申请人:PFIZER INC.
公开号:EP0173497A1
公开(公告)日:1986-03-05
Novel biologically-active tetracyclic spirohydantoin derivatives of formula
wherein
X is hydrogen, fluorine, chlorine or methyl; and R is hydrogen, alkyl, alkenyl, cycloalkyl, benzy, 4-hydroxy- benzy!, pyridyl, HSCH2-, CH3SCH2-, CH3SCH2CH2-, FCH2-, HOCH2-, CH2CH(OH)-, CH3CH(OH)CH2-, HOOCCH2-, HOOCCH2CH2-, H2NCOCH2-, H2NCOCH2CH2-, H2NCH2CH2-
COOC2H5, -CONH2, CONH(CH2)20H, -CONH cyclohexyl, -CONH-Bu, -CONH(CH2)3 N(CH3)2, -CON(C2H5)2,
phenyl or phenyl substituted by chlorine, fluorine, bromine, hydroxy, methyl, methoxy, trifluoromethyl, -COCH3, -N(CH3)2, -SCH3, -SOCH3, -SO2CH3, -COOH, -CONH2, -COOCH3 or -CON Alk, are disclosed.
These derivatives are potent inhibitors of aldose reductase and useful in treating diabetic complications are disclosed.
Pharmaceutical compositions containing the novel compounds and a method of treating chronic diabetic complications are also disclosed.
具有
生物活性的四环式新螺海因衍
生物
式中
X是氢、
氟、
氯或甲基;R是氢、烷基、烯基、环烷基、苄基、
4-羟基-苄基、
吡啶基、HS -、 S -、 S -、F -、HO -、 CH(OH)-、 CH(OH)
CH2-、HOOC -、HOOC -、H2NCO -、H2NCO -、H2N -。
COO 、-CONH2、CONH( )20H、-CONH 环己基、-CONH-Bu、-CONH( )3 N(
CH3)2、-CON(
C2H5)2、
公开了苯基或被
氯、
氟、
溴、羟基、甲基、甲氧基、三
氟甲基、-CO 、-N( )2、-S 、-SO 、-SO2 、-COOH、-CONH2、-COO 或 -CON Alk 取代的苯基。
这些衍
生物是醛糖还原酶的强效
抑制剂,可用于治疗糖尿病并发症。
还公开了含有这些新型化合物的药物组合物和治疗慢性糖尿病并发症的方法。