5-氯-7-甲基-[1,2,4]三唑并[1,5-A]吡啶 | 878259-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 中文名称: 5-氯-7-甲基-[1,2,4]三唑并[1,5-A]吡啶
• 中文别名: 5-氯-7-甲基[1,2,4]噻唑并[1,5-a]吡啶
• 英文名称: 5-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridine
• CAS: 878259-99-5
• 化学式: C₇H₆ClN₃
• mdl: MFCD08246142
• 分子量: 167.598
• InChiKey: WQABKUWTQOZTIG-UHFFFAOYSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-氯-7-甲基-[1,2,4]三唑并[1,5-A]吡啶 在 N-氯代丁二酰亚胺 、 溶剂黄146 、 过氧化苯甲酰 、 水 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 (5-chloro-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol
  参考文献：
  名称：

  [EN] SUBSTITUTED TRIAZOLO BICYCLICCOMPOUNDS AS PDE2 INHIBITORS
  [FR] BICYCLO-COMPOSÉS DE TRIAZOLE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE PDE2

  摘要：

  本发明涉及一种用于治疗与磷酸二酯酶2（PDE2）相关的中枢神经系统疾病的式（I）的取代三唑杂双环化合物，该化合物可用作治疗神经系统和精神疾病，如精神分裂症、精神病、帕金森病、帕金森病痴呆（PDD）或亨廷顿病，以及与纹状体功能不足或基底神经节功能障碍相关的化合物的用途。

  公开号：

  WO2017000277A1

文献信息

• Iron catalyzed cross coupling reactions of aromatic compounds
  申请人：——

  公开号：US20030220498A1

  公开（公告）日：2003-11-27

  A process for the production of compounds Ar—R 1 by means of a cross-coupling reaction of an organometallic reagent R 1 —M with an aromatic or heteroaromatic substrate Ar—X catalyzed by one or several iron salts or iron complexes as catalysts or pre-catalysts, present homogeneously or heterogeneously in the reaction mixture. This new invention exhibits substantial advantages over established cross coupling methodology using palladium- or nickel complexes as the catalysts. Most notable aspects are the fact that (i) expensive and/or toxic nobel metal catalysts are replaced by cheap, stable, commercially available and toxicologically benign iron salts or iron complexes as the catalysts or pre-catalysts, (ii) commercially attractive aryl chlorides as well as various aryl sulfonates can be used as starting materials, (iii) the reaction can be performed under “ligand-free” conditons, and (iv) the reaction times are usually very short.

  通过使用一种或多种铁盐或铁络合物作为催化剂或前催化剂，在有机金属试剂R1—M与芳香或杂芳底物Ar—X之间进行交叉偶联反应的方法，生产化合物Ar—R1。这一新发明相对于使用钯或镍络合物作为催化剂的传统交叉偶联方法具有显著优势。最值得注意的方面包括：(i) 昂贵和/或有毒的贵金属催化剂被廉价、稳定、商业可获得且毒理学上良性的铁盐或铁络合物替代作为催化剂或前催化剂，(ii) 商业上具吸引力的芳基氯化物以及各种芳基磺酸盐可用作起始材料，(iii) 反应可在“无配体”条件下进行，(iv) 反应时间通常非常短。
• Compounds
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10287286B2

  公开（公告）日：2019-05-14

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X1, X2, X3, Y1, Y2, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式 (I) 化合物及其药学上可接受的盐类、 其中X1、X2、X3、Y1、Y2、R1、R2和R3如说明书中所定义，本发明还提供了制备它们的工艺、含有它们的药物组合物以及它们在治疗中的用途。
• Substituted triazolo bicyclic compounds as PDE2 inhibitors
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US10357481B2

  公开（公告）日：2019-07-23

  The present invention is directed to substituted triazolo bicyclic compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

  本发明涉及式 I 的取代三唑并双环化合物，其可作为治疗剂用于治疗与磷酸二酯酶 2 (PDE2)相关的中枢神经系统疾病。本发明还涉及使用此类化合物治疗神经和精神疾病，如精神分裂症、精神病、帕金森病、帕金森病痴呆（PDD）或亨廷顿病，以及与纹状体功能低下或基底节功能障碍相关的疾病。
• 1,2,4-Triazolo-[1,5-<i>a</i>]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction
  作者：Saleh Ahmed、Andrew Ayscough、Greg R. Barker、Hannah E. Canning、Richard Davenport、Robert Downham、David Harrison、Kerry Jenkins、Natasha Kinsella、David G. Livermore、Susanne Wright、Anthony D. Ivetac、Robert Skene、Steven J. Wilkens、Natalie A. Webster、Alan G. Hendrick

  DOI：10.1021/acs.jmedchem.7b00352

  日期：2017.7.13

  Herein we describe the identification of 4-[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen -bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.
• Bioisosteric Transformations and Permutations in the Triazolopyrimidine Scaffold To Identify the Minimum Pharmacophore Required for Inhibitory Activity against <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase
  作者：Alka Marwaha、John White、Farah El_Mazouni、Sharon A Creason、Sreekanth Kokkonda、Frederick S. Buckner、Susan A. Charman、Margaret A. Phillips、Pradipsinh K. Rathod

  DOI：10.1021/jm300351w

  日期：2012.9.13

  Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in vitro growth with similar activity. Lead optimization of this series led to the recent identification of a preclinical candidate, showing good activity against P. falciparum in mice. As part of a backup program around this scaffold, we explored heteroatom rearrangement and substitution in the triazolopyrimidine ring and have identified several other ring configurations that are active as PfDHODH inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more potently than the triazolopyrimidines depending on the nature of the amino aniline substitution. DSM151, the best candidate in this series, binds with 4-fold better affinity (PfDHODH IC50 = 0.077 mu M) than the equivalent triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei model.