Compounds and Pharmaceutical Compositions for Uses in Diabetes

• US 20130225683A1
• Filed: 10/26/2011
• Published: 08/29/2013
• Est. Priority Date: 10/27/2010
• Status: Abandoned Application

• Current Assignee: Prometic Pharma SMT Limited (Liminal R&D BioSciences, Inc.)
• Original Assignee: ProMetic BioSciences, Inc. (Thomvest Asset Management, Inc.)
• Inventors: Gagnon, Lyne, Grouix, Brigette, Laurin, Pierre
• Application Number:
  US13/882,373
• Publication Number:
  US 20130225683A1
• Time in Patent Office: Days
• US Class Current: 514/559
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I, IA, IB and IC, and their pharmaceutical acceptable salts are described for prevention or treatment of diabetes or a diabetes-related disorder in a subject in need thereof. Diabetes and diabetes-related disorder include Type I diabetes, Type II diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes of adults (LADA), gestational diabetes, diabetic nephropathy, proteinuria, ketonuria, obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglyceridemia, dyslipidemia, metabolic syndrome, syndrome X, diabetic neuropathy, diabetic retinopathy, hypoglycemia, cardiovascular disease, atherosclerosis, diabetic kidney disease, ketoacidosis, thrombotic disorders, sexual dysfunction, dermatopathy, edema, metabolic syndrome and renal disorders. The related pharmaceutical compositions and methods are also described. These compounds can be used in combination with comprising a therapeutic agent for lowering or controlling blood glucose level such as metformin or a thiazolidinedione.

Claims

1-28. -28. (canceled)

29. A method for treating diabetes or a diabetes-related disorder, wherein said method comprises administering, to a subject in need of such treatment, a compound represented by Formula 1, or a pharmaceutically acceptable salt thereof:

Cy-Q 

 

Formula 1

wherein

Cy is

30. The method of claim 29, wherein the compound is represented by Formula 1A, or a pharmaceutically acceptable salt thereof:

31. The method of claim 29, wherein the compound is represented by Formula 1B, or a pharmaceutically acceptable salt thereof:

32. The method of claim 29, wherein the compound is represented by Formula 1C, or a pharmaceutically acceptable salt thereof:

33. The method of claim 29, wherein the pharmaceutically acceptable salt is a base addition salt.

34. The method of claim 33, wherein the base addition salt comprises a metal counterion selected from sodium, potassium, magnesium, calcium and lithium.

35. The method of claim 29, wherein the compound is any one of Compounds I-XVII, XIX-XXVII and XXIX-XXXIV:

36. The method of claim 35, wherein the compound is Compound I, II, V, VIII, XIV, XXIII or XXVI.

37. The method of claim 35, wherein the compound is Compound I.

38. The method of claim 35, wherein the compound is Compound XIV.

39. The method of claim 29, wherein said diabetes or diabetes-related disorder is Type I diabetes, Type II diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes of adults (LADA), gestational diabetes, diabetic nephropathy, proteinuria, ketonuria, obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglyceridemia, dyslipidemia, metabolic syndrome, syndrome X, diabetic neuropathy, diabetic retinopathy, hypoglycemia, cardiovascular disease, atherosclerosis, diabetic kidney disease, ketoacidosis, thrombotic disorders, sexual dysfunction, dermatopathy, edema or a renal disorder.

40. The method of claim 39, wherein the diabetes is Type II diabetes.

41. The method of claim 39, wherein the diabetes-related disorder is diabetic nephropathy.

42. The method of claim 39, wherein the diabetes-related disorder is proteinuria.

43. The method of claim 39, wherein the diabetes-related disorder is ketonuria.

44. The method of claim 29, wherein said use is also for decreasing ketone bodies in the urine of a subject in need thereof.

45. The method of claim 29, wherein said use is also for increasing glomerular filtration rate (GFR) in a subject in need thereof.

46. The method of claim 29, wherein said use is also for increasing insulin secretion or increasing insulin sensitivity in a subject in need thereof.

47. The method of claim 29, wherein said use is also for decreasing insulin resistance in a subject in need thereof.

48. The method of claim 29, wherein said use is also for decreasing hyperglycemia in a subject in need thereof.

49. The method of claim 29, wherein the compound is used in combination with a therapeutic agent for lowering or controlling blood glucose level.

50. The method of claim 49, wherein the therapeutic agent is metformin or thiazolidinedione.

51. A pharmaceutical composition comprising a compound as defined in claim 29 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

52. The pharmaceutical composition of claim 51, further comprising a therapeutic agent for lowering or controlling blood glucose level.

54. The pharmaceutical composition of claim 51, wherein the composition is adapted for oral administration.

53. The pharmaceutical composition of claim 53, wherein the therapeutic agent is metformin or a thiazolidinedione.