Metabolism of a Serotonin-4 Receptor Partial Agonist 4-{4-[4-Tetrahydrofuran-3-yloxy)-Benzo[d]Isoxazol-3-yloxymethyl]-Piperidin-1-ylmethyl}-Tetrahydropyran-4-ol (TBPT): Identification of an Unusual Pharmacologically Active Cyclized Oxazolidine Metabolite in Human

• Published in: Journal of pharmaceutical sciences Vol. 102; no. 9; pp. 3277 - 3293
• Main Authors: Sawant-Basak, Aarti, Coffman, Karen J., Walker, Gregory S., Ryder, Tim F., Tseng, Elaine, Miller, Emily, Lee, Carlos, Vanase-Frawley, Michelle A., Wong, John W., Brodney, Michael A., Rapp, Tracey, Obach, R. Scott
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2013; Wiley Subscription Services, Inc., A Wiley Company; Elsevier Limited
• Subjects: Animals; Blood Proteins - metabolism; Brain - metabolism; Cyclization; Dealkylation; Dogs; Female; Furans - chemistry; Furans - metabolism; Furans - pharmacokinetics; Furans - pharmacology; hepatic metabolism; Hepatocytes - metabolism; Humans; Hydroxylation; Male; mass spectrometry; metabolism; microsomes; Microsomes, Liver - metabolism; Oxazoles - chemistry; Oxazoles - metabolism; Oxazoles - pharmacokinetics; Oxazoles - pharmacology; protein binding; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT4 - metabolism; Serotonin 5-HT4 Receptor Agonists - chemistry; Serotonin 5-HT4 Receptor Agonists - metabolism; Serotonin 5-HT4 Receptor Agonists - pharmacokinetics; Serotonin 5-HT4 Receptor Agonists - pharmacology; mass spectrometry; metabolism; protein binding; microsomes; hepatic metabolism

4-{4-[4-Tetrahydrofuran-3-yloxy)-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol (PF-4995274, TBPT) is a new agent that is a partial agonist of the human serotonin-4 (5-HT4) receptor and is under investigation for neurological disorders. Metabolism of TBPT was examined in...