6-methyl-5-(6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid | 1426531-92-1

• 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: 6-methyl-5-(6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid
• 英文别名: 6-Methyl-5-(6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic Acid；6-methyl-5-[[6-(2-methylpyrazol-3-yl)pyrazolo[1,5-a]pyridine-3-carbonyl]amino]pyridine-3-carboxylic acid
• CAS: 1426531-92-1
• 化学式: C₁₉H₁₆N₆O₃
• 分子量: 376.374
• InChiKey: LGQSSBJLWKVLNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-甲基哌嗪-1-基)苄胺 、 6-methyl-5-(6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6-(1-methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-((2-(4-methylpiperazin-1-yl)benzyl)carbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide
  参考文献：
  名称：

  Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension

  摘要：

  A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. compound 25 shows 24 h occupancy of the PDGFR kinase domain; after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.

  DOI：

  10.1021/acs.jmedchem.6b00703
• 作为产物：
  描述：

  6-methyl-5-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid 、 methyl 5-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-6-methylnicotinate 、 1-甲基-1H-吡唑-5-硼酸频哪醇酯 、 、 sodium hydroxide 生成 6-methyl-5-(6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid
  参考文献：
  名称：

  Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension

  摘要：

  公式I中的双环杂环衍生物对抑制PDGF受体介导的生物活性有用。其中A为，R1，R1a，R2，R3，R4，R5，R6和X的定义如下。

  公开号：

  US08883819B2

文献信息

• [EN] BICYCLIC HETEROCYCLE DERIVATIVES FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES POUR LE TRAITEMENT D'UNE HYPERTENSION ARTÉRIELLE PULMONAIRE
  申请人：NOVARTIS AG

  公开号：WO2013030802A1

  公开（公告）日：2013-03-07

  Bicyclic heterocyclic derivatives of formula (I) useful in inhibiting PDGF receptor mediated biological activity. Wherein A is and R1, R1a, R2, R3, R4, R5, R6 and X are as defined herein.

  具有式(I)的二环杂环衍生物，可用于抑制血小板衍生生长因子受体介导的生物活性。其中A、R1、R1a、R2、R3、R4、R5、R6和X如本文所定义。
• Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension
  申请人：Bruce Ian

  公开号：US08883819B2

  公开（公告）日：2014-11-11

  Bicyclic heterocyclic derivatives of formula I useful in inhibiting PDGF receptor mediated biological activity. wherein A is and R1, R1a, R2, R3, R4, R5, R6 and X are as defined herein.

  公式I中的双环杂环衍生物对抑制PDGF受体介导的生物活性有用。其中A为，R1，R1a，R2，R3，R4，R5，R6和X的定义如下。
• US8883819B2
  申请人：——

  公开号：US8883819B2

  公开（公告）日：2014-11-11
• US9751876B2
  申请人：——

  公开号：US9751876B2

  公开（公告）日：2017-09-05
• Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension
  作者：Duncan E. Shaw、Ferheen Baig、Ian Bruce、Sylvie Chamoin、Stephen P. Collingwood、Sarah Cross、Satish Dayal、Peter Drückes、Pascal Furet、Vikki Furminger、Deborah Haggart、Martin Hussey、Irena Konstantinova、Jon C. Loren、Valentina Molteni、Sonia Roberts、John Reilly、Alex M. Saunders、Rowan Stringer、Lilya Sviridenko、Matthew Thomas、Christopher G. Thomson、Christine Tomlins、Ben Wen、Vince Yeh、Andrew C. Pearce

  DOI：10.1021/acs.jmedchem.6b00703

  日期：2016.9.8

  A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. compound 25 shows 24 h occupancy of the PDGFR kinase domain; after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.