| abstract |
The present invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising the synthetic polypeptide of Formula I: QRPRLC*-HKGP-(Nle)-C*-F(I) or a guanamine or ester thereof; and a fatty acid, The fatty acid is selected from:nâ–ˇnWherein the fatty acid is covalently attached to the N-terminus of the peptide via a polyethylene glycol linking group via one of the carboxylic acid functional groups; and wherein the two cysteine amino acids labeled with "*" are in A disulfide bond is formed between the thiol functional groups of the side chain. These conjugates are agonists of the APJ receptor. The invention also relates to a method for the manufacture of a conjugate of the invention, and to its therapeutic use, such as for the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Bruga Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, lack ofnBloody cardiovascular disease, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accident, transient ischemic attack, traumatic brain injury, muscle Atrophic lateral sclerosis, burns (including sunburn), and pre-eclampsia. The invention further provides a combination of a pharmacologically active agent and a pharmaceutical composition. |