Claims
- 1. 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.
- 2. The method according to claim 1, wherein said compound has the formula: ##STR59## wherein: K is selected from R.sup.1 and R.sup.4 ; and
- J is selected from R.sup.1, R.sup.2.sub.1 and R.sup.4 ;
- E, G and D are as defined in claim 1.
- 3. The method according to claim 2, wherein D is --C(O)--.
- 4. The method according to claim 2, wherein J is R.sup.2 optionally substituted with R.sup.4.
- 5. The method according to claim 4, wherein J is NR.sup.6 C(O)R5 or NR.sup.6 C(O)R.sup.6.
- 6. The method according to claim 5, wherein J is NR.sup.6 C(O)R.sup.6.
- 7. The method according to claim 6, wherein J is N(CH3)C(O)R.sup.6.
- 8. The method according to claim 4, wherein J is R.sup.2 substituted with NR.sup.6 C(O)OR5 or NR.sup.6 C(O)OR.sup.6.
- 9. The method according to claims 2 or 62, wherein K is (CH2)n-Y.
- 10. The method according to claim 9, wherein K is OCH3.
- 11. The method according to claim 4, wherein:
- D is --C(O)--;
- E is oxygen;
- K is OCH3; and
- G is hydrogen.
- 12. The method according to claim 7, wherein:
- D is --C(O)--;
- E is oxygen;
- K is OCH3; and
- G is hydrogen.
CROSS-REFERENCE TO RELATED U.S. APPLICATIONS
This is a continuation-in-part of U.S. application Ser. No. 08/801,780, filed Feb. 14, 1997 and now pending, which is a continuation-in-part of U.S. application Ser. No. 08/636,361, filed Apr. 23, 1996 and now U.S. Pat. No. 5,807,876.
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Number |
Name |
Date |
Kind |
4048333 |
Galabov et al. |
Sep 1977 |
|
5380879 |
Sjogren |
Jan 1995 |
|
5444072 |
Patterson et al. |
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Foreign Referenced Citations (1)
Number |
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WO 9401105 |
Jan 1994 |
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Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
801780 |
Feb 1997 |
|
Parent |
636361 |
Apr 1996 |
|