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US 5,348,957 AGranted
5-hydroxy-2-pyrimidinylmethylene derivatives useful as antiinflammatory agents
AssigneeWarner-Lambert Company
InventorsThomas R. Belliotti, David T. Connor, Catherine R. Kostlan
Life of this patent
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Abstract
The present invention compounds are 5-hydroxy-2-pyrimidinylmethylene derivatives and pharmaceutically acceptable addition salts, bases, and base salts thereof, pharmaceutical compositions and methods of use therefor. The invention compounds are found to have activity as inhibitors of 5-lipoxygenase and/or cyclooxygenase providing treatment of, for example, inflammation and GI ulcers.
Claims2
A method of treating inflammation in a human in need of such treatment which comprises administering a compound of the formula ##STR26## or a pharmaceutically acceptable acid addition or base salt thereof;
- wherein
- R.sub.1 and R.sub.2 are tertiarybutyl;
- R.sub.19 is H;
- A is
- 1) ##STR27## wherein X is S, O, NH, or CH.sub.2 ;
- and
- Y is S, O, or NH;
- 2) ##STR28## wherein X is as defined above;
- and
- B is
- i) SR.sub.7,
- ii) SOR.sub.7,
- iii) SO.sub.2 R.sub.7,
- iv) NR.sub.15 R.sub.16,
- v) NHCN,
- vi) ##STR29## vii) ##STR30## viii) ##STR31## ix) N(OR.sub.6)R.sub.4, x) N(OH)COR.sub.5,
- xi) NR.sub.4 W,
- xii) S(CH.sub.2).sub.n CO.sub.2 R.sub.6, or
- xiii) NR.sub.7 COR.sub.6
- wherein
- Z' is S, O, NH, or NCN;
- W is CO.sub.2 R.sub.7, ##STR32## n is 1, 2, or 3;
- m is 1, 2, 3, 4, or 5;
- R.sub.15 and R.sub.1 6 are independently H, lower alkyl, aralkyl, or (CH.sub.2).sub.n NR.sub.6 R.sub.7 wherein n is as defined above;
- R.sub.3 is H, alkyl, or aryl;
- R.sub.4 is H or alkyl;
- R.sub.5 is alkyl, aryl, or CF.sub.3 ;
- R.sub.6 is H or lower alkyl;
- and
- R.sub.7 is lower alkyl;
- 3) ##STR33## wherein Z is CH.sub.2, S, O, or NR.sub.8 wherein R.sub.8 is H, lower alkyl, OH, or OMe;
- or
- 4) ##STR34## wherein p is 0, 1, or 2;
- W.sub.1 is H.sub.2, O, or S;
- R.sub.9 is
- i) lower alkyl,
- ii) lower alkenyl,
- iii) SO.sub.2 CH.sub.3,
- iv) OR.sub.10,
- v) ##STR35## vi) NR.sub.12 R.sub.13, or vii) -(CH.sub.2).sub.n Y.sub.1
- wherein
- n is as defined above;
- R.sub.10 is H, lower alkyl, tosyl, or ##STR36## Y.sub.1 is --CN, --OR.sub.10, SH, SR.sub.7, ##STR37## NR.sub.12 R.sub.13 wherein R.sub.12 and R.sub.13 are as defined herein, wherein
- R.sub.7 and R.sub.10 are as defined above;
- R.sub.11 is lower alkyl, lower alkoxy, or NH.sub.2
- R.sub.14 is -OH, lower alkyl, lower alkoxy, or NH.sub.2
- R.sub.12 and R.sub.13 are each independently H, lower alkyl, lower alkenyl, (CH.sub.2).sub.q OH, (CH.sub.2).sub.q NR.sub.17 R.sub.18, or (CH.sub.2).sub.q SR.sub.7, or R.sub.12 and R.sub.13 taken together form a morpholinyl, piperidinyl, piperazinyl, or an N-methyl piperazinyl ring,
- wherein
- R.sub.7 is as defined above;
- q is an integer of 1-6;
- R.sub.17 and R.sub.18 are independently lower alkyl, in unit dosage form.
48 more elements
A method of treating Gl ulcers in a human in need of such treatment which comprises administering a compound of the formula ##STR38## or a pharmaceutically acceptable acid addition or base salt thereof;
- wherein
- R.sub.1 and R.sub.2 are tertiarybutyl;
- R.sub.19 is H;
- A is
- 1) ##STR39## wherein X is S, O, NH, or CH.sub.2 ;
- and
- Y is S, O, or NH;
- 2) ##STR40## wherein X is as defined above;
- and
- B is
- i) SR.sub.7,
- ii) SOR.sub.7,
- iii) SO.sub.2 R.sub.7,
- iv) NR.sub.15 R.sub.16,
- v) NHCN,
- vi) ##STR41## vii) ##STR42## viii) ##STR43## ix) N(OR.sub.6)R.sub.4, x) N(OH)COR.sub.5,
- xi) NR.sub.4 W,
- xii) S(CH.sub.2).sub.n CO.sub.2 R.sub.6, or
- xiii) NR.sub.7 COR.sub.6
- wherein
- Z' is S, O, NH, or NCN;
- W is CO.sub.2 R.sub.7, ##STR44## n is 1, 2, or 3;
- m is 1, 2, 3, 4, or 5;
- R.sub.15 and R.sub.1 6 are independently H, lower alkyl, aralkyl, or (CH.sub.2).sub.n NR.sub.6 R.sub.7
- wherein n is as defined above;
- R.sub.3 is H, alkyl, or aryl;
- R.sub.4 is H or alkyl;
- R.sub.5 is alkyl, aryl, or CF.sub.3 ;
- R.sub.6 is H or lower alkyl;
- and
- R.sub.7 is lower alkyl;
- 3) ##STR45## wherein Z is CH.sub.2, S, O, or NR.sub.8 wherein R.sub.8 is H, lower alkyl, OH, or OMe;
- or
- 4) ##STR46## wherein p is 0, 1, or 2;
- W.sub.1 is H.sub.2, O, or S;
- R.sub.9 is
- i) lower alkyl,
- ii) lower alkenyl,
- iii) SO.sub.2 CH.sub.3,
- iv) OR.sub.10,
- v) ##STR47## vi) NR.sub.12 R.sub.13, or vii) -(CH.sub.2).sub.n Y.sub.1
- wherein
- n is as defined above;
- R.sub.10 is H, lower alkyl, tosyl, or ##STR48## Y.sub.1 is --CN, --OR.sub.10, SH, SR.sub.7, ##STR49## NR.sub.12 R.sub.13 wherein R.sub.12 and R.sub.13 are as defined herein, wherein
- R.sub.7 and R.sub.10 are as defined above;
- R.sub.11 is lower alkyl, lower alkoxy, or NH.sub.2
- R.sub.14 is --OH, lower alkyl, lower alkoxy, or NH.sub.2
- R.sub.12 and R.sub.13 are each independently H, lower alkyl, lower alkenyl, (CH.sub.2).sub.q OH, (CH.sub.2).sub.q NR.sub.17 R.sub.18, or (CH.sub.2).sub.q SR.sub.7, or R.sub.12 and R.sub.13 taken together form a morpholinyl, piperidinyl, piperazinyl, or an N-methyl piperazinyl ring,
- wherein
- R.sub.7 is as defined above;
- q is an integer of 1-6;
- R.sub.17 and R.sub.18 are independently lower alkyl, in unit dosage form.
49 more elements
Dependencies are inferred from the claim text.