Z-10-Bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-decenoic acid | 107872-57-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Z-10-Bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-decenoic acid
• 英文别名: 10-Bromo-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-dec-2-enoic acid；(Z)-10-bromo-2-[(2,2-dimethylcyclopropanecarbonyl)amino]dec-2-enoic acid
• CAS: 107872-57-1
• 化学式: C₁₆H₂₆BrNO₃
• 分子量: 360.291
• InChiKey: NJXHMALULPICRY-LCYFTJDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Z-10-Bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-decenoic acid 在 氨 作用下， 以 水 为溶剂， 反应 4.0h， 以58%的产率得到(Z)-10-Amino-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-dec-2-enoic acid
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018
• 作为产物：
  描述：

  2,2-二甲基环丙甲酰胺 、 10-Bromo-2-oxo-decanoic acid 以 甲苯 为溶剂， 以71%的产率得到Z-10-Bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-decenoic acid
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018

文献信息

• 2-(Cyclopropane-carboxamido)-2-alkenoic acids, their esters and salts, and antibacterial compositions comprising the same and a thienamycin-type compound
  申请人：Merck & Co., Inc.

  公开号：EP0048301A1

  公开（公告）日：1982-03-31

  ω-(2-Amino-2-carboxyethylthiol-2-(cyclopropane- carboxamido)-2-alkenoic acids, their esters and salts of the formula in the Z configuration, wherein R2 is 2,2-dimethylcyclopropyl or 2,2-dichlorocyclopropyl; R' is hydrogen, loweralkyl of 1-6 carbon atoms, dialkylaminoalkyl with 1-6 carbon atoms in each alkyl group, or a pharmaceutically acceptable cation; R3 is an alkylene chain of 3-7 carbon atoms, having a terminal substituent which is 2-amino-2-carboxyethylthio, or 1-(phosphono)ethylamino which selectively inhibit the metabolism of dipeptidase (E.C:3.4.13.11) and therefore are useful in combination with antibacterial products, by preference with the thienamycin class of compounds.

  该文本描述的是公式为Z构型的2-氨基-2-羧基乙硫基-2-(环丙烷羧酰胺)-2-烯酸及其酯类和盐类，其中R2为2,2-二甲基环丙基或2,2-二氯环丙基；R'为氢、1-6碳原子的低级烷基、每个烷基中有1-6碳原子的二烷基氨基烷基或药学上可接受的阳离子；R3为一个碳数为3-7的烷基链，具有一个终端取代基，该取代基为2-氨基-2-羧基乙硫基或1-(膦酸)乙基氨基，可选择性地抑制二肽酶(E.C:3.4.13.11)的代谢，因此在与抗菌产品结合使用时有用，优选与头孢曲松类化合物结合使用。
• Combination of 2-substituted penems with dipeptidase inhibitors
  申请人：Merck & Co., Inc.

  公开号：EP0072014A1

  公开（公告）日：1983-02-16

  A novel antibacterial drup combination is provided, one component being a 2-substituted penem having the structure wherein R is -R' or -SR' wherein R' is substituted or unsubstituted: alkyl having 1-6 carbon atoms, aryl such as phenyl or phenyl alkyl having 7-12 carbon atoms, heterocyclyl or heterocyclylalkyl wherein alkyl has 1-3 carbon atoms and the heterocyclic moiety has 1-4 hetero atoms selected from 0, N, or S: and the easily removable or pharmaceutically acceptable salt or ester derivatives thereof; and the other component is a dipeptidase (E.C.3.4.13.11) inhibitor. The dual-component combination is formulated so that 1 to 3 parts by weight of the penem are employed for 30 to 1 parts by weight of the inhibitor compound.

  本发明提供了一种新型抗菌药组合，其中一种成分是具有以下结构的 2-取代戊烯 其中 R 是-R'或-SR'，其中 R' 是取代或未取代的：具有 1-6 个碳原子的烷基、芳基如苯基或具有 7-12 个碳原子的苯基烷基、杂环或杂环烷基，其中烷基具有 1-3 个碳原子，杂环分子具有 1-4 个选自 0、N 或 S 的杂原子：及其易去除的或药学上可接受的盐或酯衍生物；另一种成分是二肽酶（E.C.3.4.13.11）抑制剂。双组分组合配制成 1 至 3 份重量的青霉烯对 30 至 1 份重量的抑制剂化合物。
• Novel Z-2-acylamino-3-monosubstituted propenic acids and their esters and salts, and processes for preparing them
  申请人：Merck & Co., Inc.

  公开号：EP0010573B1

  公开（公告）日：1983-10-19
• An antibacterial composition of thienamycin-type compound and a dipeptidase inhibitor
  申请人：Merck & Co., Inc.

  公开号：EP0007614B1

  公开（公告）日：1983-01-26
• Combination of 2-substituted carbapenems with dipeptidase inhibitors
  申请人：Merck & Co., Inc.

  公开号：EP0161546B1

  公开（公告）日：1989-12-13