Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H , H , and H receptors.

Histamine is a transmitter that activates the four receptors H R to H R. The H R is found in the nervous system as an autoreceptor and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1-(2,3-dihydro-1-benzofuran-2-yl)methylpiperazines (LINS01 compounds) have the selectivity for the H R over the H R.

Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H and H Receptors with Anti-inflammatory Potential.

The histamine receptors (HRs) are traditional G protein-coupled receptors of extensive therapeutic interest. Recently, HR and HR subtypes have been targeted in drug discovery projects for inflammation, asthma, pain, cancer, Parkinson's, and Alzheimer's diseases, which includes searches for dual acting HR/HR ligands. In the present work, nine 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01 series) molecules were synthesized and evaluated as HR and HR ligands.