linopirdine linopirdine linopirdine is a putative cognition-enhancing drug with a novel mechanism of action. linopirdine blocks the kcnq2\3 heteromer m current with an ic50 of 2.4 micromolar disinhibiting acetylcholine release, and increasing hippocampal ca3-schaffer collateral mediated glutamate release onto ca1 pyramidal neurons. in a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-fos, an effect which is blocked by atropine and mk-801, suggesting linopirdine can compensate for the age related decline in acetylcholine release. linopirdine also blocks homomeric kcnq1 and kcnq4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than kcnq2/3. linopirdineclinical dataatc coden06bx09 (who) identifiers iupac name 1-phenyl-3,3-bis(pyridin-4-ylmethyl)-1,3-dihydro-2h-indol-2-one cas number105431-72-9 npubchem cid3932iuphar/bps2599chemspider3795 yuniii5tb3nz94tkeggd04741 ychemblchembl319111 ycomptox dashboard (epa)dtxsid6045163 chemical and physical dataformulac26h21n3omolar mass391.474 g·mol−13d model (jsmol)interactive image smiles o=c2n(c1ccccc1c2(cc3ccncc3)cc4ccncc4)c5ccccc5 inchi inchi=1s/c26h21n3o/c30-25-26(18-20-10-14-27-15-11-20,19-21-12-16-28-17-13-21)23-8-4-5-9-24(23)29(25)22-6-2-1-3-7-22/h1-17h,18-19h2 ykey:yejcdkjiemiwrq-uhfffaoysa-n y ny (what is this?) (verify) synthesis linopirdine synthesis: ~90%: patents ~90%: the amide formation between diphenylamine (1) and oxalyl chloride gives intermediate, cid:11594101 (2). haworth type intramolecular cyclization of the acid chloride occurs on heating to afford 1-phenylisatin (3). the reaction with 4-picoline (4) under ptc with a quat. salt afforded the carbinol, cid:10358387 (5). dehydration of the alcohol using acetic anhydride gives (6). the reduction of the olefin then afforded the indolone, cid:10470081 (7). the 3 position is now activated by the adjacent benzene ring on one side and the carbonyl group on the other. alkylation with 4-picolylchloride (8) proceeds with hydroxide as the base to afford linopirdine (9).