6-Chloro-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile | 769971-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 6-Chloro-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile
• 英文别名: 6-Chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile；6-chloro-1,3-dimethylpyrazolo[3,4-b]pyridine-5-carbonitrile
• CAS: 769971-54-2
• 化学式: C₉H₇ClN₄
• 分子量: 206.634
• InChiKey: ZFVCTMZYYFMTSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Chloro-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile 在 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 51.0h， 生成 1-(6-((2-(dimethylamino)ethyl)(methyl)amino)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3-(3-isopropoxyphenyl)urea hydrochloride
  参考文献：
  名称：

  Discovery, Optimization, and Pharmacological Characterization of Novel Heteroaroylphenylureas Antagonists of C−C Chemokine Ligand 2 Function

  摘要：

  Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of I-125-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC50 = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/jm1012903
• 作为产物：
  描述：

  5-氨基-1,3-二甲基吡唑 在 苯膦酰二氯 、 三氯氧磷 作用下， 反应 20.0h， 生成 6-Chloro-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile
  参考文献：
  名称：

  Discovery, Optimization, and Pharmacological Characterization of Novel Heteroaroylphenylureas Antagonists of C−C Chemokine Ligand 2 Function

  摘要：

  Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of I-125-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC50 = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/jm1012903

文献信息

• Antagonist of MCP-1 function, and compositions and methods of use thereof
  申请人：——

  公开号：US20040198719A1

  公开（公告）日：2004-10-07

  Compounds of formula A and formula B: 1 and their pharmaceutically acceptable salts, compositions comprising them, methods for their use, and their use in the preparation of medicaments. The compounds are antagonists of MCP-1 function, and are useful in the prevention and treatment of chronic or acute inflammatory or autoimmune diseases, such as multiple sclerosis, and in the prevention and treatment of allergic hypersensitivity disorders.

  公式A和公式B的化合物及其药学上可接受的盐，包括它们的组合物，使用方法以及它们在药物制备中的应用。这些化合物是MCP-1功能的拮抗剂，可用于预防和治疗慢性或急性炎症或自身免疫性疾病，如多发性硬化症，并用于预防和治疗过敏性过敏反应性疾病。
• US6962926B2
  申请人：——

  公开号：US6962926B2

  公开（公告）日：2005-11-08
• Discovery, Optimization, and Pharmacological Characterization of Novel Heteroaroylphenylureas Antagonists of C−C Chemokine Ligand 2 Function
  作者：Edgardo Laborde、Robert W. Macsata、Fanying Meng、Brian T. Peterson、Louise Robinson、Steve R. Schow、Reyna J. Simon、Hua Xu、Kunihisa Baba、Hideaki Inagaki、Yoshiro Ishiwata、Takahito Jomori、Yukiharu Matsumoto、Atsushi Miyachi、Takashi Nakamura、Masayuki Okamoto、Tracy M. Handel、Claude C. A. Bernard

  DOI：10.1021/jm1012903

  日期：2011.3.24

  Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of I-125-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC50 = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.