| 摘要 |
Novel nonpeptide endothelin I antagonists of Formulaare described wherein R1 is unsubstituted or substituted cycloalkyl, phenyl, naphthyl or heteroaryl, R2 is unsubstituted or substituted alkyl, aryl or heteroaryl, R3 is unsubstituted or substituted alkyl, cycloalkyl, aryl or heteroayl, and R1 and/or R2 and/or R3 are independently substituted by a total of from 1 to 4 substituents which enhance aqueous solubility with the proviso that when R2 is alkyl and is substituted, the substituent is not oxygen at the alpha-position of the furanone ring. Further described are methods for the preparation and pharmaceutical compositions of compounds of Formula I, which are useful in treating atherosclerosis, restenosis, Raynaud's phenomenon, mild or severe congestive heart failure, cerebral ischemia, cerebral infarction, embolic stroke, cerebral vasospasm, glaucoma, subarachnoid hemorrhage, hemorrhagic stroke, diabetes, gastric ulceration and mucosal damage, ischemic bowel disease, Chrohn's disease, male penile erectile dysfunction, essential or malignant hypertension, pulmonary hypertension, pulmonary hypertension after bypass, cancer, especially malignant hemangioendothelioma or prostate cancer, myocardial infarction or ischemia, acute or chronic renal failure, renal ischemia, radiocontrast-induced nephrotoxcity, endotoxic, septic hemorrhagic shock, angina, preeclampsia, asthma, arrhythmias, benign prostatic hyperplasia, and elevated levels of endothelin. |
