2-氯-7-氟-6-甲氧基-3-喹啉甲醛 | 251902-52-0

• 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
• 中文名称: 2-氯-7-氟-6-甲氧基-3-喹啉甲醛
• 英文名称: 2-chloro-7-fluoro-6-methoxy-3-quinolinecarbaldehyde
• 英文别名: 2-chloro-7-fluoro-6-methoxyquinoline-3-carbaldehyde
• CAS: 251902-52-0
• 化学式: C₁₁H₇ClFNO₂
• 分子量: 239.633
• InChiKey: QKUWYCZGAMVPER-UHFFFAOYSA-N

物化性质

• 沸点：
  383.3±37.0 °C(Predicted)
• 密度：
  1.421±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-7-氟-6-甲氧基-3-喹啉甲醛 在 sodium tetrahydroborate 、 t-Bu₃Ph 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 2-(2-Chloro-7-fluoro-6-methoxy-quinolin-3-ylmethyl)-5-ethyl-5-hydroxy-2,5,6,9-tetrahydro-8-oxa-2-aza-benzocycloheptene-1,7-dione
  参考文献：
  名称：

  Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues

  摘要：

  Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell. lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

  DOI：

  10.1021/jm980400l
• 作为产物：
  描述：

  3-氟-4-甲氧基苯胺 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-氯-7-氟-6-甲氧基-3-喹啉甲醛
  参考文献：
  名称：

  SUBSTITUTED 6,7-DIALKOXY-3-ISOQUINOLINOL DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASE 10 (PDE10A)

  摘要：

  本发明涉及具有以下公式的化合物 其中R'，R1，到R7和Ar如本文所述定义。这些化合物作为磷酸二酯酶10（PDE10A）的抑制剂，可用于治疗中枢神经系统疾病，如精神疾病，也可用于治疗例如肥胖、2型糖尿病、代谢综合征、葡萄糖不耐受、疼痛和眼科疾病。

  公开号：

  US20120214837A1

文献信息

• Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06339091B1

  公开（公告）日：2002-01-15

  The compound of the formula wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.

  该化合物的结构如下所示，其中取代基的定义如规范中所述，以及其无毒、药用可接受的盐，可用于治疗病毒感染、寄生虫病和癌症的治疗。
• New analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them
  申请人：——

  公开号：US20030004150A1

  公开（公告）日：2003-01-02

  A compound of the formula 1 wherein the substituents are defined as in the specification which compounds are useful in the treatment of cancer.

  其中取代基如规范中所定义的化合物的化学式，这些化合物在癌症治疗中很有用。
• New tetracyclic analogues of camptothecins, their preparation processes, their use as medicaments and the pharmaceutical compositions containing them
  申请人：——

  公开号：US20010000521A1

  公开（公告）日：2001-04-26

  The invention relates to new tetracyclic analogues of camptothecin, their preparation processes, their use as medicaments and the pharmaceutical compositions containing them. Said analogues, which include in particular 3-hydroxy-3-(4-oxo-4,6-dihydroindolizino [1,2-b] quinoline-2-yl)pentanoic acid, have a powerful biological activity inhibiting topoisomerase I and/or topoisomerase II.

  本发明涉及新的四环类拓扑异构酶抑制剂喜树碱类似物，其制备方法，其作为药物的使用以及含有它们的制药组合物。这些类似物，尤其包括3-羟基-3-（4-氧代-4,6-二氢吲哚并［1,2-b］喹啉-2-基）戊酸，具有强大的生物活性，能够抑制拓扑异构酶I和/或拓扑异构酶II。
• [EN] PRO-DRUGS AND COUNTERPARTS OF CAMPTOTHECIN, THEIR APPLICATION AS MEDICINES<br/>[FR] FORMES PRODROGUES ET ANALOGUES DE LA CAMPTOTHECINE, LEUR APPLICATION COMME MEDICAMENTS
  申请人：SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (S.C.R.A.S.)

  公开号：WO1998028304A1

  公开（公告）日：1998-07-02

  (EN) The invention concerns novel counterparts of camptothecin and in particular products complying with the following formulae: 8-ethyl-8,9-dihydro-8-hydroxy-1-benzyl-2$i(H),10$i(H),12$i(H-)[1,3]oxazino[5,6-$i(f)]oxepino[3',4':6,7]indolizino[1,2-$i(b)]quinolein-10,13(15$i(H))-dione; 5-ethyl-9,10-difluoro-4,5-dihydro-5-(2-amino-1-oxoethoxy)-1$i(H)-oxepino[3',4':6,7]indolizino[1,2-$i(b)]quinolein-3,15(4$i(H),13$i(H))-dione; 5-ethyl-9,10-difluoro-4,5-dihydro-5-(2-amino-1-oxopropoxy)-1$i(H)-oxepino[3',4':6,7]indolizino[1,2-$i(b)]quinolein-3,15(4$i(H),13$i(H))-dione. The invention also concerns their method of preparation, their application as medicines, the pharmaceutical compositions containing them and their use in producing tumoricidal, antiviral and parasiticide medicines.(FR) L'invention concerne de nouveaux analogues de la camptothécine et en particulier les produits répondant aux formules suivantes: 8-éthyl-8,9-dihydro-8-hydroxy-1-benzyl-2$i(H), 10$i(H), 12$i(H)-[1,3]oxazino[5,6-$i(f)]oxépino[3',4':6,7]indolizino[1,2-$i(b)]quinoléine-10,13(15$i(H))-dione; 5-éthyl-9,10-difluoro-4,5-dihydro-5-(2-amino-1-oxoéthoxy)-1$i(H)-oxépino[3',4':6,7]indolizino[1,2-$i(b)]quinoléine-3,15(4$i(H),13$i(H))-dione; 5-éthyl-9,10-difluoro-4,5-dihydro-5-(2-amino-1-oxopropoxy)-1$i(H)-oxépino[3',4':6,7]indolizino[1,2-$i(b)]quinoléine-3,15(4$i(H),13$i(H))-dione; leur procédé de préparation, leur application comme médicaments, les compositions pharmaceutiques les renfermant et leur utilisation pour la réalisation de médicaments antitumoraux, antiviraux ou antiparasitaires.

  本发明涉及新型的喜树碱衍生物，特别是符合以下化学式的产品：8-乙基-8,9-二氢-8-羟基-1-苄基-2$i(H),10$i(H),12$i(H)-[1,3]噁唑[5,6-$i(f)]氧杂环[3',4':6,7]吲哚并[1,2-$i(b)]喹啉-10,13(15$i(H))-二酮；5-乙基-9,10-二氟-4,5-二氢-5-(2-氨基-1-氧乙氧基)-1$i(H)-氧杂环[3',4':6,7]吲哚并[1,2-$i(b)]喹啉-3,15(4$i(H),13$i(H))-二酮；5-乙基-9,10-二氟-4,5-二氢-5-(2-氨基-1-氧丙氧基)-1$i(H)-氧杂环[3',4':6,7]吲哚并[1,2-$i(b)]喹啉-3,15(4$i(H),13$i(H))-二酮。本发明还涉及它们的制备方法，作为药物的应用，含有它们的制药组合物以及用于生产抗肿瘤、抗病毒和杀虫药物的用途。
• Substituted 6,7-dialkoxy-3-isoquinolinol derivatives as inhibitors of phosphodiesterase 10 (PDE10A)
  申请人：Leblond Bertrand

  公开号：US08772316B2

  公开（公告）日：2014-07-08

  The invention relates to compounds of the formula wherein R′, R1, through R7 and Ar are as defined herein. These compounds are useful as inhibitors of phosphodiesterase 10 (PDE10A) which are useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type II diabetes, metabolic syndrome, glucose intolerance, pain and ophthalmic diseases.

  本发明涉及以下式的化合物，其中R′，R1至R7和Ar的定义如本文所述。这些化合物可用作磷酸二酯酶10（PDE10A）的抑制剂，其在治疗中枢神经系统疾病，如精神病，以及在治疗肥胖症、2型糖尿病、代谢综合征、葡萄糖不耐受、疼痛和眼科疾病方面有用。