5-甲氧基嘧啶-2-甲酸 | 344325-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-甲氧基嘧啶-2-甲酸
• 英文名称: 5-methoxypyrimidine-2-carboxylic acid
• CAS: 344325-94-6
• 化学式: C₆H₆N₂O₃
• 分子量: 154.125
• InChiKey: WJCNQFLMFOMNJR-UHFFFAOYSA-N

物化性质

• 沸点：
  390.3±34.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.18
• 重原子数：
  11.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  72.31
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-甲氧基嘧啶-2-甲酸 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 3-(3-ethyl-5-(5-methoxy-2-pyrimidinyl)-1H-1,2,4-triazolyl)-N-(4-phenylbutyl)benzamide
  参考文献：
  名称：

  Modification and Biological Evaluation of a Series of 1,5-Diaryl-1,2,4-triazole Compounds as Novel Agents against Pancreatic Cancer Metastasis through Targeting Myoferlin

  摘要：

  Pancreatic cancer is one of the most common cancers with an extremely low survival rate. Metastasis, as one of the key reasons of cancer-related death, is found in more than 50% pancreatic cancer patients at diagnosis. Novel therapeutic targets and drugs blocking cancer metastasis are urgently needed. Herein, we report a series of 1,5-diaryl-1,2,4-triazole derivatives as potent antimetastatic agents. Lead compound 6y displayed effective antimetastatic activities in pancreatic cancer in vitro and in vivo. Concomitant studies indicated that 6y probably binds with myoferlin (MYOF), a novel potential antitumor metastasis target, which regulates vesicle trafficking and metastasis-related proteins. Subsequent biophysical and biochemical methods verified that 6y bound to MYOF. Mechanism studies revealed that 6y inhibited pancreatic cancer metastasis through reversing the epithelial mesenchymal transition, inhibiting the secretions of matrix metalloproteinase and blocking the receptor tyrosine kinases. Our findings suggest that that targeting MYOF with 6y may be a promising therapeutic strategy to prevent pancreatic cancer metastasis.

  DOI：

  10.1021/acs.jmedchem.9b00059
• 作为产物：
  描述：

  5-甲氧基嘧啶-2-甲腈 、 sodium hydroxide 、 水 、 盐酸 以80%的产率得到
  参考文献：
  名称：

  TUMKYAVICHYUS, S. P.;VAJNILAVICHYUS, P. J., NAUCH. TR. VUZOV LITSSR. XIMIYA I XIM. TEXNOL., 30,(1988) S. 74-78

  摘要：

  DOI：

文献信息

• [EN] IMIDAZOPYRROLIDINONE COMPOUNDS<br/>[FR] COMPOSÉS IMIDAZOPYRROLIDINONE
  申请人：NOVARTIS AG

  公开号：WO2013111105A1

  公开（公告）日：2013-08-01

  The invention relates to compounds of formula (I): (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

  这项发明涉及式(I)的化合物：(I)如本文所述，包括这种化合物的药物制剂，以及在治疗由MDM2和/或MDM4活性介导的疾病或疾病中使用这种化合物的用途和方法，以及包含这种化合物的组合物。
• Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150307465A1

  公开（公告）日：2015-10-29

  In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -, -L 2 -, and -L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

  本发明提供了多种形式的亚氨基噻二唑二氧化物化合物，包括公式(I)的化合物： 包括它们的立体异构体，以及所述立体异构体的药用可接受盐，其中R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、-L2-和-L3-都是独立选择且按本文定义。发明的新型亚氨基噻二唑二氧化物化合物出人意料地被发现具有预期的特性，使其作为BACE抑制剂以及/或用于治疗和预防与β-淀粉样蛋白（“Aβ”）生成相关的各种病理学具有优势。还公开了包含一个或多个此类化合物（单独使用和与一个或多个其他活性成分组合使用）的药物组合物，以及它们的制备方法和用于治疗与淀粉样β（Aβ）蛋白相关的病理学，包括阿尔茨海默病的方法。
• Trifluoromethyl Dihydrothiazine‐Based β‐Secretase (BACE1) Inhibitors with Robust Central β‐Amyloid Reduction and Minimal Covalent Binding Burden
  作者：Kosuke Anan、Yasuyoshi Iso、Takuya Oguma、Kenji Nakahara、Shinji Suzuki、Takahiko Yamamoto、Eriko Matsuoka、Hisanori Ito、Gaku Sakaguchi、Shigeru Ando、Kenji Morimoto、Naoki Kanegawa、Yasuto Kido、Tomoyuki Kawachi、Tamio Fukushima、Ard Teisman、Vijay Urmaliya、Deborah Dhuyvetter、Herman Borghys、Nigel Austin、An Van Den Bergh、Peter Verboven、Francois Bischoff、Harrie J. M. Gijsen、Yoshinori Yamano、Ken-ichi Kusakabe

  DOI：10.1002/cmdc.201900478

  日期：2019.11.20

  The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pKa lowering approach over the initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading to the design of 6-CF3 dihydrothiazine 8 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluoro

  β-位淀粉样蛋白前体蛋白裂解酶1（BACE1，也称为β-分泌酶）是治疗阿尔茨海默氏病的有希望的靶标。采用pKa降低初始引线的方法来减轻hERG抑制和P-gp外排，从而设计出6-CF3二氢噻嗪8（N-（3-（（4S，6S）-2-amino-4-methyl -6-（三氟甲基）-5,6-二氢-4H-1,3-噻嗪-4-基）-4-氟苯基）-5-氰基吡啶啉）。优化8导致发现15（N-（3-（（4S，6S）-2-氨基-4-甲基-6-（三氟甲基）-5,6-二氢-4H-1,3-噻嗪- 4-yl）-4-氟苯基）-5-（氟甲氧基）吡嗪-2-羧酰胺）具有出色的效能，hERG抑制，P-gp外排和代谢稳定性之间的平衡。甚至在0.16 mg / kg的剂量下，口服8也会引起犬Aβ的强烈降低。反映出降低的hERG抑制活性，高剂量时未观察到QTc延长。在人肝微粒体中使用[14 C] -KCN进行亲核试剂捕获测定，实现了1
• 2-Amino-6-(difluoromethyl)-5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 Inhibitors
  申请人：H. Lundbeck A/S

  公开号：US20160130267A1

  公开（公告）日：2016-05-12

  The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.

  本发明涉及一种新型BACE1酶抑制剂。发明的另一方面涉及含有所述化合物的药物组合物，以及利用这些化合物治疗减少Aβ沉积有益的疾病，如阿尔茨海默病。
• 2-Amino-3,5,5-trifluoro-3,4,5,6-tetrahydropyridines as BACE1 inhibitors for treatment of Alzheimer's disease
  申请人：H. LUNDBECK A/S

  公开号：US20150232449A1

  公开（公告）日：2015-08-20

  The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.

  本发明涉及新型BACE1酶抑制剂。发明的不同方面涉及包含所述化合物的药物组合物，以及利用这些化合物治疗减少Aβ沉积有益的疾病，如阿尔茨海默病。