N,N-dimethyl-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide | 102676-27-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-dimethyl-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide
• 英文别名: 1-dimethylcarbamoyl-4-(3-trimethylsilyloxypropyl)-imidazole；4-(3-trimethylsilanyloxypropyl)imidazole-1-dimethylcarboxamide；1-Dimethylcarbamoyl-4-(3-trimethylsilyloxypropyl)imidazole；N,N-dimethyl-4-(3-trimethylsilyloxypropyl)imidazole-1-carboxamide
• CAS: 102676-27-7
• 化学式: C₁₂H₂₃N₃O₂Si
• 分子量: 269.419
• InChiKey: BDFNWFFOKFZVTO-UHFFFAOYSA-N

物化性质

• 沸点：
  344.9±44.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 5-(3-chloropropyl)-1-<(4-cyanophenyl)methyl>-1H-imidazole hydrochloride
  参考文献：
  名称：

  Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

  摘要：

  A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

  DOI：

  10.1021/jm00106a038
• 作为产物：
  描述：

  3-(1-H-imidazol-4-yl)propanol 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 22.0h， 生成 N,N-dimethyl-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide
  参考文献：
  名称：

  Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

  摘要：

  A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

  DOI：

  10.1021/jm00106a038

文献信息

• Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
  作者：Tristan Delcaillau、Philip Boehm、Bill Morandi

  DOI：10.1021/jacs.1c00529

  日期：2021.3.17

  We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications

  我们描述了芳基腈和芳基硫醚之间的新官能团复分解。催化系统镍/dcype 对于实现这种完全可逆的转化，以良好的收率至关重要。此外，不含氰化物和硫醇的反应显示出高官能团耐受性和商业分子后期衍生化的高效率。最后，合成应用证明了它在多步合成中的多功能性和实用性。
• Pharmacologically active (6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05066656A1

  公开（公告）日：1991-11-19

  (6,7-dihydro-5H-pyrrolo[1,2-c]imidazolyl-5-yl)- and (5,6,7,8-tetrahydroimidazo[1,5-a]pyridinyl-5-yl) substituted 1H-benzotriazole derivatives, compositions containing the same and methods of treating estrogen dependent disorders.

  (6,7-二氢-5H-吡咯并[1,2-c]咪唑基-5-基)-和(5,6,7,8-四氢咪唑[1,5-a]吡啶基-5-基)取代的1H-苯并三唑衍生物，含有相同化合物的组合物以及治疗雌激素依赖性疾病的方法。
• Certain 1,2-benzisoxazole derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04859691A1

  公开（公告）日：1989-08-22

  Disclosed are 1,2-benzisoxazole and 1,2-benzisothiazole derivatives represented by formula I ##STR1## wherein X represents oxygen or sulfur; Z rep;esents carbon (CH) so as to complete the imidazol-1-yl ring radical or Z represents nitrogen (N) so as to complete the 1,2,4-triazol-1-yl ring radical; R.sub.1 represents hydrogen, lower alkenyl, lower alkynyl, aryl-lower alkyl or lower alkyl; R.sub.2 represents hydrogen, lower alkenyl, lower alkynyl, aryl-lower alkyl or lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylene; or R.sub.1 combined with R.sub.5 located on the Z-carbon atom of the imidazolyl radical represents C.sub.2 -C.sub.4 -alkylene; R.sub.3 and R.sub.4 independently represent hydrogen, lower alkyl, cycloalkyl, halogen, trifluoromethyl, cyano, nitro, amino, hydroxy, lower alkanoyloxy, carbocyclic aroyloxy, lower alkoxy, or carbocyclic aryl; or R.sub.3 and R.sub.4, together when located on adjacent carbon atoms, represent lower alkylenedioxy; or R.sub.3 and R.sub.4, together when located on the carbon atoms to which attached a benzo-fused or C.sub.5 -C.sub.7 -cycloalka-fused ring, respectively; R.sub.5 located on carbon represents hydrogen, lower alkyl or hydroxy-lower alkyl; R.sub.6 located on carbon represents hydrogen or lower alkyl; or when Z represents carbon, R.sub.5 located on the Z-carbon atom combined with R.sub.6 located on the adjacent carbon atom represents C.sub.3 -C.sub.5 -alkylene; and pharmaceutically acceptable salts thereof; which are active in mammals as anticonvulsant agents.

  本发明涉及表示为式I的1,2-苯并异噁唑和1,2-苯并异硫唑衍生物 ##STR1## 其中X代表氧或硫; Z代表碳(CH)，以完成咪唑-1-基环或Z代表氮(N)，以完成1,2,4-三唑-1-基环; R.sub.1代表氢，低烯丙基，低炔基，芳基-低烷基或低烷基; R.sub.2代表氢，低烯丙基，低炔基，芳基-低烷基或低烷基; 或R.sub.1和R.sub.2组合表示低烷基; 或R.sub.1与位于咪唑基上的Z-碳原子上的R.sub.5组合表示C.sub.2-C.sub.4-烷基; R.sub.3和R.sub.4独立地表示氢，低烷基，环烷基，卤素，三氟甲基，氰基，硝基，氨基，羟基，低烷酰氧基，环烷基酰氧基，低烷氧基或环烷基; 或当位于相邻碳原子上时，R.sub.3和R.sub.4组合表示低烷二氧基; 或当位于连接苯并融合或C.sub.5-C.sub.7-环烷融合环的碳原子上时，R.sub.3和R.sub.4组合分别表示; 位于碳上的R.sub.5表示氢，低烷基或羟基-低烷基; 位于碳上的R.sub.6表示氢或低烷基; 或当Z表示碳时，位于Z-碳原子上的R.sub.5与位于相邻碳原子上的R.sub.6组合表示C.sub.3-C.sub.5-烷基; 及其药学上可接受的盐; 作为哺乳动物的抗惊厥剂具有活性。
• Substituted imidazo[5-a]pyridine derviatives and other substituted
  申请人：Ciba-Geigy Corporation

  公开号：US05428160A1

  公开（公告）日：1995-06-27

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidised etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidised etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3, or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明涉及一种式子I的化合物：##STR1## 其中R.sub.1代表氢，低烷基，取代的低烷基，硝基，卤素，自由的，醚化或酯化的羟基，自由的，醚化，氧化醚化或酯化的巯基，未取代的，单取代或双取代的氨基，铵离子，自由的或功能修饰的磺酸基，自由的或功能修饰的甲酰基，C.sub.2-C.sub.20-酰基，氰基，自由的或功能修饰的羧基；R.sub.2代表氢，低烷基，取代的低烷基，卤素；自由的，醚化或酯化的羟基；自由的，醚化，氧化醚化或酯化的巯基；自由或功能修饰的羧基或酰基；其7,8-二氢衍生物；以及式I*的化合物：##STR2## 其中n表示0、1、2、3或4，而R.sub.1和R.sub.2如上述式I中所定义，并且它们的盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；这些化合物用于治疗响应于例如哺乳动物中的芳香化酶抑制的情况的用途；制备这些化合物的过程和中间体。
• Certain 1,2-benzisoxazole and 1,2-benzisothiazole derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04957931A1

  公开（公告）日：1990-09-18

  Disclosed are 1,2-benzisoxazole and 1,2-benzisothiazole derivatives represented by formula I ##STR1## wherein X represents oxygen or sulfur; Z represents carbon (CH) so as to complete the imidazol-1-yl ring radical or Z represents nitrogen (N) so as to complete the 1,2,4-triazol-l-yl ring radical; R.sub.1 represents hydrogen, lower alkenyl, lower alkynyl, aryl-lower alkyl or lower alkyl; R.sub.2 represents hydrogen, lower alkenyl, lower alkynyl, aryl-lower alkyl or lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylene; or R.sub.1 combined with R.sub.5 located on the Z-carbon atom of the imidazolyl radical represents C.sub.2 -C.sub.4 -alkylene; R.sub.3 and R.sub.4 independently represent hydrogen, lower alkyl, cycloalkyl, halogen, trifluoromethyl, cyano, nitro, amino, hydroxy, lower alkanoyloxy, carbocyclic aroyloxy, lower alkoxy, or carbocyclic aryl; or R.sub.3 and R.sub.4, together when located on adjacent carbon atoms, represent lower alkylenedioxy; or R.sub.3 and R.sub.4, together when located on the carbon atoms to which attached a benzo-fused or C.sub.5 -C.sub.7 -cycloalka-fused ring, respectively; R.sub.5 located on carbon represents hydrogen, lower alkyl or hydroxy-lower alkyl; R.sub.6 located on carbon represents hydrogen or lower alkyl; or when Z represents carbon, R.sub.5 located on the Z-carbon atom combined with R.sub.6 located on the adjacent carbon atom represents C.sub.3 -C.sub.5 -alkylene; and pharmaceutically acceptable salts thereof; which are active in mammals as anticonvulsant agents.

  本发明涉及一种公式I所表示的1,2-苯并异噁唑和1,2-苯并异硫唑衍生物，其中X代表氧或硫；Z代表碳(CH)，以完成咪唑-1-基环基，或Z代表氮(N)，以完成1,2,4-三唑-1-基环基；R.sub.1代表氢、低烯基、低炔基、芳基-低烷基或低烷基；R.sub.2代表氢、低烯基、低炔基、芳基-低烷基或低烷基；或R.sub.1和R.sub.2组合代表低烷基；或R.sub.1与位于咪唑基上的Z-碳原子上的R.sub.5组合代表C.sub.2-C.sub.4-烷基；R.sub.3和R.sub.4独立地代表氢、低烷基、环烷基、卤素、三氟甲基、氰基、硝基、氨基、羟基、低烷酰氧基、碳环芳基氧基、低烷氧基或碳环芳基；或当R.sub.3和R.sub.4位于相邻的碳原子上时，它们组合代表低烷基二氧基；或当R.sub.3和R.sub.4分别位于连接苯并融合或C.sub.5-C.sub.7-环烷基融合环的碳原子上时；位于碳上的R.sub.5代表氢、低烷基或羟基-低烷基；位于碳上的R.sub.6代表氢或低烷基；或当Z代表碳时，位于Z-碳原子上的R.sub.5与位于相邻碳原子上的R.sub.6组合代表C.sub.3-C.sub.5-烷基；以及其药学上可接受的盐；它们在哺乳动物中作为抗惊厥剂具有活性。