Guanidine derivatives
AssigneeHoffmann-La Roche Inc.
InventorsJean Ackermann, David Banner, Klaus Gubernator, Paul Hadvary, Kurt Hilpert, Klaus Muller, Ludvik Labler, Gerard Schmid, Thomas B. Tschopp, Hans P. Wessel, Beat Wirz
Life of this patent
Estimating the term…
Abstract
Compounds of the formula ##STR1## wherein L, M, R, T and X are set forth in the description, as well as hydrates or solvates thereof, which inhibit thrombin-induced platelet aggregation and clotting of fibrinogen in plasma, are described. The compounds of formula I are prepared by amidination or, depending on whether L is NH or O, by amide formation or esterification.
Claims50
A compound of the formula ##STR11## wherein R is aryl, heteroraryl or heterocyclyl,
- T is CH.sub.2 ;
- L is NH or O;
- and --N(X)--M-- is a --N(SO.sub.2 --R.sup.o)--CH.sub.2 -- group, wherein
- R.sup.o has the same significance as R, or, individually,
- X is H, --CH.sub.2 COOH, --CH.sub.2 COO--C.sub.1-4 -alkyl, --CH.sub.2 CO-- (tetra- to heptamethyleneimino) or optionally N- mono- or N-di-C.sub.1-4 -alkylated --CH.sub.2 CONH.sub.2 ;
- M is a R'--(CH.sub.2).sub.1-2 CH.dbd., R'--COCH.sub.2 CH.dbd., R"--COCH.sub.2 CH.dbd., R'--(CO).sub.1-2 NHCH.sub.2 CH.dbd. or benzyl-OCONHCH.sub.2 CH.dbd. group,
- R' is aryl, heteroaryl, cycloalkyl or heterocyclyl, and
- R" is tetra- to heptamethyleneimino optionally carrying up to 2 substituents from the group oxo, --COO--C.sub.1-4 -alkyl, --(CH.sub.2).sub.0-1 OH, --(CH.sub.2).sub.0-1 OCO--C.sub.1-4 -alkyl and optionally mono- or di-C.sub.1-4 -alkylated carbamoyl,
- a hydrate or solvate, or physiologically usable salt thereof.
A pharmaceutical composition comprising an effective amount of a compound of the formula ##STR15## wherein R is aryl, heteroraryl or heterocyclyl,
- T is CH.sub.2 ;
- L is NH or O;
- and --N(X)--M-- is a --N(SO.sub.2 -R.sup.o)--CH.sub.2 -- group, wherein
- R.sup.o has the same significance as R, or individually,
- X is H, --CH.sub.2 COOH, --CH.sub.2 COO--C.sub.1-4 -alkyl, --CH.sub.2 CO-(tetra- to heptamethyleneimino) or optionally N- mono- or N-di-C.sub.1-4 -alkylated --CH.sub.2 CONH2;
- M is a R'--(CH.sub.2).sub.1-2 CH.dbd., R'--COCH.sub.2 CH.dbd., R"--COCH.sub.2 CH.dbd., R'--(CO).sub.1-2 NHCH.sub.2 CH.dbd. or benzyl-OCONHCH.sub.2 CH.dbd. group,
- R' is aryl, heteroaryl, cycloalkyl or heterocyclyl, and
- R" is tetra- to heptamethyleneimino optionally carrying up to 2 substituents from the group oxo, --COO--C.sub.1-4 -alkyl, --(CH.sub.2).sub.0-1 OH, --(CH.sub.2).sub.0-1 OCO--C.sub.1-4 -alkyl and optionally mono- or di-C.sub.1-4 -alkylated carbamoyl, a hydrate or solvate, or physiologically usable salt thereof.
A method of inhibiting thrombin induced platelet aggregation and clotting of fibrinogen in plasma which comprises administering to a host requiring such treatment an effective amount of a compound of the formula ##STR20## wherein R is aryl, heteroraryl or heterocyclyl,
- T is CH.sub.2 ;
- L is NH or O;
- and --N(X)--M-- is a --N(SO.sub.2 --R.sup.o)--CH.sub.2 -- group,
- wherein
- R.sup.o has the same significance as R, or, individually,
- X is H, --CH.sub.2 COOH, --CH.sub.2 COO--C.sub.1-4 -alkyl, --CH.sub.2 CO--(tetra- to heptamethyleneimino) or optionally N-mono- or N-di-C.sub.1-4 -alkylated --CH.sub.2 CONH.sub.2 ;
- M is a R'--(CH.sub.2).sub.1-2 CH.dbd., R'--COCH.sub.2 CH.dbd., R"--COCH.sub.2 CH.dbd., R'--(CO).sub.1-2 NHCH.sub.2 CH.dbd. or benzyl-OCONHCH.sub.2 CH.dbd. group,
- R' is aryl, heteroaryl, cycloalkyl or heterocyclyl,
- R" is tetra- to heptamethyleneimino optionally carrying up to 2 substituents from the group oxo, --COO--C.sub.1-4 -alkyl, --(CH.sub.2).sub.0-1 OH --(CH.sub.2).sub.0-1 OCO--C.sub.1-4 -alkyl and optionally mono- or di-C.sub.1-4 -alkylated carbamoyl,
- or a hydrate or solvate, or physiologically usable salt thereof.
Dependencies are inferred from the claim text.