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Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists
- Source :
- Bioorganic & Medicinal Chemistry Letters. 22:2807-2810
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model.
- Subjects :
- Pyrrolidines
Ketone
Drug Inverse Agonism
Stereochemistry
Clinical Biochemistry
Pharmaceutical Science
1-Propanol
Biochemistry
Histamine Agonists
Methylamines
chemistry.chemical_compound
Phenols
Pharmacokinetics
Sleep Disorders, Circadian Rhythm
In vivo
Diamine
Drug Discovery
Animals
Humans
Inverse agonist
Molecule
Wakefulness
Receptor
Molecular Biology
chemistry.chemical_classification
Organic Chemistry
Ketones
Rats
chemistry
Molecular Medicine
Histamine
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....ec06339451ae51dea3f5d2188b93b94e