e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

5-Aryl-3-azabicyclo [3.2. 0] heptan-5-one ketals, compounds with morphine-like analgesic activity

TC McKenzie, JW Epstein, WJ Fanshawe…

Index: McKenzie, Thomas C.; Epstein, Joseph W.; Fanshawe, William J.; Dixon, J. Scott; Osterberg, Arnold C.; et al. Journal of Medicinal Chemistry, 1984 , vol. 27, # 5 p. 628 - 632

Full Text: HTML

Citation Number: 8

Abstract

1 2 we wished to explore the pharmacological effects of homologation of this system to l-aryl- 3-azabicyclo [3.2. 0]-heptanes, 2. The route that was employed gave 5-aryl-3-azabicyclo [3.2. 0] heptan-6-one dimethyl ketals 62 as intermediates. These, and most notably phenol 7, showed unexpected morphine-like activity. Thus, the present study is concerned with the chemical synthesis and pharmacology of the ketals 6a-d and 7. Elaboration of these ...

N-Methylmaleimide Structure

N-Methylmaleimide

p-Toluidine Structure

~%

1-methyl-3-(4-methylphenyl)pyrrole-2,5-dione Structure

1-methyl-3-(4-m...

7,7-Dimethoxy-1-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.0]heptane-2,4-dione Structure

7,7-Dimethoxy-1...

~70%

6,6-dimethoxy-5-(3-methoxyphenyl)-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-5...

3-anisidine Structure

~%

6,6-dimethoxy-5-(3-methoxyphenyl)-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-5...

3-(3-methoxyphenyl)pyrrole-2,5-dione Structure

3-(3-methoxyphe...

~%

6,6-dimethoxy-5-(3-methoxyphenyl)-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-5...

7,7-dimethoxy-3-methyl-1-phenyl-3-azabicyclo[3.2.0]heptane-2,4-dione Structure

7,7-dimethoxy-3...

~84%

6,6-dimethoxy-3-methyl-5-phenyl-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-3...

N-Methylmaleimide Structure

N-Methylmaleimide

~%

6,6-dimethoxy-3-methyl-5-phenyl-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-3...

1H-Pyrrole-2,5-dione, 1-methyl-3-phenyl- Structure

1H-Pyrrole-2,5-...

~%

6,6-dimethoxy-3-methyl-5-phenyl-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-3...

Structure

~%

6,6-dimethoxy-3-methyl-5-phenyl-3-azabicyclo[3.2.0]heptane Structure

6,6-dimethoxy-3...

6,6-dimethoxy-5-(3-methoxyphenyl)-3-methyl-3-azabicyclo(3.2.0)heptane Structure

6,6-dimethoxy-5...

~49%

3-(6,6-dimethoxy-3-methyl-3-azabicyclo[3.2.0]heptan-5-yl)phenol Structure

3-(6,6-dimethox...

N-Methylmaleimide Structure

N-Methylmaleimide

~%

3-(6,6-dimethoxy-3-methyl-3-azabicyclo[3.2.0]heptan-5-yl)phenol Structure

3-(6,6-dimethox...

3-(3-methoxyphenyl)-1-methylpyrrole-2,5-dione Structure

3-(3-methoxyphe...

~%

3-(6,6-dimethoxy-3-methyl-3-azabicyclo[3.2.0]heptan-5-yl)phenol Structure

3-(6,6-dimethox...

3-anisidine Structure

~%

3-(6,6-dimethoxy-3-methyl-3-azabicyclo[3.2.0]heptan-5-yl)phenol Structure

3-(6,6-dimethox...

4,4-dimethoxy-1-(3-methoxyphenyl)-N-methyl-1,2-cyclobutanedicarboximide Structure

4,4-dimethoxy-1...

~%

3-(6,6-dimethoxy-3-methyl-3-azabicyclo[3.2.0]heptan-5-yl)phenol Structure

3-(6,6-dimethox...

Maleimide Structure

3-anisidine Structure

~%

3-(3-methoxyphenyl)pyrrole-2,5-dione Structure

3-(3-methoxyphe...

6,6-dimethoxy-5-(3-methoxyphenyl)-3-methyl-3-azabicyclo(3.2.0)heptane Structure

6,6-dimethoxy-5...

~79%

5-(3-methoxyphenyl)-3-methyl-3-azabicyclo[3.2.0]heptan-6-one Structure

5-(3-methoxyphe...

3-(3-methoxyphenyl)-1-methylpyrrole-2,5-dione Structure

3-(3-methoxyphe...

~%

5-(3-methoxyphenyl)-3-methyl-3-azabicyclo[3.2.0]heptan-6-one Structure

5-(3-methoxyphe...

3-anisidine Structure

~%

5-(3-methoxyphenyl)-3-methyl-3-azabicyclo[3.2.0]heptan-6-one Structure

5-(3-methoxyphe...

4,4-dimethoxy-1-(3-methoxyphenyl)-N-methyl-1,2-cyclobutanedicarboximide Structure

4,4-dimethoxy-1...

~%

5-(3-methoxyphenyl)-3-methyl-3-azabicyclo[3.2.0]heptan-6-one Structure

5-(3-methoxyphe...

N-Methylmaleimide Structure

N-Methylmaleimide

Structure

~%

1H-Pyrrole-2,5-dione, 1-methyl-3-phenyl- Structure

1H-Pyrrole-2,5-...

N-Methylmaleimide Structure

N-Methylmaleimide

3-anisidine Structure

~%

3-(3-methoxyphenyl)-1-methylpyrrole-2,5-dione Structure

3-(3-methoxyphe...