RT Journal Article
SR Electronic
T1 Synthesis and labeling of a novel EGFR and HER-2 tyrosine kinase inhibitor containing 4-anilinoquinoline-3-carbonitrile nucleus
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1116
OP 1116
VO 50
IS supplement 2
A1 Chumpol Theeraladanon
A1 Ukihide Tateishi
A1 Masaaki Shiina
A1 Ryogo Minamimoto
A1 Hisashi Endo
A1 Takashi Oka
A1 Nobukazu Takahashi
A1 Tomio Inoue
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1116.abstract
AB 1116 Learning Objectives Since our novel EGFR inhibitor containing quinoline nucleus, YCU07, was previously reported. We currently have developed a more potent EGFR inhibitor according to recent studies of 4-anilinoquinoline-3-carbonitrile that function as irreversible EGFR and HER-2 tyrosine kinase inhibitory activity. To evaluate its specificity at both EGFR and HER-2 binding site, [6,7-dimethoxyethoxy]-quinolin-3-carbonitrile-4-yl]-(3-ethynylphenyl)-amine (YCU09) was synthesized and labeled with 68Ga using glutamic acid polypeptide (GAP) as chelating agent. Synthesis of YCU09 was started with 2-acetyl-4,5-dimethoxyaniline then utilized Ring Closing Metathesis (RCM) and Mukaiyama-Aldol reaction as key steps for construction of 4-anilinoquinoline-3-carbonitrile nucleus. YCU09 was conjugated to glutamic acid polypeptide (GAP) and in-house labeled with 68Ga. Synthesis of YCU09 was accomplished in 8 Steps. This methodology could be applied for assemble many substituted groups on 4-anilinoquinoline-3-carbonitrile synthesis. An efficient and practical synthetic route of YCU09 was established. It was conjugated to GAP and successfully labeled with 68Ga. Summary: An efficient and practical synthetic route of YCU09 was established. It was conjugated to GAP and successfully labeled with 68Ga.