申请人:Miles Laboratories, Inc.
公开号:US04275224A1
公开(公告)日:1981-06-23
Analogues of PGE.sub.1 having the structural formula, ##STR1## in which J is R-hydroxymethylene or S-hydroxymethylene; R.sub.1 is hydrogen; R.sub.2 is hydrogen or together with R.sub.4 is a methylene chain of 2 to 3 carbon atoms such that a cycloalkyl of 5 to 6 carbon atoms inclusive is formed; R.sub.3 is hydrogen or methyl, or together with R.sub.4 is a methylene or a lower alkylated methylene chain of 2 to 5 carbon atoms such that a cycloalkyl or a lower alkylated cycloalkyl of 4 to 7 carbon atoms inclusive is formed, or together with R.sub.4 is bicycloalkyl or bicycloalkenyl moiety having the formula: ##STR2## such that a bicycloalkyl or bicycloalkenyl compound is formed, wherein m and n are integers having a value from 0 to 3, p is an integer having a value from 0 to 4 and q is an integer having a value of from 1 to 4 and wherein the double bond of such bicycloalkenyl is in the m, n, p, or q bridge; R.sub.4 is hydrogen or methyl or together with R.sub.2 or R.sub.3 forms a cycloalkyl or bicycloalkyl or bicycloalkenyl as defined above, or together with R.sub.5 is a methylene chain of 3 to 5 carbon atoms such that a cycloalkyl of 4 to 6 carbon atoms inclusive is formed; R.sub.5 is selected from the group consisting of hydrogen, straight-chain alkyl having from 1 to 3 carbon atoms or together with R.sub.4 forms a cycloalkyl as defined above; and R.sub.6 is hydrogen or straight-chain alkyl having from 1 to 3 carbon atoms are disclosed. PGE.sub.1 ester analogues of the above formula, limited to the structures wherein two of R.sub.2, R.sub.3, R.sub.4 and R.sub.5 form a cycloalkyl, lower alkylated cycloalkyl, bicycloalkyl or bicycloalkenyl are also disclosed. The prostaglandin analogues selectively produce bronchodilation and decrease gastric secretion in vivo. Methods of preparing the analogues and starting materials required in the synthesis of the analogues are also disclosed.
具有结构式##STR1##的PGE.sub.1类似物,其中J为R-羟甲基或S-羟甲基;R.sub.1为氢;R.sub.2为氢或与R.sub.4一起形成2至3个碳原子的亚甲基链,从而形成包括5至6个碳原子的环烷基;R.sub.3为氢或甲基,或与R.sub.4一起形成2至5个碳原子的亚甲基或较低烷基化亚甲基链,从而形成包括4至7个碳原子的环烷基或较低烷基化环烷基,或与R.sub.4一起形成具有以下公式的双环烷基或双环烯基基团:##STR2##从而形成双环烷基或双环烯基化合物,其中m和n是整数,其值为0至3,p是整数,其值为0至4,q是整数,其值为1至4,其中这样的双环烯基的双键位于m、n、p或q桥上;R.sub.4为氢或甲基,或与R.sub.2或R.sub.3一起形成如上所定义的环烷基、双环烷基或双环烯基,或与R.sub.5一起形成3至5个碳原子的亚甲基链,从而形成包括4至6个碳原子的环烷基;R.sub.5选自由氢、具有1至3个碳原子的直链烷基,或与R.sub.4一起形成如上定义的环烷基;R.sub.6为氢或具有1至3个碳原子的直链烷基。此外还披露了上述公式的PGE.sub.1酯类似物,仅限于其中两个R.sub.2、R.sub.3、R.sub.4和R.sub.5形成环烷基、较低烷基化环烷基、双环烷基或双环烯基的结构。前列腺素类似物在体内选择性地产生支气管扩张并减少胃分泌。还披露了制备类似物和合成类似物所需的起始材料的方法。