1-(6-((2-(dimethylamino)ethyl)(methyl)amino)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3-(3-isopropoxyphenyl)urea hydrochloride | 1269775-42-9

• 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: 1-(6-((2-(dimethylamino)ethyl)(methyl)amino)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3-(3-isopropoxyphenyl)urea hydrochloride
• 英文别名: 1H-Pyrazolo[3,4-b]pyridine-5-carboxamide, 6-[[2-(dimethylamino)ethyl]methylamino]-1,3-dimethyl-N-[[[3-(1-methylethoxy)phenyl]amino]carbonyl]-, (Hydrochloride) (1:1)；6-[2-(dimethylamino)ethyl-methylamino]-1,3-dimethyl-N-[(3-propan-2-yloxyphenyl)carbamoyl]pyrazolo[3,4-b]pyridine-5-carboxamide;hydrochloride
• CAS: 1269775-42-9
• 化学式: C₂₄H₃₃N₇O₃*ClH
• 分子量: 504.032
• InChiKey: CXQUYODBFIUPEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基-1,3-二甲基吡唑 在 苯膦酰二氯 、 硫酸 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 71.0h， 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

文献信息

• 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.