5-methylpicolinohydrazide | 1254073-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-methylpicolinohydrazide
• 英文别名: 5-methyl-pyridine-2-carboxylic acid hydrazide；5-Methyl-pyridin-2-carbonsaeure-hydrazid；5-methyl-2-pyridinecarbohydrazide；5-methylpyridine-2-carbohydrazide
• CAS: 1254073-42-1
• 化学式: C₇H₉N₃O
• 分子量: 151.168
• InChiKey: SSIZHOAODPVTMB-UHFFFAOYSA-N

物化性质

• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methylpicolinohydrazide 在 N-溴代丁二酰亚胺(NBS) 、 伯吉斯试剂 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 生成 5-(bromomethyl)-2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridine
  参考文献：
  名称：

  选择性和生物可利用的 HDAC6 2-(二氟甲基)-1,3,4-恶二唑底物抑制剂及其生物激活机制的建模

  摘要：

  组蛋白脱乙酰酶 6 (HDAC6) 是 HDAC 家族的独特成员，主要靶向细胞质非组蛋白底物，如 α-微管蛋白、皮质素和热休克蛋白 90，以调节肿瘤中的细胞增殖、转移、侵袭和有丝分裂。我们描述了一系列作为选择性非异羟肟酸 HDAC6 抑制剂的 2-(二氟甲基)-1,3,4-恶二唑 (DFMO) 的鉴定和表征。通过比较结构-活性关系并对 HDAC6 催化机制进行量子力学计算，我们表明有效的恶二唑是 HDAC6 的亲电子底物，并提出了一种生物激活机制。我们还观察到，恶二唑固有的亲电性使其在水溶液中易于降解，并且不能排除潜在有毒产物的产生，从而限制了慢性疾病的发展。然而，恶二唑类药物具有较高的口服生物利用度和较低的体内清除率，是研究 HDAC6 在大鼠和小鼠体外和体内作用的绝佳工具。

  DOI：

  10.1021/acs.jmedchem.3c01269
• 作为产物：
  描述：

  5-甲基-2-甲酸吡啶 在 乙醇 、 硫酸 、 一水合肼 作用下， 反应 2.0h， 生成 5-methylpicolinohydrazide
  参考文献：
  名称：

  关于杂环羧酸的一些衍生物II。金属离子和生物学效应，18.平均

  摘要：

  描述了6-苯基-，4，6-二甲基-和5-甲基-吡啶甲酸的酰胺，取代的酰胺和酰肼的合成。

  DOI：

  10.1002/hlca.19540370118

文献信息

• [EN] 5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-a]PYRAZINE DERIVATIVES AS P2X7 MODULATORS<br/>[FR] DÉRIVÉS DE 5,6,7,8-TÉTRAHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZINE COMME MODULATEURS DE P2X7
  申请人：GLAXO GROUP LTD

  公开号：WO2010125102A1

  公开（公告）日：2010-11-04

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6 R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

  本发明提供了一种式(I)化合物或其药学上可接受的盐，其中A为氢、C1-4烷基、C3-6环烷基、C1-3烷氧基、C1-3烷氧基C1-4烷基、C1-2氟烷基、卤素、NR6 R7、任选取代的杂芳基(Het)或任选取代的苯基，且R1、R2、R3、R4、R5、R6和R7如说明书中所定义。这些化合物或盐被认为能够调节P2X7受体功能，并能拮抗ATP在P2X7受体上的作用。本发明还提供了该化合物或盐在治疗或预防例如炎症性疼痛、神经性疼痛、内脏疼痛、类风湿性关节炎、骨关节炎或神经退行性疾病中的用途。
• 5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-a]PYRAZINE DERIVATIVES AS P2X7 MODULATORS
  申请人：Dean David Kenneth

  公开号：US20120157436A1

  公开（公告）日：2012-06-21

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C 1-4 alkyl, C 3-6 cycloalkyl, C 1-3 alkoxy, C 1-3 alkoxy C 1-4 alkyl, C 1-2 -fluoroalkyl, halogen, NR 6 R 7 , optionally substituted heteroaryl, or optionally substituted phenyl, and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

  本发明提供了式（I）的化合物或其药学上可接受的盐： 其中，A为氢、C1-4烷基、C3-6环烷基、C1-3烷氧基、C1-3烷氧基C1-4烷基、C1-2氟代烷基、卤素、NR6R7、可选取代杂环芳基或可选取代苯基；R1、R2、R3、R4、R5、R6和R7如描述中所定义。 这些化合物或盐被认为可以调节P2X7受体功能，并能够拮抗P2X7受体上ATP的作用。本发明还提供了该化合物或盐在治疗或预防炎症性疼痛、神经病理性疼痛、内脏疼痛、类风湿性关节炎、骨关节炎或神经退行性疾病中的应用。
• 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine derivatives as P2X7 modulators
  申请人：Dean David Kenneth

  公开号：US08501946B2

  公开（公告）日：2013-08-06

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

  本发明提供了一个式（I）的化合物或其药学上可接受的盐：其中A为氢、C1-4烷基、C3-6环烷基、C1-3烷氧基、C1-3烷氧基C1-4烷基、C1-2氟代烷基、卤素、NR6R7、可选取代的杂环芳基（Het）或可选取代的苯基，而R1、R2、R3、R4、R5、R6和R7如描述中所定义。这些化合物或盐被认为可以调节P2X7受体功能，并且能够拮抗P2X7受体上ATP的作用。本发明还提供了该化合物或盐在治疗或预防例如炎症性疼痛、神经病理性疼痛、内脏疼痛、类风湿性关节炎、骨关节炎或神经退行性疾病中的用途。
• Discovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I)
  作者：Hamid R. Hoveyda、Graeme L. Fraser、Marie-Odile Roy、Guillaume Dutheuil、Frédéric Batt、Mohamed El Bousmaqui、Julien Korac、François Lenoir、Alexey Lapin、Sophie Noël、Sébastien Blanc

  DOI：10.1021/jm5017413

  日期：2015.4.9

  Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. We therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma luteinizing hormone (LH) and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogues to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models.
• US8501946B2
  申请人：——

  公开号：US8501946B2

  公开（公告）日：2013-08-06