N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-(1,2,2,6,6-pentamethylpiperidin-4-yloxy)picolinamide methanesulfonate salt | 1351521-69-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-(1,2,2,6,6-pentamethylpiperidin-4-yloxy)picolinamide methanesulfonate salt
• 英文别名: 4-(6-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenylcarbamoyl)pyridin-3-yloxy)-1,2,2,6,6-pentamethylpiperidinium methanesulfonate；N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-5-(1,2,2,6,6-pentamethylpiperidin-1-ium-4-yl)oxypyridine-2-carboxamide;methanesulfonate
• CAS: 1351521-69-1
• 化学式: CH₄O₃S*C₃₀H₄₀N₆O₄
• 分子量: 644.792
• InChiKey: ZLHAHIPJXPEGBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  184
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  五甲基哌啶醇 在 水 、 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.67h， 生成 N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-(1,2,2,6,6-pentamethylpiperidin-4-yloxy)picolinamide methanesulfonate salt
  参考文献：
  名称：

  Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases

  摘要：

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.

  DOI：

  10.1021/ml300214g

文献信息

• [EN] AZOLYL UREA COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS AZOLYLE URÉE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2011150198A1

  公开（公告）日：2011-12-01

  Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗CSF-1R激酶介导疾病的唑啉基脲化合物。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• Azolyl Urea Compounds and Methods of Use Thereof
  申请人：Liu Gang

  公开号：US20130310357A1

  公开（公告）日：2013-11-21

  Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗CSF-1R激酶介导疾病的氮杂基脲化合物。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• Co-therapy comprising a small molecule CSF-1R inhibitor and an agonistic antibody that specifically binds CD40 for the treatment of cancer
  申请人：Janssen Biotech, Inc.

  公开号：US10857230B2

  公开（公告）日：2020-12-08

  The present invention is directed to methods for treating cancer, preferably a solid tumor or hematological malignancy, including for example pancreatic cancer, lung cancer (including but not limited to non-small cell lung cancer (NSCLC)), prostate cancer, colorectal cancer, breast cancer, melanoma or non-Hodgkin's lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising, consisting or consisting essentially of (a) a small molecule CSF-1R inhibitor and (b) an agonistic antibody that binds CD40.

  本发明涉及治疗癌症的方法，优选实体瘤或血液恶性肿瘤，例如包括胰腺癌、肺癌（包括但不限于非小细胞肺癌（NSCLC））、前列腺癌、结直肠癌、乳腺癌、黑素瘤或非霍奇金淋巴瘤、或非霍奇金淋巴瘤，包括向有需要的受试者施用治疗有效量的联合疗法，该联合疗法包括或主要包括(a) 小分子 CSF-1R 抑制剂和(b) 结合 CD40 的激动抗体。
• CO-THERAPY COMPRISING A SMALL MOLECULE CSF-1R INHIBITOR AND AN AGONISTIC ANTIBODY THAT SPECIFICALLY BINDS CD40 FOR THE TREATMENT OF CANCER
  申请人：Janssen Biotech, Inc.

  公开号：US20180250398A1

  公开（公告）日：2018-09-06

  The present invention is directed to methods for treating cancer, preferably a solid tumor or hematological malignancy, including for example pancreatic cancer, lung cancer (including but not limited to non-small cell lung cancer (NSCLC)), prostate cancer, colorectal cancer, breast cancer, melanoma or non-Hodgkin's lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising, consisting or consisting essentially of (a) a small molecule CSF-1R inhibitor and (b) an agonistic antibody that binds CD40.
• Co-Therapy Comprising A Small Molecule CSF-1R Inhibitor And An Agonistic Antibody That Specifically Binds CD40 For The Treatment Of Cancer
  申请人：Janssen Biotech, Inc.

  公开号：US20210093719A1

  公开（公告）日：2021-04-01

  The present invention is directed to methods for treating cancer, preferably a solid tumor or hematological malignancy, including for example pancreatic cancer, lung cancer (including but not limited to non-small cell lung cancer (NSCLC)), prostate cancer, colorectal cancer, breast cancer, melanoma or non-Hodgkin's lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising, consisting or consisting essentially of (a) a small molecule CSF-1R inhibitor and (b) an agonistic antibody that binds CD40.