Synthesis of 2,4-Diaryl-5-pyridinylimidazoles and Related Compounds -Potential p38 Kinase Inhibitors Regulating Gene Expression of Interleukin-1

• Main Authors: Kung-Pern Wang, 王坤鵬
• Other Authors: Prof. Hsing-Jang Liu
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/v4v3wt

碩士 === 國立清華大學 === 化學系 === 92 === The first chapter of this thesis describes the generation of a focused library of 2,4,5-triarylimidazoles and the screening of biological activities of the members thereof. Starting with substituted methyl benzoates, treatment with 4-lithium picolinate gave diaryl ketone 10. Subsequent oxidation of ketone 10 with selenium dioxide then furnished diketone 8 which was exposed to excess ammonium acetate and various functionalized benzaldehydes to both generate the central imidazole ring as well as install the C-2 aryl group present in compound 4. Following this extremely robust, convenient, and high yielding synthetic protocol, a large number of 2,4-diaryl-5-(2-pyridinyl)imidazoles, 2,4-diaryl-5-(3-pyridinyl)imidazoles, and other analogous 2,4-diarylimidazoles containing various C-5 attached heterocycles were synthesized. The screening of members of this focused library revealed a number of compounds possessing antineoplastic activity. The second chapter of this thesis delineates the effort to develop a synthetic process amenable towards the generation of N-15 labeled members of above mentioned focused library. As such, Sonogashira coupling of 4-bromopyridine 41, synthesized from pyridine via a series of manipulations, with substituted arylacetylenes furnished diarylacetylenes 49. Oxidation of the carbon-carbon triple bond in 49 with potassium permanganate gave dikeone 8 which allowed for a convergence with the above described synthetic protocol for the generation of members of the focused library. The details of this and the above mentioned research is contained herein.