ethyl 4-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-chloronicotinate | 1227486-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 4-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-chloronicotinate
• 英文别名: Ethyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)amino)-6-chloronicotinate；ethyl 6-chloro-4-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]amino]pyridine-3-carboxylate
• CAS: 1227486-53-4
• 化学式: C₁₈H₂₆ClN₃O₄
• 分子量: 383.875
• InChiKey: QIGKRVPAUIWFQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-chloronicotinate 在 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl 4-[(5-carbamoyl-2-chloropyridin-4-yl)amino]piperidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3

  摘要：

  In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.007
• 作为产物：
  描述：

  4,6-二氯烟酸乙酯 、 1-Boc-4-氨基哌啶 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 120.0h， 以1.2 g的产率得到ethyl 4-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-chloronicotinate
  参考文献：
  名称：

  [EN] BICYCLIC NITROGEN CONTAINING HETEROCYCLES AS INHIBITORS OF SALT-INUCED KINASE SIK2
  [FR] HÉTÉROCYCLES BICYCLIQUES CONTENANT DE L'AZOTE EN TANT QU'INHIBITEURS DE KINASE INDUCTIBLE PAR LE SEL SIK2

  摘要：

  提供的是Formula (I)的化合物，以及其盐和溶剂合物：(Formula (I)) 其中R2、R3、X1、L、A、R6、R7和Z在规范中有定义。这些化合物是盐诱导激酶（SIK），特别是SIK2的抑制剂，并且在治疗中非常有用，特别是在治疗增生性疾病、良性肿瘤、病理性血管生成、炎症性疾病或病况、肌肉骨骼疾病或病况、自身免疫疾病、血液疾病或病况、神经系统疾病或病况、精神障碍或代谢性疾病的治疗中被使用。

  公开号：

  WO2021084266A1

文献信息

• [EN] FGFR KINASE INHIBITORS AND PHARMACEUTICAL USES<br/>[FR] INHIBITEURS DE KINASE FGFR ET UTILISATIONS PHARMACEUTIQUES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2018160076A1

  公开（公告）日：2018-09-07

  Fibroblast Growth Factor Receptor kinase inhibitors and prodrugs thereof of Formula (I) and their use for the treatment of hyper-proliferative diseases such as retinopathy, psoriasis, rheumatoid arthritis, osteoarthritis, septic arthritis, tumour metastasis, periodontal disease, cornal ulceration, proteinuria, coronary thrombosis from atherosclerotic plaque, aneurismal aorta, dystrophobic epidermolysis bullosa, degenerative cartilage loss following traumatic joint injury, osteopenias mediated by MMP activity, tempero mandibular joint disease, and demyelating disease of the nervous system.

  纤维母细胞生长因子受体激酶抑制剂及其前药的化学式(I)以及它们用于治疗过度增殖性疾病，如视网膜病变、牛皮癣、类风湿关节炎、骨关节炎、化脓性关节炎、肿瘤转移、牙周病、角膜溃疡、蛋白尿、由动脉粥样硬化斑块引起的冠状动脉血栓形成、主动脉瘤、皮肤表皮溃疡性萎缩性疾病、创伤性关节损伤后的退行性软骨丢失、由MMP活性介导的骨质疏松、颞下颌关节疾病以及神经系统脱髓鞘疾病。
• [EN] BICYCLIC NITROGEN CONTAINING HETEROCYCLES AS INHIBITORS OF SALT-INUCED KINASE SIK2<br/>[FR] HÉTÉROCYCLES BICYCLIQUES CONTENANT DE L'AZOTE EN TANT QU'INHIBITEURS DE KINASE INDUCTIBLE PAR LE SEL SIK2
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2021084266A1

  公开（公告）日：2021-05-06

  Provided are compounds of the Formula (I), and salts and solvates thereof: (Formula (I)) wherein R2, R3, X1, L, A, R6, R7 and Z are defined in the specification. The compounds are inhibitors of salt-inducible kinase (SIK), particular SIK2, and are useful in therapy, particularly in the treatment of a proliferative disorder, a benign neoplasm, pathological angiogenesis, an inflammatory disease or condition, a musculoskeletal disease or condition, an autoimmune disease, a haematological disease or condition, a neurological disease or condition, a psychiatric disorder, or a metabolic disorder.

  提供的是Formula (I)的化合物，以及其盐和溶剂合物：(Formula (I)) 其中R2、R3、X1、L、A、R6、R7和Z在规范中有定义。这些化合物是盐诱导激酶（SIK），特别是SIK2的抑制剂，并且在治疗中非常有用，特别是在治疗增生性疾病、良性肿瘤、病理性血管生成、炎症性疾病或病况、肌肉骨骼疾病或病况、自身免疫疾病、血液疾病或病况、神经系统疾病或病况、精神障碍或代谢性疾病的治疗中被使用。
• 4,6-DIAMINONICOTINAMIDE COMPOUND
  申请人：Shirakami Shohei

  公开号：US20110230467A1

  公开（公告）日：2011-09-22

  [Problem] The present invention provides a 4,6-diaminonicotinamide compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for treating diseases caused by undesirable and/or abnormal cytokine signal transduction. [Means for Solution] The present inventors have extensively studied compounds having a JAK3 inhibitory action, and as a result, they have found that a 4,6-diaminonicotinamide compound which is the compound of the present invention has an excellent JAK3 inhibitory action and is useful as an agent for preventing or treating diseases caused by undesirable and/or abnormal cytokine signal transduction, thereby completing the present invention.

  [问题] 本发明提供了一种4,6-二氨基烟酰胺化合物，该化合物可用作制药组合物的活性成分，特别是用于治疗由不良和/或异常的细胞因子信号传导引起的疾病的制药组合物。 [解决方法] 本发明人广泛研究了具有JAK3抑制作用的化合物，结果发现本发明的4,6-二氨基烟酰胺化合物具有出色的JAK3抑制作用，并且可用作预防或治疗由不良和/或异常的细胞因子信号传导引起的疾病的药剂，从而完成了本发明。
• Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3
  作者：Yutaka Nakajima、Naohiro Aoyama、Fumie Takahashi、Hiroshi Sasaki、Keiko Hatanaka、Ayako Moritomo、Masamichi Inami、Misato Ito、Koji Nakamura、Fumihiro Nakamori、Takayuki Inoue、Shohei Shirakami

  DOI：10.1016/j.bmc.2016.08.007

  日期：2016.10

  In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. (C) 2016 Elsevier Ltd. All rights reserved.