Claims
- 1. A method of treating an inflammatory disease or an autoimmune disease in a mammal by inhibiting prostaglandin G/H synthase comprising administration to the mammal of a therapeutically effective amount of a compound selected from the group of compounds represented by formula I: ##STR76## where: R.sub.1 and R.sub.5 are independently H or alkyl;
- R.sub.3 and R.sub.4 are independently H, halo, alkyl, alkyloxy, or alkylthio;
- R.sub.10 is a group represented by formula (A), (B) or (C): ##STR77## where: X is O or S;
- R.sub.12 and R.sub.16 are independently H, halo, alkyl, alkyloxy, alkylthio, cyano, or hydroxy;
- R.sub.13 and R.sub.15 are independently H, halo, alkyl, alkyloxy, or alkylthio; and
- R.sub.14 is H, halo, alkyl, haloalkyl, amino, alkylamino, dialkylamino, alkyloxy, hydroxy, alkylthio, alkenyl, alkynyl, cyano, --SO.sub.2 R.sub.17 where R.sub.17 is alkyl, or --SO.sub.2 NR.sub.18 R.sub.19 where R.sub.18 and R.sub.19 are independently H or alkyl;
- provided that at least two of R.sub.12, R.sub.13, R.sub.14, R.sub.15 and R.sub.16 are H, and that if only two of R.sub.12, R.sub.13, R.sub.14, R.sub.15, and R.sub.16 are H, the non-hydrogen substituents are not all adjacent; or R.sub.12, R.sub.15, and R.sub.16 are H and R.sub.13 and R.sub.14 together are --OCH.sub.2 O--;
- R.sub.20 is a group represented by formula (U), (V) or (W): ##STR78## where: R.sub.22 is H, halo, alkyl, cyano, trifluoromethyl, hydroxy, alkyloxy, or -CO.sub.2 R.sub.27 where R.sub.27 is H or alkyl;
- one of R.sub.23, R.sub.24, and R.sub.25 is R.sub.30 ; and
- either all the remaining R.sub.23, R.sub.24, R.sub.25, and R.sub.26 are H; or one of the remaining R.sub.23, R.sub.24, R.sub.25, and R.sub.26 is halo, alkyl, cyano, trifluoromethyl, hydroxy, or alkyloxy; and
- R.sub.30 is --OH*, --NHH*, --NH*CHO, --NH*C(X)R.sub.31, --NH*SO.sub.2 R.sub.31, --NH*C(X)NR.sub.32 R.sub.33, or --NH*SO.sub.2 NR.sub.32 R.sub.34,
- where:
- H* is hydrogen, optionally replaced by an in vivo hydrolyzable protecting group;
- R.sub.31 is alkyl, haloalkyl, hydroxyalkyl, alkenyl, benzyl, aryl, cycloamino, --CH.sub.2 SO.sub.2 Me, or --(CH.sub.2).sub.n R.sub.35, where n is an integer from 2 to 5 and R.sub.35 is alkylamino, dialkylamino, cycloamino, alkyloxy, acyloxy, or --CO.sub.2 R.sub.27 ;
- R.sub.32 is H, alkyl, or --(CH.sub.2).sub.n OR.sub.27 ;
- R.sub.33 is H, alkyl, haloalkyl, aryl, hydroxyalkyl, tetrahydrofuran-2-ylmethyl, --CH.sub.2 CO.sub.2 R.sub.27, or --(CH.sub.2).sub.n R.sub.35 ; and
- R.sub.34 is H, alkyl, acetyl, hydroxyalkyl, or --(CH.sub.2).sub.n R.sub.35 ;
- and their pharmaceutically acceptable salts.
- 2. The method of claim 1 where R.sub.20 is a group represented by formula (U) or (V) and R.sub.24 is R.sub.30.
- 3. The method of claim 2 where R.sub.10 is a group represented by formula (A) and R.sub.1 is alkyl.
- 4. The method of claim 3 where R.sub.3 is H or alkyl; R.sub.4, R.sub.5, R.sub.15, and R.sub.16 are H; and R.sub.13 is H, halo, or alkyl.
- 5. The method of claim 4 where R.sub.30 is --NHH*, --NH*SO.sub.2 R.sub.31, or --NH*SO.sub.2 NR.sub.32 R.sub.34.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional of application Ser. No. 08/864,703, filed May 28, 1997 now U.S. Pat. No. 5,952,368 and also claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Application No. 60/018,691, filed May 30, 1996. The entire disclosure of the prior application is considered as being part of the disclosure of this divisional application and is hereby incorporated by reference therein.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
3752826 |
Carson |
Aug 1973 |
|
5622948 |
Dunn et al. |
Apr 1997 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 071 399 A2 |
Sep 1983 |
EPX |
Divisions (1)
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Number |
Date |
Country |
Parent |
864703 |
May 1997 |
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