4-chloro-1-(3-methylthiophen-2-yl)-1H-pyrazole | 1313613-10-3

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 4-chloro-1-(3-methylthiophen-2-yl)-1H-pyrazole
• 英文别名: 4-chloro-1-(3-methylthiophen-2-yl)pyrazole；4-Chloro-1-(3-methylthiophen-2-yl)pyrazole
• CAS: 1313613-10-3
• 化学式: C₈H₇ClN₂S
• 分子量: 198.676
• InChiKey: PFGOWDYAAIECKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(3-methylthiophen-2-yl)-1H-pyrazole 在 吡啶 、 氯磺酸 作用下， 反应 20.0h， 生成
  参考文献：
  名称：

  Discovery of (1S,2R,3R)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors

  摘要：

  Aggrecanases, particularly aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5), are believed to be key enzymes involved in the articular cartilage breakdown that leads to osteoarthritis. Thus, aggrecanases are considered to be viable drug targets for the treatment of this debilitating disease. A cries of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates was discovered to be potent, highly selective, aid orally bioavailable aggrecanase inhibitors. These compounds have unique P1' groups comprising novel piperidine- or piperazin e-based heterocycles that are connected to a cyclopropane amino acid scaffold via a sulfamido linkage. These P1' groups are quite effective in imparting selectivity over other MMPs, and this selectivity was further increased by incorporation of a methyl substituent in the 2-position of the cyclopropane ring. In contrast to classical hydroxamate-based inhibitors that tend to lack metabolic stability, our aggrecanase inhibitors bear a carboxylate zinc-binding group and have good oral bioavailability. Lead compound 13b, characterized by the novel P1' portion of 1,2,3,4-tetrahydropyrido[3',4':4,5]imidazo [1,2-a]-pyridine ring, is a potent and selective aggrecanse inhibitor with excellent pharmacokinetic profiles.

  DOI：

  10.1021/jm101609j
• 作为产物：
  描述：

  2-溴-3-甲基噻吩 、 4-氯吡唑 在 copper(I) oxide 、 水杨醛肟 、 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 以33%的产率得到4-chloro-1-(3-methylthiophen-2-yl)-1H-pyrazole
  参考文献：
  名称：

  Discovery of (1S,2R,3R)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors

  摘要：

  Aggrecanases, particularly aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5), are believed to be key enzymes involved in the articular cartilage breakdown that leads to osteoarthritis. Thus, aggrecanases are considered to be viable drug targets for the treatment of this debilitating disease. A cries of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates was discovered to be potent, highly selective, aid orally bioavailable aggrecanase inhibitors. These compounds have unique P1' groups comprising novel piperidine- or piperazin e-based heterocycles that are connected to a cyclopropane amino acid scaffold via a sulfamido linkage. These P1' groups are quite effective in imparting selectivity over other MMPs, and this selectivity was further increased by incorporation of a methyl substituent in the 2-position of the cyclopropane ring. In contrast to classical hydroxamate-based inhibitors that tend to lack metabolic stability, our aggrecanase inhibitors bear a carboxylate zinc-binding group and have good oral bioavailability. Lead compound 13b, characterized by the novel P1' portion of 1,2,3,4-tetrahydropyrido[3',4':4,5]imidazo [1,2-a]-pyridine ring, is a potent and selective aggrecanse inhibitor with excellent pharmacokinetic profiles.

  DOI：

  10.1021/jm101609j

文献信息

• Visible-light-mediated C2-amination of thiophenes by using DDQ as an organophotocatalyst
  作者：Chunlan Song、Hong Yi、Bowen Dou、Yiying Li、Atul K. Singh、Aiwen Lei

  DOI：10.1039/c7cc01339f

  日期：——

  A direct C–H amination of thiophenes was presented via an oxidation pathway under visible-light irradiation, in which the thiophene radical cation serves as the key intermediate. Various thiophenes and azoles could be transformed into the corresponding amination products well, and H₂O was the only byproduct, which is environmentally benign.

  一种通过可见光照射在氧化途径下进行噻吩的直接C-H氨化反应被提出，其中噻吩自由基阳离子作为关键中间体。各种噻吩和唑类化合物可以很好地转化为相应的氨化产物，水是唯一的副产物，对环境无害。
• Discovery of (1<i>S</i>,2<i>R</i>,3<i>R</i>)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors
  作者：Makoto Shiozaki、Katsuya Maeda、Tomoya Miura、Masayuki Kotoku、Takayuki Yamasaki、Isamu Matsuda、Kenta Aoki、Katsutaka Yasue、Hiroto Imai、Minoru Ubukata、Akira Suma、Masahiro Yokota、Takahiro Hotta、Masahiro Tanaka、Yasunori Hase、Julia Haas、Andrew M. Fryer、Ellen R. Laird、Nicole M. Littmann、Steven W. Andrews、John A. Josey、Takayuki Mimura、Yuichi Shinozaki、Hiromi Yoshiuchi、Takashi Inaba

  DOI：10.1021/jm101609j

  日期：2011.4.28

  Aggrecanases, particularly aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5), are believed to be key enzymes involved in the articular cartilage breakdown that leads to osteoarthritis. Thus, aggrecanases are considered to be viable drug targets for the treatment of this debilitating disease. A cries of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates was discovered to be potent, highly selective, aid orally bioavailable aggrecanase inhibitors. These compounds have unique P1' groups comprising novel piperidine- or piperazin e-based heterocycles that are connected to a cyclopropane amino acid scaffold via a sulfamido linkage. These P1' groups are quite effective in imparting selectivity over other MMPs, and this selectivity was further increased by incorporation of a methyl substituent in the 2-position of the cyclopropane ring. In contrast to classical hydroxamate-based inhibitors that tend to lack metabolic stability, our aggrecanase inhibitors bear a carboxylate zinc-binding group and have good oral bioavailability. Lead compound 13b, characterized by the novel P1' portion of 1,2,3,4-tetrahydropyrido[3',4':4,5]imidazo [1,2-a]-pyridine ring, is a potent and selective aggrecanse inhibitor with excellent pharmacokinetic profiles.