Polycyclic N-Heterocyclic Compounds 74: Rearrangement Reaction of 5-Amino-1,2-dihydrofuro[2,3-c]isoquinolines with α,ω-Dibromoalkanes and Evaluation of Product Bronchodilator Activity

Abstract

Reaction of 5-amino-1,2-dihydrofuro[2,3-c]isoquinolines with 1,2-dibromoethane and 1,3-dibromopropane in the presence of a base afforded 2′,3′-dihydrospiro[cyclopropane-1,6′(5′H)-imidazo[2,1-a]isoquinolin]-5′-ones and 3′,4′-dihydro-2′H-spiro[cyclopropane-1,7′(6′H)-pyrimido[2,1-a]isoquinolin]-6′-ones, respectively. Certain of the products showed significant bronchodilator activity.

GRAPHICAL ABSTRACT

Keywords:

• Bronchodilator activity
• furo[2,3-c]isoquinoline
• rearrangement
• ring cleavage
• spiroheterocycle

ACKNOWLEDGMENTS

We are grateful to the SC-NMR Laboratory of Okayama University for 200-MHz ¹HNMR experiments. We also thank K. L. Kirk (NIDDK, NIH) for helpful suggestions.

Notes

Notes. IC₃₀ value shows the concentration of each compound, which gives 30% relaxation to tracheal contraction by carbamylcholine chloride (1.00 µM). It was calculated from the percentage of maximum relaxation produced by 100 µM papaverine.