Two short series of compounds with IH-indole skeleton, bearing hydantoin and piperazine nuclei respectively, were synthesized. Some compounds of these two series were tested for their calcium-antagonistic activity on K+-depolarized smooth muscle (rabbit auricolar artery and guineapig taenia caeci) and their negative inotropic action on atrial muscle from guinea-pig hearts.
1H-Indol-Derivate als Calciumantagonisten
Zwei kleine Reihen den Hydanto,n. bzw, den Piperazin.Ring enthaltenden lH-Indol-Derivaten wurden hergesteIlt. Einige wurden auf ihre calciumantagonistische Wirkung an + -depolarisierter glatter Muskulatur (Kaninchenohren.Arterien und Meerschweinchen.taenia caeci) und auf ihre negativ inotrope Wirkung am Vorhofmuskel aus Meerschweinchenherzen untersucht.
In recent years drugs able to interfere with calcium movement via calcium channel regulation have become increasingly important both for their various therapeutic effects in the cardiovascular diseases (ischemic cardiomyopathies, hypcrtension and arrhytmias) and for the theoretical insight they provide towards understanding a variety of cellular func-tion~'-~). liven though defined as Caz+ antagonists, these drugs are still today a heterogeneous family differing in their structure, mechanism of action, tissue specificity and therapeutic profiles6). This heterogeneity, while hindering research of new Cat+ antagonists, makes it possible to design original models outside of fixed schemes. I R2 1 2 R1 = NO,, OCH,, CL R3 = CH, , CL, COOC,H5 [for 1 and 2 with X = 01; R* = H, C, H, , COC,H5, CH2CH2N(CH3), CH3 [for 2 with X = 1,2] R4 = H. C2H5; X = 0,1,2 Arch. Pharm. (Weinheim) 321, 377-383 (1 988)
Chemistry
Compounds la-q (table 2) and 2a-r (table ) were obtained from the corresponding 1H-indole-3-carboxaldehydes 3 (table 1) (schemes 1-3, for R not explained in schemes 1-3 see pertinent tables). Scheme 1 1aminohydantoin R ' Q ) --J y r ' I k 2 3 a) SOC1, b) 1 -benzylpiperazine > Scheme 2 2 (X = 0 ) triton EtOH/Ht R' B 5 -6 \2 WZH3 H I + SCH, a) SOCi, > 2 ( X = 1 ) b) 1benzylpiperazine 5 7.