Synthesis and antispasmodic activity evaluation of bis-(papaverine) analogues.
A new series of N-substituted bis-(tetrahydropapaverine) ring systems have been synthesised in expectation of better antispasmodic activity in comparison with papaverine. The synthesis of the targeted heterocycles is described along with a discussion of their structure activity relationship. The general synthetic methods of bis-(tetrahydropapaverine) analogues involve tetrahydropapaverine, various piperazines, diisocyanates and diisothiocyanates as starting materials. Pharmacological evaluation involves the in vitro antispasmodic activity on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, N,N'-bis-[2-carbamoyl-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl]piperazine (22), was found to be the most potent muscle relaxant (IC(50): 0.31 microM).
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Jaskiran
J
Kaur
Narendra Nath
NN
Ghosh
Ramesh
R
Chandra
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010208:Papaverine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*
C490041:N,N'-bis-(2-carbamoyl-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl)piperazine; D010276:Parasympatholytics; D010879:Piperazines; D044005:Tetrahydroisoquinolines; D010208:Papaverine