ml-10302 and Alzheimer-Disease

ml-10302 has been researched along with Alzheimer-Disease* in 2 studies

Other Studies

2 other study(ies) available for ml-10302 and Alzheimer-Disease

Article	Year
Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease. European journal of medicinal chemistry, 2015, Oct-20, Volume: 103 Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine4 receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition. Topics: Alzheimer Disease; Animals; Cognition Disorders; Dogs; Dose-Response Relationship, Drug; Drug Design; Drug Partial Agonism; Humans; Molecular Structure; Pyridines; Rats; Receptors, Serotonin, 5-HT4; Structure-Activity Relationship	2015
Design, synthesis, and biological evaluation of new 5-HT4 receptor agonists: application as amyloid cascade modulators and potential therapeutic utility in Alzheimer's disease. Journal of medicinal chemistry, 2009, Apr-23, Volume: 52, Issue:8 Serotonin 5-HT(4) receptor (5-HT(4)R) agonists are of particular interest for the treatment of Alzheimer's disease because of their ability to ameliorate cognitive deficits and to modulate production of amyloid beta-protein (Abeta). However, despite the range of 5-HT(4)R agonists synthesized to date, potent and selective 5-HT(4)R agonists are still lacking. In the present study, two libraries of molecules based on the scaffold of ML10302, a highly specific and partial 5-HT(4)R agonist, were efficiently prepared by parallel supported synthesis and their binding affinities and agonist activities evaluated. Furthermore, we showed that, in vivo, the two best candidates exhibited neuroprotective activity by increasing the level of the soluble form of the amyloid precursor protein (sAPPalpha) in the cortex and hippocampus of mice. Interestingly, one of these compounds could also inhibit Abeta fibril formation in vitro. Topics: Alzheimer Disease; Aminobenzoates; Amyloid; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Biopolymers; Cell Line, Tumor; Cerebral Cortex; Cyclic AMP; Drug Design; Hippocampus; Humans; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; para-Aminobenzoates; Peptide Fragments; Piperidines; Radioligand Assay; Rats; Serotonin 5-HT4 Receptor Agonists; Structure-Activity Relationship	2009

Article

Year

Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease.

European journal of medicinal chemistry, 2015, Oct-20, Volume: 103

Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine4 receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition.

Topics: Alzheimer Disease; Animals; Cognition Disorders; Dogs; Dose-Response Relationship, Drug; Drug Design; Drug Partial Agonism; Humans; Molecular Structure; Pyridines; Rats; Receptors, Serotonin, 5-HT4; Structure-Activity Relationship

2015

Design, synthesis, and biological evaluation of new 5-HT4 receptor agonists: application as amyloid cascade modulators and potential therapeutic utility in Alzheimer's disease.

Journal of medicinal chemistry, 2009, Apr-23, Volume: 52, Issue:8

Serotonin 5-HT(4) receptor (5-HT(4)R) agonists are of particular interest for the treatment of Alzheimer's disease because of their ability to ameliorate cognitive deficits and to modulate production of amyloid beta-protein (Abeta). However, despite the range of 5-HT(4)R agonists synthesized to date, potent and selective 5-HT(4)R agonists are still lacking. In the present study, two libraries of molecules based on the scaffold of ML10302, a highly specific and partial 5-HT(4)R agonist, were efficiently prepared by parallel supported synthesis and their binding affinities and agonist activities evaluated. Furthermore, we showed that, in vivo, the two best candidates exhibited neuroprotective activity by increasing the level of the soluble form of the amyloid precursor protein (sAPPalpha) in the cortex and hippocampus of mice. Interestingly, one of these compounds could also inhibit Abeta fibril formation in vitro.

Topics: Alzheimer Disease; Aminobenzoates; Amyloid; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Biopolymers; Cell Line, Tumor; Cerebral Cortex; Cyclic AMP; Drug Design; Hippocampus; Humans; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; para-Aminobenzoates; Peptide Fragments; Piperidines; Radioligand Assay; Rats; Serotonin 5-HT4 Receptor Agonists; Structure-Activity Relationship

2009