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CONJUGADOS DE ACIDOS GRASOS Y APELINA SINTETICA CON MAYOR VIDA MEDIA.
专利权人:
NOVARTIS AG
发明人:
Frederic ZECRI,Aaron KANTER,Aimee Richardson USERA
申请号:
MX2017009534
公开号:
MX2017009534A
申请日:
2016.01.15
申请国别(地区):
MX
年份:
2018
代理人:
摘要:
The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.La invención proporciona un conjugado, o una sal farmacéuticamente aceptable del mismo, que comprende un polipéptido sintético de Fórmula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*- F (I) o una amida o éster del mismo; y un ácido graso seleccionado de: en el que dicho ácido graso está unido covalentemente al extremo N-terminal del péptido a través de una de sus funcionalidades de ácido carboxílico, opcionalmente a través de un enlazador de polietilenglicol; y en el que los dos aminoácidos de cisteína marcados con "*" forman un enlace disulfuro entre las funcionalidades tiol de su cadena lateral. Los conjugados
来源网站:
中国工程科技知识中心
来源网址:
http://www.ckcest.cn/home/

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