4-氯-2-甲基-1,8-萘啶 | 1221272-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-2-甲基-1,8-萘啶
• 中文别名: 4-氯-2-甲基-1,8-二氮杂萘
• 英文名称: 4-chloro-2-methyl-1,8-naphthyridine
• CAS: 1221272-96-3
• 化学式: C₉H₇ClN₂
• 分子量: 178.621
• InChiKey: ANAARUOUJJHNRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-氯-2-甲基-1,8-萘啶 在 sodium azide 、 15-冠醚-5 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以548 mg的产率得到4-azido-2-methyl-1,8-naphthyridine
  参考文献：
  名称：

  Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R)

  摘要：

  The insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase (RTK) involved in all stages of the development and propagation of breast and other cancers. The inhibition of IGF-1R by small molecules remains a promising strategy to treat cancer. Herein, we explore SAR around previously characterized lead compound (1), which is an aryl-heteroaryl urea (AHU) consisting of 4-aminoquinaldine and a substituted aromatic ring system. A library of novel AHU compounds was prepared based on derivatives of the 4-aminoquinoline heterocycle (including various 2-substituted derivatives, and naphthyridines). The compounds were screened for in vitro inhibitory activity against IGF-1R, and several compounds with improved activity (3-5 mu M) were identified. Furthermore, a computational docking study was performed, which identifies a fairly consistent lowest energy mode of binding for the more-active set of inhibitors in this series, while the less-active inhibitors do not adopt a consistent mode of binding. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.071
• 作为产物：
  描述：

  2-氨基烟酸 、 丙酮 在 三氯氧磷 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 6.17h， 生成 4-氯-2-甲基-1,8-萘啶
  参考文献：
  名称：

  Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R)

  摘要：

  The insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase (RTK) involved in all stages of the development and propagation of breast and other cancers. The inhibition of IGF-1R by small molecules remains a promising strategy to treat cancer. Herein, we explore SAR around previously characterized lead compound (1), which is an aryl-heteroaryl urea (AHU) consisting of 4-aminoquinaldine and a substituted aromatic ring system. A library of novel AHU compounds was prepared based on derivatives of the 4-aminoquinoline heterocycle (including various 2-substituted derivatives, and naphthyridines). The compounds were screened for in vitro inhibitory activity against IGF-1R, and several compounds with improved activity (3-5 mu M) were identified. Furthermore, a computational docking study was performed, which identifies a fairly consistent lowest energy mode of binding for the more-active set of inhibitors in this series, while the less-active inhibitors do not adopt a consistent mode of binding. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.071

文献信息

• Hetaryl-[1,8]naphthyridine derivatives
  申请人：Jonczyk Alfred

  公开号：US20120295902A1

  公开（公告）日：2012-11-22

  Novel hetaryl-[1,8]naphthyridine derivatives of formula (I) wherein R1, R2, W 1 , W 3 , W 5 and W 6 have the meaning according to claim 1 , are inhibitors of ATP consuming proteins, and can be employed, inter alia, for the treatment of tumors.

  新型杂芳基-[1,8]萘啶衍生物的化学式（I），其中R1、R2、W1、W3、W5和W6的含义如权利要求书中所述，是ATP消耗蛋白的抑制剂，可用于治疗肿瘤。
• [EN] PYRROLIDINE AND BICYCLOHETEROARYL CONTAINING OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA CONTENANT DE LA PYRROLIDINE ET DE LA BICYCLOHÉTÉROARYLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2021094312A1

  公开（公告）日：2021-05-20

  The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations; or alpha synucleinopathies, in particular Parkinson's disease, dementia due to Parkinson's (or neurocognitive disorder due to Parkinson's disease), dementia with Lewy bodies, multiple system atrophy, or alpha synucleinopathy caused by Gaucher's disease.

  本发明涉及O-GIcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗抑制OGA有益的疾病，如tau病变，特别是阿尔茨海默病或进行性上行性麻痹；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化或额颞叶痴呆；或α-突触核蛋白病，特别是帕金森病，由帕金森病引起的痴呆（或由帕金森病引起的神经认知障碍），具有Lewy小体的痴呆，多系统萎缩，或由高雪氏病引起的α-突触核蛋白病。
• HETARYLAMINONAPHTHYRIDINES
  申请人：Jonczyk Alfred

  公开号：US20120316166A1

  公开（公告）日：2012-12-13

  Novel hetarylaminonaphthyridine derivatives of formula (I) wherein X, R1, R2, R3, R4, W1, W2, W3, W5 and W6 have the meaning according to claim 1 , are inhibitors of ATP consuming proteins, and can be employed, inter alia, for the treatment of tumors.

  新型hetarylaminonaphthyridine衍生物的化学式(I)，其中X、R1、R2、R3、R4、W1、W2、W3、W5和W6的含义根据权利要求，是ATP消耗蛋白的抑制剂，可用于治疗肿瘤等。
• Synthesis and evaluation of biarylquinoline derivatives as novel HIF-1α inhibitors
  作者：Yu-Chieh Wu、Meng-Tien Lu、Tai-Hui Lin、Po-Chen Chu、Chih-Shiang Chang

  DOI：10.1016/j.bioorg.2022.105681

  日期：2022.4

  represents a promising therapeutic strategy for cancer drug development. In the present study, we designed, synthesized, and evaluated a new series of biarylquinoline derivatives as potential HIF-1α inhibitors based on structure–activity relationship. Among these derivatives, compound 7f represents the optimal agent with IC50 values of 28 nM and 15 nM in suppressing the viability of MiaPaCa-2 and MDA-MB-231

  缺氧诱导因子 (HIF)-1α 是一种关键的转录因子，在缺氧条件下有助于肿瘤细胞的侵袭性和耐药性表型。因此，靶向 HIF-1α 代表了一种有前途的癌症药物开发治疗策略。在本研究中，我们基于构效关系设计、合成和评估了一系列新的联芳基喹啉衍生物作为潜在的 HIF-1α 抑制剂。在这些衍生物中，化合物7f是抑制 MiaPaCa-2 和 MDA-MB-231 细胞活力的最佳药物，IC 50值分别为 28 nM 和 15 nM。化合物7f在抑制缺氧诱导的 MDA-MB-231 和 MiaPaCa-2 细胞迁移方面也表现出有效的功效。从机制上讲，化合物7f通过阻断转录和蛋白质翻译来抑制 HIF-1α 表达，而不是促进蛋白质降解。此外，这种 HIF-1α 下调与化合物7f同时抑制控制不同水平 HIF-1α 表达的多种信号通路的能力有关，包括由 STAT3、MEK/ERK MAPK 和 mTOR/4E-BP1
• Cyclometalated Iridium(III) and Rhodium(III) Complexes Containing Naphthyridine Ligands: Synthesis, Characterization and Biological Studies
  作者：Marion Graf、Yvonne Gothe、Nils Metzler-Nolte、Karlheinz Sünkel

  DOI：10.1002/zaac.201600378

  日期：2017.2

  The synthesis, crystal structure, and biological activity of new bis-cyclometalated compounds [M(ptpy)(2)(4-chloro-2-methyl-1,8-naphthyridine)]PF6 [M = Rh (1);M = Ir (2);ptpy = 2-(p-tolyl)pyridinato] and [M(ptpy)(2)(2-methyl-1,8-naphthyridine)]PF6 [M = Rh (3);M = Ir (4)] are described. The new compounds were prepared by the reaction of [M(-Cl)(ptpy)(2)}(2)] (M = Rh, Ir) with the corresponding naphthyridine

  新型双环金属化合物的合成、晶体结构和生物活性 [M(ptpy)(2)(4-chloro-2-methyl-1,8-naphthyridine)]PF6 [M = Rh (1);M = Ir (2);ptpy = 2-(p-tolyl)pyridinato] 和 [M(ptpy)(2)(2-methyl-1,8-naphthyridine)]PF6 [M = Rh (3);M = Ir ( 4)] 进行了描述。通过 [M(-Cl)(ptpy)(2)}(2)] (M = Rh, Ir) 与相应的萘啶配体反应制备新化合物。通过单晶 X 射线衍射研究证实了化合物 1、3 和 4 的分子结构。