1-(4-(4-amino-1H-pyrazol-1-yl)piperidin-1-yl)ethanone | 1201935-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-(4-amino-1H-pyrazol-1-yl)piperidin-1-yl)ethanone
• 英文别名: 1-(4-(4-amino-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one；1-(4-(4-Amino-1H-pyrazol-1-yl)piperidin-1-yl)ethanone；1-[4-(4-aminopyrazol-1-yl)piperidin-1-yl]ethanone
• CAS: 1201935-45-6
• 化学式: C₁₀H₁₆N₄O
• 分子量: 208.263
• InChiKey: ZBDUJLPJSXTFSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-(4-amino-1H-pyrazol-1-yl)piperidin-1-yl)ethanone 生成 7-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-3-(5-(5-(2-methoxyphenyl)-1H-imidazol-2-yl)-2-methylphenyl)-1-methyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one
  参考文献：
  名称：

  7-AMINO-3,4-DIHYDROPYRIMIDOPYRIMIDIN-2-ONE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES AND THERAPEUTIC PHARMACEUTICAL COMPOSITION COMPRISING SAME

  摘要：

  本公开涉及一种7-氨基-3,4-二氢嘧啶嘧啶-2-酮衍生物化合物，其对癌细胞具有出色的抗增殖作用，其药学上可接受的盐，水合物或立体异构体，其生产方法，包含其作为活性成分的用于预防，缓解或治疗癌症转移和增殖性疾病的药物组合物，以及针对癌细胞的抗癌组合物。该化合物表现出优异的癌细胞抑制活性和抗增殖效果，因此在抑制癌细胞，预防癌症转移和增殖性疾病或治疗癌症方面具有有效性。

  公开号：

  EP4092029A1
• 作为产物：
  描述：

  4-(4-nitro-1H-pyrazol-1-yl)piperidine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 1-(4-(4-amino-1H-pyrazol-1-yl)piperidin-1-yl)ethanone
  参考文献：
  名称：

  [EN] BENZETHERS AND ANILINES OF PYRAZOLYL-AMINO-PYRIMIDINYL DERIVATIVES, AND COMPOSITIONS AND METHODS THEREOF
  [FR] BENZYLÉTHERS ET ANILINES DE DÉRIVÉS DE PYRAZOLYL-AMINO-PYRIMIDINYLE, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS

  摘要：

  提供一种新型的口服和/或局部可用的、选择性和有效的JAK抑制剂，作为安全有效的治疗各种疾病和紊乱的药物。还提供了这些化合物的药物组合物以及它们的制备和使用方法。

  公开号：

  WO2020207414A1

文献信息

• [EN] NOVEL KINASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2014060113A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种具有公式（I）的新化合物，能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物在治疗多种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和激素相关疾病。
• Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors
  作者：Sébastien L. Degorce、Anna Aagaard、Rana Anjum、Iain A. Cumming、Coura R. Diène、Charlene Fallan、Tony Johnson、Karl-Johan Leuchowius、Alexandra L. Orton、Stuart Pearson、Graeme R. Robb、Alan Rosen、Graeme B. Scarfe、James S. Scott、James M. Smith、Oliver R. Steward、Ina Terstiege、Michael J. Tucker、Paul Turner、Stephen D. Wilkinson、Gail L. Wrigley、Yafeng Xue

  DOI：10.1016/j.bmc.2020.115815

  日期：2020.12

  In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline

  在本文中，我们报告了我们通过一系列C4截短和C2扩展在一系列5-氮杂喹唑啉中提高人体清除率的努力。大量的DMPK研究使我们能够解决醛氧化酶（AO）的高代谢以及人肝细胞和肝脏微粒体固有清除率中的意料不到的差异。我们的努力最终以发现5-氮杂喹唑啉35（它对IRAK4表现出极好的选择性）和结合共价BTK抑制剂alababrutinib的MyD88 / CD79双突变ABC-DLBCL表现出协同体外活性。
• [EN] PYRAZOLO[4,3-D]PYRIMIDINES AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2014060112A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及具有式（I）的新化合物，其能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗多种疾病。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和激素相关疾病。
• Novel and Potent Small Molecules against Melanoma Harboring BRAF Class I/II/III Mutants for Overcoming Drug Resistance
  作者：Namkyoung Kim、Injae Shin、Jiwon Lee、Eunhye Jeon、Younghoon Kim、Seongshick Ryu、Eunhye Ju、Wonjeong Cho、Taebo Sim

  DOI：10.3390/ijms22073783

  日期：——

  Melanoma accounts for the majority of skin cancer deaths. About 50% of all melanomas are associated with BRAF mutations. BRAF mutations are classified into three classes with regard to dependency on RAF dimerization and RAS signaling. The most frequently occurring class I BRAF V600 mutations are sensitive to vemurafenib whereas class II and class III mutants, non-V600 BRAF mutants are resistant to vemurafenib. Herein we report six pyrimido[4,5-d]pyrimidin-2-one derivatives possessing highly potent anti-proliferative activities on melanoma cells harboring BRAF class I/II/III mutants. Novel and most potent derivative, SIJ1777, possesses not only two-digit nanomolar potency but also 2 to 14-fold enhanced anti-proliferative activities compared with reference compound, GNF-7 against melanoma cells (SK-MEL-2, SK-MEL-28, A375, WM3670, WM3629). Moreover, SIJ1777 substantially inhibits the activation of MEK, ERK, and AKT and remarkably induces apoptosis and significantly blocks migration, invasion, and anchorage-independent growth of melanoma cells harboring BRAF class I/II/II mutations while both vemurafenib and PLX8394 have little to no effects on melanoma cells expressing BRAF class II/III mutations. Taken together, our six GNF-7 derivatives exhibit highly potent activities against melanoma cells harboring class I/II/III BRAF mutations compared with vemurafenib as well as PLX8394.

  黑色素瘤是皮肤癌死亡的主要原因。约50％的黑色素瘤与BRAF突变相关。BRAF突变根据对RAF二聚化和RAS信号的依赖性分为三类。最常见的I类BRAF V600突变对维姆拉芬尼敏感，而II类和III类突变，即非V600 BRAF突变对维姆拉芬尼具有抗药性。本文报道了六种嘧啶并[4,5-d]嘧啶-2-酮衍生物，具有高度有效的抗黑色素瘤细胞增殖活性，携带BRAF I / II / III突变。新颖而最有效的衍生物SIJ1777不仅具有两位数纳摩尔的有效性，而且与参考化合物GNF-7相比，在黑色素瘤细胞（SK-MEL-2，SK-MEL-28，A375，WM3670，WM3629）上具有2至14倍的增强抗增殖活性。此外，SIJ1777显着抑制MEK，ERK和AKT的活化，并显着诱导细胞凋亡，并显著阻止携带BRAF I / II / III突变的黑色素瘤细胞的迁移，侵袭和无定形生长，而维姆拉芬尼和PLX8394对表达BRAF II / III突变的黑色素瘤细胞几乎没有影响。综上所述，我们的六种GNF-7衍生物与维姆拉芬尼以及PLX8394相比，在携带I / II / III类BRAF突变的黑色素瘤细胞中表现出高效活性。
• NOVEL KINASE INHIBITORS
  申请人：ORIGENIS GMBH

  公开号：US20150259340A1

  公开（公告）日：2015-09-17

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及式（I）的新型化合物，能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗各种疾病。这些疾病包括自身免疫性疾病、炎症性疾病、骨病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。