1,4 3,6-DIANHYDROHEXITOL NITRATE DERIVATIVES .1. SYNTHESIS AND ANTIANGINAL ACTIVITY OF ALKYLPIPERAZINE DERIVATIVES/

A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1,4:3,6-dianhydro -L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds w ith the aryl-heteroatom (O, S, or N)-propyl group. Among them, the phe nylthiopropyl-substituted compound 13 exhibited the most potent activi ty. Furthermore, intraduodenal administration (i.d.) of 13 tended to d ecrease left ventricular end-diastolic pressure (LVEDP) in a propranol ol-induced heart failure model (dogs) and showed a potent protective e ffect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is u nder further study as an orally active nitrate.