6,9-METHANO-PGI2 ANALOGUES

摘要

Prostaglandin I2 analogues of the formula: II [wherein the symbol between the carbon atoms in positions 5 and 6 represents a single or double bond, Y represents ethylene or trans-vinylene, R1 represents hydrogen, alkyl of 1 to 12 carbon atoms, aralkyl of 7 to 12 carbon atoms, cycloalkyl of 4 to 7 carbon atoms optionally substituted by alkyl of 1 to 4 carbon atoms, phenyl optionally substituted by chlorine, trifluoromethyl, alkyl of 1 to 4 carbon atoms or phenyl, a -CmH2mCOOR7 group (wherein m represents an integer of from 1 to 12 and R7 represents alkyl of 1 to 4 carbon atoms), a -CnH2nOR8 group (wherein n represents an integer of from 2 to 12 and R8 represents hydrogen or alkyl of 1 to 4 carbon atoms) or a group (wherein R9 and R10 each represent alkyl of 1 to 4 carbon atoms and n is as hereinbefore defined), R2 represents hydrogen or a hydroxy-protecting group, R3 represents hydrogen or a hydroxy-protecting group which is eliminated under acidic conditions, R4 represents hydrogen, methyl or ethyl, R5 represents a single bond or alkylene of 1 to 4 carbon atoms optionally substituted by a chlorine atom (provided that, when R5 is alkylene substituted by chlorine, R6 represents hydrogen or alkyl) R6 represents hydrogen, alkyl or 1 to 8 carbon atoms, cycloalkyl of 4 to 7 carbon atoms optionally substituted by alkyl of 1 to 8 carbon atoms, or phenyl or phenoxy optionally substituted by cholrine, trifluoromethyl or alkyl of 1 to 4 carbon atoms, and when represents a double bond that bond is E, Z or a mixture thereof and when, represents a single bond, the absolute configuration of C6 is R, S or a mixture thereof] and, when R2 and R3 represent hydrogen, cyclodextrin clathrates of such acids and esters and, when R1, R2 and R3 represent hydrogen, non-toxic salts thereof and, when R1 represents in which n, R9 and R10 are as hereinbefore defined, non-toxic acid addition salts thereof, are new compounds, possessing prostaglandin-like activity.