1-(3-二甲胺基)丙基-1H-吡唑-4-胺 | 1296308-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(3-二甲胺基)丙基-1H-吡唑-4-胺
• 英文名称: 1-(3-(dimethylamino)propyl)-1H-pyrazol-4-amine
• 英文别名: 1-[3-(dimethylamino)propyl]pyrazol-4-amine
• CAS: 1296308-45-6
• 化学式: C₈H₁₆N₄
• 分子量: 168.242
• InChiKey: WQDVJBJATWTUDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-(7-chloro-1-methyl-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide 、 1-(3-二甲胺基)丙基-1H-吡唑-4-胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 仲丁醇 为溶剂， 反应 1.0h， 以62%的产率得到N-(3-(7-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-1-methyl-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Novel and Potent Small Molecules against Melanoma Harboring BRAF Class I/II/III Mutants for Overcoming Drug Resistance

  摘要：

  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。

  DOI：

  10.3390/ijms22073783
• 作为产物：
  描述：

  N,N-dimethyl-3-(4-nitropyrazol-1-yl)propan-1-amine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 生成 1-(3-二甲胺基)丙基-1H-吡唑-4-胺
  参考文献：
  名称：

  PYRIMIDINE CARBOXAMIDE COMPOUNDS

  摘要：

  Pyrimidinyl compounds of formula I: (I), for use in methods of inhibiting Wee 1 A kinase.

  公开号：

  WO2024145505A1

文献信息

• [EN] HETEROCYCLYL PYRAZOLOPYRIMIDINE ANALOGUES AS JAK INHIBITORS<br/>[FR] ANALOGUES D'HÉTÉROCYCLYL PYRAZOLOPYRIMIDINE EN TANT QU'INHIBITEURS DE JAK
  申请人：CELLZOME LTD

  公开号：WO2011048082A1

  公开（公告）日：2011-04-28

  The present invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及式(I)的化合物，其中X1至X5，Y，Z1至Z3和R的含义如描述和权利要求中所述。所述化合物可用作JAK抑制剂，用于治疗或预防免疫、炎症、自身免疫、过敏性疾病和免疫介导性疾病。该发明还涉及包括所述化合物的药物组合物，以及制备这类化合物以及用作药物的用途。
• [EN] HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONTENANT UN COEUR INDOLE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011071716A1

  公开（公告）日：2011-06-16

  Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.

  公开了抑制RSK的新颖化合物，制造此类化合物的方法以及包含此类化合物的药物组合物。还公开了使用本发明的化合物治疗RSK2调控失调的方法。
• NOVEL IMIDAZOPYRIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING CANCER
  申请人：DAEGU-GYEONGBUK MEDICAL INNOVATION FOUNDATION

  公开号：US20190315738A1

  公开（公告）日：2019-10-17

  The present invention relates to a novel imidazopyridine derivative, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. The novel imidazopyridine derivative according to the present invention, a stereoisomer thereof and a pharmaceutically acceptable salt thereof can effectively inhibit cancer-related kinases, are excellent in inhibiting proliferation of cancer cells in a cancer cell line, and effectively inhibit proliferation of cancer cells (cancer cell apoptosis) in a cancer cell heterograft model, and thus can be useful as a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. Also, the novel imidazopyridine derivative according to the present invention, the stereoisomer thereof, and the pharmaceutically acceptable salt thereof can effectively inhibit Src and Fyn, thereby being useful as a pharmaceutical composition for preventing or treating the Src and Fyn related diseases, and in particular, have been confirmed to be useful in diabetic nephropathy in animal model experiments. Therefore, the compound of the present invention can be effective as a pharmaceutical composition containing the same as an active ingredient for preventing or treating diabetic nephropathy.

  本发明涉及一种新的咪唑吡啶衍生物，一种制备该衍生物的方法，以及含有该衍生物作为活性成分用于预防或治疗癌症的药物组合物。根据本发明的新的咪唑吡啶衍生物及其立体异构体和药学上可接受的盐可以有效抑制与癌症相关的激酶，在癌细胞系中抑制癌细胞增殖方面表现出优异，有效抑制癌细胞在癌细胞异种移植模型中的增殖（癌细胞凋亡），因此可以作为含有该衍生物作为活性成分的药物组合物用于预防或治疗癌症。此外，根据本发明的新的咪唑吡啶衍生物、其立体异构体和药学上可接受的盐可以有效抑制Src和Fyn，因此可用作预防或治疗与Src和Fyn相关疾病的药物组合物，特别在动物模型实验中已确认在糖尿病肾病中有用。因此，本发明的化合物可以作为含有该衍生物作为活性成分的药物组合物，有效预防或治疗糖尿病肾病。
• Identification of Pyridinyltriazine Derivatives as Potent panFGFR Inhibitors against Gatekeeper Mutants for Overcoming Drug Resistance
  作者：SeongShick Ryu、Yunju Nam、Namkyoung Kim、Injae Shin、Eunhye Jeon、Younghoon Kim、Nam Doo Kim、Taebo Sim

  DOI：10.1021/acs.jmedchem.1c01776

  日期：2022.4.28

  various cancers, resistance to the FGFR inhibitors caused by acquired secondary mutations has emerged. To discover novel FGFR inhibitors capable of inhibiting FGFR mutations, including gatekeeper mutations, we designed and synthesized several new pyridinyltriazine derivatives. A structure–activity relationship (SAR) study led to the identification of 17a as a highly potent panFGFR inhibitor against wild-type

  尽管 FGFR 抑制剂有望治疗各种癌症，但已经出现了由获得性二次突变引起的对 FGFR 抑制剂的耐药性。为了发现能够抑制 FGFR 突变（包括看门人突变）的新型 FGFR 抑制剂，我们设计并合成了几种新的吡啶基三嗪衍生物。一项构效关系 (SAR) 研究将17a鉴定为针对野生型和突变型 FGFR 的高效 panFGFR 抑制剂。值得注意的是，17a在激酶抑制和细胞活性方面优于 infigratinib，尤其是针对 V555M-FGFR3。分子动力学模拟清楚地解释了为什么 pyridinyltraizine 衍生物17a具有针对 V555M-FGFR3 的活性。而且，17a通过 FGFR 信号传导阻断、细胞周期停滞和细胞凋亡显着抑制携带 FGFR 突变的癌细胞的增殖。此外，17a和17b在 TEL-V555M-FGFR3 Ba/F3 异种移植小鼠模型中表现出显着的功效，并且17a比 infigratinib
• HETEROCYCLYL PYRAZOLOPYRIMIDINE ANALOGUES AS JAK INHIBITORS
  申请人：Ramsden Nigel

  公开号：US20120252779A1

  公开（公告）日：2012-10-04

  The invention relates to compounds of formula (I) wherein X 1 to X 5 , Y, Z 1 to Z 3 , and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及公式（I）的化合物，其中X1至X5，Y，Z1至Z3和R的含义如所述及权利要求中所述。所述化合物可用作JAK抑制剂，用于治疗或预防免疫、炎症、自身免疫、过敏性疾病和免疫介导性疾病。本发明还涉及包括所述化合物的制药组合物、制备这种化合物以及用作药物的用途。