Enamine derivatives

A compound according to formula (1):

• wherein
• R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted pyridyl, pyrimidinyl, naphthyridinyl, quinolinyl or isoquinolinyl group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)—,
• in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof;
• R2 is a hydrogen atom or a C1-6alkyl group;
• the ring Cy is an unsaturated cycloaliphatic or heterocycloaliphatic ring containing X, in which X is a N atom or a C(RW) group;
• RW is a group RZ;
• RX which may be present or any available carbon atom of the ring Cy is a oxo (═O), thioxo (═S) or imino (═NR30) group in which R30 is an aliphatic, heteroaliphatic, cycloaliphatic, heterocycloaliphatic, aromatic or hetero-aromatic group;
• m is zero or the integer 1, 2 or 3;
• RZ which may be present on any available carbon or nitrogen atom of the ring Cy is selected from a halogen atom or -(Alk4)vL1(Alk1)nR3 in which Alk4 is a straight or branched C1-3 alkylene chain, v is zero or the integer 1, L1 is a covalent bond or a linker atom or group, n is zero or the integer 1, Alk1 is an optionally substituted aliphatic chain and R3 is a hydrogen atom or a —CN, —NO2 or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or hetero-aromatic group;
• p is zero or the integer 1, 2, 3 or 4;
• provided that Cy is not a cyclobutenedione group;
• and the salts, solvates, hydrates and N-oxides thereof.

A compound according to formula (1):

• wherein
• R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)—,
• in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof;
• R2 is a hydrogen atom or a C1-6alkyl group;
• the ring Cy is an unsaturated heterocycloaliphatic ring containing X, in which X is a N atom;
• RX which may be present or any available carbon atom of the ring Cy is a oxo (═O), thioxo (═S) or imino (═NR30) group in which R30 is an aliphatic, heteroaliphatic, cycloaliphatic, heterocycloaliphatic, aromatic or hetero-aromatic group;
• m is zero or the integer 1, 2 or 3;
• RZ which may be present on any available carbon or nitrogen atom of the ring Cy is selected from a halogen atom or -(Alk4)vL1(Alk1)nR3 in which Alk4 is a straight or branched C1-3 alkylene chain, v is zero or the integer 1, L1 is a covalent bond or a linker atom or group, n is zero or the integer 1, Alk1 is an optionally substituted aliphatic chain and R3 is a hydrogen atom or a —CN, —NO2 or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or hetero-aromatic group;
• p is zero or the integer 1, 2, 3 or 4;
• provided that Cy is not a cyclobutenedione group;
• and the salts, solvates, hydrates and N-oxides thereof.

A compound selected from the group consisting of:

• (S)-3-[4-[(2,6-Naphthyridinyl)amino]phenyl[-2-[(2-(1-ethylpropyl)-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[4-[(3-Methyl-2,7-naphthyridinyl)oxy]phenyl]-2-[(2-propyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[(4-[3-Methyl-2,7-naphthyridinyl]oxy)phenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[(4-(2,7-Naphthyridin-1-yl)oxy)phenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[4-[(3,5-Dichloropyrid-4-yl)carboxamido)phenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[4-[(3-Methyl-2,7-naphthyridin-1-yl)amino]phenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (S)-3-[4-(-2′,6′-Dimethoxy)biphenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (2S)-3-[4-(2,6-Naphthyridin-1-yl)amino)phenyl]-2-[(2-isobutyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (2S)-3-[4-(2,6-Naphthyridin-1-yl)amino)phenyl]-2-[(2-isopropyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (2S)-3-[4-(2,6-Naphthyridin-1-yl)amino)phenyl]-2-[(2-allyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• (2S)-3-[4-(2,6-Naphthyridin-1-yl)amino)phenyl]-2-[(2-propyl-3-oxo-1-cyclopentenyl)amino]propionic acid;
• and the salts, solvates, hydrates and N-oxides and carboxylic acid esters thereof.

A method for the prophylaxis or treatment of a disease or disorder in a mammal in which the extravasation of leukocytes plays a role, comprising administering to a mammal suffering from such a disease or disorder a therapeutically effective amount of a compound according to formula (1):

• wherein
• R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)—,
• in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof;
• R2 is a hydrogen atom or a C1-6alkyl group;
• the ring Cy is an unsaturated cycloaliphatic or heterocycloaliphatic ring containing X, in which X is a N atom or a C(RW) group;
• RW is a group RZ;
• RX which may be present or any available carbon atom of the ring Cy is a oxo (═O), thioxo (═S) or imino (═NR30) group in which R30 is an aliphatic, heteroaliphatic, cycloaliphatic, heterocycloaliphatic, aromatic or hetero-aromatic group;
• m is zero or the integer 1, 2 or 3;
• RZ which may be present on any available carbon or nitrogen atom of the ring Cy is selected from a halogen atom or -(Alk4)vL1(Alk1)nR3 in which Alk4 is a straight or branched C1-3 alkylene chain, v is zero or the integer 1, L1 is a covalent bond or a linker atom or group, n is zero or the integer 1, Alk1 is an optionally substituted aliphatic chain and R3 is a hydrogen atom or a —CN, —NO2 or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or hetero-aromatic group;
• p is zero or the integer 1, 2, 3 or 4;
• provided that Cy is not a cyclobutenedione group;
• and the salts, solvates, hydrates and N-oxides thereof.