Synthesis of a series of compounds related to betaxolol, a new .beta.1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases
| Autor: | Philippe Manoury, Jean Binet, Jean Rousseau, Françoise Lefèvre-Borg, I Cavero |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Male
Adrenergic beta-Antagonists Guinea Pigs Propranolol In Vitro Techniques Pharmacology Betaxolol Propanolamines Structure-Activity Relationship Pharmacokinetics Drug Discovery medicine Animals Potency Anesthetics Local Antihypertensive Agents Biotransformation Metoprolol Chemistry Antagonist Rana esculenta Biological activity Rats Bioavailability Kinetics Cardiovascular Diseases Chronic Disease Molecular Medicine Female medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 30:1003-1011 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00389a008 |
| Popis: | A series of para-substituted phenoxypropanolamines has been synthesized and tested for beta-adrenoceptor blocking activity. Some derivatives (8, 11, 12, 20, 21) exhibited greater in vitro potency than the reference drugs metoprolol and propranolol. This series, in contrast to propranolol but similar to metoprolol, possesses cardioselectivity. The 3-[p-[(cycloalkylmethoxy)ethyl]phenoxy]-1-substituted-amino-2-prop anol derivatives 8 (cyclopropylmethoxyethyl: betaxolol) and 11 (cyclobutylmethoxyethyl) produced antihypertensive effects in spontaneously hypertensive rats. Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina. |
| Databáze: | OpenAIRE |
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