916078-39-2Relevant academic research and scientific papers
Beyond organic solvents: synthesis of a 5-HT4receptor agonist in water
Bailey, J. Daniel,Helbling, Edward,Mankar, Amey,Stirling, Matthew,Hicks, Fred,Leahy, David K.
supporting information, p. 788 - 795 (2021/02/09)
Reducing or eliminating organic solvent use in pharmaceutical manufacturing is perhaps the most effective way to reduce the environmental, health, and safety impacts of drug substance manufacturing. With this in mind, we have developed a process to manufacture an investigational 5-HT4receptor agonist that is conducted almost entirely in water, including multiple controlled isolations. Key transformations carried out in aqueous media include a benzimidazole cyclization, amide bond formation, reductive amination, and a selective oxidation of an aliphatic alcohol. Compared to the first-generation manufacturing process using organic solvents, the aqueous process described here uses 77% less material inputs, 94% less organic solvent, and, surprisingly, 48% less water, while improving overall yield from 35% to 56%.
Discovery and SAR of N-(1-((substituted piperidin-4-yl)methyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide derivatives: 5-Hydroxytryptamine receptor 4 agonist as a potent prokinetic agent
Park, Jung Sang,Im, Weonbin,Choi, Sunghak,Park, Sook Jin,Jung, Jun Min,Baek, Ki Seon,Son, Han Pyo,Sharma, Satyasheel,Kim, In Su,Jung, Young Hoon
, p. 75 - 88 (2016/01/09)
A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affinities and low hERG affinities. Several types of analogs were obtained and screened for 5-HT4 binding, hERG blocking, agonism, and gastric emptying assessment. Among the analogues, compound 23g showed promising results compared with the other analogs with respect to gastric emptying rates in rats. Therefore, we suggest that it may be a clinical candidate for the development of a potent prokinetic agent to treat GI disorders.
BENZIMIDAZOLE-CARBOXAMIDE COMPOUNDS AS 5-HT4, RECEPTOR AGONISTS
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Page/Page column 25-26, (2008/06/13)
The invention relates to benzimidazole-carboxamide 5-HT 4 receptor agonist compounds of formula (I) wherein R1 and X are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates
