1-amino-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-propan-2-ol

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-amino-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-propan-2-ol
• 英文别名: 1-amino-1-(4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl)propan-2-ol
• 化学式: C₉H₁₇NO₄
• 分子量: 203.238
• InChiKey: ZVXUVJXJJCJKKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  73.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-amino-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-propan-2-ol 、 4-(苄氧基)苯-1-磺酰氯 在 三乙胺 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-benzyloxy-N-[2-hydroxy-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-propyl]-benzenesulfonamide
  参考文献：
  名称：

  Selective inhibitors of aggrecanase in osteoarthritis treatment

  摘要：

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的方法，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。该发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中 X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基组成的群； 附加条件： 当X为碳时，R7和R8均为氢，且R1、R2、R3和R4中至少一个为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在，R7为氢或下式的基团： 其中，Y为-CH2-NH2或-NH-CH3；以及 当X为氮且R7为H时，R3和R4一起形成羰基。

  公开号：

  EP1081137A1

文献信息

• Selective inhibition of aggrecanase in osteoarthritis treatment
  申请人：Noe C. Mark

  公开号：US20050227997A1

  公开（公告）日：2005-10-13

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC 50 s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R 1 and R 2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R 1 and R 2 is methyl; R 3 and R 4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R 3 and R 4 may be taken together to form a carbonyl group; and R 5 and R 6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R 7 and R 8 are both hydrogen and at least one of R 1 , R 2 , R 3 , and R 4 is hydroxy; when X is carbon and R 5 is para-halo, then at least one of R 6 , R 3 , and R 4 is not hydrogen; when X is nitrogen, then R 8 is not present and R 7 is hydrogen or a group of the formula: wherein, Y is —CH 2 —NH 2 or —NH—CH 3 ; and when X is nitrogen and R 7 is H, then R 3 and R 4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的抑制剂，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。这项发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成一个羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基；附加条件： 当X为碳时，R7和R8都是氢，且至少一个R1、R2、R3和R4为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在且R7为氢或一个公式的基团： 其中，Y为—CH2—NH2或—NH—CH3；以及 当X为氮且R7为H时，R3和R4一起形成一个羰基。
• US7030242B2
  申请人：——

  公开号：US7030242B2

  公开（公告）日：2006-04-18
• Selective inhibitors of aggrecanase in osteoarthritis treatment
  申请人：Pfizer Products Inc.

  公开号：EP1081137A1

  公开（公告）日：2001-03-07

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl; R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; and R5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy; when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen; when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is -CH2-NH2 or -NH-CH3; and when X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的方法，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。该发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中 X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基组成的群； 附加条件： 当X为碳时，R7和R8均为氢，且R1、R2、R3和R4中至少一个为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在，R7为氢或下式的基团： 其中，Y为-CH2-NH2或-NH-CH3；以及 当X为氮且R7为H时，R3和R4一起形成羰基。