1-(2-morpholino-6-nitrooxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶唑并吡啶类
• 英文名称: 1-(2-morpholino-6-nitrooxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol
• 英文别名: 1-(2-Morpholin-4-yl-6-nitro-[1,3]oxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol；1-(2-morpholin-4-yl-6-nitro-[1,3]oxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol
• 化学式: C₁₅H₁₉N₅O₅
• 分子量: 349.346
• InChiKey: BVERZBSJNFOGAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(2-morpholino-6-nitrooxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以95%的产率得到5-(4-fluoropiperidin-1-yl)-2-morpholino-6-nitrooxazolo[4,5-b]pyridine
  参考文献：
  名称：

  [EN] BICYCLIC HETEROCYCLYL DERIVATIVES AS IRAK4 INHIBITORS
  [FR] DÉRIVÉS HÉTÉROCYCLYLES BICYCLIQUES COMME INHIBITEURS DE IRAK4

  摘要：

  本发明提供了式（I）的双环杂环基激酶酶抑制剂化合物，其作为激酶抑制剂在治疗上具有疗效，特别是IRAK4抑制剂。其中A、Y、Z、X1、X2、X3、R1、R3、'm'、'n'和'p'在规范中给出了含义，并且具有治疗和预防疾病或疾病的药用盐或其立体异构体，在特定情况下用于由激酶酶介导的疾病或疾病的治疗。本发明还提供了包括至少一种式（I）化合物的药物组合物，与药用载体、稀释剂或赋形剂一起。

  公开号：

  WO2015104688A1
• 作为产物：
  描述：

  2-氯-5-羟基吡啶 在 吡啶 、 硫酸 、 氢气 、 potassium carbonate 、 potassium nitrate 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.5h， 生成 1-(2-morpholino-6-nitrooxazolo[4,5-b]pyridin-5-yl)piperidin-4-ol
  参考文献：
  名称：

  Discovery of CA-4948, an Orally Bioavailable IRAK4 Inhibitor for Treatment of Hematologic Malignancies

  摘要：

  Small molecule potent IRAK4 inhibitors from a novel bicyclic heterocycle class were designed and synthesized based on hits identified from Aurigene's compound library. The advanced lead compound, CA-4948, demonstrated good cellular activity in ABC DLBCL and AML cell lines. Inhibition of TLR signaling leading to decreased IL-6 levels was also observed in whole blood assays. CA-4948 demonstrated moderate to high selectivity in a panel of 329 kinases as well as exhibited desirable ADME and PK profiles including good oral bioavailability in mice, rat, and dog and showed >90% tumor growth inhibition in relevant tumor models with excellent correlation with in vivo PD modulation. CA-4948 was well tolerated in toxicity studies in both mouse and dog at efficacious exposure. The overall profile of CA-4948 prompted us to select it as a clinical candidate for evaluation in patients with relapsed or refractory hematologic malignancies including non-Hodgkin lymphoma and acute myeloid leukemia.

  DOI：

  10.1021/acsmedchemlett.0c00255

文献信息

• BICYCLIC HETEROCYCLYL DERIVATES AS IRAK4 INHIBITORS
  申请人：AURIGENE DISCOVERY TECHNOLOGIES LIMITED

  公开号：US20160340366A1

  公开（公告）日：2016-11-24

  The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors, wherein A, Y, Z, X 1 , X 2 , R 1 , R 3 , ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了公式（I）的双环杂环基激酶酶抑制剂化合物，作为激酶抑制剂在治疗上具有疗效，特别是IRAK4抑制剂，在其中A、Y、Z、X1、X2、R1、R3、‘m’、‘n’和‘p’的含义如规范中所给定，并且在治疗和预防疾病或紊乱方面有用，特别是在通过激酶酶介导的疾病或紊乱中的使用，特别是IRAK4酶。本发明还提供了包含至少一种公式（I）的化合物的制剂，与其一起使用的药用载体、稀释剂或赋形剂。
• METHOD OF PREPARING OXAZOLO[4,5-B]PYRIDINE AND THIAZOLO[4,5-B]PYRIDINE DERIVATIVES AS IRAK4 INHIBITORS FOR TREATING CANCER
  申请人：Aurigene Discovery Technologies Limited

  公开号：EP3466955A1

  公开（公告）日：2019-04-10

  The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors. wherein A, Y, Z, X1, X2, X3, R1, R3, 'm', 'n' and 'p' have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了式(I)的双环杂环激酶酶抑制剂化合物，它们作为激酶抑制剂，特别是IRAK4抑制剂，具有治疗作用。 其中A、Y、Z、X1、X2、X3、R1、R3、'm'、'n'和'p'具有说明书中给出的含义及其药学上可接受的盐或立体异构体，这些化合物对治疗和预防疾病或紊乱有用，特别是它们在激酶酶，尤其是IRAK4酶介导的疾病或紊乱中的用途。本发明还提供由至少一种式（I）化合物及其药学上可接受的载体、稀释剂或赋形剂组成的药物组合物。
• (R) AND (S) ENANTIOMER OF N-(5-(3-HYDROXYPYRROLIDIN-1-YL)-2-MORPHOLINOOXAZOLO[4,5-B]PYRIDIN-6-YL)-2-(2-METHYLPYRIDIN-4-YL)OXAZOLE-CARBOXAMIDE AS IRAK4 INHIBITORS FOR TREATING CANCER AND INFLAMMATORY DISEASES
  申请人：Aurigene Discovery Technologies Limited

  公开号：EP3805233A1

  公开（公告）日：2021-04-14

  Provided are bicyclic heterocyclyl kinase enzyme inhibitor compounds and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme, such as e.g. cancer and inflammatory diseases.

  提供双环杂环激酶抑制剂化合物 及其药学上可接受的盐类，可用于治疗和预防疾病或紊乱，特别是用于由激酶，尤其是IRAK4酶介导的疾病或紊乱，例如癌症和炎症性疾病。
• Bicyclic heterocyclyl derivatives as IRAK4 inhibitors
  申请人：Aurigene Discovery Technologies Limited

  公开号：US10640517B2

  公开（公告）日：2020-05-05

  The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors. wherein A, Y, Z, X1, X2, X3, R1, R3, ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了式(I)的双环杂环激酶酶抑制剂化合物，它们作为激酶抑制剂，特别是IRAK4抑制剂，具有治疗作用。 其中A、Y、Z、X1、X2、X3、R1、R3、'm'、'n'和'p'具有说明书中给出的含义及其药学上可接受的盐或立体异构体，这些化合物对治疗和预防疾病或紊乱有用，特别是它们在激酶酶，尤其是IRAK4酶介导的疾病或紊乱中的用途。本发明还提供了药物组合物，其中包含至少一种式（I）化合物及其药学上可接受的载体、稀释剂或赋形剂。
• BICYCLIC HETEROCYCLYL DERIVATIVES AS IRAK4 INHIBITORS
  申请人：Aurigene Discovery Technologies Limited

  公开号：EP3094329A1

  公开（公告）日：2016-11-23