Z-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid | 74589-65-4

• 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-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid
• 英文别名: 2-Octenoic acid, 2-(((2,2-dimethylcyclopropyl)carbonyl)amino)-；(Z)-2-[(2,2-dimethylcyclopropanecarbonyl)amino]oct-2-enoic acid
• CAS: 74589-65-4
• 化学式: C₁₄H₂₃NO₃
• 分子量: 253.342
• InChiKey: WIESNNVNXBYTFK-FLIBITNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 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-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid 生成 (+)-(Z)-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic 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-氧代辛酸 、 2,2-二甲基环丙甲酰胺 以 甲苯 为溶剂， 以10%的产率得到Z-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic 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

• BRIDGED LIPOGLYCOPEPTIDES THAT POTENTIATE THE ACTIVITY OF BETA-LACTAM ANTIBACTERIALS
  申请人：Gallant Michel

  公开号：US20130244929A1

  公开（公告）日：2013-09-19

  The present invention provides novel lipoglycopeptide compounds which are Type 1 signal peptidase inhibitors (SpsB). Compounds of the present invention are useful for the treatment of various bacterial related infectious diseases, particularly when used as a potentiator of a β-lactam antibiotic such as imipenem and ertapenem. Accordingly, the present invention provides a method for the treatment of bacterial related infections using the compounds described herein, either alone or in combination with a β-lactam antibiotic.

  本发明提供了一种新型的脂肽多糖肽类化合物，它们是一类信号肽酶抑制剂（SpsB）。本发明的化合物可用于治疗各种细菌相关感染疾病，特别是在与β-内酰胺类抗生素（如亚胺培南和依达拉奉）一起使用时作为增效剂。因此，本发明提供了一种使用本文所述化合物单独或与β-内酰胺类抗生素联合治疗细菌相关感染的方法。
• Crystalline N-formimidoyl thienamycin
  申请人：Merck & Co., Inc.

  公开号：EP0006639A1

  公开（公告）日：1980-01-09

  Disclosed is crystalline N-formimidoyl thienamycin and a process for its preparation.

  本发明公开了晶体 N-甲酰亚胺基硫霉素及其制备方法。
• Antibacterial compositions comprising a beta-lactam-type compound and a 3-substituted propenoate
  申请人：Merck & Co., Inc.

  公开号：EP0028778A1

  公开（公告）日：1981-05-20

  An antibacterial composition comprising (a) cephaloridine and a 3-substituted propenoate of either of the formula wherein e.g. R2 and R3 are hydrocarbon radicals; a terminal hydrogen in R3 can be replaced by several groups; R' is hydrogen or C1-C6 alkyl or dialkylaminoalkyl, n is 3 to 5 and Y is heterocyclic or phenyl optionally substituted with hydroxyl, oxo, carboxyl, or methyl or (b) thienamycin, N-guanyl or N-formimidoyl thienamycin and a compound of formula II. The propenoate compounds prevent nephrotoxicity of the antibiotics. The antibiotic to propenoate weight ratio is from about 1 to 0.1-3.

  一种抗菌组合物，包括(a) 头孢里定和式中任一的 3-取代的丙烯酸酯 其中，例如 R2 和 R3 是烃基；R3 中的末端氢可被多个基团取代；R'是氢或 C1-C6 烷基或二烷基氨基烷基，n 是 3 至 5，Y 是杂环或苯基，可任选被羟基、氧代、羧基或甲基取代；或 (b) 噻喃霉素、N-鸟苷酰基或 N-甲酰亚胺酰基噻喃霉素和式 II 的化合物。丙烯酸盐化合物可防止抗生素的肾毒性。抗生素与丙烯酸酯的重量比约为 1 至 0.1-3。
• Antibacterial composition of thienamycin type compound and a dipeptidase inhibitor
  申请人：Merck & Co., Inc.

  公开号：EP0048025A1

  公开（公告）日：1982-03-24

  Novel compounds of the general formula wherein R2 is 2,2-dimethylcyclopropyl or 2,2-dichlorocyclopropyl; R1 is hydrogen, loweralkyl of 1-6 carbon atoms, dialkylaminoalkyl, or a pharmaceutically acceptable cation; R3 is a hydrocarbon chain of 3-7 carbon atoms, optionally having a terminal substituent which is trimethylammonium, amidino, guanidino, 2-amino-2-carboxyethyl- thio, or ureido, 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.

  通式中 R2 为 2,2-二甲基环丙基或 2,2-二氯环丙基；R1 为氢、1-6 个碳原子的低级烷基、二烷基氨基烷基或药学上可接受的阳离子；R3 为 3-7 个碳原子的烃链，任选具有一个末端取代基，该取代基为三甲基铵、脒基、胍基、2-氨基-2-羧乙基硫代或脲基，可选择性地抑制二肽酶（E.C.3.4.13.11）的代谢，因此可优先与噻吩霉素类化合物结合使用。
• Oral absorption enhancement of carboxylic acid pharmaceuticals using (5-alkyl-2-oxo-1,3-dioxolen-4-yl)methyl ester group
  申请人：Merck & Co., Inc.

  公开号：EP0070013A1

  公开（公告）日：1983-01-19

  The (5-R-2-oxo-1,3-dioxolen-4-yl)methyl moiety: wherein R is loweralkyl of 1-6 carbon atoms, especially methyl or t-butyl; when utilized as an ester on a pharmaceutical having a carboxylic acid functionality, enhances oral absorption of the pharmaceutical. This effect is applicable to a broad range of pharmaceutically active substances, including antibiotics, and antihypertensives as well as other classes of therapeutic agents.

  (5-R-2-氧代-1,3-二氧戊环-4-基)甲基： 其中 R 是 1-6 个碳原子的低级烷基，特别是甲基或叔丁基；当作为酯用于具有羧酸官能团的药物时，可促进药物的口服吸收。这种效果适用于多种药物活性物质，包括抗生素、抗高血压药以及其他类别的治疗剂。