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Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
More than 10 years earlier, Baeckvall and his group (Pàmies and Baeckvall, 2001) developed an efficient kinetic resolution of racemic β-hydroxy nitriles via Candida antarctica lipase (Novozyme-435)-catalyzed transesterification in toluene at 80°C with 4-chlorophenyl acetate as acylating agent. A variety of racemic alkyl, aryl, and aryloxymethyl substituted β-hydroxy nitriles was efficiently transformed to the corresponding enantiomerically pure acetates. The combination with a Ru-complex-catalyzed alcohol racemization led to a DKR enabling the synthesis of enantiomerically pure acetates with ee’s up to 99%, and yields up to 85%. Examples are the synthesis of Denopamine and Propanolol precursors (see the below scheme). Denopamine is an orally administered drug acting as a β1 adrenergic receptor (ADRB1) agonist and used to treat angina as well as congestive heart failure and for clearing pulmonary edema. Propranolol, already detected 1964, belongs to the drug class of non-selective beta blockers. It is used to treat among others high blood pressure, cardiovascular hypertension, angina pectoris, tachyarrhythmia, myocardial infarction, or tachycardia and is administered intravenously or orally. The drug is on the World Health Organization’s List of Essential Medicines (WHO Model List of Essential Medicines (19th List)”; World Health Organization. April 2015).
Sympathomimetic Amines: Actions and Uses
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
Denopamine (TA-064) is also a β1-adrenoceptor partial agonist, but has a maximum inotropic effect in isolated cardiac tissues nearer to that of isoprenaline (75–80%). It binds to cardiac α-adrenoceptors but the inotropic effect is exclusively via β-adrenoceptors (Kohi et al. 1993). Denopamine has been used in the long-term treatment of patients with heart failure but its actions are again considerably reduced in isolated tissue from heart failure patients, presumably due to the down-regulated status of β1-adrenoceptors (Brodde 1991).
Recent advances in the treatment of Brugada syndrome
Published in Expert Review of Cardiovascular Therapy, 2018
Mariana Argenziano, Charles Antzelevitch
Agents that augment the L-type calcium channel current, such as β adrenergic agonists like isoproterenol, denopamine, or orciprenaline, are effective as well [136,179,194,199–201]. Isoproterenol, sometimes in combination with quinidine, has been reported to successfully suppress VF storms and to normalize the ST elevation, particularly in children [181,188,189,202–204]. Spontaneous VF in patients with BrS is often mediated by an increase in vagal tone and is amenable to treatment by an increase of sympathetic tone via the administration of isoproterenol. In the latest HRS/EHRA/APHRS consensus document, isoproterenol is a Class IIa indication for BrS patients presenting with electrical storms (Figure 4) [31].
Pathobiology and evolving therapies of coronary artery vasospasm
Published in Baylor University Medical Center Proceedings, 2021
Monish A. Sheth, Robert J. Widmer, Hari K. Dandapantula
Other therapies have also been suggested for CAV. Fasudil, a selective Rho-kinase inhibitor, has been shown to prevent ACh-induced CAV.45 Denopamine, a beta-1-selective agonist, has been shown to reduce both the frequency and severity of CAV in a small study.46 Administration of the endothelin antagonist bosentan in a case report resulted in complete resolution of symptoms that were refractory to commonly used antianginals, and these symptoms recurred when the drug was inadvertently withdrawn.47 Although prospective, randomized, placebo-controlled studies are needed for validation, Sang-yong et al48 showed that among 21 patients refractory to conventional medications, adding cilostazol for 2 weeks showed a 78.9% relative reduction in the angina intensity score and 73.5% in the angina frequency score (P < 0.001). Nicorandil, like nitrates, triggers smooth muscle relaxation via the nitrous oxide pathway and has additional actions as an arterial K + ATP channel agonist, resulting in more “balanced” arterial and venous vasodilatation than nitrates.49 This agent is not currently available in the US. Amiodarone is another spasmolytic drug that effects smooth muscle relaxation by different mechanisms and appears to be useful for the chronic treatment and prevention of CAV. The vasodilator property of amiodarone is achieved by both direct action and noncompetitive alpha receptor antagonism of coronary vasculature, though it has not been studied much in clinical use.50 Ketanserin, a serotonin inhibitor, has failed to be of value in the treatment of CAV, as shown in both spontaneous and ergonovine-induced CAV in a small study.51 Replacement of magnesium has been shown to promote coronary vasodilatation and suppress coronary vasospasm.52 There is a controversial role of adding vitamin C and vitamin E. Coronary stenting, coronary artery bypass surgery, and surgical sympathectomy have been studied as well.53,54