Sphingosine-1-phosphate receptor modulators for the treatment of cardiopulmonary disease

Abstract

The present invention provides compounds effective as sphingosine-1-phosphate receptor modulators for the treatment of cardiopulmonary disorders such as hypertension (including malignant hypertension), angina, myocardial infarction, arrhythmia , congestive heart failure, coronary heart disease, atherosclerosis, angina, dysrhythmia, cardiomyopathy (including hypertensive cardiomyopathy), heart failure, cardiac arrest, bronchitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis , croup, emphysema, pleurisy, pulmonary fibrosis, pneumonia, pulmonary embolism, pulmonary hypertension, mesothelioma, ventricular conduction abnormalities, complete cardiac obstruction, adult respiratory distress syndrome, sepsis syndrome, idiopathic pulmonary Fibrosis, scleroderma, systemic sclerosis, retroperitoneal fibrosis, prevention of keloid formation, or cirrhosis.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application Serial No. 62 / 056,946, filed September 29, 2014, the disclosure of which is incorporated herein by reference in its entirety. [0003] Statement of Government Support [0004] This invention was made with US government support (National Institutes of Health Grant No. MH084512). Accordingly, the US Government may have certain rights in this invention. Background technique [0005] Antagonism of sphingosine-1-phosphate receptor (S1PR) subtype 3 has been proposed for therapeutic use in asthma, chronic obstructive pulmonary disease and other therapeutic uses based on receptor expression and pharmacological antagonism of gene deletion. Five high-affinity G-protein-coupled receptors for sphingomyelin 1-phosphate (S1P) were identified (1), and S1PR 1 The crystal structure of (2). This collection of receptors is medically important because the nonselective S1PR...

AI Technical Summary

Problems solved by technology

Taken together, the available evidence strongly suggests that, with the systemic S1PR 3 Downregulation of S1PR proposed by antagonists 3 DC signaling may open new therapeutic opportunities in sepsis syndrome

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