4-chloro-2-(2-chloro-pyridin-4-yl)-quinazoline | 861418-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-chloro-2-(2-chloro-pyridin-4-yl)-quinazoline
• 英文别名: 4-Chloro-2-(2-chloropyridin-4-yl)quinazoline
• CAS: 861418-44-2
• 化学式: C₁₃H₇Cl₂N₃
• 分子量: 276.125
• InChiKey: WXCARTUZUBOCGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-2-(2-chloro-pyridin-4-yl)-quinazoline 、 N-Boc-哌嗪 以 N-甲基吡咯烷酮 为溶剂， 生成 Tert-butyl 4-[2-(2-chloropyridin-4-yl)quinazolin-4-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  Identification of Orally Available Naphthyridine Protein Kinase D Inhibitors

  摘要：

  A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.

  DOI：

  10.1021/jm100075z
• 作为产物：
  描述：

  2-(2-chloropyridin-4-yl)quinazolin-4-ol 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 反应 2.0h， 生成 4-chloro-2-(2-chloro-pyridin-4-yl)-quinazoline
  参考文献：
  名称：

  [EN] SUBSTITUTED DIAZABICYCLOHEPTANES AND THEIR USE AS PROTEIN KINASE INHIBITORS
  [FR] DIAZABICYCLOHEPTANES SUBSTITUES ET LEUR UTILISATION COMME INHIBITEURS DE LA PROTEINE KINASE

  摘要：

  本发明涉及治疗性的重氮双环吡啶类化合物及其在治疗关节炎、类风湿关节炎、银屑病性关节炎或骨关节炎、器官移植、急性移植或异种移植和同种移植排斥、缺血再灌注损伤、移植耐受诱导、多发性硬化症、炎症性肠病、溃疡性结肠炎、克罗恩病、狼疮、移植物抗宿主病、T细胞介导的超敏反应疾病、接触性超敏反应、延迟型超敏反应、对麸质敏感性肠病、1型糖尿病、银屑病、接触性皮炎、Hashimoto甲状腺炎、Sjogren综合症、自身免疫性甲状腺功能亢进症、Graves'病、Addison病、自身多腺体疾病、自身性脱发、恶性贫血、白癜风、自身性垂体功能减退症、格林-巴雷综合征、自身免疫疾病、肾小球肾炎、血清病、荨麻疹、呼吸道过敏、哮喘、花粉症、过敏性鼻炎、皮肤过敏、硬皮病、真菌病、急性炎症反应、急性呼吸窘迫综合征、皮肌炎、斑秃、慢性光化性皮炎、湿疹、Behcet病、掌跖症病、脓皮病、塞扎里综合征、特应性皮炎、系统性硬化症、硬皮病、2型糖尿病和PKCθ或其他PKC家族激酶被激活、过度表达或促进肿瘤生长或肿瘤细胞存活、T细胞白血病、胸腺瘤、T和B细胞淋巴瘤、结肠癌、乳腺癌和肺癌或对化疗药物具有抗性的治疗中的应用。

  公开号：

  WO2005070934A1

文献信息

• [EN] SUBSTITUTED DIAZABICYCLOHEPTANES AND THEIR USE AS PROTEIN KINASE INHIBITORS<br/>[FR] DIAZABICYCLOHEPTANES SUBSTITUES ET LEUR UTILISATION COMME INHIBITEURS DE LA PROTEINE KINASE
  申请人：AMGEN INC

  公开号：WO2005070934A1

  公开（公告）日：2005-08-04

  The present invention relates to therapeutic diazobicyclo pyridines and their use in the treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T -cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism,Graves' Disease, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, autoimmune diseases, glomerulonephritis, serum sickness, uticaria, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, scleracielma, mycosis fungoides, acute inflammatory responses, acute respiratory distress syndrome, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, Type II diabetes and cancers where PKC theta or other PKC-family kinases are activated, overexpressed or facilitate tumor growth or survival of tumor cells, T cell leukemia, thymoma, T and B cell lymphoma, colon carcinoma, breast carcinoma and lung carcinoma or provides resistance to chemotherapeutic drugs.

  本发明涉及治疗性的重氮双环吡啶类化合物及其在治疗关节炎、类风湿关节炎、银屑病性关节炎或骨关节炎、器官移植、急性移植或异种移植和同种移植排斥、缺血再灌注损伤、移植耐受诱导、多发性硬化症、炎症性肠病、溃疡性结肠炎、克罗恩病、狼疮、移植物抗宿主病、T细胞介导的超敏反应疾病、接触性超敏反应、延迟型超敏反应、对麸质敏感性肠病、1型糖尿病、银屑病、接触性皮炎、Hashimoto甲状腺炎、Sjogren综合症、自身免疫性甲状腺功能亢进症、Graves'病、Addison病、自身多腺体疾病、自身性脱发、恶性贫血、白癜风、自身性垂体功能减退症、格林-巴雷综合征、自身免疫疾病、肾小球肾炎、血清病、荨麻疹、呼吸道过敏、哮喘、花粉症、过敏性鼻炎、皮肤过敏、硬皮病、真菌病、急性炎症反应、急性呼吸窘迫综合征、皮肌炎、斑秃、慢性光化性皮炎、湿疹、Behcet病、掌跖症病、脓皮病、塞扎里综合征、特应性皮炎、系统性硬化症、硬皮病、2型糖尿病和PKCθ或其他PKC家族激酶被激活、过度表达或促进肿瘤生长或肿瘤细胞存活、T细胞白血病、胸腺瘤、T和B细胞淋巴瘤、结肠癌、乳腺癌和肺癌或对化疗药物具有抗性的治疗中的应用。
• Substituted heterocyclic compounds and methods of use
  申请人：Cao Guo-Qiang

  公开号：US20050182072A1

  公开（公告）日：2005-08-18

  The present invention relates to therapeutic diazobicyclo pyridines and their use in the treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T -cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Graves' Disease, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, autoimmune diseases, glomerulonephritis, serum sickness, uticaria, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, scleracielma, mycosis flugoides, acute inflammatory responses, acute respiratory distress syndrome, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, Type II diabetes and cancers where PKC theta or other PKC-family kinases are activated, overexpressed or facilitate tumor growth or survival of tumor cells, T cell leukemia, thymoma, T and B cell lymphoma, colon carcinoma, breast carcinoma and lung carcinoma or provides resistance to chemotherapeutic drugs.

  本发明涉及治疗用的二氮杂双环吡啶及其在治疗关节炎、类风湿性关节炎、银屑病性关节炎或骨关节炎、器官移植、急性移植或异种移植和同种移植排斥、缺血再灌注损伤、移植耐受诱导、多发性硬化症、炎症性肠病、溃疡性结肠炎、克罗恩病、红斑狼疮、移植物抗宿主病、T细胞介导的超敏反应性疾病、接触性超敏反应、迟发型超敏反应、麦糊疹性肠病、1型糖尿病、银屑病、接触性皮炎、桥本甲状腺炎、干燥综合症、自身免疫性甲状腺功能亢进症、格雷夫斯病、亚当逊病、自身免疫性多发性内分泌腺疾病、自身免疫性脱发症、恶性贫血、白癜风、自身免疫性下丘脑功能减退症、格林-巴利综合症、自身免疫性疾病、肾小球肾炎、血清病、荨麻疹、呼吸道过敏、哮喘、花粉热、过敏性鼻炎、皮肤过敏、硬皮病、浆液性腺瘤、急性炎症反应、急性呼吸窘迫综合症、皮肌炎、斑秃、慢性光化性皮炎、湿疹、Behcet病、掌跖角化症、脓疱性荨麻疹、Sezary综合症、特应性皮炎、系统性硬化病、硬皮症、2型糖尿病和PKC theta或其他PKC家族激酶被激活、过度表达或促进肿瘤生长或肿瘤细胞存活、T细胞白血病、胸腺瘤、T和B细胞淋巴瘤、结肠癌、乳腺癌和肺癌或提供对化疗药物的抗性。
• SUBSTITUTED DIAZABICYCLOHEPTANES AND THEIR USE AS PROTEIN KINASE INHIBITORS
  申请人：Amgen Inc.

  公开号：EP1727821A1

  公开（公告）日：2006-12-06
• US7582631B2
  申请人：——

  公开号：US7582631B2

  公开（公告）日：2009-09-01
• Identification of Orally Available Naphthyridine Protein Kinase D Inhibitors
  作者：Erik L. Meredith、Ophelia Ardayfio、Kimberly Beattie、Markus R. Dobler、Istvan Enyedy、Christoph Gaul、Vinayak Hosagrahara、Charles Jewell、Keith Koch、Wendy Lee、HansJoerg Lehmann、Timothy A. McKinsey、Karl Miranda、Nikos Pagratis、Margaret Pancost、Anup Patnaik、Dillon Phan、Craig Plato、Ming Qian、Vasumathy Rajaraman、Chang Rao、Olga Rozhitskaya、Thomas Ruppen、Jie Shi、Sarah J. Siska、Clayton Springer、Maurice van Eis、Richard B. Vega、Anette von Matt、Lihua Yang、Taeyoung Yoon、Ji-Hu Zhang、Na Zhu、Lauren G. Monovich

  DOI：10.1021/jm100075z

  日期：2010.8.12

  A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.