摘要
本文设计,合成了2-(E)-取代苯亚甲基环戊酮(Ⅰ)类化合物18个及其Mannich碱盐酸盐(Ⅱ)类化合物11个,其中22个为新化合物。初步药理结果显示:对于角叉菜胶诱发的大鼠足趾水肿,Ⅰ_4,Ⅰ_(12)及Ⅰ_(13)口服有较显著的抑制作用,水溶性Ⅱ类化合物皮下注射有极强的抑制作用,其中Ⅱ_3于50,25和12.5 mg/kg剂量下抑制率分别为95.8%,70.3%和44.2%,它与布洛芬效力(25 mg/bg抑制率72.9%)相当.Ⅱ类化合物体外对L1210细胞及体内对荷艾氏腹水癌小鼠均有一定抗癌活性。
It has been known that non-steroidal antiinflammatory drugs (NSAIDs) act by preventing cyclooxygenase products of arachidonic acid. In recent years, research on non-steroid dual inhibitors of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), which should represent a novel class of antiinflammatory drugs with a wider spectrum of activity than classical NSAIDs, hasbeencarriedout. Inthepresent paper, a total of 29 compounds including 18 compounds of 2-(E)-(un) substituted benzylidene cyclopentanone (Ⅰ) derivatives and 11 compounds of 2-(E)-(un)substituted benzylidene-5-dimethylaminomethyl cyclopentanone (Ⅱ) derivatives were synthesized as dual inhibitors of CO/5-LO. Preliminary pharmacological test showed that Ⅰ_4, Ⅱ_(12) and Ⅰ_(13) given orally have significant inhibiting effect on carrageenan induced rat paw edema and most compounds of type Ⅱ exhibited potent effect when given subcutaneously. In particular, Ⅱ_3, which inhibited by 95.8%, 70.34%, and 44.2% at 50, 25, and 12.5 mg/kg respectivily, was similar to Ibuprofen.Some compounds of type Ⅱ exhibited anticancer activity both in vitro (IC_(50) ranging from 2.93 to 18.06/μmol/L on L1210)and in vivo (maximum increase of life span was 97.5% on EAC in mice).
出处
《药学学报》
CAS
CSCD
北大核心
1991年第3期183-192,共10页
Acta Pharmaceutica Sinica
基金
国家自然科学基金
关键词
环戊酮
MANNICH碱
抗炎
抗癌
2-(E)-(un) substituted benzylidene cyclopentanone
Mannich base hydrochloride
Dual inhibitors of cyclooxygenase and 5-lipoxygenase
Antinflammation
Anticancer
