2-(5-氨基-1-甲基-1H-吡唑-3-基)-2-甲基丙腈 | 1012879-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(5-氨基-1-甲基-1H-吡唑-3-基)-2-甲基丙腈
• 英文名称: 2-(5-amino-1-methyl-1H-pyrazol-3-yl)-2-methylpropanenitrile
• 英文别名: 2-(5-amino-1-methylpyrazol-3-yl)-2-methylpropanenitrile
• CAS: 1012879-86-5
• 化学式: C₈H₁₂N₄
• 分子量: 164.21
• InChiKey: LZPVJPXUQZMWTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-N-乙基-5-(三氟甲基)嘧啶-2-胺 、 2-(5-氨基-1-甲基-1H-吡唑-3-基)-2-甲基丙腈 在 三氟乙酸 作用下， 以 正丁醇 为溶剂， 反应 1.0h， 以11%的产率得到2-(5-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)-amino)-1-methyl-1H-pyrazol-3-yl)-2-methylpropanenitrile
  参考文献：
  名称：

  Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

  摘要：

  Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the neuroscience research community because it is one of the most compelling targets for a potential disease-modifying Parkinson's disease therapy. Herein, we disclose structurally diverse small molecule inhibitors suitable for assessing the implications of sustained in vivo LARK2 inhibition. Using previously reported aminopyrazole 2 as a lead molecule, we were able to engineer structural modifications in the solvent-exposed region of the ATP-binding site that significantly improve human hepatocyte stability, rat free brain exposure, and CYP inhibition and induction liabilities. Disciplined application of established optimal CNS design parameters culminated in the rapid identification of GNE-0877 (11) and GNE-9605 (20) as highly potent and selective LRRK2 inhibitors. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies.

  DOI：

  10.1021/jm401654j
• 作为产物：
  描述：

  2-氰基-2-甲基丙酸乙酯 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 27.0h， 生成 2-(5-氨基-1-甲基-1H-吡唑-3-基)-2-甲基丙腈
  参考文献：
  名称：

  [EN] COMPOUND, COMPOSITIONS, AND METHODS
  [FR] COMPOSÉS, COMPOSITIONS, ET PROCÉDÉS

  摘要：

  披露了具有LRRK2抑制剂活性的化合物。这些化合物具有公式(I)，包括立体异构体、互变异构体、药物可接受的盐和前药。还披露了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。

  公开号：

  WO2017087905A1

文献信息

• Kinase inhibitors useful for the treatment of proliferative diseases
  申请人：Flynn L. Daniel

  公开号：US20080114006A1

  公开（公告）日：2008-05-15

  The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

  本发明涉及一种新型激酶抑制剂和调节剂化合物，用于治疗各种疾病。更具体地说，本发明涉及这样的化合物、激酶/化合物加合物、治疗疾病的方法以及合成化合物的方法。优选地，这些化合物对Raf激酶及其疾病多态性的激酶活性调节是有用的。本发明的化合物在哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑色素瘤、结肠直肠癌、卵巢癌、乳头状甲状腺癌、非小细胞肺癌和间皮瘤的治疗中发挥作用。本发明的化合物也在治疗类风湿性关节炎和视网膜病变，包括糖尿病性视网膜神经病变和黄斑变性方面发挥作用。
• Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
  申请人：Deciphera Pharmaceuticals, Inc.

  公开号：US08188113B2

  公开（公告）日：2012-05-29

  The present invention relates to novel dihydropyridopyrimidinyl, dihydronaphthyridinyl, and related compounds which are kinase inhibitors and modulator useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

  本发明涉及一种新型的二氢吡啶吡嗪基，二氢萘嗪基和相关化合物，这些化合物是激酶抑制剂和调节剂，可用于治疗各种疾病。更具体地说，本发明涉及这些化合物，激酶/化合物加合物，治疗疾病的方法以及合成这些化合物的方法。优选地，这些化合物对Raf激酶及其疾病多态体的激酶活性的调节具有用处。本发明的化合物在哺乳动物癌症治疗中，特别是人类癌症治疗中，包括但不限于恶性黑色素瘤、结肠直肠癌、卵巢癌、乳头状甲状腺癌、非小细胞肺癌和间皮瘤中具有用处。本发明的化合物在类风湿性关节炎和视网膜病变治疗中也具有用处，包括糖尿病性视网膜神经病变和黄斑变性。
• KINASE INHIBITORS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Flynn Daniel L.

  公开号：US20120289540A1

  公开（公告）日：2012-11-15

  The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

  本发明涉及新型激酶抑制剂和调节剂化合物，可用于治疗各种疾病。更具体地说，本发明涉及这种化合物、激酶/化合物加合物、治疗疾病的方法以及化合物的合成方法。优选地，这些化合物可用于调节Raf激酶及其疾病多态性的激酶活性。本发明的化合物在哺乳动物癌症治疗中特别是人类癌症治疗中，包括但不限于恶性黑色素瘤、结直肠癌、卵巢癌、乳头状甲状腺癌、非小细胞肺癌和间皮瘤等方面有用。本发明的化合物还在类风湿性关节炎和视网膜病变，包括糖尿病视网膜神经病变和黄斑变性的治疗中有用。
• Compound, compositions, and methods
  申请人：Denali Therapeutics Inc.

  公开号：US11214565B2

  公开（公告）日：2022-01-04

  Compounds having activity as LRRK2 inhibitors are disclosed. The compounds are of formula (I) including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds are also disclosed.

  本发明公开了具有 LRRK2 抑制剂活性的化合物。这些化合物为式（I）化合物，包括其立体异构体、同系物、药学上可接受的盐和原药。还公开了与制备和使用此类化合物相关的方法，以及包含此类化合物的药物组合物。
• COMPOUND, COMPOSITIONS, AND METHODS
  申请人：Denali Therapeutice Inc.

  公开号：US20180327391A1

  公开（公告）日：2018-11-15

  Compounds having activity as LRRK2 inhibitors are disclosed. The compounds are of formula (I) including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds are also disclosed.