Muscarinic antagonists

A compound having the structural formula I, ##STR180## including all isomers and pharmaceutically acceptable salts, esters, and solvates thereof,

• wherein Y and Z are each N:
• X is --O--, --S--, --SO--, --SO.sub.2 --, --NR.sup.6 --, --CO--, --CH.sub.2 --, --CS--, --C(OR.sup.5).sub.2 --, --C(SR.sup.5).sub.2 --, --CONR.sup.20 --, --C(alkyl).sub.2 --, --C(H)(alkyl)--, --NR.sup.20 --SO.sub.2 --, --NR.sup.20 CO--, ##STR181## acyl, cycloalkyl, cycloalkyl substituted with up to two alkyl groups, cycloalkenyl, bicycloalkyl, arylalkenyl, benzyl, benzyl substituted with up to three independently selected R.sup.3 groups, cycloalkylalkyl, polyhaloacyl, benzyloxyalkyl, alkenylcarbonyl, alkylarylsulfonyl, alkoxycarbonylaminoacyl, alkylsulfonyl, or arylsulfonyl, additionally, R and X may combine to form the group Prot--(NOAA).sub.r --NH-- wherein r is an integer of 1 to 4, Prot is a nitrogen protecting group and when r is 1, NOAA is a naturally occuring amino acid or an enantiomer thereof, or when r is 2 to 4, each NOAA is an independently selected naturally occuring amino acid or an enantiomer thereof;
• R.sup.1 and R.sup.21 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkyl, alkynyl, cyano, aminoalkyl, alkoxycarbonyl, aminocarbonyl, hydroxyguanidino, alkoxycarbonylalkyl, phenyl alkyl, alkylcarbonlyoxyalkyl, ##STR182## H, --OH, (provided R.sup.1 and R.sup.21 are both not --OH and Y is not N), formyl, --CO alkyl, --COacyl, --COaryl, and hydroxyalkyl;
• additionally R.sup.1 and R.sup.21 together may form the group .dbd.CH.sub.2, .dbd.N--OR.sup.5, ##STR183## --C(halo).sub.2, in further addition, R.sup.1 and R.sup.21 together with the carbon atom to which they are attached may form the group ##STR184## or R.sup.1 and R.sup.21 together with the carbon atom to which they are attached may form a saturated heterocyclic ring containing 3 to 7 carbon atoms and one group selected from S, O, and NH;
• R.sup.2 is H, alkyl, alkenyl, cycloalkyl, cycloalkyl substituted with 1 to 3 independently selected R.sup.3 groups, cycloalkenyl, hydroxyC.sub.2 -C.sub.20 alkyl, alkynyl, alkylamide, cycloalkylalkyl, hydroxyarylalkyl, bicycloalkyl, alkynyl, acylaminoalkyl, arylalkyl, hydroxyalkoxyalkyl, azabicyclo, alkylcarbonyl, alkoxyalkyl, aminocarbonylalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylamino(alkyl)alkyl;
• alkylcarbonyloxyalkyl, arylhydroxyalkyl, alkylcarbonylamino(alkyl)alkyl, dialkylamino, ##STR185## (wherein q is an integer of 0 to 2) ##STR186## wherein n is 1-3 ##STR187## wherein m is an integer of 4 to 7, ##STR188## wherein t is an integer of 3 to 5, ##STR189## (wherein R.sup.29 is H, alkyl, acyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylsulfonyl, arylsulfonyl), ##STR190## (wherein Q is O, NOH, or NO-alkyl), or when Z is --CH--, R.sup.2 may also be alkoxycarbonyl, hydroxymethyl, --N(R.sup.8).sub.2 ;
• R.sup.3, R.sup.4, R.sup.22, R.sup.24, and R.sup.25 are independently selected from the group consisting of H, halo, alkoxy, benzyloxy, benzyloxy substituted by nitro or aminoalkyl, haloalkyl, polyhaloalkyl, nitro, cyano, sulfonyl, hydroxy, amino, alkylamino, formyl, alkylthio, polyhaloalkoxy, acyloxy, trialkylsilyl, alkylsulfonyl, arylsulfonyl, acyl, alkoxycarbonyl alkylsulfinyl;
• --OCONH.sub.2, --OCONH-alkyl, --OCON(alkyl).sub.2, --NHCOO-alkyl, --NHCO-alkyl, phenyl, hydroxyalkyl, or morpholino;
• each R.sup.5 and R.sup.6 is independently selected from the group consisting of H and alkyl, provided that when X is C(OR.sup.5).sub.2 or C(SR.sup.5).sub.2, both R.sup.5 groups cannot be H, and in addition, when X is C(OR.sup.5).sub.2 or C(SR.sup.5).sub.2, the two R.sup.5 groups in X may be joined to form --(CH.sub.2).sub.p -- wherein p is an integer of 2 to 4;
• R.sup.7 is independently selected from the group consisting of H, alkyl, arylalkyl, cycloalkyl, aryl and aryl substituted with R.sup.3 and R.sup.4 as defined herein;
• each R.sup.8 is independently selected from the group consisting of H, hydroxyalkyl, or alkyl or two R.sup.8 groups may be joined to form an alkylene group;
• R.sup.9 is H, alkyl, or acyl;
• R.sup.20 is H, phenyl or alkyl;
• and
• R.sup.27 and R.sup.28 are independently selected from the group consisting of H, alkyl, hydroxyalkyl, arylalkyl, aminoalkyl, haloalkyl, thioalkyl, alkylthioalkyl, carboxyalkyl, imidazolyalkyl, and indolyalkyl, additionally R.sup.27 and R.sup.28 may combine to form an alkylene group.