氮杂吲哚5氟吲哚类衍生物的设计合成和抗肿瘤活性筛选及2哌嗪基苯甲酰胺类化合物库的构建药物化学专业论文.docxVIP

浙 江 浙 江 大 学 硕 士 学 位 论 文 A b s tra e t A b s tr a C t M o st o f th e sig n a l tra n sd u e tio n P a th w a y s a re m e d ia te d b y P ro te in k in a se s re g u la tin g e v e ry a sP e e t o f e e ll f u n e tio n in e lu d in g e e ll g r o w th ，d i且七re n tia tio n ，m ig r a tio n ， a n d a p o P to s is . O v e r e x P re s s e d P ro te in k in a s e s w e re re su lt in m a n y d is e a s e s s u e h a s e a n e e r s . P ro te in ty r o s in e k in a s e s a r e a k in d o f th e m a in P ro te in k in a s e . In re e e n t y e a rs ， w ith P ro te in t梦 o s in e k in a se s ta rg e t in h ib ito r stu d y m o re a n d m o re ，e a n c e r tre a tm e n t h a s b e e n a c h ie v e d in e n c o u r a g in g im P o r ta n t P ro g r e s s . T h e re a r e tw o e la s s e s o f P T K s P re se n t in c e lls : th e re e e P to r P ro te in ty r o sin e k in a s e s a n d t he n o n r e e e P to r P ro te in ty ro sin e k in a s e s . T h e f irst e h a P te r o f th e P aP e r w ill in tro d u e e P r o te in ty r o sin e k in a s e s a n d c lin ic a l liste d d r u g s . D is s e r ta tio n e h a r t 2 m a in ly in tro d u e e s th e s y n th e sis o f a z a o x in d o le a n d 5 一flu o ro o x in d o le d eri v ativ e s (six ty) w h ich are o n th e b a sis o f th e d rug o f su n itin ib . A se r ie s o f in d o lin 一2 一o n e s w e re f ou n d to h a v e m o d e ra te a n titLlln o r a e tiv ity a g a in s t t h e s e le e te d tu m o r e e ll lin e s . C o m P o u n d s Z H L 2 0 l O 一9 w e re f o u n d to h a v e m o re P o te n t eyto to x ieity (IC 5o= 12 .9 7 拼M an d 1 5 .7 8 卜M ) ag ain st K B cell lin e an d th e K 5 6 2 cell lin e co m p ared to S u n itin ib (IC 5o= 2 1 .9 1协M an d 2 1.9 7 协M ). C o m P o u n d lib ra r y 15 th e so u re e o f n e w d r u g d e v e lo P m e n t.