Synthesis and Myorelaxant Activity of Fused 1,4‐Dihydropyridines on Isolated Rabbit Gastric Fundus

Abstract

Strategy, Management and Health PolicyPreclinical Research In the present study, 25 novel condensed 1,4‐dihydropyridine (DHP) derivatives bearing cyclopentane, cyclohexane, or tetrahydrothiopene ring with a bulky and lipophilic moiety (3‐pyridylmethyl) in the ester group were synthesized via a modified Hantzsch reaction, and their calcium channel modulator activities were assayed on isolated rabbit gastric fundus smooth muscle strips. To evaluate the myorelaxant effects of the compounds, the maximum relaxant response (Emax) and pD 2 values were calculated. The results indicated that all compounds produced concentration‐dependent relaxation and the introduction of five‐ or six‐membered rings to the DHP nucleus and 3‐pyridiylmethyl moiety to the ester group led to potent calcium antagonists.

Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

“…1 H NMR and 13 C NMR spectra were recorded in dimethyl sulfoxide (DMSO-d 6 ) solutions on a Varian Mercury 400, 400 MHz high performance digital FT-NMR spectrometer (USA) using tetramethylsilane (TMS) as internal standard. Chemical shift s were reported in parts per million (ppm).…”

“…The muscle relaxant activities of DHP1-DHP6 and of NIF, as a reference, were evaluated by measuring the values of maximum relaxant eff ects (E max , %) and the negative logarithm of the half-maximal eff ective concentration EC 50 (in mol L -1 ) (pD 2 ) on isolated rabbit gastric fundus smooth muscle strips according to the method reported in the literature (13) ) pre-contracted strips. The compounds were dissolved in dimethyl sulfoxide (DMSO) (< 0.01 %).…”

“…In our previous study, several condensed DHP derivatives were synthesized via a modifi ed Hantzsch reaction, bearing a cyclopentane, cyclohexane or tetrahydrothiopene ring with a bulky and lipophilic moiety (3-pyridylmethyl) in the ester group (13). Hantzsch reaction is the one-pot classical method for the synthesis of 1,4-DHPs, which involves cyclocondensation of an aldehyde, two equivalents of a 1,3-dicarbonyl compound and ammonia, generally in refl uxing ethanol.…”

“…Structures of all compounds were elucidated by spectral methods (IR, 1 H NMR, 13 C NMR and mass spectrometry) and confi rmed by elemental analysis. In the IR spectra, a characteristic N-H stretching band appeared at about 3300 cm -1 .…”

“…Fused DHPs obtained by introducing the DHP ring into condensed ring systems have shown good calcium antagonistic eff ects (11,12). Recently, a series of new condensed 1,4-DHP derivatives, having a dimethyl-substituted cyclohexane ring fused with a 3-pyridylmethyl moiety, have been synthesized by our research groups (13,14).…”