2-(pyrimidin-2-yl)benzoic acid

• 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: 2-(pyrimidin-2-yl)benzoic acid
• 英文别名: 2-pyrimidin-2-ylbenzoic acid
• 化学式: C₁₁H₈N₂O₂
• 分子量: 200.197
• InChiKey: BCLGTIBYZQQFJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(((3R,6R)-6-Methylpiperidin-3-yl)oxy)isonicotinonitrile 、 2-(pyrimidin-2-yl)benzoic acid 在 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-{[(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylphenyl)carbonyl]piperidin-3-yl]oxy}pyridine-4-carbonitrile
  参考文献：
  名称：

  Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties

  摘要：

  Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype. Judicious selection of the substituents on the pyridine ring and benzamide groups led to 6b; which was highly potent, OX2R selective, and exhibited excellent development properties. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.066
• 作为产物：
  描述：

  邻溴苯甲酸甲酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 potassium acetate 、 sodium carbonate 、 sodium hydroxide 作用下， 以 2-甲基四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 19.0h， 生成 2-(pyrimidin-2-yl)benzoic acid
  参考文献：
  名称：

  [EN] NOVEL N-[(PYRAZINYLOXY)PROPANYL]BENZAMIDES
  [FR] NOUVEAUX N-[(PYRAZINYLOXY)PROPANYL]BENZAMIDES

  摘要：

  这项发明涉及式(I)的化合物，其制备方法，含有它们的药物组合物以及它们在治疗与促觉肽亚型1受体相关的疾病中的应用。Ar、R1、R2和R3的含义如描述中所示。

  公开号：

  WO2017178339A1

文献信息

• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• [EN] NOVEL N-[(PYRAZINYLOXY)PROPANYL]BENZAMIDES<br/>[FR] NOUVEAUX N-[(PYRAZINYLOXY)PROPANYL]BENZAMIDES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2017178339A1

  公开（公告）日：2017-10-19

  This invention relates to compounds of formula (I) a process for their preparation, pharmaceutical compositions containing them and their use in the treatment of conditions having an association with the orexin sub-type 1 receptor. Ar, R1, R2 and R3 have meanings given in the description.

  这项发明涉及式(I)的化合物，其制备方法，含有它们的药物组合物以及它们在治疗与促觉肽亚型1受体相关的疾病中的应用。Ar、R1、R2和R3的含义如描述中所示。
• Discovery and optimisation of 1-acyl-2-benzylpyrrolidines as potent dual orexin receptor antagonists
  作者：Jodi T. Williams、John Gatfield、Catherine Roch、Alexander Treiber、Francois Jenck、Martin H. Bolli、Christine Brotschi、Thierry Sifferlen、Bibia Heidmann、Christoph Boss

  DOI：10.1039/c5md00074b

  日期：——

  1-acyl-2-benzylpyrrolidines were discovered as potent and competitive dual orexin receptor antagonists. Metabolic stability was improved to afford oral exposure, and aqueous solubility was increased by twentyfold, providing compounds suitable for preclinical evaluation. Compound 27 showed insurmountable antagonism at both orexin 1 and orexin 2 receptor subtypes and displayed a comparable sleep-promoting

  从在大鼠和人肝微粒体中具有高固有清除率和低水溶性的噻吩并哌啶前导化合物开始，发现了一系列新型的1-酰基-2-苄基吡咯烷酮，它们是有效且具有竞争力的双重orexin受体拮抗剂。改善了代谢稳定性以提供口服暴露，并且水溶性增加了二十倍，从而提供了适合临床前评估的化合物。化合物27对orexin 1和orexin 2受体亚型均显示出不可克服的拮抗作用，并且在大鼠中具有与Almorexant和suvorexant相当的促睡眠作用。
• Herbicidally Active Composition
  申请人：Hupe Eike

  公开号：US20100190794A1

  公开（公告）日：2010-07-29

  The present invention relates to herbicidally active compositions comprising at least one piperazinedione compound of the formula I in which: R x , R y are each hydrogen or together are a chemical bond; R 1 is cyano or nitro; R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy; R 3 is fluorine or hydrogen; R 4 is methyl; R 5 is hydrogen, methyl or ethyl; R 6 is hydrogen, methyl or ethyl; and R 7 is hydrogen or halogen; and at least one further active compound selected from the group consisting of b1) lipid biosynthesis inhibitors; b2) acetolactate synthase inhibitors (ALS inhibitors); b3) photosynthesis inhibitors; b4) protoporphyrinogen-IX oxidase inhibitors, b5) bleacher herbicides; b6) enolpyruvyl shikimate 3-phosphate synthase inhibitors (EPSP inhibitors); b7) glutamine synthetase inhibitors; b8) 7,8-dihydropteroate synthase inhibitors (DHP inhibitors); b9) mitose inhibitors; b10) inhibitors of the synthesis of very long chain fatty acids (VLCFA inhibitors); b11) cellulose biosynthesis inhibitors; b12) decoupler herbicides; b13) auxin herbicides; b14) auxin transport inhibitors; b15) other herbicides, and C) safeners.

  本发明涉及具有至少一种式I的哌嗪二酮化合物的除草活性组合物： 其中： Rx，Ry分别为氢或一起为化学键； R1为氰基或硝基； R2为氢、氟、氯、C1-C2-烷基、乙烯基或C1-C2-烷氧基； R3为氟或氢； R4为甲基； R5为氢、甲基或乙基； R6为氢、甲基或乙基；以及 R7为氢或卤素； 以及从以下组中选择的至少一种进一步活性化合物： b1）脂质生物合成抑制剂； b2）乙酰乳酸合成酶抑制剂（ALS抑制剂）； b3）光合作用抑制剂； b4）原卟啉原生物合成酶抑制剂； b5）漂白剂除草剂； b6）烯丙基酮酸磷酸合酶抑制剂（EPSP抑制剂）； b7）谷氨酰胺合成酶抑制剂； b8）7,8-二氢叶酸合成酶抑制剂（DHP抑制剂）； b9）有丝分裂抑制剂； b10）非常长链脂肪酸合成抑制剂（VLCFA抑制剂）； b11）纤维素生物合成抑制剂； b12）解偶联剂除草剂； b13）生长素除草剂； b14）生长素转运抑制剂； b15）其他除草剂；以及 C）安全剂。
• [EN] FUSED HETEROARYL DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'HÉTÉROARYLES FUSIONNÉS EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DES ORÉXINES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016101119A1

  公开（公告）日：2016-06-30

  Fused heteroaryl derivative compounds which are antagonists of orexin receptors are provided. The compounds can be used in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. Also provided is a composition which comprises the compound can be use to prevent or treat such diseases in which orexin receptors are involved.

  提供了与异杂环衍生物化合物，这些化合物是促进睡眠的受体拮抗剂。这些化合物可用于潜在治疗或预防涉及促进睡眠的受体的神经和精神疾病。还提供了一种包含该化合物的组合物，可用于预防或治疗涉及促进睡眠的受体的这类疾病。