US 2017/0360730 A1 · MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO

Abstract

The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: Pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack, angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

Claims79

Dependent claims

A method for the treatment of a PGI2 receptor mediated disorder in an individual, comprising administering to said individual in need thereof, a therapeutically effective amount of a compound selected from compounds of Formula (XIIIa) and pharmaceutically acceptable salts, solvates and hydrates thereof:

wherein:
R1 and R2 are each independently selected from:
H, C1-C6 alkyl, aryl and heteroaryl;
wherein C1-C6 alkyl, aryl and heteroaryl are each optionally substituted with one or two substituents selected from:
C1-C6 alkoxy, C1-C6 alkyl, aryl, C1-C6 haloalkoxy, C1-C6 haloalkyl and halogen;
X is O or NR3;
R3 is selected from H and C1-C6 alkyl;
and
Q is selected from:
OH, —NHCH2CH2SO3H, 1-carboxyethylamino, 1-carboxy-4-guanidinobutylamino, 3-amino-1-carboxy-3-oxopropylamino, 1,2-dicarboxyethylamino, 1-carboxy-2-mercaptoethylamino, 4-amino-1-carboxy-4-oxobutylamino, 3 -carboxy-1-carboxylatopropylamino, carboxymethylamino, 1-carboxy-2-(1H-imidazol-4-yl)ethylamino, 1-carboxy-2-methylbutylamino, 1-carboxy-3-methylbutylamino, 5-amino-1-carboxypentylamino, 1-carboxy-3-(methylthio)propylamino, 1-carboxy-2-phenylethylamino, 2-carboxypyrrolidin-1 -yl, 1 -carboxy-2-hydroxyethyl amino, 1 -carboxy-2-hydroxypropylamino, 1 -carboxy-2-(1H-indol-3 -yl)ethyl amino, 1 -carboxy-2-(4-hy droxyphenyl)ethyl amino and 1 -carboxy-2-methyl propyl amino.

7 more elements

Dependencies are inferred from the claim text.

Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto

Life of this patent

Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto

Life of this patent

Abstract

Claims79