The quinoline nucleus of the previously described 4-phenylquinoline-3- carboxamides NK1 receptor ligands 7 has been transformed into either substituted or azole - (i.e., triazole or tetrazole) fused pyridine moieties of compounds 9 and 10, respectively, in order to obtain NK1 receptor ligands showing lower molecular weight or higher hydrophilicity. The program of molecular manipulations produced NK1 receptor ligands showing affinity in the nanomolar range. In particular, 4-methyl-1-piperazinyl derivative 9j showed an IC50 value of 4.8 nM and was proved to behave as a NK1 antagonist blocking Sar9-SP-sulfone induced proliferation and migration of microvascular endothelial cells. Therefore, compound 9j has been labeled with [11C]CH3I (t 1/2 = 20.4 min, β+ = 99.8%) starting from the corresponding des-methyl precursor 9i using with a radiochemical yield of about 10% (not decay corrected) and a specific radioactivity >1 Ci/μmol in order to be used as a radiotracer in next PET studies. © 2011 Elsevier Ltd. All rights reserved.
Giuliani, G., Cappelli, A., Matarrese, M., Masiello, V., Turolla, E., Monterisi, C., et al. (2011). Non-peptide NK1 receptor ligands based on the 4-phenylpyridine moiety. BIOORGANIC & MEDICINAL CHEMISTRY, 19(7), 2242-2251 [10.1016/j.bmc.2011.02.031].
Non-peptide NK1 receptor ligands based on the 4-phenylpyridine moiety
TUROLLA, ELIA ANNA;FAZIO, FERRUCCIO;
2011
Abstract
The quinoline nucleus of the previously described 4-phenylquinoline-3- carboxamides NK1 receptor ligands 7 has been transformed into either substituted or azole - (i.e., triazole or tetrazole) fused pyridine moieties of compounds 9 and 10, respectively, in order to obtain NK1 receptor ligands showing lower molecular weight or higher hydrophilicity. The program of molecular manipulations produced NK1 receptor ligands showing affinity in the nanomolar range. In particular, 4-methyl-1-piperazinyl derivative 9j showed an IC50 value of 4.8 nM and was proved to behave as a NK1 antagonist blocking Sar9-SP-sulfone induced proliferation and migration of microvascular endothelial cells. Therefore, compound 9j has been labeled with [11C]CH3I (t 1/2 = 20.4 min, β+ = 99.8%) starting from the corresponding des-methyl precursor 9i using with a radiochemical yield of about 10% (not decay corrected) and a specific radioactivity >1 Ci/μmol in order to be used as a radiotracer in next PET studies. © 2011 Elsevier Ltd. All rights reserved.
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