Bicyclic aryl sphingosine 1-phosphate analogs

摘要

597596 Disclosed is a fused bicyclic compound of formula (IIa), (IIIa), (IIIb), (IIIc), (IIIf), (IIIg), (IVa), (IVb), (IVc), (VIa), (VIb) or (VIc) where the substituents are as disclosed in the specification. The fused bicycle is naphthalene, isoquinoline, quinoline, quinazoline, or indole. Examples of the compounds are: 4-(6-(cis-4-tert-butylcyclohexyloxy)-3,4-dihydroisoquinolin-2(1H)-yl)butanoic acid; 2-(((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)amino)ethylphosphonic acid; and 2-(2-(5-(trans-4-tert-butylcyclohexyloxy)indolin-1-yl)-2-oxoethylamino)ethylphosphonic acid. Also disclosed are pharmaceutical compositions comprising the compound and the use of the compounds in the manufacture of a medicament. The medicament is useful in the treatment of a pathological condition or symptom in a mammal, wherein the activity of sphingosine 1-phosphate receptors is implicated and agonism of such activity is desired. Examples of conditions that could be treated by the compounds are multiple sclerosis, autoimmune diseases, chronic inflammatory disorders, asthma, inflammatory neuropathies, arthritis, transplantation, Crohn’s disease, ulcerative colitis, lupus erythematosis, psoriasis, ischemia-reperfusion injury, solid tumours, tumour metastasis, diseases associated with angiogenesis, vascular diseases, pain conditions, acute viral diseases, inflammatory bowel conditions, insulin or non-insulin dependent diabetes.