Acf Chemiefarma N.v.

Ronus De Bode

Hans B Trijzelaar

Hendricus B Welle

Handricus B Welle

The invention is concerned with novel quinicine and cinchonicine derivatives having cardiovascular activities of the formula or a salt thereof, ##STR1## in which A--B is --CH.sub.2 --CH.sub.2, --CHOH--CH.sub.2 --, --CH.sub.2 --CHOH--, --C(O)--CH.sub.2 --, --CH.sub.2 --C(O)--, --C(NOR.sup.4)--CH.sub.2 -- or --CH.sub.2 --C(NOR.sup.4)--; R.sup.1 is hydrogen, hydroxy or lower alkoxy; R.sup.2 is ethyl or vinyl; R.sup.3 is C.sub.2-8 alkyl, C.sub.1-8 hydroxyalkyl, lower alkoxy-alkyl or lower alkanoyloxyalkyl, C.sub.3-6 cycloalkyl, hydroxycycloalkyl, lower alkoxycycloalkyl or lower alkanoyloxycycloalkyl, cycloalkyl lower alkyl, hydroxy-, lower alkoxy- or lower alkanoyloxycycloalkyl lower alkyl; cyano, cyano lower alkyl, lower alkenyl, lower alkynyl, tetrahydrofuryl, mono- or di-lower alkylamino lower alkyl, mono- or di-lower alkylamino lower hydroxy alkyl; optionally substituted phenyl, phenyl lower alkyl or phenyl hydroxy lower alkyl, optionally substituted diphenyl lower alkyl, optionally substituted phenyl lower alkenyl, optionally substituted benzoyl or benzoyl lower alkyl, optionally substituted heteroaryl or heteroaryl lower alkyl, or optionally substituted heteroaroyl or heteroaroyl lower alkyl; R.sup.4 is lower alkyl, and Z is hydrogen, lower alkyl or optionally substituted phenyl, or Z and R.sup.3 together with the carbon atom to which they are attached form a C.sub.3-6 cycloalkyl group, whereby the substituents at the 3- and 4-position of the piperidine ring are in the cis-position, excluding N-[C.sub.2-6 alkyl, C.sub.2-6 hydroxyalkyl, NN-di-lower alkylamino lower alkyl, optionally substituted C.sub.7-11 aralkyl] substituted derivatives of quinicine and cinchonicine. The compounds of the formula may be in the form of their optically active enantiomers and/or their therapeutically acceptable salts. Methods for the preparation of the compounds of the formula are also disclosed and form part of the invention.

Quinoline derivatives and pharmaceutical compositions and methods for

The invention is concerned with novel quinoline derivatives of the formula ##STR1## or a salt thereof, in which A--B is --CH.sub.2 --CH.sub.2 --, --CHOH--CH.sub.2 --, --CH.sub.2 --CHOH--, --CH.sub.2 --C(O)--, --C(NOR.sup.4)--CH.sub.2 -- or --CH.sub.2 --C(NOR.sup.4)--, R.sup.1 is hydrogen, hydroxy or lower alkoxy, R.sup.2 is lower alkyl, R.sup.3 is ethyl or vinyl, R.sup.4 is lower alkyl, whereby the substituents at the 3- and 4-position of the piperidine ring are in the cis-position. The compounds of the formula may be in the form of the optically active enantiomers and/or their therapeutically acceptable salts. Furthermore the invention provides pharmaceutical compositions possessing cardiovascular activities in which as active compound at least a compound of the above formula is used. Methods for the preparation of the pharmaceutical compositions and of the active compounds are also included by the invention.

Quinoline derivatives, pharmaceutical compositions containing such

The invention is concerned with novel quinoline derivatives having cardiovascular activities of formula 1 ##STR1## in which A--B is --CH.sub.2 --CH.sub.2 --, --CHOH--CH.sub.2, --CH.sub.2 --CHOH--, --C(O)--CH.sub.2 --, --CH.sub.2 --C(O)--, --C(NOR.sup.5)--CH.sub.2 -- or --CH.sub.2 --C(NOR.sup.5)--; R.sup.1 is hydrogen, hydroxy or lower alkoxy; R.sup.2 is lower alkyl, hydroxy, lower alkoxy or CF.sub.3 ; R.sup.3 is ethyl or vinyl; R.sup.4 is C.sub.1-9 alkyl, C.sub.2-9 hydroxyalkyl or lower alkoxyalkyl, C.sub.5-6 cycloalkyl, C.sub.3-6 cycloalkyl lower alkyl, cyano lower alkyl, lower alkenyl, lower alkynyl, tetrahydrofurfuryl, mono- or di-lower alkylamino lower alkyl; mono- or di-lower alkylamino lower hydroxyalkyl; phenyl C.sub.1-4 alkyl, phenyl C.sub.1-4 hydroxy-alkyl, diphenyl C.sub.1-4 alkyl, benzoyl C.sub.1-4 alkyl, furyl C.sub.1-4 alkyl, thienyl C.sub.1-4 alkyl, furoyl C.sub.1-4 alkyl or thienoyl C.sub.1-4 alkyl, which groups may be optionally substituted in the aromatic nucleus, and R.sup.5 is lower alkyl, whereby the substituents at the 3- and 4-positions of the piperidine ring are in the cis-position. The compounds of the formula may be in the form of their optically active enantiomers and/or their therapeutically acceptable salts. Furthermore the invention provides pharmaceutical compositions possessing cardiovascular activities, in which as active compound at least a compound of the above formula is used. Methods for the preparation of the pharmaceutical compositions and of the active compounds are also disclosed and covered by the invention.

The invention is concerned with quinoline derivatives having cardiovascular activities of the formula ##STR1## or a salt thereof, in which A--B is --CH.sub.2 --CH.sub.2 --, --CHOH--CH.sub.2, --CH.sub.2 --CHOH--, --C(O)--CH.sub.2 --, --CH.sub.2 --C(O)--, --C(NOR.sup.4)--CH.sub.2 --CH.sub.2 -- or --CH.sub.2 --C(NOR.sup.4), R.sup.1 is hydrogen, hydroxy or lower alkoxy, R.sup.2 is hydroxy, lower alkoxy, trifluoromethyl, R.sup.3 is ethyl or vinyl and R.sup.4 is lower alkyl. The compounds of the formula may be in the form of their optically active enantiomers and/or their therapeutically acceptable salts. Furthermore the invention provides pharmaceutical compositions possessing cardiovascular activities, in which as active compound at least a compound of the above formula is used. Methods for the preparation of the pharmaceutical compositions and of the active compounds are also disclosed and covered by the invention.

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Bilthoven, Netherlands

Ronus De Bode