 | |
| Clinical data | |
|---|---|
| ATC code | |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| IUPHAR/BPS | |
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C26H21N3O |
| Molar mass | 391.474 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
 N Y (what is this?) (verify) | |
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[1] disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1pyramidal neurons.[2] 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.[3] Linopirdine also blocks homomeric KCNQ1 and KCNQ4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than KCNQ2/3.[1] Linopirdine also acts as a glycine receptor antagonist in concentrations typical for Kv7 studies in the brain.[4]
The amide formation betweendiphenylamine (1) andoxalyl chloride [79-37-8] gives intermediate,CID:11594101 (2). Haworth type intramolecular cyclization of the acid chloride occurs on heating to afford 1-phenylisatin [723-89-7] (3). The reaction with4-picoline (4) under PTC with a Quat. salt afforded the carbinol,CID:10358387 (5). Dehydration of the alcohol usingacetic anhydride gives [33546-08-6] (6). The reduction of the olefin then afforded theindolone,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 [10445-91-7] (8) proceeds with hydroxide as the base to afford Linopirdine (9).
