N,N-diacylpiperazines

A compound of structural formula:

• ##STR23## or a pharmaceutically acceptable salt thereof, wherein:
• R.sup.1a is
• 1) H,
• 2) C.sub.1-8 alkyl,
• 3) phenyl, either unsubstituted or substituted with one or two substituents selected from:
• a) --C.sub.1-4 alkyl,
• b) halo,
• e) --OH,
• d) --CF.sub.3,
• e) --NH.sub.2,
• f) --NH(C.sub.1-4 alkyl),
• g) --N(C.sub.1-4 alkyl).sub.2,
• h) --CO.sub.2 H,
• i) --CO.sub.2 (C.sub.1-4 alkyl), and
• j) --C.sub.1-4 alkoxy;
• or
• 4) C.sub.1-4 alkyl-phenyl, wherein the phenyl is either unsubstituted or substituted with one or two substituents selected from:
• a) --C.sub.1-4 alkyl,
• b) halo,
• e) --OH,
• d) --CF.sub.3,
• e) --NH.sub.2,
• f) --NH(C.sub.1-4 alkyl),
• g) --N(C.sub.1-4 alkyl).sub.2,
• h) --CO.sub.2 H,
• i) --CO.sub.2 (C.sub.1-4 alkyl), and
• j) --C.sub.1-4 alkoxy;
• R.sup.1b is selected from:
• 1) R.sup.1a,
• 2) --C.sub.3-7 cycloalkyl, and
• 3) --CH.sub.2 --R.sup.1a ;
• R.sup.2a and R.sup.2b are independently phenyl, either unsubstituted or substituted with one or two substituents selected from:
• 1) --C.sub.1-4 alkoxy,
• 2) halo,
• 3) --OH,
• 4) --CF.sub.3,
• 5) --NH.sub.2,
• 6) --NH(C.sub.1-4 alkyl),
• 7) --N(C.sub.1-4 alkyl).sub.2,
• 8) --CO.sub.2 H,
• 9) --CO.sub.2 (C.sub.1-4 alkyl), and
• 10) --C.sub.1-6 alkyl, either unsubstituted or substituted with:
• a) halo,
• b) --OH,
• c) --CF.sub.3,
• d) --NH.sub.2,
• e) --NH(C.sub.1-4 alkyl),
• f) --N(C.sub.1-4 alkyl).sub.2,
• g) --CO.sub.2 H,
• h) --CO.sub.2 (C.sub.1-4 alkyl), and
• i) --C.sub.1-4 alkoxy,
• j) --S(O).sub.x (C.sub.1-4 alkyl) wherein X is 0, 1 or 2,
• k) --C.sub.3-7 cycloalkyl;
• and the phenyl groups of R.sup.2a and R.sup.2b may be joined together at the ortho carbon atoms through a carbon-carbon single bond or a C.sub.1-3 alkylene to form a tricyclic group with the X.sup.2 to which they are attached;
• X.sup.1 is --N, --CH or O, with the proviso that if X.sup.1 is O, R.sup.1a is absent;
• X.sup.2 is --N or --CH, with the proviso that if X.sup.1 is --CH, X.sup.2 is not --CH;
• R.sup.3 is
• 1) --C.sub.1-4 alkyl,
• 2) --CO.sub.2 R.sup.6,
• 3) --CH.sub.2 OCOR.sup.6,
• 4) --CH.sub.2 OH,
• 5) --CH.sub.2 OR.sup.5,
• 6) --CH.sub.2 S(O).sub.x R.sup.5,
• 7) --CH.sub.2 OCONR.sup.5 R.sup.6,
• 8) --CH.sub.2 CONR.sup.5 R.sup.6,
• 9) --CONR.sup.5 R.sup.6,
• 10) --CO.sub.2 R.sup.8,
• 11) --CH.sub.2 CO.sub.2 R.sup.6,
• 12) --CH.sub.2 CO.sub.2 R8,
• 13) --CONHSO.sub.2 R.sup.9,
• 14) --CH.sub.2 N(R.sup.6)CONR.sup.5 R.sup.6,
• 15) --CH.sub.2 NH.sub.2,
• 16) --CH.sub.2 NH(C.sub.1-4 alkyl), or
• 17) --CH.sub.2 N(C.sub.1-4 alkyl).sub.2 ;
• wherein
• R.sup.5 is C.sub.1-6 alkyl either unsubstituted or substituted with:
• 1) --halo,
• 2) --OH,
• 3) --CF.sub.3,
• 4) --NH.sub.2,
• 5) --NH(C.sub.1-4 alkyl),
• 6) --N(C.sub.1-4 alkyl).sub.2,
• 7) --CO.sub.2 H,
• 8) --CO.sub.2 (C.sub.1-4 alkyl),
• 9) --C.sub.3-7 cycloalkyl, or
• 10) phenyl, either unsubstituted or substituted with
• a) --C.sub.1-4 alkyl,
• b) --halo,
• c) --OH,
• d) --CF.sub.3,
• e) --NH.sub.2,
• f) --NH(C.sub.1-4 alkyl),
• g) --N(C.sub.1-4 alkyl).sub.2,
• h) --CO.sub.2 H, or
• i) --CO.sub.2 (C.sub.1-4 alkyl);
• R.sup.6 is --H or C.sub.1-4 alkyl;
• or
• R.sup.5 and R.sup.6 can be joined together to form with the nitrogen to which they are attached a ring of the formula --N(CH.sub.2 CH.sub.2).sub.2 L, wherein L is:
• i) a single bond,
• ii) --CH.sub.2 --,
• iii) --O--,
• iv) --S(O).sub.p --, or
• v) --NR.sup.7 ;
• R.sup.7 is
• 1) --H,
• 2) --C.sub.1-6 alkyl, unsubstituted or substituted with --OH, --C.sub.1-4 alkoxy, or --N(C.sub.1-4 alkyl).sub.2,
• 3) --aryl, wherein aryl is phenyl, either unsubstituted or substituted with
• a) --C.sub.1-4 alkyl,
• b) --halo,
• c) --OH,
• d) --CF.sub.3,
• e) --NH.sub.2,
• f) --NH(C.sub.1-4 alkyl),
• g) --N(C.sub.1-4 alkyl).sub.2,
• h) --CO.sub.2 H, or
• i) --CO.sub.2 (C.sub.1-4 alkyl);
• 4) --CH.sub.2 -aryl, wherein aryl is as defined above;
• R.sup.8 is
• 1) --H
• 2) ##STR24## wherein R.sup.10 is a) --C.sub.1-6 alkyl,
• b) --aryl, wherein aryl is as defined above, or
• c) --CH.sub.2 -aryl, wherein aryl is as defined above,
• 3) --CH.sub.2 -aryl, wherein aryl is as defined above;
• R.sup.9 is
• 1) --aryl, wherein aryl is as defined above,
• 2) --C.sub.3-7 cycloalkyl,
• 3) --polyfluoro-C.sub.1-4 alkyl
• 4) --C.sub.1-6 alkyl, either unsubstituted or substituted with
• a) --aryl, wherein aryl is as defined above,
• b) --OH,
• c) --SH,
• d) --C.sub.1-4 alkyl,
• e) --C.sub.3-7 cycloalkyl,
• f) --C.sub.1-4 alkoxy,
• g) --C.sub.1-4 alkylthio,
• h) --CF.sub.3,
• i) --halo,
• j) --NO.sub.2,
• k) --CO.sub.2 R.sup.6,
• l) --N(R.sup.6).sub.2, wherein the R.sup.6 groups are the same or different,
• m) --NH aryl,
• n) --N(aryl).sub.2,
• o) --PO.sub.3 H,
• p) --PO(OH)(OC.sub.1-4 alkyl) or
• q) a ring of the formula --N(CH.sub.2 CH.sub.2).sub.2 L, wherein L is as defined above;
• and
• R.sup.4 is H or R.sup.3.