申请人:Eli Lilly and Company
公开号:US04283329A1
公开(公告)日:1981-08-11
Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality; R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl; R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m --U--CH.sub.3 in which U is --S-- or >S--O and m is 1 or 2; R.sub.3 is hydrogen, C.sub.1 -C.sub.4 primary or secondary alkyl, cyclopropylmethyl, or allyl; R.sub.4 is hydrogen, C.sub.1 -C.sub.5 primary or secondary alkyl, --(CH.sub.2).sub.n --X--(CH.sub.2).sub.p --CH.sub.3 in which X is --O--, --S--, >S--O or ##STR2## n is 1 or 2, and p is 0 or 1, phenyl, or monosubstituted phenyl in which the substituent is halo, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, C.sub.1 -C.sub.3 alkyl, or trifluoromethyl; R.sub.5 is hydrogen or C.sub.1 -C.sub.4 primary alkyl; and Z is --CH.sub.2 OR.sub.6, ##STR3## in which R.sub.6 is hydrogen or C.sub.1 -C.sub.3 alkyl and R.sub.7 is C.sub.1 -C.sub.3 alkyl; subject to the proviso that one but not both of R.sub.3 and R.sub.5 is other than hydrogen; are useful analgesic agents.
该公式的化合物及其药学上可接受的非毒性酸加成盐,其中L和D定义手性;R1为氢或C1-C3一级烷基;R2为C1-C4一级或二级烷基,烯丙基,环丙基甲基,C1-C2羟基烷基或--(CH2)m--U--CH3,其中U为--S--或>S--O,m为1或2;R3为氢,C1-C4一级或二级烷基,环丙基甲基或烯丙基;R4为氢,C1-C5一级或二级烷基,--(CH2)n--X--(CH2)p--CH3,其中X为--O--,--S--,>S--O或##STR2## n为1或2,p为0或1,苯基或单取代苯基,其中取代基为卤素,羟基,C1-C3烷氧基,硝基,C1-C3烷基或三氟甲基;R5为氢或C1-C4一级烷基;Z为--CH2OR6,##STR3##其中R6为氢或C1-C3烷基,R7为C1-C3烷基;条件是R3和R5中的一个而不是两个不是氢,有用的镇痛药剂。