3-bromo-5-methoxymethylisoxazole | 1220521-36-7

• 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: 3-bromo-5-methoxymethylisoxazole
• 英文别名: 3-Bromo-5-(methoxymethyl)isoxazole；3-bromo-5-(methoxymethyl)-1,2-oxazole
• CAS: 1220521-36-7
• 化学式: C₅H₆BrNO₂
• 分子量: 192.012
• InChiKey: PXHOIDXCRSJZCB-UHFFFAOYSA-N

物化性质

• 沸点：
  233.3±25.0 °C(Predicted)
• 密度：
  1.589±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-5-methoxymethylisoxazole 、 (R)-4-Boc-2-甲基哌嗪 在 三氟甲烷磺酸甲酯 、 三苯基膦 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以22%的产率得到(R)-1-tert-butoxycarbonyl-4-(5-methoxymethylisoxazol-3-yl)-3-methylpiperazine
  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：

  1,1-二溴甲醛肟 、 甲基炔丙基醚 在 potassium hydrogencarbonate 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以84%的产率得到3-bromo-5-methoxymethylisoxazole
  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

• 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.