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Your search keyword '"Serotonin 5-HT2 Receptor Agonists pharmacokinetics"' showing total 3 results
Start Over Descriptor "Serotonin 5-HT2 Receptor Agonists pharmacokinetics" Journal bioorganic medicinal chemistry letters
3 results on '"Serotonin 5-HT2 Receptor Agonists pharmacokinetics"'

1. Discovery of a lead series of potent benzodiazepine 5-HT 2C receptor agonists with high selectivity in functional and binding assays.

Author

Ren A, Zhu X, Feichtinger K, Lehman J, Kasem M, Schrader TO, Wong A, Dang H, Le M, Frazer J, Unett DJ, Grottick AJ, Whelan KT, Morgan ME, Sage CR, and Semple G

Subjects
Animals, Benzodiazepines chemical synthesis, Benzodiazepines metabolism, Benzodiazepines pharmacokinetics, Dogs, Drug Discovery, Drug Stability, Heterocyclic Compounds, 3-Ring chemical synthesis, Heterocyclic Compounds, 3-Ring metabolism, Heterocyclic Compounds, 3-Ring pharmacokinetics, Humans, Macaca fascicularis, Male, Mice, Microsomes metabolism, Molecular Structure, Rats, Sprague-Dawley, Serotonin 5-HT2 Receptor Agonists chemical synthesis, Serotonin 5-HT2 Receptor Agonists metabolism, Serotonin 5-HT2 Receptor Agonists pharmacokinetics, Structure-Activity Relationship, Benzodiazepines pharmacology, Heterocyclic Compounds, 3-Ring pharmacology, Receptor, Serotonin, 5-HT2C metabolism, Serotonin 5-HT2 Receptor Agonists pharmacology
Abstract

A series of potential new 5-HT 2 receptor scaffolds based on a simplification of the clinically studied, 5-HT 2C R agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT 2C receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Published
2020
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2. Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones as 5-HT2C receptor agonists.

Author

Fevig JM, Feng J, Rossi KA, Miller KJ, Wu G, Hung CP, Ung T, Malmstrom SE, Zhang G, Keim WJ, Cullen MJ, Rohrbach KW, Qu Q, Gan J, Pelleymounter MA, and Robl JA

Subjects
Animals, Half-Life, Heterocyclic Compounds, 3-Ring chemistry, Heterocyclic Compounds, 3-Ring pharmacokinetics, Humans, Isoquinolines chemical synthesis, Isoquinolines pharmacokinetics, Male, Pyrroles pharmacokinetics, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2A chemistry, Receptor, Serotonin, 5-HT2A metabolism, Receptor, Serotonin, 5-HT2B chemistry, Receptor, Serotonin, 5-HT2B metabolism, Receptor, Serotonin, 5-HT2C metabolism, Serotonin 5-HT2 Receptor Agonists chemistry, Serotonin 5-HT2 Receptor Agonists pharmacokinetics, Structure-Activity Relationship, Heterocyclic Compounds, 3-Ring chemical synthesis, Isoquinolines chemistry, Pyrroles chemical synthesis, Pyrroles chemistry, Receptor, Serotonin, 5-HT2C chemistry, Serotonin 5-HT2 Receptor Agonists chemical synthesis
Abstract

A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT(2C) agonism with excellent selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2013
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3. Novel 6,7,8,9-tetrahydro-5H-1,4,7,10a-tetraaza-cyclohepta[f]indene analogues as potent and selective 5-HT(2C) agonists for the treatment of metabolic disorders.

Author

Tye H, Mueller SG, Prestle J, Scheuerer S, Schindler M, Nosse B, Prevost N, Brown CJ, Heifetz A, Moeller C, Pedret-Dunn A, and Whittaker M

Subjects
Animals, Aza Compounds chemistry, Azepines pharmacokinetics, Azepines therapeutic use, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels antagonists & inhibitors, Ether-A-Go-Go Potassium Channels metabolism, Heterocyclic Compounds, 3-Ring pharmacokinetics, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Indenes pharmacokinetics, Indenes therapeutic use, Male, Pyrimidines chemistry, Rats, Rats, Wistar, Receptor, Serotonin, 5-HT2A chemistry, Receptor, Serotonin, 5-HT2A metabolism, Receptor, Serotonin, 5-HT2B chemistry, Receptor, Serotonin, 5-HT2B metabolism, Receptor, Serotonin, 5-HT2C metabolism, Serotonin 5-HT2 Receptor Agonists pharmacokinetics, Serotonin 5-HT2 Receptor Agonists therapeutic use, Structure-Activity Relationship, Azepines chemistry, Heterocyclic Compounds, 3-Ring chemistry, Indenes chemistry, Metabolic Diseases drug therapy, Receptor, Serotonin, 5-HT2C chemistry, Serotonin 5-HT2 Receptor Agonists chemistry
Abstract

The discovery of a novel series of 5-HT(2C) agonists based on a tricyclic pyrazolopyrimidine scaffold is described. Compounds with good levels of in vitro potency and moderate to good levels of selectivity with respect to the 5-HT(2A) and 5-HT(2B) receptors were identified. One of the analogues (7 g) was found to be efficacious in a sub-chronic weight loss model. A key limitation of the series of compounds was that they were found to be potent inhibitors of the hERG ion channel. Some compounds, bearing polar side chains were identified which showed a much reduced hERG liability however these compounds were sub-optimal in terms of their in vitro potency or selectivity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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