2-chloro-8-methoxyquinoxaline | 659729-70-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-chloro-8-methoxyquinoxaline
• 英文别名: 2-Chlor-8-methoxy-chinoxalin
• CAS: 659729-70-1
• 化学式: C₉H₇ClN₂O
• 分子量: 194.62
• InChiKey: JSVCPIOLVZAREV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-8-methoxyquinoxaline 在 ammonium hydroxide 、 copper(l) iodide 、 三氯化铝 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 、 苯 为溶剂， 反应 2.17h， 生成 8-[6-(4-trifluoromethyl-phenyl)pyrimidin-4-yloxy]quinoxalin-2-ylamine
  参考文献：
  名称：

  Novel Vanilloid Receptor-1 Antagonists:  2. Structure−Activity Relationships of 4-Oxopyrimidines Leading to the Selection of a Clinical Candidate

  摘要：

  A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23, a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent "on-target" biochemical challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clinical trials.

  DOI：

  10.1021/jm070190p
• 作为产物：
  描述：

  8-methoxy-1H-quinoxalin-2-one 在 三氯氧磷 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成 2-chloro-8-methoxyquinoxaline
  参考文献：
  名称：

  Vanilloid receptor ligands and their use in treatments

  摘要：

  嘌呤醚及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、伴有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧灼性疼痛、交感神经维持性疼痛、感觉缺失综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿生殖、胃肠或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道紊乱、胃溃疡、十二指肠溃疡、腹泻、由坏死剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。

  公开号：

  US20050176726A1

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Wang Hui-Ling

  公开号：US20050176726A1

  公开（公告）日：2005-08-11

  Pyrimidine ethers and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  嘌呤醚及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、伴有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧灼性疼痛、交感神经维持性疼痛、感觉缺失综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿生殖、胃肠或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道紊乱、胃溃疡、十二指肠溃疡、腹泻、由坏死剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• [EN] NOVEL BICYCLIC ANTIBIOTICS<br/>[FR] NOUVEAUX ANTIBIOTIQUES BICYCLIQUES
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2010084152A1

  公开（公告）日：2010-07-29

  Compounds of formula (I) wherein X1, X3; X4 and X6, each independently of the others, represents a nitrogen atom or CR2, with the proviso that at least one of X1, X3; X4 and X6 represents a nitrogen atom; X2 represents C-H, C-(C1-C6alkyl), C-(C1-C6alkoxy), C-halogen, C-COOH; X5 represents C-H or C-(C1-C6alkyl), C-halogen; R1 and R2, independently of one another, represent hydrogen or a substituent selected from hydroxy, halogen, carboxy, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, mercapto, cyano, nitro, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylamino- carbonyloxy, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylcarbonyloxy, C1-C6alkyl- sulfonyloxy, C1 -C6heteroalkylcarbonyloxy, C5-C6heterocyclylcarbonyloxy, C1-C6heteroalkyl, C1-C6heteroalkoxy, wherein heteroalkyl, heteroalkoxy groups or heterocyclyl comprise 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, in which substituents the alkyl moieties are unsubstituted or further substituted by halogeno, cyano, hydroxy, C1-C4alkoxy, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or substituted phenoxy or phenylcarbonyl, unsubstituted or substituted C5-C6heterocyclyl or carboxy; A1 represents a divalent group of one of the formulae -O-(CH2)m-(CH2)-, -S-(CH2)m-(CH2)- or -(C=O)O-(CH2)m-(CH2)-, wherein the (CH2)m moiety is optionally substituted by C1-C4alkyl, C2-C4alkenyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, morpholinomethyl, halogen, carboxy, hydroxy, C1-C4alkoxy; C1 -C4alkoxyC1 -C4alkyl, C1 -C4alkoxy(C1 -C4alkylenoxy)C1 -C4alkyl, benzyloxyC1 - C4alkyl, amino, mono- or di-(C1-C4alkyl)amino or acylamino, in which substituents the alkyl moieties can be further substituted by 1 or more fluoro atoms m is 0, 1 or 2, provided that the number of atoms in the direct chain between the two terminal valencies of A1 is at least 3, which group A1 is linked to A2 via the terminal (CH2)-moiety; A2 is a group selected from C3-C8cycloalkylene; saturated and unsaturated 4 to 8- membered heterocyclodiyl with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, which group A2 is unsubstituted or substituted; R4 represents hydrogen or C1 -C4alkyl; A3 represents C1-C4alkylene, C2-C4alkenylene, >C=O, -C(O)C1-C3alkylene-, -C(=O)NH-, or a group selected from -C2H4NH-, -C2H4O-, and -C2H4S- being linked to the adjacent NR4-group via the carbon atom; and G represents aryl or heteroaryl, which is unsubstituted or substituted and n is 0, 1 or 2; or a pharmaceutically acceptable salts, hydrates or solvates thereof are valuable antibacterial agents.

  式(I)中的化合物，其中X1、X3、X4和X6，每个独立地代表氮原子或CR2，但X1、X3、X4和X6中至少有一个代表氮原子；X2代表C-H、C-(C1-C6烷基)、C-(C1-C6烷氧基)、C-卤素、C-COOH；X5代表C-H或C-(C1-C6烷基)、C-卤素；R1和R2独立地代表氢或从羟基、卤素、羧基、氨基、C1-C6烷基氨基、二(C1-C6烷基)氨基、巯基、氰基、硝基、C1-C6烷基、C1-C6烷氧基、C1-C6烷硫基、C1-C6烷基氧基羰氧、C2-C6烯基、C2-C6炔基、C1-C6烷基羰氧、C1-C6烷基磺酰氧、C1-C6杂烷基羰氧、C5-C6杂环烷基羰氧、C1-C6杂烷基、C1-C6杂烷氧基中选择的取代基；A1代表以下式之一的二价基团：-O-(CH2)m-(CH2)-、-S-(CH2)m-(CH2)-或-(C=O)O-(CH2)m-(CH2)-，其中(CH2)m基团可选择地由C1-C4烷基、C2-C4烯基、C3-C6环烷基、C3-C6环烷基甲基、吗啉基甲基、卤素、羧基、羟基、C1-C4烷氧基；C1-C4烷氧基C1-C4烷基、C1-C4烷氧基(C1-C4烷氧基)C1-C4烷基、苄氧基C1-C4烷基、氨基、单或二-(C1-C4烷基)氨基或酰胺基取代，其中取代基的烷基基团可以进一步由1个或多个氟原子取代；m为0、1或2，前提是A1的两个末端价的直链中的原子数至少为3，该基团A1通过末端(CH2)-基团与A2连接；A2是选择自C3-C8环烷基烯；饱和和不饱和的含氮、氧和硫的1、2或3个杂原子的4至8环杂环二基团，该基团A2未取代或取代；R4代表氢或C1-C4烷基；A3代表C1-C4亚烷基、C2-C4烯亚烷基、>C=O、-C(O)C1-C3烷基-、-C(=O)NH-，或选择自-C2H4NH-、-C2H4O-和-C2H4S-的基团，通过碳原子与相邻的NR4基团连接；G代表芳香族或杂芳基，未取代或取代，n为0、1或2；或其药学上可接受的盐、水合物或溶剂合物是有价值的抗菌剂。
• [EN] VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS<br/>[FR] LIGANDS DE RECEPTEUR VANILLOIDE ET LEUR UTILISATION DANS DES TRAITEMENTS
  申请人：AMGEN INC

  公开号：WO2004014871A1

  公开（公告）日：2004-02-19

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  含有通用结构和组成的化合物及其组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群性头痛、混合性血管和非血管综合症、紧张性头痛、普通炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定的膀胱疾病、牛皮癣、带有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛及相关的高敏性和触痛，神经痛及相关的高敏性和触痛、糖尿病神经病疼痛、烧伤后神经痛、交感神经维持的疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸道、泌尿生殖系统、胃肠道或血管区域的内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、普通胃肠疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• [EN] PYRIMIDINE DERIVATIVES FOR USE AS VANILLOID RECEPTOR LIGANDS AND THEIR USE IN THE TREATMENT OF PAIN<br/>[FR] DERIVES DE PYRIMIDINE UTILISES COMME LIGANDS DE RECEPTEUR DE VANILLOIDE ET LEUR UTILISATION DANS LE TRAITEMENT DE LA DOULEUR
  申请人：AMGEN INC

  公开号：WO2005077944A1

  公开（公告）日：2005-08-25

  Pyrimidine ethers and compositions containing them, fo use as vanilloid receptor ligands for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders. Wherein R1 - R4 and X are as defined in the claims.

  含有嘧啶醚化合物的组合物，用作vanilloid受体配体，用于治疗急性、炎症性和神经病理性疼痛、牙痛、普通头痛、偏头痛、群集性头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定膀胱疾病、牛皮癣、具有炎症成分的皮肤疾病、慢性炎症状态、炎症性疼痛及相关的高敏性和触痛、神经病理性疼痛及相关的高敏性和触痛、糖尿病性神经病疼痛、交感神经维持的疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠或血管区域内脏运动障碍、创伤、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。其中R1-R4和X的定义如权利要求中所述。
• Novel Bicyclic Antibiotics
  申请人：Gaucher Berangere

  公开号：US20120040957A1

  公开（公告）日：2012-02-16

  Compounds of formula (I) wherein X1, X3; X4 and X6, each independently of the others, represents a nitrogen atom or CR2, with the proviso that at least one of X1, X3; X4 and X6 represents a nitrogen atom; X2 represents C—H, C—(C1-C6alkyl), C—(C1-C6alkoxy), C-halogen, C—COOH; X5 represents C—H or C—(C1-C6alkyl), C-halogen; R1 and R2, independently of one another, represent hydrogen or a substituent selected from hydroxy, halogen, carboxy, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, mercapto, cyano, nitro, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylamino-carbonyloxy, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylcarbonyloxy, C1-C6alkyl-sulfonyloxy, C1-C6heteroalkylcarbonyloxy, C5-C6heterocyclyl-carbonyloxy, C1-C6heteroalkyl, C1-C6heteroalkoxy, wherein heteroalkyl, heteroalkoxy groups or heterocyclyl comprise 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, in which substituents the alkyl moieties are unsubstituted or further substituted by halogeno, cyano, hydroxy, C1-C4alkoxy, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or substituted phenoxy or phenylcarbonyl, unsubstituted or substituted C5-C6heterocyclyl or carboxy; A1 represents a divalent group of one of the formulae —O—(CH 2 ) m —(CH 2 )—, —S—(CH 2 ) m —(CH 2 )— or —(C═O)O—(CH 2 ) m —(CH 2 )—, wherein the (CH 2 ) m moiety is optionally substituted by C1-C4alkyl, C2-C4alkenyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, morpholinomethyl, halogen, carboxy, hydroxy, C1-C4alkoxy; C1-C4alkoxyC1-C4alkyl, C1-C4alkoxy(C1-C4alkylenoxy)C1-C4alkyl, benzyloxyC1-C4alkyl, amino, mono- or di-(C1-C4alkyl)amino or acylamino, in which substituents the alkyl moieties can be further substituted by 1 or more fluoro atoms m is 0, 1 or 2, provided that the nunber of atoms in the direct chain between the two terminal valencies of A 1 is at least 3, which group A 1 is linked to A 2 via the terminal (CH 2 )-moiety; A 2 is a group selected from C 3 -C 8 cycloalkylene; saturated and unsaturated 4 to 8 -membered heterocyclodiyl with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, which group A 2 is unsubstituted or substituted; R 4 represents hydrogen or C 1 -C 4 alkyl; A 3 represents C 1 -C 4 alkylene, C 2 -C 4 alkenylene, >C═O, —C(O)C 1 -C 3 alkylene-, —C(═O)NH—, or a group selected from —C 2 H 4 NH—, —C 2H 4 O—, and —C 2 H 4 S— being linked to the adjacent NR 4 -group via the carbon atom; and G represents aryl or heteroaryl, which is unsubstituted or substituted and n is 0, 1 or 2; or a pharmaceutically acceptable salts, hydrates or solvates thereof are valuable antibacterial agents.

  化合物式(I)中，其中X1、X3、X4和X6分别独立地表示氮原子或CR2，但至少其中一个表示氮原子；X2表示C-H、C-(C1-C6烷基)、C-(C1-C6烷氧基)、C-卤素、C-COOH；X5表示C-H或C-(C1-C6烷基)、C-卤素；R1和R2独立地表示氢或从羟基、卤素、羧基、氨基、C1-C6烷基氨基、二(C1-C6烷基)氨基、巯基、氰基、硝基、C1-C6烷基、C1-C6烷氧基、C1-C6烷基硫基、C1-C6烷基氨基羰氧基、C2-C6烯基、C2-C6炔基、C1-C6烷基羰氧基、C1-C6烷基磺酰氧基、C1-C6杂烷基羰氧基、C5-C6杂环基羰氧基、C1-C6杂烷基、C1-C6杂烷氧基中选择的取代基，其中杂烷基、杂烷氧基或杂环基包括1、2或3个从氮、氧和硫选择的杂原子，在这些取代基中，烷基基团未取代或进一步取代为卤代、氰基、羟基、C1-C4烷氧基、C1-C4烷基羧基、C1-C4烷氧羰基、未取代或取代的苯氧基或苯基羧基、未取代或取代的C5-C6杂环基或羧基；A1表示一个二价基团，其中之一为式之一的基团-O-(CH2)m-(CH2)-、-S-(CH2)m-(CH2)-或-(C═O)O-(CH2)m-(CH2)-，其中(CH2)m基团可以选择地被C1-C4烷基、C2-C4烯基、C3-C6环烷基、C3-C6环烷基甲基、吗啉基甲基、卤素、羧基、羟基、C1-C4烷氧基取代；C1-C4烷氧基C1-C4烷基、C1-C4烷氧基(C1-C4烷氧基)C1-C4烷基、苄氧基C1-C4烷基、氨基、单取代或双取代(C1-C4烷基)氨基或酰基氨基，在这些取代基中，烷基基团可以进一步取代1个或多个氟原子，m为0、1或2，前提是A1的两个端面价之间的直链原子数至少为3，该基团A1通过端面(CH2)基团与A2相连；A2是选择自C3-C8环烷基、饱和和不饱和的1、2或3个从氮、氧和硫选择的杂环二基，该基团A2未取代或取代；R4表示氢或C1-C4烷基；A3表示C1-C4烷基、C2-C4烯基、>C═O、-C(O)C1-C3烷基、-C(═O)NH-或选择自-C2H4NH-、-C2H4O-和-C2H4S-的基团，通过碳原子与相邻的NR4基团相连；G表示未取代或取代的芳基或杂芳基，其中n为0、1或2；或其药学上可接受的盐、水合物或溶剂。这些化合物是有价值的抗菌剂。