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Design, Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor Antagonists.

ABSTRACT: In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK i values of 8.6 and 8.1, respectively.

SUBMITTER: Hanessian S

PROVIDER: S-EPMC4027792 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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Design, Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor Antagonists.

Hanessian Stephen S Jennequin Thomas T Boyer Nicolas N Babonneau Vincent V Soma Udaykumar U Mannoury la Cour Clotilde C Millan Mark J MJ De Nanteuil Guillaume G

ACS medicinal chemistry letters 20140213 5

In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK i values of 8.6 and 8.1, respectively. ...[more]

PMID: 24900878

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