Quinoline 衍生物之設計、合成與生物活性評估

Abstract

The aim of this dissertation is to design, synthesis and biological evaluation of quinoline analogues of medicinal interest. Quinoline or 8-quinolinol heterocycles are considered as ideal leads for further optimization in search for novel compounds of medicinal interest. In Chapter 1, we developed novel 8-quinolinols, 8-methoxyquinolines substituted at C2 position with long carbon chain (C9-C13) alcohols, long chain alkyl bromides or long chain fatty acetates. In this study, we designed a skeleton, which might serve as Zn++ metal ions chelator and nerve growth stimulator. It is interesting to note that, these compounds are free of cytotoxicity, making them as ideal candidate for AD. In addition, several compounds demonstrated intense fluorescence under UV light. Therefore, they might serve as efficient candidate for studying the activity in living cells. In Chapter 2, series of antitumor quinoline analogues (nonhalogenated 10-15 and halogenated 18-80 styrylquinolines) and halogenated amide quinolines 91-96 were prepared. Many styryl analogues demonstrated potent antitumor activity with GI50 in the submicromolar range against HepG2 tumor cells. The best compounds 2-[2-(4-Acetyl-oxyphenyl)vinyl]-5-chloro-7-iodo-8-methoxyquinoline (50), 2-[2-(4-Hydroxyphenyl)vinyl]-5-chloro-7-iodo-8-met-hoxyquinoline (67) in this series showed GI50 of 20 nM and caused S-phase arrest. The detail SAR study showed that presence of 8-hydroxy or 8-acetoxy group and polar substituents on styryl phenyl ring are required for potent anticancer activity. Replacement of styryl bond with amide or substitution of 8-methoxy group results in loss of anticancer potency. In Chapter 3, we describe nonreductive method of selective deiodination. In the presence of tertiary amine and catalytic amount of water several iodinated compounds underwent deiodination of ortho-iodo group. The prominent future of this reaction that it selectively removes ortho-iodo group without any effect on para-iodo group and other halogens. Absence of reducing agent and short reaction times are the additional future of this reaction. In Chapter 4, we report novel styrylquinolines as novel candidate for small molecule based organic light emitting diodes (SMOLED). Compounds DCSQM and DCSQA based on donor-conjugated-acceptor architecture (D-π-A) showed different emission pattern in solvents of varying polarity. Both compounds exhibited excellent thermal and electrochemical properties. Device fabricated using DCSQM showed blue emission thus making itself as ideal candidate for OLED device.