Intermediate-duration reversible neuromuscular blocking agents of the formula (I) ##STR1## where B and C are preferably para or may be meta and are each ##STR2## where W is CH.sub.2 or most preferably CH.dbd.CH R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and are each hydrogen or lower alkoxy of 1 to 4 carbon atoms and preferably methoxy, Y is lower alkyl of 1 to 4 carbon atoms and preferably methyl, Z is hydrogen, lower alkyl of 1 to 4 carbon atoms, cyclopentyl, cyclohexyl, benzyl, or ##STR3## where ALKYL has 1 to 4 carbon atoms preferably where the O-ALKYL is at the 2, 3, 4 or 5 positions such as 4-methoxy benzyl and is most preferably 3,4-dimethoxy benzyl or 3, 4, 5-trimethoxybenzyl, n is 2, 3 or 4, most preferably 2 or 3 provided that at least one of R.sub.1 to R.sub.4 is lower alkoxy and most preferably where R.sub.1 and R.sub.4 is hydrogen and R.sub.2 and R.sub.3 are methoxy and X is a pharmaceutically acceptable anion. The neuromuscular blocking agents of formula I are useful for administration to a patient to cause skeletal muscle relaxation during surgery and are normally administered intravenously in a pharmaceutically acceptable carrier.
This invention provides the neuromuscular blocking agents of formula (I): ##STR1## where B and C are each a group of formula (II) and are meta or para to one another: ##STR2## wherein D is CH.sub.2 CH.sub.2 or CH.dbd.CH (preferably trans); Y is alkyl of 1-4 carbon atoms (methyl, ethyl, propyl or butyl); E and F and H or OCH.sub.3 ; X.sup.- is an anion, preferably pharmaceutically acceptable; and the substituted benzyl and substituted propyl groups are in a trans relationship relative to each other in the nitrogen-containing ring. Methods for preparing the compounds, pharmaceutical formulations containing the compounds, and their use are also described.
Muscle relaxant nitrogen bridge tetrahydroisoquinolines are disclosed. The novel compounds are represented by the formula ##STR1## wherein A is ##STR2## M represents --(CH.sub.2).sub.n --Z--(CH.sub.2).sub.n or ##STR3## R is a C.sub.1-3 alkoxy group, or adjacent Rs are a methylenedioxy group, R.sub.1 is lower alkyl; n is 1-6; m is 2 or 3; p is 1-3; Z is --N.sup.+ (R.sub.2 R.sub.3)--, --N(R.sub.4)--, ##STR4## and --N[(CH.sub.2).sub.n --A--R.sub.5 ]--; R.sub.2 and R.sub.3 are independently lower alkyl groups wherein a carbon atom within the chain may be replaced by a heteroatom, lower cycloalkyl, lower cycloalkyl lower alkyl, aryl, aryl lower alkyl, a 4- to 6-member heteroring or may be combined with the nitrogen to form a heteroring; R.sub.4 is a straight- or branched- chain C.sub.1-10 alkyl wherein a carbon atom within the chain may be replaced by a heteroatom, lower cycloalkyl, lower cycloalkyl lower alkyl, aryl, or a heteroring, which groups may be substituted or unsubstituted; or ##STR5## R.sub.5 is lower alkyl or lower alkenyl; Y is hydrogen, lower alkyl wherein a carbon atom within the chain may be replaced by a heteroatom, lower alkoxy, aryl, aryloxy, lower cycloalkyl, lower cycloalkyl lower alkyl, a 4- to 6-member heteroring or --NR.sub.2 R.sub.3 ; X.sup.- is a pharmaceutically acceptable anion, and optically active forms thereof, meso forms thereof, cis-trans isomeric forms thereof and racemates thereof.
4761418 - Novel compounds - Owned by Burroughs Wellcome Co. (Research Triangle Park, NC) General Hospital Corporation (Boston, MA)
Neuromuscular blocking agents of formula (1) which are useful as skeletal muscle relaxants during surgery are disclosed. ##STR1## and X is an anion, preferably pharmaceutically acceptable.
Tetrahydroisoquinoline compounds of formula I ##STR1## and pharmaceutically acceptable salts and lipophilic ester thereof have utility as analgesics and in the treatment of psychoses, Parinson's disease, Lesch-Nyan syndrome, attention deficit disorder or cognitive impairment or in the relief of drug dependence or tardive dyskinesia.
