AI Article Synopsis
- - The study focuses on the development of 4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives, specifically highlighting compound 14 (CT53986) as a strong and targeted inhibitor of PDGFR phosphorylation.
- - It includes a detailed investigation of the structure-activity relationship (SAR) in the arylamine segment, C-7 appendage, and thiourea part of the compounds.
- - Additionally, the research synthesized bioisosteres of thiourea and quinazoline to compare their inhibitory effects, along with describing the pharmacokinetic (PK) profiles for the
Article 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.
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| http://dx.doi.org/10.1016/j.bmcl.2004.07.041 | DOI Listing |
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