Allophanic acid derivatives
AssigneeZeneca Limited
InventorsGeorge R. Brown, Richard E. Shute
Life of this patent
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Abstract
The invention concerns allophanic acid derivatives of formula I R.sup.1 --N(R.sup.2)CO--N(R.sup.3)CO--X.sup.1 --Q--X.sup.2 --GI and pharmaceutically acceptable metabolically labile esters or amides thereof, and pharmaceutically acceptable salts thereof, in which R.sup.1, R.sup.2, R.sup.3, X.sup.1, Q X.sup.2 and G have the meanings given in the specification. The invention also concerns processes for the preparation of the allophanic acid derivatives of formula I, pharmaceutical compositions containing them and their use as inhibitors of the binding of fibrinogen to glycoprotein IIb/IIIa.
Claims12
A pharmaceutical composition comprising an allophanic acid derivative of formula I
- R.sup.1 --N(R.sup.2)CO--N(R.sup.3)CO--X.sup.1 --Q--X.sup.2 --GI
- wherein R.sup.1 represents a group of formula II or III ##STR2## in which A is attached meta or para to the position where the group NR.sup.2 CONR.sup.3 CO is attached and is selected from aminomethyl, guanidino and R.sup.a N=C(NH.sub.2)-- where R.sup.a is hydrogen or phenyl which us unsubstituted or substituted by i or 2 of halogeno, (1-4C)alkyl, (1-4c) alkoxy, cyano and nitro,
- E is CH or N,
- Z.sup.1 is hydrogen, halogeno, (1-4C)alkyl, (1-4C)alkoxy, cyano or nitro,
- T is N or CH, and
- X.sup.3 is a bond, (1-4C)alkylene or, when T is CH, oxy(1-3C)alkylene;
- R.sup.2 and R.sup.3, which may be the same or different, represent hydrogen, (1-4C)alkyl or ar(1-4c)alkyl;
- X.sup.1 is a bond or (1-4C) alkylene;
- Q is a group of formula Iv or V ##STR3## in which Z.sup.2 is hydrogen, halogone, (1-4c)alkyl, (1-4C)alkoxy, cyano or nitro, and
- Z.sup.3 is a group of formula X.sup.2 --G.sup.a in which X.sup.2 can have any of the values given hereinafter for X.sup.2 and G.sup.a can have any of the values given hereinafter for G, or G.sup.a has any of the values given hereinbefore for Z.sup.2 ;
- X.sup.2 is a bond, (1-4C)alkylene, oxy(1-3C)alkylene or a group of formula CH.sub.2 CH(NHXR.sup.4) in which X is SO.sub.2, CO or CO.sub.2 and R.sup.4 is (1-6C)alkyl, (6-12c)aryl or (6-12C)aryl(1-4C)alkyl, in any of which the aryl group may optionally be substituted by (1-4C)alkyl;
- and
- G is a carboxy group or a pharmaceutically acceptable metabolically labile ester or amide thereof;
- and pharmaceutically acceptable salts thereof, together with a pharmaceutically acceptable diluent or carrier.
A method of inhibiting platelet aggregation is a warm-blooded mammal requiring such treatment, which comprises administering a platelet aggregation inhibiting effective amount of an allophanic acid derivative of formula I
- R.sup.1 --N(R.sup.2)CO--N(R.sup.3)CO--X.sup.1 --Q--X.sup.2 --GI
- wherein R.sup.1 represents a group of formula II or III ##STR4## in which A is attached meta or para to the position where the group NR.sup.2 CONR.sup.3 CO is attached and is selected from aminomethyl, guanidino and R.sup.a N.dbd.C(NH.sub.2)-- where R.sup.a is hydrogen or phenyl which us unsubstituted or substituted by 1 or 2 of halogeno, (1-4C)alkyl, (1-4c)alkoxy, cyano and nitro,
- E is CH or N,
- Z.sup.1 is hydrogen, halogeno, (1-4C)alkyl, (1-4C)alkoxy, cyano or nitro,
- T is N or CH, and
- X.sup.3 is a bond, (1-4C)alkylene or, when T is CH, oxy(1-3C)alkylene;
- R.sup.2 and R.sup.3, which may be the same or different, represent hydrogen, (1-4C)alkyl or ar(1-4C)alkyl;
- X.sup.1 is a bond or (1-4c)alkylene;
- Q is a group of formula IV or V ##STR5## in which Z.sup.2 is hydrogen, halogeno, (1-4C)alkyl, (1-4C)alkoxy, cyano or nitro, and
- Z.sup.3 is a group of formula X.sup.2 --G.sup.a in which X.sup.2 can have any of the values given hereinafter for X.sup.2 and G.sup.a can have any of the values given hereinafter for G, or G.sup.a has any of the values given hereinbefore for Z.sup.2 ;
- X.sup.2 is a bond, (1-4c)alkylene, oxy(1-3C)alkylene or a group of formula CH.sub.2 CH(NHXR.sup.2) in which X is SO.sub.2, Co or CO.sub.2 and R.sup.4 is (1-6c)alkyl, (6-12C)aryl or (6-12C)aryl(1-4C)alkyl, in any of which the aryl group may optionally be substituted by (1-4C)alkyl;
- and
- G is a carboxy group or a pharmaceutically acceptable metabolically labile ester or amide thereof;
- and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.