N-arylalkyl derivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and process for their preparation.

摘要

PCT No. PCT/CS92/00015 Sec. 371 Date Nov. 18, 1993 Sec. 102(e) Date Nov. 18, 1993 PCT Filed May 27, 1992 PCT Pub. No. WO92/21671 PCT Pub. Date Dec. 10, 1992.New N-Arylalkylderivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)- enantiomers represented by general formula (I), where R1, R2 and R3 represent H, or R1 and R2 represent H and R3 represent H or R1 and R2 represent methoxy and R3 represents H and their pharmaceutically acceptable organic or inorganic acid addition salts exhibit in pharmacological tests pronounced hypotensive activity as a result of their calcium channel blocking and alpha1-adrenergic blocking activity and pronounced antithrombotic action. In a form of pharmaceutical preparations, they are suitable for the treatment and prevention of cardiovascular diseases and other disorders. New compounds of general formula (I) by N-alkylation of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)-enantiomers by derivatives of 2 phenyl-2-isopropyl-5-oxovaleronitrile under the conditions of reductive alkylation or with derivatives of 5-bromo-2-phenyl-2-isopropylvaleronitrile, which can be prepared by allylation of alpha-isopropylbenzyl cyanide and subsequent addition of hydrogen bromide under free radical conditions to the obtained alpha-allyl-alpha-isopropylbenzyl cyanide and its derivatives.