Claims
- 1. A compound of Formula I
- 2. A compound of claim 1 wherein Rb is hydrogen.
- 3. A compound of claim 1 wherein Rb is hydrogen and R1 is hydrogen.
- 4. A compound of claim 1 wherein
Rb is hydrogen; R1 is hydrogen; R2 is 48 or —C(RaRa)n—X; and each X is independently aryl or heteroaryl.
- 5. A compound of claim 4 wherein aryl is phenyl and heteroaryl is pyridyl.
- 6. A compound of claim 4 wherein
R2 is —C(RaRa)n—X, each Ra is independently methyl, ethyl or hydrogen; and X is phenyl or pyridyl.
- 7. A compound of claim 1 wherein
Rb is hydrogen; R1 is hydrogen; R2 is 49 and each X is independently phenyl or pyridyl.
- 8. A compound of Formula I
- 9. A compound of claim 8 wherein when Q is substituted phenyl or substituted pyridyl, the substituents are selected from —OC1-C8alkyl, C1-C8alkyl or halogen.
- 10. The compound:
- 11. The compound:
- 12. The compound:
- 13. The compound:
- 14. The compound:
- 15. The compound:
- 16. A method of treating or preventing atherosclerosis, the method comprising the step of administering to a patient having or at risk of having atherosclerosis a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 17. A method of treating or preventing obesity, the method comprising the step of administering to an obese patient or a patient at risk of becoming obese a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 18. A method of treating or preventing hypercholesterolemia, the method comprising the step of administering to a patient having or at risk of having hypercholesterolemia a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 19. A method of treating or preventing hyperlipidemia, the method comprising the step of administering to a patient having or at risk of having hyperlipidemia a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 20. A method of treating or preventing hypertriglyceridemia, the method comprising the step of administering to a patient having or at risk of having hypertriglyceridemia a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 21. A method of treating or preventing hypoalphalipoproteinemia, the method comprising the step of administering to a patient having or at risk of having hypoalphalipoproteinemia a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 22. A method of treating or preventing pancreatitis, the method comprising the step of administering to a patient having or at risk of having pancreatitis a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 23. A method of treating or preventing diabetes, the method comprising the step of administering to a patient having or at risk of having diabetes a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 24. The method of claim 23 wherein the diabetes is non-insulin dependent diabetes mellitus (Type II).
- 25. A method of treating or preventing myocardial infarction, the method comprising the step of administering to a patient having or at risk of having myocardial infarction a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 26. A method of treating or preventing a stoke, the method comprising the step of administering to a patient having or at risk of having a stroke a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 27. A method of treating or preventing restenosis, the method comprising the step of administering to a patient having or at risk of having restenosis a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 28. A method of treating or preventing Syndrome X, the method comprising the step of administering to a patient having or at risk of having Syndrome X a therapeutically effective amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 29. A method of inhibiting apolipoprotein B secretion, the method comprising administering to a patient in need of apolipoprotein B secretion inhibition an apolipoprotein B secretion inhibiting amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 30. A method of inhibiting microsomal triglyceride transfer protein, the method comprising administering to a patient in need of microsomal triglyceride transfer protein inhibition a microsomal triglyceride transfer protein inhibiting amount of a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 31. A pharmaceutical composition comprising a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 32. The compound:
7-amino-quinoline-3-carboxylic acid ethyl ester; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid.
- 33. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (dipyridin-2-yl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (dipyridin-2-yl-methyl)-amide, ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (dipyridin-2-yl-methyl)-amide, bis-ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide, ethanesulfonate; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide, ethanesulfonate; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide, bis-ethanesulfonate; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide, ethanesulfonate; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide, bis-ethanesulfonate, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 34. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-carbamoyl-2-phenyl-ethyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (carbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid propylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (2,2,2-trifluoro-ethyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-methyl-1-phenyl-ethyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid cyclopentylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-phenyl-propyl)-amide; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-phenyl-ethyl)-amide, ethanesulfonate; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-phenyl-ethyl)-amide, ethanesulfonate, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 35. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide, ethanesulfonate; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide, ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (pyridin -2-ylmethyl)-amide, ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (2-pyridin-2-yl-ethyl)-amide, ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethylamide, ethanesulfonate; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid butylamide, ethanesulfonate, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 36. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (thiophen-2-ylmethyl)-amide, ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-methyl-1-pyridin-2-yl-ethyl)-amide; (S)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; (R)-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide ethanesulfonate; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 4-methoxy-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 4-chloro-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 4-methyl-benzylamide; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid cyclopropylmethyl-amide, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 37. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 4-fluoro-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid isopropyl-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid benzhydryl-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid cyclopropylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid [1-(4-fluoro-phenyl)-ethyl]-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 3-methyl-benzylamide; or 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 3-methoxy-benzylamide, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 38. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 3-chloro-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 2-fluoro-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 3-fluoro-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 2-methyl-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 2-methoxy-benzylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid 2-chloro-benzylamide; 4′-trifluoromethyl-biphenyl-2-carboxylic acid [3-(pyrrolidine-1-carbonyl)-quinolin-7-yl]-amide; 4′-trifluoromethyl-biphenyl-2-carboxylic acid [3-(morpholine-4-carbonyl)-quinolin-7-yl]-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid diethylamide; or 4′-trifluoromethyl-biphenyl-2-carboxylic acid [3-(piperidine-1-carbonyl)-quinolin-7-yl]-amide, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 39. A kit for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X, the kit comprising:
a) a first pharmaceutical composition comprising a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug. b) a second pharmaceutical composition comprising a second compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X; and c) a container for containing the first and second compositions.
- 40. A method for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X, the method comprising the step of administering to a patient having or at risk of having atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X a therapeutically effective amount of a compound of claim 1, a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug in combination with at least one additional compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X.
- 41. The method of claim 40 wherein the additional compound is a HMG-CoA reductase inhibitor.
- 42. The method of claim 40 wherein the additional compound is a MTP inhibitor.
- 43. The method of claim 40 wherein the additional compound is a HMG-CoA synthase inhibitor.
- 44. The method of claim 40 wherein the additional compound is an ACAT inhibitor.
- 45. The method of claim 40 wherein the additional compound is a CETP inhibitor.
- 46. The method of claim 40 wherein the additional compound is a lipase inhibitor.
- 47. The method of claim 40 wherein the additional compound is a glucosidase inhibitor.
- 48. A pharmaceutical composition comprising a compound of claim 1, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug, and at least one additional compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X.
- 49. The composition of claim 48 wherein the additional compound is a HMG-CoA reductase inhibitor.
- 50. The composition of claim 48 wherein the additional compound is a MTP inhibitor.
- 51. The composition of claim 48 wherein the additional compound is a HMG-CoA synthase inhibitor.
- 52. The composition of claim 48 wherein the additional compound is an ACAT inhibitor.
- 53. The composition of claim 48 wherein the additional compound is a CETP inhibitor.
- 54. The composition of claim 48 wherein the additional compound is a lipase inhibitor.
- 55. The composition of claim 48 wherein the additional compound is a glucosidase inhibitor.
- 56. A compound of Formula II
- 57. A compound of claim 56 wherein A is
- 58. A compound of claim 56 wherein each RQ is hydrogen.
- 59. A compound of claim 56 wherein R3 is hydrogen.
- 60. A compound of claim 56 wherein B is
- 61. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid [bis-4-fluoro-phenyl)-methyl]-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid benzyl-ethyl-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (3-phenyl-propyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl-pyridin -2-ylmethyl-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid phenethyl-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid phenylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (2-methoxy-ethyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-methyl-3-phenyl-propyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid indan-1-ylamide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (3,3-diphenyl-propyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (4-phenyl-butyl)-amide; [R]-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid [(4-fluoro-phenyl)-pyridin-2-yl-methyl]-amide; [S]-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid [(4-fluoro-phenyl)-pyridin-2-yl-methyl]-amide; 2-methyl-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (2-methoxy-ethyl)-amide; [S]-2-methyl-7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; [R]-7-[2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; [R]-7-[2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [S]-7-[2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; [R]-7-[2-(6-methyl-pyridin-3-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-[2-(5-methyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [S]-7-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; [R]-7-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; [R]-7-[(2-p-tolyl-pyridine-3-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-{[2-(4-isopropyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-{[2-(4-tert-butyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-{[2-(4-methoxy-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; [R]-7-{[2-(4-ethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-[(4′-tert-butyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-[(4′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid acid (di-pyridin -2-yl-methyl)-amide; 7-[(4′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid acid (1-pyridin -2-yl-propyl)-amide; 7-(2-benzofuran-2-yl-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[(4′-isopropyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-[(4′-isopropyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-isopropyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(3′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-ethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[(4′-ethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(4′-tert-butyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(4′-ethylsulfanyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-ethylsulfanyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin -2-yl-propyl)-amide; 7-(2-naphthalen-2-yl-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-(2-benzo[1,3]dioxol-5-yl-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(3′,4′-dimethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(2′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(3′-fluoro-4′-methyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[(4′-ethoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-ethoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(4′-ethoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-[2-(2,3-dihydro-benzofuran-5-yl)-benzoylamino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-propoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-propoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(4′-butoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-[(4′-butoxy-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(3-methyl-4-oxo-2-phenyl-4H-chromene-8-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[(3-methyl-4-oxo-2-phenyl-4H-chromene-8-carbonyl)-amino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[(3-methyl-4-oxo-2-phenyl-4H-chromene-8-carbonyl)-amino]-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-benzoylamino)-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-(2-cyclohexylmethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-benzoylamino]-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-benzoylamino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-3-methoxy-benzoylamino]-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-3-methoxy-benzoylamino]-quinoline-3-carboxylic acid (phenyl-pyridin-2-yl-methyl)-amide; 7-[2-(bicyclo[2.2.1]hept-2-ylmethoxy)-3-methoxy-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-(2-pentyloxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(2-pentyloxy-benzoylamino)-quinoline-3-carboxylic (phenyl-pyridin-2-yl-methyl)-amide; 7-(2-pentyloxy-benzoylamino)-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-(3-methoxy-2-pentyloxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(3-methoxy-2-pentyloxy-benzoylamino)-quinoline-3-carboxylic acid (phenyl-pyridin -2-yl-methyl)-amide; 7-(3-methoxy-2-pentyloxy-benzoylamino)-quinoline-3-carboxylic acid (1-pyridin-2-yl-propyl)-amide; 7-(2-benzyloxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(2-cyclopentylethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-[3-methoxy-2-(4,4,4-trifluoro-butoxy)-benzoylamino]-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-[3-methoxy-2-(3-methyl-butoxy)-benzoylamino]-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-(2-cyclobutylmethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-(2-cyclopentylmethoxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 2-hexyloxy-3-methoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin-2-yl-methyl)-amide; 7-(2-cyclohexylethoxy-3-methyl-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 7-(2-cyclohexylmethoxy-3-methyl-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide; 2-methyl-7-[2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 2-methyl-7-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 2-ethyl-7-[2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 2-ethyl-7-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-{[6-methyl-2-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-[(6-methyl-4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-[3-methyl-2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-[3,5-dimethyl-2-(5-trifluoromethyl-pyridin-2-yl)-benzoylamino]-quinoline-3-carboxylic acid (1-pyridin-2-yl-ethyl)-amide; 7-(3-chloro-2-cyclohexylmethoxy-benzoylamino)-quinoline-3-carboxylic acid (di-pyridin -2-yl-methyl)-amide, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 62. A method of treating or preventing atherosclerosis, the method comprising the step of administering to a patient having or at risk of having atherosclerosis a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 63. A method of treating or preventing obesity, the method comprising the step of administering to an obese patient or a patient at risk of becoming obese a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 64. A method of treating or preventing hypercholesterolemia, the method comprising the step of administering to a patient having or at risk of having hypercholesterolemia a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 65. A method of treating or preventing hyperlipidemia, the method comprising the step of administering to a patient having or at risk of having hyperlipidemia a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 66. A method of treating or preventing hypertriglyceridemia, the method comprising the step of administering to a patient having or at risk of having hypertriglyceridemia a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 67. A method of treating or preventing hypoalphalipoproteinemia, the method comprising the step of administering to a patient having or at risk of having hypoalphalipoproteinemia a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 68. A method of treating or preventing pancreatitis, the method comprising the step of administering to a patient having or at risk of having pancreatitis a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 69. A method of treating or preventing diabetes, the method comprising the step of administering to a patient having or at risk of having diabetes a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 70. The method of claim 69 wherein the diabetes is non-insulin dependent diabetes mellitus (Type II).
- 71. A method of treating or preventing myocardial infarction, the method comprising the step of administering to a patient having or at risk of having myocardial infarction a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 72. A method of treating or preventing a stoke, the method comprising the step of administering to a patient having or at risk of having a stroke a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 73. A method of treating or preventing restenosis, the method comprising the step of administering to a patient having or at risk of having restenosis a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 74. A method of treating or preventing Syndrome X, the method comprising the step of administering to a patient having or at risk of having Syndrome X a therapeutically effective amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 75. A method of inhibiting apolipoprotein B secretion, the method comprising administering to a patient in need of apolipoprotein B secretion inhibition an apolipoprotein B secretion inhibiting amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 76. A method of inhibiting microsomal triglyceride transfer protein, the method comprising administering to a patient in need of microsomal triglyceride transfer protein inhibition a microsomal triglyceride transfer protein inhibiting amount of a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 77. A pharmaceutical composition comprising a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
- 78. A kit for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X, the kit comprising:
a) a first pharmaceutical composition comprising a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug. b) a second pharmaceutical composition comprising a second compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X; and c) a container for containing the first and second compositions.
- 79. A method for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X, the method comprising the step of administering to a patient having or at risk of having atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X a therapeutically effective amount of a compound of claim 56, a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug in combination with at least one additional compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X.
- 80. A pharmaceutical composition comprising a compound of claim 56, or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug, and at least one additional compound useful for the treatment or prevention of atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X.
- 81. The compound:
7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (pentylcarbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid (diethylcarbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid -S-(pentylcarbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid -S-(diethylcarbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid -R-(pentylcarbamoyl-phenyl-methyl)-amide; 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid -R-(diethylcarbamoyl-phenyl-methyl)-amide, or a pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutically acceptable salt of the prodrug.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This is a divisional application of U.S. application number 09/711,281, filed Nov. 9, 2000, now allowed, which claims priority from U.S. provisional application number 60/164,803, filed Nov. 10, 1999 and U.S. provisional application number 06/224,956, filed Aug. 11, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60164803 |
Nov 1999 |
US |
|
60224956 |
Aug 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09711281 |
Nov 2000 |
US |
Child |
10054455 |
Jan 2002 |
US |