The present invention relates to disubstituted alkyne derivatives. These compounds are useful for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases.

The present invention relates to disubstituted alkyne derivatives. These compounds are useful for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases.

The present disclosure provides methods of identifying patients who have partial or total resistance to HIF-2 inhibitors or who develop partial or total resistance to HIF-2 inhibitors after treatment and providing suitable treatment to these patients.

The present disclosure provides methods of identifying patients who have partial or total resistance to HIF-2 inhibitors or who develop partial or total resistance to HIF-2 inhibitors after treatment and providing suitable treatment to these patients.

The present invention is directed to a method for treating cardiovascular diseases such as acute myocardial infarction, atherosclerosis, heart failure, stroke, thrombosis, carditis (including acute myocarditis, acute pericarditis and complicated pericarditis), cardiac allograft rejection, cardiomyopathy, and peripheral vascular diseases. The method comprises administering to a subject in need thereof dapansutrile, in an effective amount. A preferred route of administration is oral administration.

The present invention is directed to a method for treating cardiovascular diseases such as acute myocardial infarction, atherosclerosis, heart failure, stroke, thrombosis, carditis (including acute myocarditis, acute pericarditis and complicated pericarditis), cardiac allograft rejection, cardiomyopathy, and peripheral vascular diseases. The method comprises administering to a subject in need thereof dapansutrile, in an effective amount. A preferred route of administration is oral administration.

The present invention provides a prophylactic and/or therapeutic agent for amyotrophic lateral sclerosis (ALS), which contains one or more kinase inhibitors selected from the group consisting of an epithelial cell growth factor receptor (EGFR) inhibitor, a fibroblast growth factor receptor (FGFR) inhibitor, an Aurorakinase inhibitor, a protein kinase A (PKA) inhibitor, a protein kinase C (PKC) inhibitor, an MEK inhibitor, an Met inhibitor, a JNK inhibitor, a Syk inhibitor and a JAK inhibitor, a prostaglandin analogue and an estrogen receptor antagonist, or one or more kinase inhibitors selected from the group consisting of Tivozanib and an analog thereof, SB 216763, Cdk2 Inhibitor II, BUDESONIDE, RIBOFLAVIN, alpha-TOCHOPHEROL, AMODIAQUINE, SU9516, Sunitinib and an analog thereof, GSK-3 Inhibitor XIII, Bisindolylmaleimide I, HYDROQUINONE, FLUNISOLIDE, MGCD-265, Indirubin-3′-monoxime, HYDRASTINE (1R,9S), PIPERINE, BUTAMBEN, Axitinib and an analog thereof, APOMORPHINE, FENBUFEN, Bosutinib (SKI-606) and an analog thereof, a Wee1 Inhibitor, Cdk2 Inhibitor IV, NU6140, 3-hydroxybutyric acid, AT9283, Imatinib, Nilotinib, Rebastinib, and Bafetinib for the prophylaxis and/or treatment of ALS. Particularly, using a compound already on the market as a pharmaceutical product, a pharmaceutical product for the prophylaxis or treatment of ALS can be developed rapidly at a low cost.

The present invention provides a prophylactic and/or therapeutic agent for amyotrophic lateral sclerosis (ALS), which contains one or more kinase inhibitors selected from the group consisting of an epithelial cell growth factor receptor (EGFR) inhibitor, a fibroblast growth factor receptor (FGFR) inhibitor, an Aurorakinase inhibitor, a protein kinase A (PKA) inhibitor, a protein kinase C (PKC) inhibitor, an MEK inhibitor, an Met inhibitor, a JNK inhibitor, a Syk inhibitor and a JAK inhibitor, a prostaglandin analogue and an estrogen receptor antagonist, or one or more kinase inhibitors selected from the group consisting of Tivozanib and an analog thereof, SB 216763, Cdk2 Inhibitor II, BUDESONIDE, RIBOFLAVIN, alpha-TOCHOPHEROL, AMODIAQUINE, SU9516, Sunitinib and an analog thereof, GSK-3 Inhibitor XIII, Bisindolylmaleimide I, HYDROQUINONE, FLUNISOLIDE, MGCD-265, Indirubin-3′-monoxime, HYDRASTINE (1R,9S), PIPERINE, BUTAMBEN, Axitinib and an analog thereof, APOMORPHINE, FENBUFEN, Bosutinib (SKI-606) and an analog thereof, a Wee1 Inhibitor, Cdk2 Inhibitor IV, NU6140, 3-hydroxybutyric acid, AT9283, Imatinib, Nilotinib, Rebastinib, and Bafetinib for the prophylaxis and/or treatment of ALS. Particularly, using a compound already on the market as a pharmaceutical product, a pharmaceutical product for the prophylaxis or treatment of ALS can be developed rapidly at a low cost.

A method of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO by providing a composition comprising a compound set forth in Formula (I):

##STR00001##

A method of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO by providing a composition comprising a compound set forth in Formula (I):

##STR00001##