环丙基萘啶羧酸 | 100361-18-0

• 物质功能分类: 化学试剂 - 有机试剂 - 芳烃
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 环丙基萘啶羧酸
• 中文别名: 1-环丙基-4-氧代-6-氟-7-氯-1,4-二氢-1,8-萘啶-3-甲酸；1-环丙基-6-氟-7-氯-4-氧-1,4-二氢-1,8-萘啶-3-羧酸；环丙萘啶羧酸
• 英文名称: 7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic Acid
• 英文别名: 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid；7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid；7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 100361-18-0
• 化学式: C₁₂H₈ClFN₂O₃
• 分子量: 282.659
• InChiKey: OXNZWNNMJBOZQO-UHFFFAOYSA-N

物化性质

• 熔点：
  209-212 °C
• 沸点：
  485.9±45.0 °C(Predicted)
• 密度：
  1.727±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温且干燥

制备方法与用途

用途：用于制备吉米沙星等喹诺酮类药物的中间体。

反应信息

• 作为反应物：
  描述：

  环丙基萘啶羧酸 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 7.0h， 生成 *,R^*)>-7-<3-<(2-amino-1-oxopropyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011
• 作为产物：
  描述：

  3-环丙基氨基-2-(2,6-二氯-5-氟吡啶-3-羰基)丙烯酸酯 在 potassium phosphate 、 盐酸 、 溶剂黄146 作用下， 以 乙腈 、 水 为溶剂， 生成 环丙基萘啶羧酸
  参考文献：
  名称：

  Novel lead generation of an anti-tuberculosis agent active against non-replicating mycobacteria: exploring hybridization of pyrazinamide with multiple fragments

  摘要：

  The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited > 10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log(10) kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.

  DOI：

  10.1007/s00044-015-1352-6
• 作为试剂：
  描述：

  环丙基萘啶羧酸 、 t-butyl 8-(methoxyimino)-2,6-diazaspiro[3,4]octane-2-carboxylate 在 环丙基萘啶羧酸 作用下， 以93.9的产率得到1-cyclopropyl-6-fluoro-7-[(5E)-5-methoxyimino-2-[(2-methylpropan-2-yl)oxycarbonyl]-2,7-diazaspiro[3.4]octan-7-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Quinolone carboxylic acid derivatives

  摘要：

  本发明涉及喹诺酸衍生物，其具有比现有喹诺系抗生素更优异和广泛的抗菌活性。更具体地说，它涉及由以下式1表示的新型喹诺酸衍生物，其具有7-[8-(alkoxyimino)-2,6-diazaspiro[3.4]oct-6-yl]衍生物作为取代基，以及其药学上可接受的盐和同分异构体：1其中A是C-H、C-F、C-Cl、C-O-CH3或氨基；R1是环丙基或2,4-二氟苯基；R2是C1-4烷基；C3是氢或C1-4烷基。

  公开号：

  US20020035258A1

文献信息

• Azabicyclo quinolone and naphthyridinone carboxylic acids
  申请人：Pfizer Inc

  公开号：US05164402A1

  公开（公告）日：1992-11-17

  Quinolone carboxylic acids 7-substituted by azabicyclo groups have antibacterial activity.

  喹诺酮羧酸7位被氮杂双环基团取代的化合物具有抗菌活性。
• [EN] ANTIBACTERIAL QUINOLONE DERIVATIVES<br/>[FR] DÉRIVÉS DE QUINOLONE ANTIBACTÉRIENS
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2021009212A1

  公开（公告）日：2021-01-21

  The invention relates to compounds of Formula I which are useful as antibacterial agents in medicine.

  这项发明涉及到一种化合物，其化学式为I，可用作医学上的抗菌剂。
• Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine
  作者：Paul R. McGuirk、Martin R. Jefson、Douglas D. Mann、Nancy C. Elliott、Polly Chang、Eugene P. Cisek、C. Peter Cornell、Thomas D. Gootz、Susan L. Haskell

  DOI：10.1021/jm00082a001

  日期：1992.2

  diazabicycloalkyl side chains investigated at the 7-position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (2), (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (4), 8-methyl-3,8-diazabicyclo[3.2.1]octane (5), 9-methyl-3,9-diazabicyclo[4.2.1]nonane (6), 1,4-diazabicyclo[3.2.2]nonane (7), 1,4-diazabicyclo[3.3.1]nonane (8), and 9-methyl-3

  一系列被各种C8（H，F，Cl，N）和N1（乙基，环丙基，乙烯基，2-氟乙基，4-氟苯基，2,4-二氟苯基）取代基取代的新颖的6-氟-7-二氮杂双环烷基喹诺酮羧酸，以及9-氟-10-二氮杂双环烷基吡啶并苯并恶嗪羧酸，并针对一系列重要的兽医病原菌进行了抗菌活性评估。在7位（苯并恶嗪10位）研究的二氮杂双环烷基侧链包括（1S，4S）-5-甲基-2,5-二氮杂双环[2.2.1]庚烷（2），（1S，4S）-2， 5-二氮杂双环[2.2.1]庚烷（3），（1R，4R）-5-甲基-2,5-二氮杂双环[2.2.1]庚烷（4），8-甲基-3,8-二氮杂双环[3.2。 1]辛烷（5），9-甲基-3,9-二氮杂双环[4.2.1]壬烷（6），1,4-二氮杂双环[3.2.2]壬烷（7），1,4-二氮杂双环[3.3.1] ]壬烷（8）和9-甲基-3,9-二氮杂双环[3.3.1]壬烷（9）。在这些侧链中，体外效能不是
• 7-Azetidinylquinolones as Antibacterial Agents. 2. Synthesis and Biological Activity of 7-(2,3-Disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic Acids. Properties and Structure-Activity Relationships of Quinolones with an Azetidine Moiety
  作者：Jordi Frigola、Antoni Torrens、Jose A. Castrillo、Josep Mas、David Vano、Juana M. Berrocal、Carme Calvet、Leonardo Salgado、Jordi Redondo

  DOI：10.1021/jm00050a016

  日期：1994.11

  3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria

  一系列7-（2,3-二取代-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸，在1处具有不同的取代基制备5-，5-和8-位，以研究对氮杂环丁烷部分2位上的取代基的效能和理化性质的影响。在体外确定针对革兰氏阳性和革兰氏阴性细菌的标题化合物的活性，并使用小鼠感染模型确定所选衍生物的体内功效。发现6b，6c和6d的X射线晶体结构与相应的AM1计算的几何结构合理吻合。建立了所有合成的7-氮杂环丁烷基喹诺酮类和萘啶类的抗菌能力与计算出的电子性质和实验容量因子之间的相关性。将所选衍生物的抗菌功效，药代动力学和理化性质与相关的7-（3-氨基-1-氮杂环丁烷基）和7-（3-氨基-3-甲基-1-氮杂环丁烷基）类似物进行了比较（第1部分，请参见： J. Med。Chem。1993，36，801-810）。N-1处的环丙基或取代的苯基与C-7处的反-3-氨基-2-甲基-1-氮杂
• [EN] FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES FONCTIONNALISÉS UTILISÉS EN TANT QUE MODULATEURS DU STIMULATEUR DES GÈNES DE L'INTERFÉRON (STING)
  申请人：RYVU THERAPEUTICS S A

  公开号：WO2021116446A1

  公开（公告）日：2021-06-17

  The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).

  这项发明涉及化合物-连接物构造和化合物的抗体药物偶联物，其化学式为(I)，可用作STING（干扰素基因刺激剂）调节剂。

表征谱图