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Design and Novel Synthesis of a Nonpeptide Cholecystokynin Antagonist(PDF)


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Design and Novel Synthesis of a Nonpeptide Cholecystokynin Antagonist
WeiYunyang JosephP.Konopelski ①
School of Chemical Engineering,NUST,Nanjing 210094)
pharmaceutical chemistry organic synthesis asparagine cholecystokynin condensat ion
Cholecystoky nin( cck) is a poly pept ide hormone w hich plays an important role in the digest ive t ract w here it predominant ly interact s w ith cck-A receptor, and also in the central nervous system where it essentially act s as a neurotransmitter throug h cck-B type receptors. Some non-pept ide compounds also possess the aff inity for cck receptors and become the subject of intense research. Herein the design and sy nthesis of similar compounds of the non-pept ide cck antagonist ( + ) RP66803 containing tet rahydropyrimidinone ring instead of pyrrolidine ring w ere reported. T he sy nthesis started w ith asparagine t-butyl ester, w hich reacted w ith benzaldehyde toform an imine. Treat ing the imine w ith glycine chloride led to coupling and cyclization to form an intermediate, 3-pheny-l 4-aminomethylcarbony-l 5-t-buty-l carbonyl tetrahydropy rimidinone, and then reacted w ith m-tolylisocyanate to form the desired product in 42 % overall yield( based on asparagine t-buty l ester) .


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Last Update: 2013-03-25