleus and is specifically represented by the following formula(I): wherein: R¹ isa hydrogen atom or, a C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl or -C(RA)(RB)COOH group wherein RA and RB are independently a hydrogen atom or a C₁₋₄ alkyl group, or form a C₃₋₇ cycloalkyl group together with the carbon atom to which they are attached; R² isan unsubstituted or substituted amino, C₁₋₄ alkyl or C₃₋₇ cycloalkyl group; and n isan integer ranging from 2 to 7.

  本发明涉及新型头孢菌素化合物，其具有强大和广泛的抗菌活性的药用可接受的无毒盐、生理水解酯、水合物、溶剂合物和其异构体。本发明的化合物在头孢菌素核的3-位置具有(4-氨基-1-取代-烷基嘧啶-4-基)硫甲基基团，具体由以下式(I)表示：其中：R¹是氢原子或C₁₋₄烷基、C₂₋₄烯基、C₂₋₄炔基或-C(RA)(RB)COOH基团，其中RA和RB独立地是氢原子或C₁₋₄烷基，或者与它们所连接的碳原子一起形成C₃₋₇环烷基基团；R²是未取代或取代的氨基、C₁₋₄烷基或C₃₋₇环烷基基团；n是一个范围从2到7的整数。
• Cephalosporin derivatives
  申请人：Mochida Pharmaceutical Co., Ltd.

  公开号：US04888332A1

  公开（公告）日：1989-12-19

  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 novel cephalosporin derivatives according to the present invention contain condensed heterocyclic groups, particularly a triazolopyrimidine ring or a thiadiazolopyrimidine ring as substituents at the 3-position of the cephem skeleton, and a hydroxyimino, an alkyloxyimino or an acyloxyimino 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、其制备方法、以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体化合物和其制备方法。本发明的新型头孢菌素衍生物包含紧缩杂环基团，特别是三唑嘧啶环或噻唑嘧啶环作为头孢菌素骨架的3位取代基，并且在头孢菌素骨架的7位取代基是羟肟基、烷氧基肟基或酰氧基肟基。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。
• Synthesis of HR 916 B: The First Technically Feasible Route to the 1-(Pivaloyloxy)ethyl Esters of Cephalosporins
  作者：Klaus Fleischmann、Friedhelm Adam、Walter Dürckheimer、Winfried Hertzsch、Rolf Hörlein、Heiner Jendralla、Theo Wollmann、Christian Lefebvre、Philippe Mackiewicz、Jean-Michel Roul

  DOI：10.1002/jlac.199619961106

  日期：1996.11

  An efficient synthesis of HR 916 B (4), the orally active 1-(RS)-(pivaloyloxy)ethyl prodrug ester of the cephalosporin cefdaloxime, was developed and applied on a multi-kg scale. AMCA (8) was prepared by exchange of the acetoxy group of fermentation product ACA (7) with the nucleophile methanol under acidic conditions. Its 7-amino group was acylated with mixed anhydride 14 to give 15. Carboxylic acid

  有效合成头孢菌素头孢菌肟的口服活性1-（RS）-（新戊酰氧基）乙基前药酯HR 916 B（4），并以多千克规模应用。通过在酸性条件下将发酵产物ACA（7）的乙酰氧基与亲核甲醇进行交换来制备AMCA（8）。用混合酸酐14酰化其7-氨基，得到15。分别用碘代醇酯27或溴代醇酯30酯化羧酸15以得到酰基16。同时除去氨基保护基和氧代保护基提供了前药HR 916 3，其通过甲苯磺酸盐4的沉淀得以纯化和稳定。相对于AMCA（8）（四个步骤），总产量4（比率5/6 = 0.65）为39％，相对于ACA（7）（五个步骤）为15％。