Inhibitors of IMPDH enzyme

A method of inhibiting IMPDH activity in a mammal comprising the step of administering to said mammal a compound of the formula:

• ##STR58## wherein:
• E is oxygen;
• G and G' are independently selected from the group consisting of R.sup.1 and H;
• D is selected from the group consisting of C(O), C(S) and S(O).sub.2 ;
• B is phenylene;
• B' is phenyl;
• wherein each of B and B' optionally comprises up to 3 substituents, wherein:
• the first of said substituents, if present, is selected from R.sup.1, R.sup.2, R.sup.4 or R.sup.5,
• the second of said substituents, if present, is selected from R.sup.1 or R.sup.4, and
• the third of said substituents, if present, is R.sup.1 ;
• wherein:
• each R.sup.1 is independently selected from 1,2-methylenedioxy, 1,2-ethylenedioxy, R.sup.6 or (CH.sub.2).sub.n -Y;
• wherein n is 0, 1 or 2;
• and
• Y is selected from halogen, CN, NO.sub.2, CF.sub.3, OCF.sub.3, OH, SR.sup.6, S(O)R.sup.6, SO.sub.2 R.sup.6, NH.sub.2, NHR.sup.6, N(R.sup.6)2, NR.sup.6 R.sup.8, COOH, COOR.sup.6 or OR.sup.6 ;
• each R.sup.2 is independently selected from (C.sub.1 -C.sub.4)-straight or branched alkyl, or (C.sub.2 -C.sub.4)-straight or branched alkenyl or alkynyl;
• and each R.sup.2 optionally comprises up to 2 substituents, wherein:
• the first of said substituents, if present, is selected from R.sup.1, R.sup.4 and R.sup.5 and
• the second of said substituents, if present, is R.sup.1 ;
• each R.sup.4 is independently selected from OR.sup.5, OC(O)R.sup.6, OC(O)R.sup.5, OC(O)OR.sup.6, OC(O)OR.sup.5, OC(O)N(R.sup.6).sub.2, OP(O)(OR.sup.6).sub.2, SR.sup.6, SR.sup.5, S(O)R.sup.6, S(O)R.sup.5, SO.sub.2 R.sup.6, SO.sub.2 R.sup.5, SO.sub.2 N(R.sup.6).sub.2, SO.sub.2 NR.sup.5 R.sup.6, SO.sub.3 R.sup.6, C(O)R.sup.5, C(O)OR.sup.5, C(O)R.sup.6, C(O)OR.sup.6, NC(O)C(O)R.sup.6, NC(O)C(O)R.sup.5, NC(O)C(O)OR.sup.6, NC(O)C(O)N(R.sup.6).sub.2, C(O)N(R.sup.6).sub.2, C(O)N(OR.sup.6)R.sup.6, C(O)N(OR.sup.6)R.sup.5, C(NOR.sup.6)R.sup.6, C(NOR.sup.6)R.sup.5, N(R.sup.6).sub.2, NR.sup.6 C(O)R.sup.1, NR.sup.6 C(O)R.sup.6, NR.sup.6 C(O)R.sup.5, NR.sup.6 C(O)OR.sup.6, NR.sup.6 C(O)OR.sup.5, NR.sup.6 C(O)N(R.sup.6).sub.2, NR.sup.6 C(O)NR.sup.5 R.sup.6, NR.sup.6 SO.sub.2 R.sup.6, NR.sup.6, SO.sub.2 R.sup.5, NR.sup.6 SO.sub.2 N(R.sup.6).sub.2, NR.sup.6 SO.sub.2 NR.sup.5 R.sup.6, N(OR.sup.6)R.sup.6, N(OR.sup.6)R.sup.5, P(O)(OR.sup.6)N(R.sup.6).sub.2, and P(O)(OR.sup.6).sub.2 ;
• each R.sup.5 is a monocyclic or a bicyclic ring system consisting of 5 to 6 members per ring, wherein said ring system optionally comprises up to 4 heteroatoms selected from N, O, or S, and wherein a CH.sub.2 adjacent to said N, O or S maybe substituted with C(O);
• and each R.sup.5 optionally comprises up to 3 substituents, each of which, if present, is R.sup.1 ;
• each R.sup.6 is independently selected from H, (C1-C4)-straight or branched alkyl, or (C2-C4)-straight or branched alkenyl;
• and each R.sup.6 optionally substituted with R.sup.7 ;
• R.sup.7 is a monocyclic or a bicyclic ring system consisting of 5 to 6 members per ring, wherein said ring system optionally comprises up to 4 heteroatoms selected from N, O, or S, and wherein a CH.sub.2 adjacent to said N, O or S maybe substituted with C(O);
• and each R.sup.7 optionally comprises up to 2 substituents independently chosen from H, (C.sub.1 -C.sub.4)-straight or branched alkyl, or (C.sub.2 -C.sub.4) straight or branched alkenyl, 1,2-methylenedioxy, 1,2-ethylenedioxy, or (CH.sub.2).sub.n -Z;
• R.sup.8 is an amino protecting group;
• and
• n is 0, 1 or 2.