Arginine mimetics as factor X
View Patent ↗The invention relates generally to a novel type of arginine mimetics which are inhibitors of factor X a ; to pharmaceutical compositions which comprise these mimetics; and to the use of these arginine mimetics for producing compositions for antithrombotic therapy.
1. A compound of structural formula I:
wherein:
L 1 is a linker which is a member selected from the group consisting of —CO—, —CO—NH—, and —COO;
R 4 is t-butyl, phenyl, benzyl, fluorenyl, or adamantyl;
L 2 is a linker which is a member selected from the group consisting of a bond, —OR 5 —, —NH—R 5 —, —NH—NH—R 5 , and —CH 2 —R 5 —, wherein R 5 is —(CH 2 ) m — and m is 1 to 3, or L 2 is a linker which is NH—CHR 9 —COO—(CH 2 ) m wherein m is 1 to 5 and R 9 is a derivatized or underivatized side chain of a natural amino acid;
R 7 is a phenyl, piperidinepyrrol, furan, thiophene, pyridine, naphthalene, anthracene or indole radical which is unsubstituted or is substituted by one or more R 8 radicals, wherein R 8 is a basic substituent or a substituent functioning as a hydrogen bond donor or acceptor or a halogen; and
R 3 is an amidino, guanidino, amino, alkylamino, aminoalkyl or amide radical and is at the 3 position of the aromatic ring of the phenylalanine radical.
2. The compound of claim 1 , wherein R 8 is an amidino, guanidino, amino, alkylamino, aminoalkyl, or amide radical.
3. The compound of claim 1 , wherein the phenylalanine radical is (R)-chiral.
4. N-1-Adamantyloxycarbonyl-D-3-amidophenylalanine-(2-phenyl)-1-ethylamide.
5. N-1-Adamantyloxycarbonyl-D-3-amidophenylalanine-propylamide.
6. N-1-Adamantyloxycarbonyl-D-3-amidophenylalanine-propylamide benzylamide.
7. The compound of claim 1 , in the form of a pharmaceutically acceptable salt.
8. The compound of claim 7 , wherein the pharmaceutically acceptable salt is a hydrochloride.
9. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable vehicle.
10. N-1-adamantyloxycarbonyl-D3-amidino-phenylalanine-2-phenyl-1 ethylamide.