2007-11-6Relevant articles and documents
Photodegradation products of propranolol: The structures and pharmacological studies
Uwai, Koji,Tani, Marie,Ohtake, Yosuke,Abe, Shinya,Maruko, Akiko,Chiba, Takashi,Hamaya, Yoshiro,Ohkubo, Yasuhito,Takeshita, Mitsuhiro
, p. 357 - 365 (2005)
Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are unstable in light should be carefully handled to protect their potency and ensure their safety. Propranolol (1), a β-adrenergic receptor antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due to its naphthalene skeleton, this drug may be both light unstable and a photosensitizing agent. In this study, we isolated three photodegraded products of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N-formylpropranolol (4). The structures of these compounds were determined by spectroscopic methods and chemical syntheses. We also examined the acute toxicities of these substances in mice and their binding to β-adrenergic receptors using rat cerebellum cortex membranes. Although the photoproducts isolated in this study did not exhibit any acute toxicity or significant binding to β-adrenergic receptors, these results serve as a warning to single-dose packaging systems, as propranolol (1) must be handled carefully to protect the compound from light-induced degradation.
Acetylation of (R,S)-propranolol catalyzed by Candida antarctica lipase B: An experimental and computational study
Escorcia, Andres M.,Molina, Daniel,Daza, Martha C.,Doerr, Markus
, p. 21 - 29 (2013/11/06)
The chemo- and enantioselectivity of the Candida antarctica lipase B (CalB)-catalyzed acetylation reaction of (R,S)-propranolol using vinyl acetate as acyl donor and toluene as organic solvent was studied. Because of the poor solubility of propranolol in toluene small quantities of methanol were added as cosolvent. The effects of the propranolol/vinyl acetate ratio, the enzyme purification procedure and the methanol concentration on the reaction were investigated. The reactions occurring in the system were quantitatively investigated using 1H and 13C NMR spectroscopy. The major reactions were the hydrolysis and alcoholysis of vinyl acetate, as a consequence of the presence of residual water and methanol in the reaction medium. Furthermore, the NMR analysis confirmed that O-acetyl-propranolol was formed exclusively. The reaction was also found to be enantioselective favoring the faster transformation of the R-propranolol. In addition to the experiments, molecular modeling was used to study the formation of the reactive Michaelis complexes between propranolol and acetylated CalB, using a combined molecular docking and molecular dynamics (MD) procedure. Only for the O-acetylation we found binding modes of the substrate leading to formation of the product, which explains the experimentally observed chemoselectivity of CalB.
Optical purity determination by NMR: Use of chiral lanthanide shift reagents and a base line technique
Dewar,Kwakye,Parfitt,Sibson
, p. 802 - 806 (2007/10/02)
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