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Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia
- Source :
- Bioorganicmedicinal chemistry letters. 19(15)
- Publication Year :
- 2009
-
Abstract
- The benzimidazole core of the selective non-brain-penetrating H 1 -antihistamine mizolastine was used to identify a series of brain-penetrating H 1 -antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H 1 -antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile.
- Subjects :
- Benzimidazole
ERG1 Potassium Channel
medicine.medical_treatment
Chemistry, Pharmaceutical
Clinical Biochemistry
hERG
Histamine Antagonists
Pharmaceutical Science
Pharmacology
Biochemistry
Rats, Sprague-Dawley
chemistry.chemical_compound
Structure-Activity Relationship
Pharmacokinetics
In vivo
Sleep Initiation and Maintenance Disorders
Drug Discovery
medicine
Animals
Humans
Molecular Biology
biology
Electromyography
Organic Chemistry
Antagonist
Brain
Electroencephalography
Ether-A-Go-Go Potassium Channels
Rats
chemistry
Models, Chemical
Drug Design
biology.protein
Molecular Medicine
Antihistamine
Benzimidazoles
Histamine
Mizolastine
medicine.drug
Subjects
Details
- ISSN :
- 14643405
- Volume :
- 19
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry letters
- Accession number :
- edsair.doi.dedup.....a66e9f7c78f6eb714a299f657f109cb6