2-氨基-3-甲基-6H-吡啶并[5,6-e]苯并咪唑-7-酮 | 108043-88-5

• 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-氨基-3-甲基-6H-吡啶并[5,6-e]苯并咪唑-7-酮
• 中文别名: 4-(乙酯基&lt乙氧羰基&gt亚硝氨基)-4-(3-吡啶基)丁醛
• 英文名称: 2-Amino-3,6-dihydro-3-methyl-7H-imidazo(4,5-f)quinoline-7-one
• 英文别名: 2-amino-3-methyl-6H-imidazo[4,5-f]quinolin-7-one
• CAS: 108043-88-5
• 化学式: C₁₁H₁₀N₄O
• 分子量: 214.22
• InChiKey: RRWYTKOWRFCKBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-amino-3-methyl-6H-imidazo[4,5-f]quinolin-7-one;hydrobromide 、 sodium hydroxide 以46%的产率得到
  参考文献：
  名称：

  BASHIR, MOHAMAD;KINGSTON, DAVID G. I.;CARMAN, ROBERT J.;TASSELL, ROGER L.+, HETEROCYCLES, 26,(1987) N 11, C. 2877-2886

  摘要：

  DOI：

文献信息

• Molecular flux rates through critical pathways measured by stable isotope labeling in vivo, as biomarkers of drug action and disease activity
  申请人：The Regents of the University of California

  公开号：US10466253B2

  公开（公告）日：2019-11-05

  The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides the necessary information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through one or more metabolic pathways of interest. By this method, a comparison between subjects and control subjects reveals the effects of the chemical entity or entities on the biomarkers. This, in turn, allows for the identification of potential therapeutic uses or toxicities of the compound. Combinations of compounds can also be systematically evaluated for complementary, synergistic, or antagonistic actions on the metabolic pathways of interest, using the methods of the present invention as a strategy for identifying and confirming novel therapeutic or toxic combinations of compounds.

  本文所述方法可对受试者的化合物进行评价，以评估其疗效或毒性作用。分析目标是被认为与疾病发病机制有关的一个或多个基本生化过程（即代谢过程）。一个或多个生化过程中的分子通量率可作为生物标志物，并与对照受试者（即未接触化合物的受试者）的分子通量率（即生物标志物）进行量化和比较。受试者体内的生物标志物相对于对照受试者体内的生物标志物的任何变化，都可为评估给药的疗效或毒性效应提供必要的信息，并在需要时进一步开发化合物。在本发明的一个方面，给受试者施用稳定同位素标记的底物分子，并以揭示通过一条或多条相关代谢途径的分子通量速率的方式将标记结合到靶分子中。通过这种方法，受试者与对照受试者之间的比较可以揭示化学实体对生物标志物的影响。这反过来又可以确定化合物的潜在治疗用途或毒性。还可以使用本发明的方法系统地评估化合物组合对相关代谢途径的互补、协同或拮抗作用，以此作为识别和确认新型治疗或毒性化合物组合的策略。
• Isolation of epithelial cells or their biochemical contents from excreta after in vivo isotopic labeling
  申请人：Hellerstein K. Marc

  公开号：US20050238577A1

  公开（公告）日：2005-10-27

  The methods of the present invention allow for the non-invasive or minimally invasive isolation of epithelial cells or their biochemical contents from excreta after in vivo isotopic labeling. Once isolated, the labeled epithelial cells or their labeled biochemical contents find use as kinetic biomarkers of diseases of epithelial tissues including epithelial cancers and epithelial proliferative disorders such as psoriasis and benign prostate hyperplasia. The biomarkers are useful in diagnosing a disease of epithelial tissue origin, monitoring therapeutic efficacy of compounds or combinations of compounds used to treat diseases of epithelial tissue origin, screen new chemical entities or biological factors or combinations of chemical entities or biological factors, or mixtures thereof, for therapeutic activity in animal models of diseases of epithelial tissue origin or in human clinical trials, or test for toxicity on epithelial tissues from exposure to therapeutic compounds or new chemical entities or environmental chemicals such as industrial or occupational chemicals, environmental pollutants, food additives, and cosmetics.

  本发明的方法可以在体内同位素标记后，从排泄物中非侵入性或微侵入性地分离上皮细胞或其生化内容物。一旦分离出来，标记的上皮细胞或其标记的生化内容物可用作上皮组织疾病的动力学生物标记物，包括上皮癌和上皮增生性疾病，如牛皮癣和良性前列腺增生。这些生物标志物可用于诊断上皮组织源性疾病、监测用于治疗上皮组织源性疾病的化合物或化合物组合的疗效、筛选新的化学实体或生物因子或化学实体或生物因子组合或其混合物，以确定其在上皮组织源性疾病动物模型或人体临床试验中的治疗活性，或检测暴露于治疗化合物或新化学实体或环境化学品（如工业或职业化学品、环境污染物、食品添加剂和化妆品）对上皮组织的毒性。
• In vivo measurement of the relative fluxes through ribonucleotide reductase vs. deoxyribonucleoside pathways using isotopes
  申请人：Hellerstein K. Marc

  公开号：US20050255509A1

  公开（公告）日：2005-11-17

  The methods of the present invention allow for the measurement of ribonucleotide reductase (RR) activity, an important enzyme in the de novo DNA synthesis pathway. Ribonucleotide reductase converts all four ribonucleotides to their deoxy form and is a rate-controlling step in this pathway. Biosynthetic pathways of deoxyribonucleotides (dN) have received considerable attention in the context of anti-proliferative chemotherapy. Inhibitors of various steps in dN biosynthesis, including inhibitors of RR are among the most useful chemotherapeutic agents in cancer, viral infections, and other therapeutic uses. DNA synthesis from the dN salvage pathway is also an important component to DNA replication. The relative contributions from RR vs. salvage pathways are critical to the actions and effectiveness of chemotherapeutic agents that act on nucleoside metabolic pathways. Until now, however, it has not been possible to study these metabolic processes in vivo. Disclosed within are methods of measuring RR activity in vivo and in vitro which find use, among other things, in drug discovery, development, and approval.

  本发明的方法可以测量核糖核苷酸还原酶（RR）的活性，RR 是 DNA 新合成途径中的一种重要酶。核糖核苷酸还原酶将所有四种核糖核苷酸转化为脱氧形式，是该途径中的一个速率控制步骤。在抗增殖化疗方面，脱氧核苷酸（dN）的生物合成途径受到了广泛关注。dN 生物合成各步骤的抑制剂，包括 RR 的抑制剂，是癌症、病毒感染和其他治疗用途中最有用的化疗药物之一。dN 挽救途径的 DNA 合成也是 DNA 复制的重要组成部分。RR与挽救途径的相对贡献对于作用于核苷代谢途径的化疗药物的作用和效果至关重要。然而，到目前为止，还无法在体内研究这些代谢过程。本研究公开了体内和体外测量 RR 活性的方法，这些方法主要用于药物发现、开发和审批。
• SCREENING FOR MODULATORS OF METALYATION PATHWAYS FOR METALLOPROTEINS
  申请人：Viamet Pharmaceuticals, Inc.

  公开号：EP1938107A2

  公开（公告）日：2008-07-02
• MICROTUBULE SYNTHESIS AS A BIOMARKER
  申请人：Kinemed, Inc.

  公开号：EP1949085A2

  公开（公告）日：2008-07-30