(R,S)-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid | 117620-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (R,S)-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
• 英文别名: 3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid；2-Methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),11-tetraene-11-carboxylic acid
• CAS: 117620-86-7；56346-16-8
• 化学式: C₁₃H₁₁NO₄
• 分子量: 245.235
• InChiKey: ANIMQFJMACSGNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  环庚胺 、 (R,S)-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以47%的产率得到N-cycloheptyl-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w
• 作为产物：
  描述：

  1-(2-硝基苯氧基)乙酮 在 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 140.0 ℃ 、405.33 kPa 条件下， 反应 4.0h， 生成 (R,S)-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w

文献信息

• Tri-, tetra-substituted-3-aminopyrrolidine derivative
  申请人：Takahashi Hisashi

  公开号：US20060264428A1

  公开（公告）日：2006-11-23

  A quinolone synthetic antibacterial agent and a therapeutic agent for an infection which exhibit broad spectrum and strong antibacterial activity for both Gram positive and Gram negative bacteria, and which are also highly safe are provided. The compound provided is represented by following formula (I): wherein R 1 and R 2 represent hydrogen atom, or the like; R 3 represents an alkyl group containing 1 to 6 carbon atoms, or the like; R 4 and R 5 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like, with the proviso that R 4 and R 5 do not simultaneously represent hydrogen atom; or the substituents R 4 and R 5 together represent (a) a 3- to 6-membered cyclic structure including the carbon atom shared by R 4 and R 5 to form a spirocyclic structure with the pyrrolidine ring; R 6 and R 7 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like; R 8 represents a halogen-substituted alkyl group containing 1 to 6 carbon atoms, or the like; X 1 represents hydrogen atom or a halogen atom; A represents nitrogen atom or a moiety represented by formula (II):

  提供了一种喹诺酮合成抗菌剂和治疗感染的药物，对革兰氏阳性和革兰氏阴性细菌均表现出广谱和强效的抗菌活性，并且具有很高的安全性。所提供的化合物由以下式（I）表示： 其中R1和R2代表氢原子，或类似物；R3代表含有1至6个碳原子的烷基基团，或类似物；R4和R5独立地代表氢原子，含有1至6个碳原子的烷基基团，或类似物，但R4和R5不同时代表氢原子；或取代基R4和R5一起代表（a）包括由R4和R5共享的碳原子形成螺环结构与吡咯烷环形成螺环结构的3至6成员环结构；R6和R7独立地代表氢原子，含有1至6个碳原子的烷基基团，或类似物；R8代表含有1至6个碳原子的卤代烷基基团，或类似物；X1代表氢原子或卤原子；A代表氮原子或由式（II）表示的基团。
• TRI-, TETRA-SUBSTITUTED-3-AMINOPYRROLIDINE DERIVATIVE
  申请人：TAKAHASHI Hisashi

  公开号：US20090253726A1

  公开（公告）日：2009-10-08

  A quinolone synthetic antibacterial agent and a therapeutic agent for an infection which exhibit broad spectrum and strong antibacterial activity for both Gram positive and Gram negative bacteria, and which are also highly safe are provided. The compound provided is represented by formula (I):

  提供了一种喹诺酮合成抗菌剂和治疗感染的药物，具有广谱和强大的抗菌活性，对革兰氏阳性和革兰氏阴性细菌均有作用，并且非常安全。所提供的化合物由式（I）表示。
• CYCLOALKYL-SUBSTITUTED AMINOMETHYLPYRROLIDINE DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1134219A1

  公开（公告）日：2001-09-19

  This invention provides a quinolone derivative which exerts strong antibacterial action upon various bacteria and has high safety, and it relates to a compound having a structure of formula (I), its salts and hydrates thereof: R1 and R2: hydrogen, alkyl; n: 1 to 4; Q: following structure (Ia): [R3: alkyl, alkenyl, halogenoalkyl, cyclic alkyl, aryl, heteroaryl, alkoxyl, alkylamino; R4: hydrogen, alkylthio; R5: hydrogen, amino, hydroxyl, thiol, halogenomethyl, alkyl, alkenyl, alkynyl, alkoxyl; X1: halogen, hydrogen, A1: nitrogen, structure of formula (II): (X2: hydrogen, amino, halogen, cyano, halogenomethyl, halogenomethoxyl, alkyl, alkenyl, alkynyl, alkoxyl; R4 and R3 or X2 and R3 may together form a cyclic structure; Y: hydrogen, various ester forming groups]}.

  本发明提供了一种对多种细菌具有较强抗菌作用且安全性高的喹诺酮衍生物，它涉及一种具有式(I)结构的化合物及其盐类和水合物： R1和R2：氢、烷基；n：1至4；Q：以下结构（Ia）： [R3：烷基、烯基、卤代烷基、环烷基、芳基、杂芳基、烷氧基、烷基氨基；R4：氢、烷硫基；R5：氢、氨基、羟基、硫醇、卤代甲基、烷基、烯基、炔基、烷氧基；X1：卤素、氢，A1：氮，式（II）结构： (X2：氢、氨基、卤素、氰基、卤代甲基、卤代甲氧基、烷基、烯基、炔基、烷氧基；R4 和 R3 或 X2 和 R3 可共同形成环状结构；Y：氢、各种形成酯的基团]}。
• TRI- OR TETRA-SUBSTITUTED-3-AMINOPYRROLIDINE DERIVATIVES
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1882689A1

  公开（公告）日：2008-01-30

  A quinolone synthetic antibacterial agent and a therapeutic agent for an infection which exhibit broad spectrum and strong antibacterial activity for both Gram positive and Gram negative bacteria, and which are also highly safe are provided. The compound provided is represented by following formula (I): wherein R1 and R2 represent hydrogen atom, or the like; R3 represents an alkyl group containing 1 to 6 carbon atoms, or the like; R4 and R5 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like, with the proviso that R4 and R5 do not simultaneously represent hydrogen atom; or the substituents R4 and R5 together represent (a) a 3- to 6-membered cyclic structure including the carbon atom shared by R4 and R5 to form a spirocyclic structure with the pyrrolidine ring; R6 and R7 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like; R8 represents a halogen-substituted alkyl group containing 1 to 6 carbon atoms, or the like; X1 represents hydrogen atom or a halogen atom; A represents nitrogen atom or a moiety represented by formula (II):

  本发明提供了一种喹诺酮类合成抗菌剂和一种治疗感染的药物，对革兰氏阳性菌和革兰氏阴性菌均具有广谱、强效的抗菌活性，而且安全性高。所提供的化合物由下式(I)表示： 其中 R1 和 R2 代表氢原子或类似物；R3 代表含有 1 至 6 个碳原子的烷基或类似物；R4 和 R5 独立地代表氢原子、含有 1 至 6 个碳原子的烷基或类似物，但 R4 和 R5 不同时代表氢原子；或取代基 R4 和 R5 共同代表 (a) 3 至 6 元环状结构，包括 R4 和 R5 共用的碳原子，与吡咯烷环形成螺环结构；R6 和 R7 独立代表氢原子、含 1 至 6 个碳原子的烷基或类似物；R8 代表含 1 至 6 个碳原子的卤素取代烷基或类似物；X1 代表氢原子或卤素原子；A 代表氮原子或式 (II) 所代表的分子：
• Tri-or tetra-substituted-3-aminopyrrolidine deritatives
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2463274A1

  公开（公告）日：2012-06-13

  A compound of the following formula (19) or (20): wherein R11 represents a hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, or a substituted carbonyl group derived from an amino acid, a dipeptide, or a tripeptide, or a protective group of the amino acid; the alkyl group being optionally substituted with a substituent selected from the group consisting of hydroxy group, amino group, halogen atom, an alkylthio group containing 1 to 6 carbon atoms, and an alkoxy group containing 1 to 6 carbon atoms; R21 represents a hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or a cycloalkyl group containing 3 to 6 carbon atoms or a protective group of the amino acid; the alkyl group being optionally substituted with a substituent selected from the group consisting of hydroxy group, amino group, halogen atom, an alkylthio group containing 1 to 6 carbon atoms, and an alkoxy group containing 1 to 6 carbon atoms; R3 represents a methyl group; ethyl group; vinyl group; fluoro-substituted methyl group or ethyl group; methyl group or ethyl group having amino group or hydroxy group; and methyl group having thiomethyl group or methoxy group; R4 and R5 together form cyclopropane ring or cyclobutane ring including the carbon atom shared by R4 and R5 to form a spirocyclic structure; R6 and R7 independently represent hydrogen atoms, and R13 represents protective group of the amino group.

  下式(19)或(20)的化合物： 其中 R11 代表氢原子、含 1 至 6 个碳原子的烷基、含 3 至 6 个碳原子的环烷基、或衍生自氨基酸、二肽或三肽的取代羰基、或氨基酸的保护基；烷基可任选被选自羟基、氨基、卤素原子、含 1 至 6 个碳原子的烷硫基和含 1 至 6 个碳原子的烷氧基的取代基所取代； R21 代表氢原子、含 1 至 6 个碳原子的烷基、含 3 至 6 个碳原子的环烷基或氨基酸的保护基；该烷基可任选被选自羟基、氨基、卤素原子、含 1 至 6 个碳原子的烷硫基和含 1 至 6 个碳原子的烷氧基组成的取代基取代； R3 代表甲基；乙基；乙烯基；氟取代的甲基或乙基；具有氨基或羟基的甲基或乙基； 以及具有硫代甲基或甲氧基的甲基； R4 和 R5 共同形成环丙烷环或环丁烷环，包括 R4 和 R5 共有的碳原子，形成螺环结构； R6 和 R7 分别代表氢原子，以及 R13 代表氨基的保护基团。