N-羟基-4-(羟基甲基)苯甲酰胺 | 635702-23-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-羟基-4-(羟基甲基)苯甲酰胺
• 英文名称: N-hydroxy-4-(hydroxymethyl)benzimidamide
• 英文别名: Benzenecarboximidamide,N-hydroxy-4-(hydroxymethyl)-；N'-hydroxy-4-(hydroxymethyl)benzenecarboximidamide
• CAS: 635702-23-7
• 化学式: C₈H₁₀N₂O₂
• 分子量: 166.18
• InChiKey: XAVQRXUCPQYHBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  78.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-羟基-4-(羟基甲基)苯甲酰胺 在 四丙基高钌酸铵 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 8.33h， 生成 4-(5-(4-异丙氧基-3-(三氟甲基)苯基)-1,2,4-恶二唑-3-基)苯甲醛
  参考文献：
  名称：

  NOVEL PHOSPHONIC ACIDS AS S1P RECEPTOR MODULATORS

  摘要：

  本发明涉及新型膦酸衍生物，其制备方法，含有它们的药物组合物以及它们作为调节鞘氨醇-1-磷酸受体的药物的用途。

  公开号：

  US20120129814A1
• 作为产物：
  描述：

  4-(羟甲基)苯甲腈 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以100%的产率得到N-羟基-4-(羟基甲基)苯甲酰胺
  参考文献：
  名称：

  新 S1PR1 化合物的合成和体外评估以及先导 F-18 放射性示踪剂在啮齿动物中的初步评估

  摘要：

  通过用新的极性基团替换化合物4的氮杂环丁烷-3-羧酸部分，设计并合成了 13 个新的 1-磷酸鞘氨醇受体 1 (S1PR1) 配体。确定了这些新类似物对 S1PR1 的体外结合效力。在 13 种新化合物中，四种化合物9a 、 10c 、 12b和16b显示出高 S1PR1 结合效力， IC 50值分别为 13.2 ± 3.2、14.7 ± 1.7、9.7 ± 1.6 和 6.3 ± 1.3 nM；这四种配体与 S1PR2-5 的进一步结合研究表明，它们对 S1PR1 的选择性高于其他 S1PR。铅放射性示踪剂[ 18 F] 12b的放射合成具有良好的放射化学收率（∼14.1%）、高放射化学纯度（>98%）和良好的比活性（∼54.1 GBq/μmol，衰减校正到合成结束） ，EOS）。在啮齿动物中进行了离体放射自显影和初始生物分布研究，表明 [ 18 F] 12b能够穿透血脑屏障 (BBB)，并具有高脑摄取率（注射后

  DOI：

  10.1016/j.ejmech.2018.03.035

文献信息

• HETEROAROMATIC COMPOUNDS FOR USE AS HIF INHIBITORS
  申请人：Härter Michael

  公开号：US20110301122A1

  公开（公告）日：2011-12-08

  The present application relates to novel substituted aryl compounds, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

  本申请涉及新型取代芳基化合物，其制备方法，它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应缺氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步的治疗措施结合使用。
• Aryl compounds with aminoalkyl substituents and their use
  申请人：Härter Michael

  公开号：US20110312930A1

  公开（公告）日：2011-12-22

  The present application relates to novel aryl compounds with aminoalkyl substituents, to processes for their preparation, to their use for treatment and/or prevention of diseases and to their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

  本申请涉及具有氨基烷基取代基的新型芳基化合物，涉及其制备方法，涉及它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应低氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步的治疗措施结合使用。
• [EN] 5-(BIPHENYL-4-YL)-3-PHENYL-1,2,4-OXADIAZOLYL DERIVATIVES AS LIGANDS ON THE SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTORS<br/>[FR] DÉRIVÉS DE 5-(BIPHÉNYL-4-YL)-3-PHÉNYL-1,2,4-OXADIAZOLYLE COMME LIGANDS SUR LES RÉCEPTEURS AU SPHINGOSINE-1-PHOSPHATE (S1P)
  申请人：MERCK SERONO SA

  公开号：WO2012004287A1

  公开（公告）日：2012-01-12

  The present invention provides compounds of Formula (I), as selective S1 P1 inhibitors, as well as their use for treating multiple sclerosis and other diseases.

  本发明提供了化合物I的公式，作为选择性S1 P1抑制剂，以及它们用于治疗多发性硬化症和其他疾病的用途。
• HETEROCYCLICALLY SUBSTITUTED ARYL COMPOUNDS AS HIF INHIBITORS
  申请人：Härter Michael

  公开号：US20130196964A1

  公开（公告）日：2013-08-01

  The present application relates to novel aryl compounds with heterocyclic substituents, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

  本申请涉及具有杂环取代基的新型芳基化合物，其制备方法，它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应缺氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步治疗措施结合使用。
• 1,2,4-oxadiazole derivatives and their therapeutic use
  申请人：Laboratorios Almirall, S.A.

  公开号：EP2202232A1

  公开（公告）日：2010-06-30

  New derivatives of general formula (I), or pharmaceutically acceptable salts or N-oxides thereof wherein, A is selected from the group consisting of -N-, -O- and -S-; B and C are independently selected from the group consisting of-N- and -O-, with the proviso that at least two of A, B and C are nitrogen atoms; G1 is selected from the group consisting of -CH2-, -NH- and -O-; G2 is selected from the group consisting of -NR4- and -O-; R1 represents: ➢ a 8 to 10 membered bicyclic N-containing heteroaryl group optionally substituted with a C1-4 carboxyalkyl group or a C1-4 aminoalkyl group, ➢ a pyridyl group optionally substituted with one or more substituents selected from hydroxy groups, C1-4 alkyl groups, C1-4 carboxyalkyl groups, C1-4 haloalkyl groups, C1-4 alkoxy groups, amino groups, C1-4 aminoalkyl groups and C1-4 aminoalkoxy groups, ➢ a pyridone group substituted with one or more C1-4 alkyl groups; C1-4 haloalkyl groups or C1-4 aminoalkyl groups, or ➢ a group of formula: wherein: • Ra represents a hydrogen atom, a halogen atom, a C1-4 alkyl group, C3-4 cycloalkyl group or a -CF3 group; • Rb represents a hydrogen atom, a halogen atom, a C14 alkyl group, a -CF3 group or a C1-4 alkoxy group; • Rd represents a hydrogen atom, a C1-4 alkyl group or a C1-4 alkoxy group; • Rc represents: ○ a hydrogen atom, a C1-4 hydroxyalkyl group, a C1-4 aminoalkyl group which is optionally substituted with one or more substituents selected from halogen atoms, hydroxy groups and -CF3 groups; ○ a 4 to 6-membered saturated N-containing heterocyclic ring optionally substituted with a C1-2 carboxyalkyl group; ○ -(CH2)(0-4)-C(O)OR', -(CH2)(0-4)-C(O)NR'R", -(CH2)(0-4)-NHC(O)R", -S(O)2NR'R", -O-(CH2)(2-4)NR'R", -O-(CH2)(1-4)C(O)OR", -O-(CH2)(1-4)-C(O)NR'R", -(CH2)(0-4)-NR'R", -(CH2)(0-4)-CONHS(O)2R', -(CH2)(0-4)-NHS(O)2R' or -(CH2)(0-3)-N H-(CH2)(1-3)-(NH)(0-1)S(O)2R' wherein, ■ R' represents a hydrogen atom or a C1-4 alkyl group, ■ R" represents a hydrogen atom, a C1-4 alkyl group, a C3-4 cycloalkyl group, a C1-4 carboxyalkyl group, a C1-4 haloalkyl group, a C1-4 hydroxyalkyl group or a 6 membered, saturated N-containing heterocyclic ring, or ■ R' and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected from N and O, and which is optionally substituted with a carboxy or a C1-4 carboxyalkyl group, or Rc together with Rd form a C5-6 cycloalkyl group optionally substituted by a -NHRf group, wherein Rf is selected from the group consisting of a hydrogen atom and a carboxymethyl group; R2 and R3 are independently selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyl groups; and R4 is selected from the group consisting of a hydrogen atom, a phenyl group, a C3-4 cycloalkyl-C1-4 alkyl group, C1-4 aminoalkyl group, C1-4 haloalkyl group and a linear or branched C1-4 alkyl group which is optionally substituted by a phenyl or a pyridyl group.

  通用公式（I）的新衍生物，或其药用可接受盐或N-氧化物，其中， A选自-N-，-O-和-S-组成的群; B和C分别选自-N-和-O-组成的群，但至少有两个A，B和C是氮原子; G1选自-CH2-，-NH-和-O-组成的群; G2选自-NR4-和-O-组成的群; R1代表: ➢一个含氮杂环的8到10成员双环基团，可选择地取代为C1-4羧基烷基基团或C1-4氨基烷基基团， ➢一个吡啶基，可选择地取代为一个或多个取代基，所选取代基包括羟基、C1-4烷基基团、C1-4羧基烷基基团、C1-4卤代烷基基团、C1-4烷氧基团、氨基、C1-4氨基烷基基团和C1-4氨氧基团， ➢一个吡啶酮基，取代为一个或多个C1-4烷基基团；C1-4卤代烷基基团或C1-4氨基烷基基团，或 ➢一个公式的基团： 其中: • Ra代表氢原子、卤原子、C1-4烷基基团、C3-4环烷基基团或-CF3基团; • Rb代表氢原子、卤原子、C14烷基基团、- 基团或C1-4烷氧基团; • Rd代表氢原子、C1-4烷基基团或C1-4烷氧基团; • Rc代表: ○氢原子、C1-4羟基烷基基团、C1-4氨基烷基基团，可选择地取代为一个或多个取代基，所选取代基包括卤原子、羟基和- 基团; ○一个4到6成员饱和的含氮杂环环，可选择地取代为C1-2羧基烷基基团; ○-( )(0-4)-C(O)OR'，-( )(0-4)-C(O)NR'R"，-( )(0-4)-NHC(O)R"，-S(O)2NR'R"，-O-( )(2-4)NR'R"，-O-( )(1-4)C(O)OR"，-O-( )(1-4)-C(O)NR'R"，-( )(0-4)-NR'R"，-( )(0-4)-CONHS(O)2R'，-( )(0-4)-NHS(O)2R'或-( )(0-3)-N H-( )(1-3)-(NH)(0-1)S(O)2R'其中， ■ R'代表氢原子或C1-4烷基基团， ■ R"代表氢原子、C1-4烷基基团、C3-4环烷基基团、C1-4羧基烷基基团、C1-4卤代烷基基团、C1-4羟基烷基基团或6成员饱和的含氮杂环环，或 ■ R'和R"与它们连接的氮原子一起形成一个4到6成员的杂环基团，该基团包含一个N原子和可选择地一个进一步选择自N和O的原子，并可选择地取代为羧基或C1-4羧基烷基基团， 或Rc与Rd一起形成一个可选择地由-NHRf基团取代的C5-6环烷基基团，其中Rf选自氢原子和羧甲基基团; R2和R3分别选自氢原子、卤原子和C1-4烷基基团;和 R4选自氢原子、苯基团、C3-4环烷基-C1-4烷基基团、C1-4氨基烷基基团、C1-4卤代烷基基团和可选择地由苯基或吡啶基取代的线性或支链C1-4烷基基团。