Maspero, Marco published the artcileTacrine-xanomeline and tacrine-iperoxo hybrid ligands: Synthesis and biological evaluation at acetylcholinesterase and M1 muscarinic acetylcholine receptors, Application of 2-Aminobenzonitrile(Flakes or Chunks), the main research area is xanomeline tacrine iperoxo hybrid preparation acetylcholinesterase muscarinic acetylcholine receptor; Allosteric modulation; Bitopic ligands; Ellman’s assay; Inositol monophosphate; Iperoxo; M(1) muscarinic acetylcholine receptor; Multitarget compounds; Phospholipase C; Tacrine; Xanomeline.
A set of new hybrid derivatives, in which apolymethylene spacer chain of variable length connected the pharmacophoric moiety of xanomeline are synthesized ,anM1/M4preferring orthosteric muscarinic agonist, with that of tacrine, a well-known acetylcholinesterase (AChE) inhibitor abletoallosterically modulatemuscarinicacetylcholinereceptors(mAChRs). When tested in vitro in a colorimetric assay for their ability to inhibit AChE, the new compounds showed higher or similar potency compared to that of tacrine. Docking analyses were performed on the most potent inhibitors to rationalize their exptl. inhibitory power against AChE. Next, the signaling cascade at M1 mAChRs by exploring the interaction of Gαq-PLC-β3 proteins through split luciferase assays and the myo-Inositol 1 phosphate (IP1) accumulation in cells is evaluated. The results were compared with those obtained on the known derivatives, two quite potent AChE inhibitors in which tacrine is linked to iperoxo, an exceptionally potent muscarinic orthosteric activator. Interestingly, it was found that iprexo tacrine hybrids behaved as partial agonists of the M1 mAChR, at variance with hybrids containing xanomeline as the orthosteric mol. fragment, which were all unable to activate the receptor subtype response.
Bioorganic Chemistry published new progress about Alzheimer disease. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Application of 2-Aminobenzonitrile(Flakes or Chunks).
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts