2-(2,6-difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carboxamide | 1082443-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2,6-difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carboxamide
• 英文别名: 2-(2,6-difluorophenyl)-5-[4-(morpholine-4-carbonyl)anilino]-1,3-oxazole-4-carboxamide
• CAS: 1082443-84-2
• 化学式: C₂₁H₁₈F₂N₄O₄
• 分子量: 428.395
• InChiKey: AERWMYXDWZVUFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氟苯甲酰氯 在 亚硝酸特丁酯 、 硫酸 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 copper(ll) bromide 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 乙腈 、 正丁醇 为溶剂， 反应 18.63h， 生成 2-(2,6-difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carboxamide
  参考文献：
  名称：

  WO2008/139161

  摘要：

  公开号：

文献信息

• [EN] PHARMACEUTICAL COMPOUNDS<br/>[FR] COMPOSÉS PHARMACEUTIQUES
  申请人：SAREUM LTD

  公开号：WO2015032423A1

  公开（公告）日：2015-03-12

  The invention provides a compound which is an amide of the formula (2): or a salt or stereoisomer thereof; wherein: R7 is selected from chlorine and fluorine; R3, R4, R5 and R6 are each independently selected from hydrogen, fluorine and chlorine; n is 0, 1 or 2; Q1 is selected from C(=O), S(=O) and SO2; A is absent or is NR2; R1 is selected from: - hydrogen; - an optionally substituted C1-6 non-aromatic hydrocarbon group; and - 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms, the carbocyclic and heterocyclic rings and bridged bicyclic heterocyclic rings being optionally substituted; R2 is selected from hydrogen and C1-4 alkyl; or NR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen- containing heterocyclic ring optionally containing a second heteroatom ring member selected from nitrogen and oxygen; with the provisos that: (i) no more than two of R3 to R6 are other than hydrogen; and (ii) when R7 and R6 are both fluorine, then one of R3 to R5 is chlorine or fluorine and/or R1-A-Q1 is selected from ethylsulfonyl and isopropylsulfonyl. Also provided are pharmaceutical compositions containing the compounds and their therapeutic uses.

  本发明提供的化合物是公式（2）的酰胺或其盐或立体异构体；其中：R7从氯和氟中选择；R3、R4、R5和R6各自独立地从氢、氟和氯中选择；n为0、1或2；Q1从C（=O）、S（=O）和SO2中选择；A不存在或为NR2；R1从：-氢；-可选择取代的C1-6非芳香烃基；和-含有一个或两个杂原子环成员（选自O、N和S）的3-至7元非芳香碳环和杂环，并且是由七个至九个环成员的桥接双环杂环，其中一个或两个是氮原子，所述碳环和杂环以及桥接双环杂环可选择取代；R2从氢和C1-4烷基中选择；或NR1R2形成一个可选择取代的4-至7元非芳香含氮杂环，可选择包含第二个杂原子环成员，选自氮和氧；但前提是：（i）R3至R6中不超过两个不是氢；（ii）当R7和R6均为氟时，那么R3至R5中的一个为氯或氟和/或R1-A-Q1选择自乙基磺酰基和异丙基磺酰基。还提供了含有该化合物的药物组合物及其治疗用途。
• Oxazole tyrosine kinase inhibitors
  申请人：Reader John Charles

  公开号：US08378095B2

  公开（公告）日：2013-02-19

  The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Ar1 is a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted by one or more substituents R1; Ar2 Js a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R2; and R1 and R2 are as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases.

  本发明提供了一种化合物，其为公式（1）的酰胺或其盐、溶剂合物、N-氧化物或互变异构体；其中：a为0或1；b为0或1：前提是a和b的和为0或1；T为O或NH；Ar1为单环或双环的5-至10-成员芳基或杂芳基，包含最多4个从O、N和S中选择的杂原子，并且可以被一个或多个取代基R1取代；Ar2为单环或双环的5-至10-成员芳基或杂芳基，包含最多4个从O、N和S中选择的杂原子，并且可以被一个或多个取代基R2取代；其中R1和R2如权利要求所定义。这些化合物是激酶抑制剂，特别是FLT3、FLT4和Aurora激酶的抑制剂。
• OXAZOLE TYROSINE KINASE INHIBITORS
  申请人：Sareum Limited

  公开号：US20130102592A1

  公开（公告）日：2013-04-25

  The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Ar 1 is a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted en by one or more substituents R 1 ; Ar 2 Js a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R 2 ; and R 1 and R 2 are as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases.

  本发明提供了一种化合物，其为公式（1）的酰胺或其盐、溶剂合物、N-氧化物或互变异构体；其中：a为0或1；b为0或1：前提是a和b的和为0或1；T为O或NH；Ar1为含有最多4个来自O、N和S的杂原子的单环或双环5-至10-成员芳基或杂芳基基团，并且可以被一个或多个取代基R1取代；Ar2为含有最多4个来自O、N和S的杂原子的单环或双环5-至10-成员芳基或杂芳基基团，并且可以被一个或多个取代基R2取代；R1和R2如权利要求所定义。该化合物是激酶抑制剂，特别是FLT3、FLT4和Aurora激酶的抑制剂。
• PHARMACEUTICAL COMPOUNDS
  申请人：SAREUM LIMITED

  公开号：US20130231340A1

  公开（公告）日：2013-09-05

  The invention provides a method of inhibiting a TYK2 kinase, which method comprises bringing into contact with the TYK2 kinase an effective TYK2 kinase-inhibiting amount of a compound having the formula (0): or a salt or stereoisomer thereof. The invention also provides a novel subset of compounds within formula (0) as well as pharmaceutical compositions containing them and their use in medicine.

  本发明提供了一种抑制TYK2激酶的方法，该方法包括将具有以下式子（0）的化合物或其盐或立体异构体的有效TYK2激酶抑制剂量与TYK2激酶接触。本发明还提供了公式（0）内的新化合物子集，以及包含它们的药物组合物及其在医学中的应用。
• TYK2 KINASE INHIBITORS
  申请人：Sareum Limited

  公开号：EP3040336A1

  公开（公告）日：2016-07-06

  The invention provides a compound for use in a method for the diagnosis and treatment of a disease state or condition mediated by TYK2 kinase, which method comprises (i) screening a patient to determine whether a disease or condition from which the patient is or may be suffering is one which would be susceptible to treatment with a compound having activity against the kinase; and (ii) where it is indicated that the disease or condition from which the patient is thus susceptible, thereafter administering to the patient an effective TYK2 inhibiting amount of the compound, wherein the compound has the formula (0): or is a salt or stereoisomer thereof; wherein: n is 0, 1 or 2; Ar1 is selected from an optionally substituted phenyl, pyridyl, thienyl and furanyl; Q1 is selected from C(=O), S(=O) and SO2; A is absent or is NR2; R1 is selected from hydrogen, an optionally substituted C1-6 non-aromatic hydrocarbon group and an optionally substituted 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms; or NR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic ring optionally containing a second heteroatom ring member selected from nitrogen and oxygen. The invention also provides compounds for use in the diagnosis and treatment of various autoimmune and inflammatory diseases through the inhibition of TYK2 kinase.

  本发明提供了一种用于诊断和治疗由 TYK2 激酶介导的疾病状态或病症的方法的化合物，该方法包括：(i) 筛选患者，以确定患者正在或可能患有的疾病或病症是否容易受到具有抗激酶活性的化合物的治疗；(ii) 如果表明患者容易患有该疾病或病症，则向患者施用有效的 TYK2 抑制量的化合物，其中化合物具有式 (0)： 或其盐或立体异构体；其中 n 是 0、1 或 2； Ar1 选自任选取代的苯基、吡啶基、噻吩基和呋喃基； Q1 选自 C（=O）、S（=O）和 SO2； A 不存在或为 NR2； R1 选自氢、任选取代的 C1-6 非芳香烃基团和任选取代的 3 至 7 元非芳香碳环和杂环，这些环含有一个或两个选自 O、N 和 S 的杂原子环成员，以及由 7 至 9 个环成员（其中一个或两个为氮原子）组成的桥接双环杂环；或 NR1R2 形成任选取代的 4 至 7 元非芳香族含氮杂环，任选含有选自氮和氧的第二个杂原子环成员。 本发明还提供了通过抑制 TYK2 激酶用于诊断和治疗各种自身免疫性和炎症性疾病的化合物。