Author(s): Heath JA, Mehrotra MM, Chi S, Yu JC, Hutchaleelaha A,
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Abstract 4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives such as 14 (CT53986) have been identified to be potent and selective inhibitors of the phosphorylation of PDGFR. SAR-investigations are described in the arylamine segment, C-7 appendage, and the thiourea moiety. Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity. PK profiles of the optimized compounds in rat, dog, and cynomolgus monkey are described.
This article was published in Bioorg Med Chem Lett
and referenced in Medicinal Chemistry