8-(3-Biaryl)phenylquinoline phosphodiesterase-4 inhibitors

A compound represented by Formula (I):

• or a pharmaceutically acceptable salt, wherein
• S1, S2, and S3 are independently
• 1. H,
• 2. —OH,
• 3. halogen,
• 4. —C1-C6alkyl,
• 5. —O—C1-C6alkyl optionally substituted with 1, 2 or 3 halogens, or —CN;
• R1 is
• 1. —(C1-C6alkyl)-SOn—(C1-C6alkyl) group, optionally substituted with 1, 2 or 3 substituents;
• wherein each substituent is independently a halogen, —OH and —CN,
• 2. —C(O)—O-aryl,
• 3. —C(O)—NH-aryl,
• 4. —C(O)—NH-heterocycle or N-oxide thereof,
• 5. —C(O)—NH—C1-C6alkyl,
• 6. —C(O)—NH-cycloC3-C6alkyl,
• 7. —C1-C6alkyl, optionally substituted with 1 to 6 halogens and 1 hydroxy,
• 8. —COOH,
• 9. —C1-C6alkyl-COOH,
• 10. —O—C1-C6alkyl,
• 11. —cycloC3-C6alkyl,
• 12. —C3-C6alkyl-heterocycle,
• 13. aryl,
• 14. heterocycle,
• 15. carbonyl,
• 16. carbamoyl, or
• 17. —SOn—(C1-C6alkyl);
• each n is independently 0, 1, or 2;
• Ar1 and Ar2 are each independently an aryl or heterocycle or an N-oxide thereof;
• R2 is
• 1. Hydrogen,
• 2. aryl optionally substituted with 1, 2 or 3 substituents selected from halogen,
• 3. heterocycle optionally substituted with 1, 2 or 3 halogens,
• 4. —C1-C6alkyl optionally substituted with 1, 2 or 3 substituents selected from hydroxy and halogen,
• 5. —COOH,
• 6. 1, 2 or 3 halogens,
• 7. —SOn—(C1-C6alkyl),
• 8. —N(H)—S(O)n—C1-C6alkyl,
• 9. —O—C1-C6alkyl substituents each optionally substituted with 1, 2 or 3 halogens,
• 10. —C(O)—N(H)—C3-C6cycloalkyl, or
• 11. —C(O)—C1-C6alkyl;
• R3 is
• 1. Hydrogen,
• 2. —C1-C6alkyl optionally substituted with hydroxy, —S(O)nC1-C6alkyl, heterocycle, or 1, 2, 3, 4, 5 or 6 halogens,
• 3. aryl or C6-C12cycloalkyl optionally substituted with phenyl, —C1-C6alkyl, —S(O)nC1-C6alkyl, —C(O)—O—C1-C6alkyl, —COOH, hydroxy-C1-C6alkyl- or 1, 2 or 3 halogens,
• 4. heterocycle or optionally substituted with 1, 2 or 3 substituents independently selected from phenyl, halogen, C1-C6alkyl, hydroxyC1-C6alkyl, —COOH, —C(O)—O—C1-C6alkyl,
• 5. amino,
• 6. —C(O)—O—C1-C6alkyl,
• 7. —C1-C6alkyl-O-phenyl optionally substituted with 1, 2 or 3 halogens,
• 8. —C1-C6alkyl-phenyl optionally substituted with 1 or 2 substituents selected from hydroxy and halo,
• 9. —COOH,
• 10. Halogen,
• 11. —SOn—(C1-C6alkyl),
• 12. —N(H)—S(O)n—C1-C6alkyl optionally substituted with 1, 2 or 3 halogen,
• 13. —N(H)—C(O)—C1-C6alkyl,
• 14. —N(H)-heterocycle optionally substituted with 1, 2 or 3 halogens,
• 15. —N(H)-aryl optionally substituted with 1, 2 or 3 halogens,
• 16. —N(H)—C1-C6alkyl optionally substituted with 1, 2 or 3 halogens,
• 17. —C(O)—N(H)—C1-C6alkyl optionally substituted with 1, 2 or 3 halogens,
• 18. —C(O)—NH—C3-C6cycloalkyl,
• 19. —O—C1-C6alkyl optionally substituted with 1, 2 or 3 halogens or phenyl optionally substituted with 1, 2, or 3 halogen;
• R4 is
• 1. H,
• 2. Halogen,
• 3. —CN
• 4. —C1-C6alkyl,
• 5. —O—C1-C6alkyl optionally substituted with 1, 2 or 3 halogens,
• 6. —C1-C6alkyl-phenyl with phenyl optionally substituted with halogen, or
• 7. Oxo.