(3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists

A compound represented by Formula A:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1, R2, R3 and R4 are each independently selected from the group consisting of:
• —H, —F, —Cl, —Br, —I, —CN, —OH, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C1-5alkoxy,
• wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C1-5alkoxy are each optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH, C1-8alkoxy and —CO2H,
• and any two of R1, R2, R3 and R4 may be joined together with the atoms to which they are attached to form a saturated monocyclic ring of 3 to 8 atoms optionally containing 1 or 2 oxygen atoms;
• R5 is selected from the group consisting of:
• —H, —F, —Cl, —Br, —I, —CN, —OH, C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy,
• wherein said C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy are each optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH and C1-8alkoxy;
• R6 is selected from the group consisting of:
• phenyl and pyridinyl, each optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —CN, —OH, —NR7R8, —NO2, phenyl, thienyl, C1-4alkyl, C3-6cycloalkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C3-6cycloalkoxy, C1-4alkylthio and C2-4acyloxy,
• wherein said phenyl, C1-4alkyl, C3-6cycloalkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C3-6cycloalkoxy, C1-4alkylthio and C1-4acyloxy are each optionally substituted from one up to the maximum number of substitutable positions with a substituent independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH and C1-8alkoxy,
• R7 and R8 are independently selected from the group consisting of:
• —H, C1-6alkyl, C2-6alkenyl and C2-6alkynyl, wherein said C1-6alkyl, C2-6alkenyl and C2-6alkynyl are each optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH and C1-5alkoxy, and
• R7 and R8 may be joined together with the nitrogen atom to which they are attached to form a saturated monocyclic ring of 3 to 8 atoms, optionally containing 1 or 2 oxygen atoms, said ring is optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH and C1-5alkoxy;
• U, V and W are each;
• —C(R9)—;
• each R9 is independently selected from the group consisting of:
• —H, —F, —Cl, —Br, —I, —CN, —OH, C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy,
• wherein said C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy are each optionally substituted with one to three substituents independently selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH and C1-8alkoxy;
• For U or V, R9 and R1 or R9 and R2 may be joined together with the atoms to which they are attached to form a 5 membered ring, thus forming a fused partially aromatic bicyclic ring system of 9 atoms with the 6-membered aromatic ring to which R9 is attached;
• the ring
• J is selected from the group consisting of:
• —CO2H,
• each R14 is independently selected from the group consisting of:
• —H and —CH3.