4-(4,6-dichloro-5-methylpyrimidin-2-yl)morpholine | 60703-50-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(4,6-dichloro-5-methylpyrimidin-2-yl)morpholine
• 英文别名: 4,6-Dichloro-5-methyl-2-morpholinopyrimidine
• CAS: 60703-50-6
• 化学式: C₉H₁₁Cl₂N₃O
• 分子量: 248.112
• InChiKey: GPXLZHROXAUNHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4,6-dichloro-5-methylpyrimidin-2-yl)morpholine 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 12.0h， 生成 4-(4-(3-chloro-4-fluorophenyl)-5-methyl-6-{4-[3-(trifluoromethyl)(2-pyridyl)]piperazinyl}pyrimidin-2-yl)morpholine
  参考文献：
  名称：

  [EN] BIARYL PIPERAZINYL-PYRIDINE ANALOGUES
  [FR] ANALOGUES DE BIARYL PIPERAZINYL-PYRIDINE

  摘要：

  公开号：

  WO2005007648A3
• 作为产物：
  描述：

  5-methyl-2-morpholinopyrimidine-4,6-diol 在 N,N-二乙基苯胺 、 三氯氧磷 作用下， 反应 2.0h， 生成 4-(4,6-dichloro-5-methylpyrimidin-2-yl)morpholine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDIN-4-YLAMINA ANALOGUES AS VANILLOID RECEPTOR LIGANDS
  [FR] ANALOGUES DE PYRIMIDINE-4-YLAMINE SUBSTITUES CONSTITUANT DES LIGANDS DES RECEPTEURS VANILLOIDES

  摘要：

  提供了取代的嘧啶基-4-胺类似物，化学式如下：(I)，其中变量如本文所述。这些化合物是配体，可用于调节体内或体外的辣椒素受体活性，并在治疗与人类、驯养的伴侣动物和家畜动物中的病理性受体激活相关的疾病方面特别有用。提供了用于治疗这些疾病的药物组合物和方法，以及用于受体定位研究的这些配体的方法。

  公开号：

  WO2005009977A1

文献信息

• [EN] 2 -MORPHOLINOPYRIMIDINES AND THEIR USE AS PI3 KINASE INHIBITORS<br/>[FR] 2-MORPHOLINOPYRIMIDINES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE PI3
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009066084A1

  公开（公告）日：2009-05-28

  Morpholino pyrimidines of formula (I): wherein R1 is selected from -Y-R6 and -NR4R5; R2 is a N-containing monocyclic heteroaryl group which is selected from pyridyl, isoxazolyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxazolyl, furanyl, thienyl, triazolyl and tetrazolyl and which is unsubstituted or substituted by halo, -CN, -NR10R11, -OR10, -C(O)R10, -NR10C(O)R11, - N(C(O)R11)2, -NR10C(O)NR10R11, -SO2R10R11, -SO2NR10R11, -C(=O)OR10, -C(=O)NR10R11, halo-C1 -C6 alkyl and unsubstituted C1-C12 alkyl; R3 is selected from H, C1-C6 alkyl and C1-C6 alkoxy; Y is selected from a direct bond, -(CR2)m-, C2-C6 alkenylene, C2-C6 alkynylene, -(CR2)p-O-(CR2) t-, -(CR2)p-NR-(CR2) t, -(CR2)p-NR-(CR2)n-C(O)-, -(CR2)p-NR-C(O)- (CR2)n-, -(CR2)p-C(O)-NR-(CR2) t, -(CR2)p-C(O)-(CR2)n-NR-(CR2)t,- and -(CR2)p- C(O)-(CR2)n-; R6 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic ring, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted, C1-C6 alkyl, -NR2, -OR, -NR(CO)R and - C(O)NR2; R4 and R5, which are the same or different, are both C1-C6 alkyl which is unsubstituted or substituted, or R4 and R5 together form, with the nitrogen atom to which they are attached, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted; each R, which are the same or different when more than one is present in a given group, is independently H, C1-C6 alkyl which is unsubstituted or substituted or a 5- to 12-membered aryl or heteroaryl group which is unsubstituted or substituted; R10 and R11, which are the same or different, are independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C3-C8 cycloalkyl; n is 0 or an integer of 1 to 6; m is an integer of 1 to 6; p is 0 or an integer of 1 to 6; and t is 0 or an integer of 1 to 6, with the proviso that t is an integer of 2 to 6 when R6 is linked to Y through a constituent O or N atom of R6; and the pharmaceutically acceptable salts thereof, subject to various provisos, have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour, particularly that associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式(I)的吗哥啉嘧啶，其中R1从-Y-R6和-NR4R5中选择；R2是一种含氮的单环杂环芳基，选择自吡啶基、异噁唑基、咪唑基、吡唑基、吡咯基、噻唑基、吡啶嗪基、嘧啶基、吡嗪基、噁唑基、呋喃基、噻吩基、三唑基和四唑基，未取代或取代为卤素、-CN、-NR10R11、-OR10、-C(O)R10、-NR10C(O)R11、-N(C(O)R11)2、-NR10C(O)NR10R11、-SO2R10R11、-SO2NR10R11、-C(=O)OR10、-C(=O)NR10R11、卤代-C1-C6烷基和未取代的C1-C12烷基；R3从H、C1-C6烷基和C1-C6烷氧基中选择；Y从直接键、-(CR2)m-、C2-C6烯基、C2-C6炔基、-(CR2)p-O-(CR2)t-、-(CR2)p-NR-(CR2)t、-(CR2)p-NR-(CR2)n-C(O)-、-(CR2)p-NR-C(O)-(CR2)n-、-(CR2)p-C(O)-NR-(CR2)t、-(CR2)p-C(O)-(CR2)n-NR-(CR2)t和-(CR2)p-C(O)-(CR2)n-中选择；R6从未饱和的5-至12成员碳环或杂环环中选择，饱和的5、6或7成员N含杂环基，未取代或取代，C1-C6烷基，-NR2，-OR，-NR(CO)R和-C(O)NR2中选择；R4和R5，相同或不同，均为未取代或取代的C1-C6烷基，或R4和R5与它们连接的氮原子形成未取代或取代的饱和的5、6或7成员N含杂环基；每个R，当在给定的基团中存在多个时，相同或不同，独立地为H，未取代或取代的C1-C6烷基或未取代或取代的5-至12成员芳基或杂环基；R10和R11，相同或不同，独立地选择自H，C1-C6烷基，C2-C6烯基，C2-C6炔基和C3-C8环烷基；n为0或1至6的整数；m为1至6的整数；p为0或1至6的整数；t为0或1至6的整数，但当R6通过R6的一个成分O或N原子与Y连接时，t为2至6的整数；以及其药学上可接受的盐，受各种规定限制，具有PI3K抑制剂的活性，因此可用于治疗由于异常细胞生长、功能或行为引起的疾病和紊乱，特别是与PI3激酶相关的癌症、免疫紊乱、心血管疾病、病毒感染、炎症、代谢/内分泌紊乱和神经系统紊乱。还描述了合成这些化合物的方法。
• [EN] SUBSTITUTED HETEROCYCLIC DIARYLAMINE ANALOGUES<br/>[FR] ANALOGUES DE DIARYLAMINE HETEROCYCLIQUES SUBSTITUES
  申请人：NEUROGEN CORP

  公开号：WO2005007646A1

  公开（公告）日：2005-01-27

  Substituted heterocyclic diarylamine analogues of Formula I are provided: wherein X, Y and Z are independently N or optionally substituted C, and other variables are as described in the specification. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了公式I的取代杂环二芳基胺类似物：其中X、Y和Z分别是N或可选择取代的C，其他变量如规范中所述。这些化合物是配体，可用于在体内或体外调节特定受体活性，并在治疗与人类、驯养伴侣动物和家畜动物中的病理受体激活相关的疾病方面特别有用。提供了用于治疗这些疾病的药物组合物和使用它们的方法，以及用于受体定位研究的这类配体的使用方法。
• [EN] SUBSTITUTED PYRIMIDIN-4-YLAMINA ANALOGUES AS VANILLOID RECEPTOR LIGANDS<br/>[FR] ANALOGUES DE PYRIMIDINE-4-YLAMINE SUBSTITUES CONSTITUANT DES LIGANDS DES RECEPTEURS VANILLOIDES
  申请人：NEUROGEN CORP

  公开号：WO2005009977A1

  公开（公告）日：2005-02-03

  Substituted pyrimidyl-4-ylamine analogues are provided, of the Formula: (I) wherein variables are as described herein. Such compounds are ligands that may be used to modulate Vanilloid receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了取代的嘧啶基-4-胺类似物，化学式如下：(I)，其中变量如本文所述。这些化合物是配体，可用于调节体内或体外的辣椒素受体活性，并在治疗与人类、驯养的伴侣动物和家畜动物中的病理性受体激活相关的疾病方面特别有用。提供了用于治疗这些疾病的药物组合物和方法，以及用于受体定位研究的这些配体的方法。
• Biaryl piperazinyl-pyridine analogues
  申请人：Bakthavatchalam Rajagopal

  公开号：US20070027155A1

  公开（公告）日：2007-02-01

  Biaryl piperazinyl-pyridine analogues are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了公式为：其中变量如此处所述的Biaryl piperazinyl-pyridine类似物。这些化合物是配体，可用于调节体内或体外特定受体活性，并且在治疗与人类、家养伴侣动物和家畜动物的病理性受体激活相关的疾病方面特别有用。提供了用于治疗此类疾病的制药组合物和方法，以及用于受体定位研究的这些配体的方法。
• Substituted heterocyclic diarylamine analogues
  申请人：Bakthavatchalam Rajagopal

  公开号：US20070043049A1

  公开（公告）日：2007-02-22

  Substituted heterocyclic diarylamine analogues of Formula I are provided: wherein X, Y and Z are independently N or optionally substituted C, and other variables are as described in the specification. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了式I的替代杂环二芳基胺类似物：其中X、Y和Z独立地为N或可选择被取代的C，其他变量如说明书所述。这些化合物是配体，可用于体内或体外调节特定受体活性，并特别适用于治疗与人类、家养伴侣动物和家畜动物的病理性受体激活相关的疾病。提供了用于治疗这些疾病的制药组合物和使用它们的方法，以及使用这些配体进行受体定位研究的方法。