5H-[1,2]benzisothiazolo[2,3-a]quinoline-5-ones and analogs as antiinflammatory agents

A compound of Formula I:

• ##STR13## or a pharmaceutically acceptable salt or prodrug form thereof, wherein:
• X.sup.1, X.sup.2, X.sup.3, and X.sup.4 are independently CH or N, provided that 0-1 of X are N with the remaining X groups being CH;
• Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently CH or N, provided that 0-1 of Z are N with the remaining Z groups being CH or Z.sup.1 and Z.sup.4 are N and Z.sup.2 and Z.sup.3 are CH;
• provided that X.sup.1, X.sup.2, X.sup.3, X.sup.4, Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are not all CH;
• Y is O or S;
• A is S or Se;
• R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are independently selected from the following groups:
• hydrogen;
• C.sub.1 -C.sub.8 alkyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkenyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkynyl substituted with 0-3 R.sup.20 ;
• C.sub.3 -C.sub.8 cycloalkyl substituted with 0-3 R.sup.20 ;
• C.sub.6 -C.sub.10 bicycloalkyl substituted with 0-3 R.sup.20 ;
• aryl substituted with 0-3 R.sup.21 ;
• a C.sub.6 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.21 ;
• F;
• Cl;
• Br;
• I;
• NO.sub.2 ;
• OR.sup.12 ;
• OC(.dbd.O)R.sup.12 ;
• OC(.dbd.O)OR.sup.12 ;
• OC(.dbd.O)ON(R.sup.12).sub.2 ;
• N(R.sup.12).sub.2 ;
• NR.sup.12 C(.dbd.O)R.sup.12 ;
• NR.sup.12 C(O.dbd.O)OR.sup.12 ;
• NR.sup.12 SO.sub.2 R.sup.12 ;
• NR.sup.12 C(.dbd.O)N(R.sup.12).sub.2 ;
• SO.sub.3 H;
• SR.sup.12 ;
• S(O)R.sup.12 ;
• SO.sub.2 /r.sup.12 ;
• SO.sub.2 N(R.sup.12).sub.2 ;
• C(.dbd.O)R.sup.12 ;
• CO.sub.2 R.sup.12 ;
• C(.dbd.O)N(R.sup.12).sub.2 ;
• CSN(R.sup.12).sub.2 ;
• C(.dbd.O)NR.sup.12 OR.sup.12 ;
• and CN;
• R.sup.7 is selected from the group consisting of:
• hydrogen;
• C.sub.1 -C.sub.8 alkyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkenyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkynyl substituted with 0-3 R.sup.20 ;
• C.sub.3 -C.sub.8 cycloalkyl substituted with 0-3 R.sup.20 ;
• C.sub.6 -C.sub.10 bicycloalkyl substituted with 0-3 R.sup.20 ;
• aryl substituted with 0-3 R.sup.21 ;
• a C.sub.6 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.21 ;
• F;
• Cl;
• Br;
• I;
• NO.sub.2 ;
• OR.sup.12 ;
• OC(.dbd.O)R.sup.12 ;
• OC(.dbd.O)OR.sup.12 ;
• OC(.dbd.O)ON(R.sup.12).sub.2 ;
• N(R.sup.12).sub.2 ;
• NR.sup.12 C(.dbd.O)R.sup.12 ;
• NR.sup.12 C(.dbd.O)OR.sup.12 ;
• NR.sup.12 SO.sub.2 R.sup.12 ;
• NR.sup.12 C(.dbd.O)N(R.sup.12).sub.2 ;
• SO.sub.3 H;
• SR.sup.12 ;
• S(O)R.sup.12 ;
• SO.sub.2 R.sup.12 ;
• SO.sub.2 N(R.sup.12).sub.2 ;
• C(.dbd.O)R.sup.12 ;
• CO.sub.2 R.sup.12 ;
• C(.dbd.O)N(R.sup.12).sub.2 ;
• CSN(R.sup.12).sub.2 ;
• C(.dbd.O)NR.sup.12 OR.sup.12 ;
• and CN;
• R.sup.12 is independently selected at each occurence from the group consisting of:
• hydrogen;
• C.sub.1 -C.sub.8 alkyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkenyl substituted with 0-3 R.sup.20 ;
• C.sub.2 -C.sub.8 alkynyl substituted with 0-3 R.sup.20 ;
• C.sub.3 -C.sub.8 cycloalkyl substituted with 0-3 R.sup.20 ;
• C.sub.6 -C.sub.10 bicycloalkyl substituted with 0-3 R.sup.20 ;
• aryl substituted with 0-3 R.sup.21 ;
• a C.sub.6 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.21 ;
• R.sup.20 is independently selected at each occurence from the group consisting of:
• C.sub.1 -C.sub.5 alkyl;
• C.sub.2 -C.sub.4 alkenyl;
• C.sub.3 -C.sub.10 cycloalkyl;
• C.sub.3 -C.sub.6 cycloalkylmethyl;
• C.sub.2 -C.sub.6 alkoxyalkyl;
• --C(.dbd.O)NR.sup.23 R.sup.24 ;
• --C(.dbd.O)NR.sup.23 OR.sup.23 ;
• CN;
• --C(.dbd.NH)NHR.sup.23 ;
• --CO.sub.2 R.sup.23 ;
• --C(.dbd.O)R.sup.23 ;
• --CSN(R.sup.23).sub.2 ;
• --OC(.dbd.O)R.sup.23 ;
• --OC(.dbd.O)OR.sup.23 ;
• --OR.sup.23 ;
• --OC(.dbd.O)NR.sup.23 R.sup.24 ;
• --NR.sup.23 R.sup.24 ;
• --NHC(.dbd.NH)NHR.sup.23 ;
• --NR.sup.24 C(.dbd.O)R.sup.23 ;
• .dbd.NOR.sup.24 ;
• --NR.sup.24 C(.dbd.O)OR.sup.24 ;
• --NR.sup.23 C(.dbd.O)NR.sup.23 R.sup.24 ;
• --NR.sup.24 SO.sub.2 NR.sup.23 R.sup.24 ;
• --NR.sup.24 SO.sub.2 R.sup.23 ;
• SO.sub.3 H;
• SR.sup.23 ;
• --S(.dbd.O)R.sup.23 ;
• --SO.sub.2 R.sup.23 ;
• --SO.sub.2 NR.sup.23 R.sup.24 keto;
• F;
• Cl;
• Br;
• I;
• NO.sub.2 ;
• a C.sub.5 -C.sub.14 carbocyclic residue substituted with 0-3 R.sup.23 ;
• aryl substituted with 0-3 R.sup.21 ;
• R.sup.21, when a substituent on carbon, is independently selected at each occurence from the group consisting of:
• phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.7 -C.sub.10 arylalkyl, C.sub.1 -C.sub.4 alkoxy, --NR.sup.23 R.sup.24, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl, C.sub.1 -C.sub.4 alkylcarbonylamino, --SO.sub.2 R.sup.23, --S(.dbd.O)R.sup.23, --SO.sub.2 NR.sup.23 R.sup.24, SO.sub.3 H, CF.sub.3, OR.sup.23, CHO, CH.sub.2 OR.sup.23, CO.sub.2 R.sup.23, C(.dbd.O)R.sup.23, --NHSO.sub.2 R.sup.24, --OCH.sub.2 CO.sub.2 H or
• R.sup.21 may be a 3- or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, or --NR.sup.23 R.sup.24 ;
• or, when R.sup.21 is attached to a saturated carbon atom, it may be carbonyl or thiocarbonyl;
• R.sup.21, when a substituent on nitrogen, is selected from one or more of the following:
• phenyl, benzyl, phenethyl, hydroxy, C.sub.1 -C.sub.4 hydroxyalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, --NR.sup.23 R.sup.24, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl;
• R.sup.23 is H, phenyl, benzyl or C.sub.1 -C.sub.6 alkyl;
• R.sup.24 is H, phenyl, benzyl or C.sub.1 -C.sub.6 alkyl;
• R.sup.23 and R.sup.24 can alternatively join to form --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --CH.sub.2 CH.sub.2 N(R.sup.25)CH.sub.2 CH.sub.2 --;
• R.sup.25 is H or CH.sub.3.