Substituted biphenyl isoxazole sulfonamides

A compound of the formula ##STR17## or an enantiomer, diastereomer or pharmaceutically acceptable salt thereof,

• wherein:
• one of X and Y is N and the other is O;
• Q is N or NR.sup.15 ;
• J is 0, S, N or NR.sup.15 ;
• K is C.dbd.O or CH;
• the dotted line .alpha. between Q and K denotes an optional double bond when Q is N and K is CH;
• the dotted line .beta. between K and J denotes an optional double bond when K is CH and J is N;
• with the proviso that said .alpha. and .beta. double bonds may not simultaneously be present;
• R.sup.1 and R.sup.2, when present, and R.sup.3 and R.sup.4, are each directly bonded to a ring carbon and are each independently
• (a) hydrogen;
• (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3 ;
• (c) halo;
• (d) hydroxyl;
• (e) cyano;
• (f) nitro;
• (g) --C(O)H or --C(O)R.sup.5 ;
• (h) --CO.sub.2 H or --CO.sub.2 R.sup.5 ;
• (i) --Z.sup.4 --NR.sup.6 R.sup.7 ;
• or
• (j) --Z.sup.4 --N(R.sup.10)--Z.sup.5 --NR.sup.8 R.sup.9 ;
• or
• (k) R.sup.3 and R.sup.4 together are alkylene or alkenylene, either of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached;
• R.sup.5 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3 ;
• R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are each independently
• (a) hydrogen;
• or
• (b) alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3 ;
• or
• R.sup.6 and R.sup.7 together are alkylene or alkenylene, either of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3, completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atom to which they are attached;
• or any two of R.sup.8, R.sup.9 and R.sup.10 together are alkylene or alkenylene, either of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
• R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are each independently
• (a) hydrogen;
• (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z.sup.1, Z.sup.2 and Z.sup.3,
• (c) heterocyclo, substituted heterocyclo or heterocyclooxy;
• (d) halo;
• (e) hydroxyl;
• (f) cyano;
• (g) nitro;
• (h) --C(O) H or --C(O)R.sup.5 ;
• (i) --CO.sub.2 H or --CO.sub.2 R.sup.5 ;
• (j) --SH, --S(O).sub.n R.sup.5, --S(O).sub.m --OH, --S(O).sub.m --OR.sup.5, --O--S(O).sub.m --OR.sup.5, --O--S(O).sub.m OH or --O--S(O).sub.m --OR.sup.5 ;
• (k) --Z.sup.4 --NR.sup.6 R.sup.7 ;
• or
• (l) --Z.sup.4 --N(R.sup.10)--Z.sup.5 --NR.sup.8 R.sup.9 ;
• Z.sup.1, Z.sup.2 and Z.sup.3 are each independently
• (a) hydrogen;
• (b) halo;
• (c) hydroxy;
• (d) alkyl;
• (e) alkenyl;
• (f) aryl;
• (g) aralkyl;
• (h) alkoxy;
• (i) aryloxy;
• (j) aralkoxy;
• (k) heterocyclo, substituted heterocyclo or heterocyclooxy,
• (l) --SH, --S(O).sub.n Z.sup.6, --S(O).sub.m --OH, --S(O).sub.m --OZ.sup.6, --O--S(O).sub.m --Z.sup.6, --O--S(O).sub.m OH or --O--S(O).sub.m --OZ.sup.6 ;
• (m) oxo;
• (n) nitro;
• (o) cyano;
• (p) --C(O)H or --C(O)Z.sup.6 ;
• (q) --CO.sub.2 H or --CO.sub.2 Z.sup.6 ;
• (r) --Z.sup.4 --NZ.sup.7 Z.sup.8 ;
• (s) --Z.sup.4 --N(Z.sup.11)--Z.sup.5 --H;
• (t) --Z.sup.4 --N(Z.sup.11)--Z.sup.5 --Z.sup.6 ;
• or
• (u) --Z.sup.4 --N(Z.sup.11)--Z.sup.5 --Z.sup.7 Z.sup.8 ;
• Z.sup.4 and Z.sup.5 are each independently
• (a) a single bond;
• (b) --Z.sup.9 --S(O).sub.n --Z.sup.10 --;
• (c) --Z.sup.9 --C(O)--Z.sup.10 --;
• (d) --Z.sup.9 --C (S)--Z.sup.10 --;
• (e) --Z.sup.9 --O---Z.sup.10 --;
• (f) --Z.sup.9 --S--Z.sup.10 --;
• (g) --Z.sup.9 --O--C(O)--Z.sup.10 --;
• or
• (h) --Z.sup.9 --C(O)--O--Z.sup.10 --;
• Z.sup.6 is alkyl;
• alkyl substituted with one to three groups selected from halogen, aryl, aryloxy and alkoxy;
• alkenyl;
• alkynyl;
• cycloalkyl;
• cycloalkyl substituted with one to three groups selected from alkyl, aryl, alkenyl and alkoxyaryl;
• cycloalkyl to which is fused a benzene ring;
• aryloxy substituted with one or two halogens;
• cycloalkylalkyl;
• cycloalkenyl;
• cycloalkenylalkyl;
• aryl;
• aryl substituted with methylenedioxy or one to four groups selected from alkyl, dialkylamino, cyano, halogen, trihaloalkyl, alkoxy and trihaloalkoxy;
• or heterocyclo or substituted heterocyclo;
• Z.sup.7 and Z.sup.8 are each independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, aryl or aralkyl or Z.sup.7 and Z.sup.8 together are alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atom to which they are attached;
• Z.sup.9 and Z.sup.10 are each independently a single bond, alkylene, alkenylene or alkynylene;
• Z.sup.11 is
• (a) hydrogen;
• or
• (b) alkyl, alkyl substituted with one, two or three halogens, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, aryl or aralkyl;
• or any two of Z.sup.7.sub., Z.sup.8 and Z.sup.11 together are alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
• R.sup.15 is hydrogen, alkyl, hydroxyethoxy methyl or methoxyethoxy methyl;
• each m is independently 1 or 2;
• each n is independently 0, 1 or 2;
• and
• p is 0 or an integer from 1 to 2.