6-bromo-2,4-dichloroquinoline-3-carbonitrile | 138580-81-1

• 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: 6-bromo-2,4-dichloroquinoline-3-carbonitrile
• CAS: 138580-81-1
• 化学式: C₁₀H₃BrCl₂N₂
• 分子量: 301.957
• InChiKey: NFMFHDSCFZKRNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-2,4-dichloroquinoline-3-carbonitrile 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 6-bromo-4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile
  参考文献：
  名称：

  PDE9抑制剂及其用途

  摘要：

  本发明属于医药技术领域，具体涉及式(I)所示的PDE9抑制剂化合物或其药学上可接受的盐、异构体，本发明还涉及这些化合物的药物制剂、药物组合物及其应用。R1、R2、环A、L、m和n如说明书中所定义。本发明化合物可用于制备治疗或者预防由PDE9介导的相关疾病的药物。

  公开号：

  CN111410659B
• 作为产物：
  描述：

  2-氨基-5-溴苯甲酸 在 硫酸 、 sodium ethanolate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 100.33h， 生成 6-bromo-2,4-dichloroquinoline-3-carbonitrile
  参考文献：
  名称：

  PDE9抑制剂及其用途

  摘要：

  本发明属于医药技术领域，具体涉及式(I)所示的PDE9抑制剂化合物或其药学上可接受的盐、异构体，本发明还涉及这些化合物的药物制剂、药物组合物及其应用。R1、R2、环A、L、m和n如说明书中所定义。本发明化合物可用于制备治疗或者预防由PDE9介导的相关疾病的药物。

  公开号：

  CN111410659B

文献信息

• [EN] PYRAZOLO[4,3-C]QUINOLINE DERIVATIVES FOR INHIBITION OF β-GLUCURONIDASE<br/>[FR] DÉRIVÉS DE PYRAZOLO[4,3-C]QUINOLINE POUR L'INHIBITION DE Β-GLUCURONIDASE
  申请人：DCB-USA LLC

  公开号：WO2016191576A1

  公开（公告）日：2016-12-01

  The present invention provides novel pyrazolo[4,3-c]quinoline derivatives exhibiting specifically inhibition activity to microbiota β-glucuronidase, whereby providing potent activities to prevent chemotherapy-induced diarrhea (CID) of cancers. Therefore, the compounds of the present invention can be used as (1) chemotherapy-adjuvant to prevent chemotherapy-induced diarrhea (CID) and enhance chemotherapeutic efficiency of cancers; (2) health-food supplement to prevent the carcinogens induced colon carcinoma.

  本发明提供了一种新型的吡唑并[4,3-c]喹啉衍生物，其具有特异性抑制微生物群体β-葡萄糖醛酸酶的活性，从而提供了强大的活性，以预防癌症化疗引起的腹泻。因此，本发明的化合物可以用作(1)化疗辅助剂，以预防化疗引起的腹泻，并增强癌症的化疗效果；(2)健康食品补充剂，以预防致癌物质引起的结肠癌。
• PYRAZOLO[4,3-C]QUINOLINE DERIVATIVES FOR INHIBITION OF B-GLUCURONIDASE
  申请人：Kaohsiung Medical University

  公开号：EP3662751A1

  公开（公告）日：2020-06-10

  The present invention provides novel pyrazolo[4,3-c]quinoline derivatives exhibiting specifically inhibition activity to microbiota β-glucuronidase, whereby providing potent activities to prevent chemotherapy-induced diarrhea (CID) of cancers. Therefore, the compounds of the present invention can be used as (1) chemotherapy-adjuvant to prevent chemotherapy-induced diarrhea (CID) and enhance chemotherapeutic efficiency of cancers; (2) health-food supplement to prevent the carcinogens induced colon carcinoma.

  本发明提供的新型吡唑并[4,3-c]喹啉衍生物对微生物群β-葡萄糖醛酸酶具有特异性抑制活性，从而提供了预防癌症化疗诱导腹泻（CID）的强效活性。因此，本发明的化合物可用作（1）化疗辅助剂，预防化疗诱导性腹泻（CID），提高癌症的化疗效率；（2）保健食品，预防致癌物质诱导的结肠癌。
• Pyrazolo[4,3-C] quinoline derivatives for inhibition of β-glucuronidase
  申请人：Kaohsiung Medical University

  公开号：US11052072B2

  公开（公告）日：2021-07-06

  The present invention provides novel pyrazolo[4,3-c]quinoline derivatives exhibiting specifically inhibition activity to microbiota β-glucuronidase, whereby providing potent activities to prevent chemotherapy-induced diarrhea (CID) of cancers. Therefore, the compounds of the present invention can be used as (1) chemotherapy-adjuvant to prevent chemotherapy-induced diarrhea (CID) and enhance chemotherapeutic efficiency of cancers; (2) health-food supplement to prevent the carcinogens induced colon carcinoma.

  本发明提供的新型吡唑并[4,3-c]喹啉衍生物对微生物群β-葡萄糖醛酸酶具有特异性抑制活性，从而提供了预防癌症化疗诱导腹泻（CID）的强效活性。因此，本发明的化合物可用作（1）化疗辅助剂，预防化疗诱导性腹泻（CID），提高癌症的化疗效率；（2）保健食品，预防致癌物质诱导的结肠癌。
• Pyrazolo[4,3-c]quinoline derivatives for inhibition of β-glucuronidase
  申请人：Kaohsiung Medical University

  公开号：US11135206B2

  公开（公告）日：2021-10-05

  The present invention provides novel pyrazolo[4,3-c]quinoline derivatives exhibiting specifically inhibition activity to microbiota β-glucuronidase, whereby providing potent activities to prevent chemotherapy-induced diarrhea (CID) of cancers. Therefore, the compounds of the present invention can be used as (1) chemotherapy-adjuvant to prevent chemotherapy-induced diarrhea (CID) and enhance chemotherapeutic efficiency of cancers; (2) health-food supplement to prevent the carcinogens induced colon carcinoma.

  本发明提供的新型吡唑并[4,3-c]喹啉衍生物对微生物群β-葡萄糖醛酸酶具有特异性抑制活性，从而提供了预防癌症化疗诱导腹泻（CID）的强效活性。因此，本发明的化合物可用作（1）化疗辅助剂，预防化疗诱导性腹泻（CID），提高癌症的化疗效率；（2）保健食品，预防致癌物质诱导的结肠癌。
• Specific Inhibition of Bacterial β-Glucuronidase by Pyrazolo[4,3-<i>c</i>]quinoline Derivatives via a pH-Dependent Manner To Suppress Chemotherapy-Induced Intestinal Toxicity
  作者：Kai-Wen Cheng、Chih-Hua Tseng、Chia-Ning Yang、Cherng-Chyi Tzeng、Ta-Chun Cheng、Yu-Lin Leu、Yu-Chung Chuang、Jaw-Yuan Wang、Yun-Chi Lu、Yeh-Long Chen、Tian-Lu Cheng

  DOI：10.1021/acs.jmedchem.7b00963

  日期：2017.11.22

  The direct inhibition of bacterial,beta-glucuronidase (beta G) activity is expected to reduce the reactivation of glucuronide-conjugated drugs in the intestine, thereby reducing drug toxicity. In this study, we report on the effects of pyrazolo [4,3-c] quinolines acting as a new class of bacterial beta G-specific inhibitors in a pH-dependent manner. Refinement of this chemotype for establishing structure-activity relationship resulted in the identification of potential leads. Notably, the oral administration of 3-amino-4-(4-fluorophenylamino)-1H-pyrazolo[4,3-c]quinoline (42) combined with chemotherapeutic CPT-11 treatment prevented CPT-11-induced serious diarrhea while maintaining the antitumor efficacy in tumor-bearing mice. Importantly, the inhibitory effects of 42 to E. coli beta G was reduced as the pH decreased due to the various surface charges of the active pocket of the enzyme, which may make their combination more favorable at neutral pH. These results demonstrate novel insights into the potent bacterial beta G-specific inhibitor that would allow this inhibitor to be used for the purpose of reducing drug toxicity.