897617-91-3Relevant academic research and scientific papers
Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor
Salovich, James M.,Vinson, Paige N.,Sheffler, Douglas J.,Lamsal, Atin,Utley, Thomas J.,Blobaum, Anna L.,Bridges, Thomas M.,Le, Uyen,Jones, Carrie K.,Wood, Michael R.,Scott Daniels,Jeffrey Conn,Niswender, Colleen M.,Lindsley, Craig W.,Hopkins, Corey R.
body text, p. 5084 - 5088 (2012/09/07)
Herein we describe the discovery and development of a novel class of M 4 positive allosteric modulators, culminating in the discovery of ML293. ML293 exhibited modest potency at the human M4 receptor (EC50 = 1.3 μM) and excellent efficacy as noted by the 14.6-fold leftward shift of the agonist concentration-response curve. ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1 h, [Brain] = 10.3 μM, B:P = 0.85).
