3-(4-bromo-1-methyl-1H-pyrazol-3-yl)prop-2-enoic acid | 941608-79-3

• 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: 3-(4-bromo-1-methyl-1H-pyrazol-3-yl)prop-2-enoic acid
• 英文别名: 3-(4-Bromo-1-methylpyrazol-3-yl)prop-2-enoic acid
• CAS: 941608-79-3
• 化学式: C₇H₇BrN₂O₂
• 分子量: 231.049
• InChiKey: IKAWKMQWICVMKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromo-1-methyl-1H-pyrazol-3-yl)prop-2-enoic acid 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 lithium hydroxide 、 偶氮二异丁腈 、 碘 、 三正丁基氢锡 、 碳酸氢钠 、 sodium carbonate 、 N,N-二异丙基乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 苯 为溶剂， 反应 103.0h， 生成 beta-Substituted cyclohexanecarboxamide, 10
  参考文献：
  名称：

  β-Substituted cyclohexanecarboxamide cathepsin K inhibitors: Modification of the 1,2-disubstituted aromatic core

  摘要：

  Further SAR study around the central 1,2-disubstituted phenyl of the previously disclosed Cat K inhibitor (-)-1 has demonstrated that the solvent exposed P2-P3 linker can be replaced by various 5- or 6-membered heteroaromatic rings. While some potency loss was observed in the 6-membered heteroaromatic series (IC50 = 1 nM for pyridine-linked 4 vs 0.5 nM for phenyl-linked (+/-)-1), several inhibitors showed a significantly decreased shift in the bone resorption functional assay (10-fold for pyridine 4 vs 53-fold for (-)-1). Though this shift was not reduced in the 5-membered heteroaromatic series, potency against Cat K was significantly improved for thiazole 9 (IC50 = 0.2 nM) as was the pharmacokinetic profile of N-methyl pyrazole 10 over our lead compound (-)-1. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.028
• 作为产物：
  描述：

  4-溴-1-甲基-吡唑-3-甲醛 、 丙二酸 在 四氢吡咯 、 吡啶 作用下， 反应 2.0h， 以97%的产率得到3-(4-bromo-1-methyl-1H-pyrazol-3-yl)prop-2-enoic acid
  参考文献：
  名称：

  β-Substituted cyclohexanecarboxamide cathepsin K inhibitors: Modification of the 1,2-disubstituted aromatic core

  摘要：

  Further SAR study around the central 1,2-disubstituted phenyl of the previously disclosed Cat K inhibitor (-)-1 has demonstrated that the solvent exposed P2-P3 linker can be replaced by various 5- or 6-membered heteroaromatic rings. While some potency loss was observed in the 6-membered heteroaromatic series (IC50 = 1 nM for pyridine-linked 4 vs 0.5 nM for phenyl-linked (+/-)-1), several inhibitors showed a significantly decreased shift in the bone resorption functional assay (10-fold for pyridine 4 vs 53-fold for (-)-1). Though this shift was not reduced in the 5-membered heteroaromatic series, potency against Cat K was significantly improved for thiazole 9 (IC50 = 0.2 nM) as was the pharmacokinetic profile of N-methyl pyrazole 10 over our lead compound (-)-1. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.028

文献信息

• Cathepsin cysteine protease inhibitors
  申请人：Bayly Christopher

  公开号：US20070167635A1

  公开（公告）日：2007-07-19

  This invention relates to a class of compounds having the general formula (I) which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  本发明涉及一类具有通式(I)的化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普西林K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，例如骨质疏松症。
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS
  申请人：Merck Canada Inc.

  公开号：EP1644326B1

  公开（公告）日：2016-11-02
• US7405229B2
  申请人：——

  公开号：US7405229B2

  公开（公告）日：2008-07-29