Phosphonic acid derivates and their use as P2Y

1. A compound of formula I

wherein

R 1 represents phenyl, wherein the phenyl is unsubstituted or substituted 1 to 3 times by substituents each independently selected from the group consisting of halogen, methyl, methoxy, trifluoromethyl and trifluoromethoxy;

W represents a bond, and R 2 represents alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl or heteroaryl; or

W represents —O— and R 2 represents alkyl, cycloalkyl, hydroxyalkyl or heterocyclyl; or

W represents —NR 3 —, R 2 represents alkyl, alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl, alkoxyalkyl, heterocyclyl, cycloalkyl, aryl or aralkyl and R 3 represents hydrogen or alkyl; or

W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a heterocyclic ring of 4 to 7 members wherein the members needed to complete said heterocyclic ring are each independently selected from —CH 2 —, —CHR x —, —O—, —S—, —CO— and —NR y —, it being understood however that said heterocyclic ring does not contain more than one member selected from the group consisting of —CHR x —, —O—, —S—, —CO— and —NR y —, R x representing hydroxy, hydroxymethyl, alkoxymethyl or alkoxy and R y representing hydrogen or alkyl;

or W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, an imidazolyl, pyrazolyl, 1,2,3-triazolyl or 1,2,4-triazolyl ring, which ring may be substituted by an alkyl group;

R a represents hydrogen or methyl;

R b represents hydrogen or methyl;

R 4 represents alkoxy;

n represents 0, 1, 2 or 3, V represents a bond, and m represents 0; or

n represents 0 or 1, V represents phenyl, and m represents 0; or

n represents 1, V represents phenyl, and m represents 1;

R 5 and R 8 are identical and represent each hydroxy, unsubstituted phenyloxy, unsubstituted benzyloxy, a group —O—(CHR 6 )—O—C(═O)—R 7 , a group —O—(CHR 6 )—O—C(═O)—O—R 7 , a group —O—(CHR 6 )—C(═O)—O—R 9 , a group —NH-(CHR 10 )—C(═O)—O—R 9 or a group —NH—C(CH 3 ) 2 —C(═O)—O—R 9 ; or

P(O)R 5 R 8 represents a group selected from the following structures

wherein the arrow marks the point of attachment to the remaining part of compounds of formula I;

R 6 represents hydrogen or (C 1 -C 3 )alkyl;

R 7 represents (C 1 -C 4 )alkyl or unsubstituted (C 3 -C 6 )cycloalkyl;

R 9 represents (C 1 -C 4 )alkyl;

R 10 represents hydrogen, (C 1 -C 4 )alkyl, unsubstituted phenyl or unsubstituted benzyl;

or a pharmaceutically acceptable salt thereof.

2. A compound of formula I according to claim 1 , wherein V represents a bond or a pharmaceutically acceptable salt thereof.

3. A compound of formula I according to claim 1 , wherein V represents phenyl;

or a pharmaceutically acceptable salt thereof.

4. A compound of formula I according to claim 1 , wherein, when V represents a bond, then m represents 0 and n represents 1, 2 or 3;

or a pharmaceutically acceptable salt thereof.

5. A compound of formula I according to claim 1 , wherein R 1 represents unsubstituted phenyl;

or a pharmaceutically acceptable salt thereof.

6. A compound of formula I according to claim 1 , wherein W represents a bond;

or a pharmaceutically acceptable salt thereof.

7. A compound of formula I according to claim 1 , wherein W represents —O—;

or a pharmaceutically acceptable salt thereof.

8. A compound of formula I according to claim 1 , wherein W represents —NR 3 —, R 2 represents alkyl, alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl, alkoxyalkyl, heterocyclyl, cycloalkyl, phenyl or phenylalkyl and R 3 represents hydrogen or alkyl; or wherein W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a heterocyclic ring of 4 to 7 members wherein the members needed to complete said heterocyclic ring are each independently selected from —CH 2 —, —CHR x —, —O— and —NR y —, it being understood however that said heterocyclic ring does not contain more than one member selected from the group consisting of —CHR x —, —O— and —NR y —, R x representing hydroxy, hydroxymethyl, alkoxymethyl or alkoxy and R y representing alkyl or wherein W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a pyrazolyl ring which may be unsubstituted or monosubstituted by an alkyl group;

or a pharmaceutically acceptable salt thereof.

9. A compound of formula I according to claim 1 , wherein R 4 represents (C 2 -C 4 )alkoxy;

or a pharmaceutically acceptable salt thereof.

10. A compound of formula I according to claim 1 , wherein R 5 and R 8 are identical and represent hydroxy;

or a pharmaceutically acceptable salt thereof.

11. A compound of formula I according to claim 1 , which is selected from the group consisting of:

4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid ethyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4- {(S)-2-[(2-phenyl-6-pyrazol-1-yl-pyrimidine-4-carbonyl)-amino]-4-phosphono-butyryl}-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-(4-methyl-pyrazol-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl) -piperazine-1-carboxylic acid butyl ester;

4-[(S)-2-({2-phenyl-6-[(S)-(tetrahydro-furan-3-yl)oxy]-pyrimidine-4-carbonyl}-amino)-4-phosphono-butyryl]-piperazine-1-carboxylic acid butyl ester;

4-{(S)-2-[(2-phenyl-6-pyrrolidin-1-yl-pyrimidine-4-carbonyl)-amino]-4-phosphono-butyryl}-piperazine-1-carboxylic acid butyl ester;

4-{(S)-2-[(6-isopropylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-4-phosphono-butyryl}-piperazine-1-carboxylic acid butyl ester;

4-{(S)-2-[(6-morpholin-4-yl-2-phenyl-pyrimidine-4-carbonyl)-amino]-4-phosphono-butyryl}-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-(4-methyl-piperazin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl) -piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-methylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-dimethylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-ethylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-isopropylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[2-(4-fluoro-phenyl)-6-(S)-3-methoxy-pyrrolidin-1-yl)-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-p-tolyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[2-(2-fluoro-phenyl)-6-(S)-3-methoxy-pyrrolidin-1-yl)-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[2-(3-fluoro-phenyl)-6-(S)-3-methoxy-pyrrolidin-1-yl)-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-methoxy-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-methyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-cyclopropylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(2-phenyl-6-phenylamino-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-benzylamino-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-[(R)-2-({2-phenyl-6-[(R)-(tetrahydro-furan-3-yl)amino]-pyrimidine-4-carbonyl}-amino)-3-phosphono-propionyl]-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(3-hydroxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-[(R)-2-({6-[(2-methoxy-ethyl)-methyl-amino]-2-phenyl-pyrimidine-4-carbonyl}-amino)-3-phosphono-propionyl]-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(2-ethoxycarbonyl-ethylamino)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(2-carboxy-ethylamino)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(2,6-diphenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-pip erazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(2-phenyl-6-thiophen-3-yl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(4-methoxy-phenyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-cyclopropyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-butyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-[(R)-2-({2-phenyl-6-[(S)-(tetrahydro-furan-3-yl)oxy]-pyrimidine-4-carbonyl}-amino)-3-phosphono-propionyl]l-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-2-methyl-piperazine-1-carboxylic acid ethyl ester;

4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid ethyl ester;

4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-((1S,2S)-2-methoxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-((1S,2S)-2-hydroxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(2-hydroxy-ethylamino)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(2-hydroxymethyl-piperidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(3-methoxy-propyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(3-hydroxy-butyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-(3-trifluoromethyl-phenyl)-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-4-[bis-(2,2-dimethyl-propionyloxymethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;

4-((S)-4-(bis-isobutyryloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;

4((S)-4-{bis-[(2,2-dimethyl-propionyloxy)-ethoxy]-phosphoryl}-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-[bis-(2,2-dimethyl-propionyloxymethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-{bis-[1-(2,2-dimethyl-propionyloxy)-ethoxy]-phosphoryl}-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[bis-(1-isobutyryloxy-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[bis-(1-propionyloxy-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(bis-isobutyryloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester; and 4-(2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-phosphono-acetyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

12. A compound of formula I according to claim 1 , which is selected from the group consisting of:

4-((R)-2-{[6-(2-Hydroxy-ethoxy)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-5-phosphono-pentanoyl)-piperazine-1-carboxylic acid butyl ester;

4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphono-phenyl)-propionyl]-piperazine-1-carboxylic acid ethyl ester;

4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphono-phenyl)-propionyl]-piperazine-1-carboxylic acid butyl ester;

4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphonomethyl-phenyl)-propionyl]-piperazine-1-carboxylic acid ethyl ester;

4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphonomethyl-phenyl)-propionyl]-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-5-phosphono-pentanoyl)-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-Isopropyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(3-Methoxymethyl-azetidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl) -piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-Cyclopentyloxy-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid ethyl ester;

4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphono-phenyl) -propionyl]-piperazine-1-carboxylic acid ethyl ester;

4-[2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-(4-phosphono-phenyl) -acetyl]-piperazine-1-carboxylic acid ethyl ester;

4-[2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-(4-phosphono-phenyl)-acetyl]-piperazine-1-carboxylic acid butyl ester;

4-[2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-(3-phosphono-phenyl)-acetyl]-piperazine-1-carboxylic acid ethyl ester;

4-[2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-(3-phosphono-phenyl)-acetyl]-piperazine-1-carboxylic acid butyl ester;

4-[2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-2-(2-phosphono-phenyl)-acetyl]-piperazine-1-carboxylic acid butyl ester;

4-((R)-2-{[6-(4-Methyl-piperazin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-{(R)-2-[(6-Morpholin-4-yl-2-phenyl-pyrimidine-4-carbonyl)-amino]-3-phosphono-propionyl}-piperazine-1-carboxylic acid butyl ester;

N,N′-Bis-(ethoxycarbonylmethyl)-3-{(S)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-oxo-4-(4-butoxy-carbonyl-piperazin-1-yl)-butyl-phosphonic acid diamide;

4(R)-3-(Bis-acetoxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Bis-propionyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Bis-butyryloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

N,N′-Bis-(ethoxycarbonylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-ethoxycarbonylethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-(methoxycarbonylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-methoxycarbonyl-2-methyl-propyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-(tert-butyloxycarbonylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-methoxycarbonylpropyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-methoxycarbonyl-2,2-dimethyl-propyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-y1)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-tert-butyloxycarbonylethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-methoxycarbonyl-2-phenyl-ethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl -pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-methoxycarbonylphenylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-((S)-1-methoxycarbonylethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-(propyloxycarbonylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-(isopropyloxycarbonylmethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

N,N′-Bis-(2-ethoxycarbonyl-prop-2-yl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-butoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

4-((R)-3-(Bis-methoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-(Bis-ethoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Bis-isopropoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Bis-tert-butoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[Bis-(1-ethyloxycarbonyloxy-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[Bis-(1-isopropyloxycarbonyloxy-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[Bis-(1-cyclohexyloxycarbonyloxy-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Diphenoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-[Bis-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[Bis-(3-oxo-1,3-dihydro-isobenzofuran-1-yloxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-(Bis-ethoxycarbonylmethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4-((R)-3-[Bis-((S)-1-ethoxycarbonyl-ethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4(R)-3-(Bis-benzyloxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

4((S)-3-(Bis-acetoxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4((S)-3-(Bis-butyryloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

N,N′-Bis-((S)-1-ethoxycarbonylethyl)-2-{(S)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-ethoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

4((S)-3-(Bis-ethoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4(R)-3-(Bis-acetoxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4(R)-3-(Bis-butyryloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

N,N′-Bis-((S)-1-ethoxycarbonylethyl)-2-{(R)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-ethoxy-carbonyl-piperazin-1-yl)-propyl-phosphonic acid diamide;

4-((R)-3-(Bis-ethoxycarbonyloxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

4((S)-3-[4-(Bis-butyryloxymethoxy-phosphoryl)-phenyl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

N,N′-Bis-((S)-1-ethoxycarbonylethyl)-4-[2-{(S)-[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-oxo-3-(4-ethoxy-carbonyl-piperazin-1-yl)-propyl]-phenyl-phosphonic acid diamide; and

4((S)-3-[4-(Bis-ethoxycarbonyloxymethoxy-phosphoryl)-phenyl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

or a pharmaceutically acceptable salt thereof.

13. A medicament comprising the compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising the compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

15. A method for treating occlusive vascular disorders comprising administering the compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

16. A compound of formula I according to claim 2 , wherein n represents 1;

or a pharmaceutically acceptable salt thereof.

17. A compound of formula I according to claim 2 , wherein n represents 2;

or a pharmaceutically acceptable salt thereof.

18. A compound of formula I according to claim 16 , wherein R 1 represents unsubstituted phenyl;

or a pharmaceutically acceptable salt thereof.

19. A compound of formula I according to claim 17 , wherein R 1 represents unsubstituted phenyl;

or a pharmaceutically acceptable salt thereof.

20. A compound of formula I according to claim 18 , wherein W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a heterocyclic ring of 4 to 6 members wherein the members needed to complete said heterocyclic ring are each independently selected from —CH 2 —, —CHR x —, —O— and —NR y —, it being understood however that said heterocyclic ring does not contain more than one member selected from the group consisting of —CHR x —, —O— and —NR y —, R x representing hydroxy, hydroxymethyl, methoxymethyl or methoxy and Ry representing methyl;

or a pharmaceutically acceptable salt thereof.

21. A compound of formula I according to claim 19 , wherein W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a heterocyclic ring of 4 to 6 members wherein the members needed to complete said heterocyclic ring are each independently selected from —CH 2 —, —CHR x , —O— and —NR y —, it being understood however that said heterocyclic ring does not contain more than one member selected from the group consisting of —CHR x —, —O— and —NR y —, R x representing hydroxy, hydroxymethyl, methoxymethyl or methoxy and Ry representing methyl;

or a pharmaceutically acceptable salt thereof.

22. A compound of formula I according to claim 20 , wherein R 4 represents (C 2 -C 4 )alkoxy;

or a pharmaceutically acceptable salt thereof.

23. A compound of formula I according to claim 21 , wherein R 4 represents (C 2 -C 4 )alkoxy;

or a pharmaceutically acceptable salt thereof.

24. A compound of formula I according to claim 22 , wherein R 5 and R 8 are identical and represent hydroxy;

or a pharmaceutically acceptable salt thereof.

25. A compound of formula I according to claim 23 , wherein R 5 and R 8 are identical and represent hydroxy;

or a pharmaceutically acceptable salt thereof.

26. A compound of formula I according to claim 22 , wherein R 5 and R 8 are identical and represent each unsubstituted phenyloxy, unsubstituted benzyloxy, a group —O—(CHR 6 )—O—C(═O)—R 7 , a group —O—(CHR 6 )—O—C(═O)—O—R 7 , a group —O—(CHR 6 )—C(═O)—O—R 9 , a group)—NH—(CHR 10 )—C(═O)—O—R 9 or a group —NH—C(CH 3 ) 2 —C(═O)—O—R 9 ;

or a pharmaceutically acceptable salt thereof.

27. A compound of formula I according to claim 23 , wherein R 5 and R 8 are identical and represent each unsubstituted phenyloxy, unsubstituted benzyloxy, a group —O—(CHR 6 )—O—C(═O)—R 7 , a group —O—(CHR 6 )—O—C(═O)—O—R 7 , a group —O—(CHR 6 )—C(═O)—O—R 9 , a group —NH—(CHR 10 )—C(═O)—O—R 9 or a group —NH—C(CH 3 ) 2 —C(═O)—O—R 9 ;

or a pharmaceutically acceptable salt thereof.

28. A compound of formula I according to claim 1 , wherein

R 1 represents phenyl;

W represents —NR 3 — and R 2 and R 3 form, together with the nitrogen that carries them, a heterocyclic ring of 5 members wherein the members needed to complete said heterocyclic ring are each independently selected from —CH 2 — and —CHR x —, it being understood however that said heterocyclic ring does not contain more than one —CHR x — group, R x representing alkoxy;

R a represents hydrogen;

R b represents hydrogen;

R 4 represents alkoxy;

n represents 1 or 2, V represents a bond, and m represents 0;

R 5 and R 8 are identical and represent each a group —O—(CHR 6 )—O—C(═O)—R 7 , a group —O—(CHR 6 )—O—C(═O) 13 O—R 7 or a group) —NH—(CHR 10 )—C(═O) 13 O—R 9 ; or

P(O)R 5 R 8 represents

wherein the arrow marks the point of attachment to the remaining part of compounds of formula I;

R 6 represents hydrogen;

R 7 represents (C 1 -C 4 )alkyl;

R 9 represents (C 1 -C 4 )alkyl;

R 10 represents hydrogen, (C 1 -C 4 )alkyl or unsubstituted phenyl;

or a pharmaceutically acceptable salt thereof.

29. The compound according to claim 1 , wherein the compound is 4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

30. The compound according to claim 1 , wherein the compound is 4((S)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-4-phosphono-butyryl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

31. The compound according to claim 1 , wherein the compound is 4-((R)-2-{[6-(2-hydroxymethyl-piperidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

32. The compound according to claim 1 , wherein the compound is 4((S)-4-[bis-(isobutyryloxymethoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

33. The compound according to claim 1 , wherein the compound is 4-[(S)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-(4-phosphono-phenyl)-propionyl]-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

34. The compound according to claim 1 , wherein the compound is 4-((R)-2-{[6-(3-Methoxymethyl-azetidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

35. The compound according to claim 1 , wherein the compound is 4-((R)-2-{[6-(4-Methyl-piperazin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

36. The compound according to claim 1 , wherein the compound is 4-{(S)-2-[(6-Morpholin-4-yl-2-phenyl-pyrimidine-4-carbonyl)-amino]-4-phosphono-butyryl}-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

37. The compound according to claim 1 , wherein the compound is 4(R)-3-(Bis-acetoxymethoxy-phosphoryl)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

38. The compound according to claim 1 , wherein the compound is 4(R)-3-[Bis-(isopropoxycarbonyloxy-methoxy)-phosphoryl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid butyl ester;

or a pharmaceutically acceptable salt thereof.

39. The compound according to claim 1 , wherein the compound is 4((S)-3-[4-(Bis-(ethoxycarbonyloxy-methoxy)-phosphoryl)-phenyl]-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester;

or a pharmaceutically acceptable salt thereof.