| 摘要 |
The present invention relates to sphingosine-1-phosphate (S1P) receptors and compounds of the general formula:;;that are useful in the treatment and prevention of conditions associated with such receptors. More specifically, the present invention relates to the synthesis and use of sphingosine 1-phosphate receptor 2 (S1P2) antagonists that are useful in the treatment of cancer, atherosclerosis, diabetic retinopathy, and other inflammatory diseases. Among these inflammatory diseases that could be treated with these S1P2 antagonist are those characterized by fibrosis including chronic lung disease, chronic kidney and liver disease, chronic heart disease, and skin diseases such as sclerosis/scleroderma. The S1P2 antagonists can also be used in the treatment of glioblastoma multiforme (brain cancer), pediatric neuroblastoma, and other cancers. |
| 主权项 |
1. A sphingosine-1-phosphate receptor 2 (S1P2) antagonist of the formula: wherein R1 is -allyl, —CH3, or —CH2CH2CH2OH, R2 is —H, —CH2CO2H, —CH2CH2OH, —CH2CH2CH2OH, —CH2CONH2, or —CH2CO2Et and R3 is 4-substituted-2,6-dichloropyridine, 4-substituted-2-chloro-6-hydroxyethyl pyridine, 4-substituted-2-chloro-6-hydroxypropyl pyridine, 4-substituted-2-(aminoethyl)-6-chloro pyridine, 4-substituted-2-(aminoethylmethyl)-6-chloro pyridine, 5-substituted-2,3-dichloro thiophene, with the proviso that R1 cannot be —CH3 if R2 is —H, and their physiologically acceptable salts and solvates |
