Metoprolol structure

This is the drug Metoprolol, a beta-blocker). Obviously, a great many deductions have to be made to arrive at a structure from scratch in this way and whilst each one in this example is valid in its own right and they all fit together perfectly well with no obvious conflicts, structural verification via the HMQC/HMBC route would be advisable ... 

Metoprolol tartarate, molecular formula and structure, 5 95t Metribuzin, 13 322 Metrics, 24 196 Metrologia, 15 769 Metropolis, Nicholas, 26 1001 Metropolis criterion, 26 1006, 1024,... 

Fig. 3.8 Structures of propranolol (1), betaxolol (2), metoprolol (3) and talinolol (4) and their respective extraction by the gastointestinal tract (E(g. i.)) and liver E(h)...

Ciprofloxacin (Cipro, Cipro XR, Proquin XR) [Antibiotic/ Fluoroquinolone] Uses Rx lower resp tract, sinuses, skin skin structure, bone/joints, urinary tract Infxns including prostatitis Action Quinolone antibiotic DNA gyrase Dose Adults. 250-750 mg PO ql2h XR 500-1000 mg PO q24h or 200-400 mg IV ql2h in renal impair Caution [C, /-] Children <18 y Contra Component sensitivity Disp Tabs, susp, inj SE Restlessness, N/V/D, rash, ruptured tendons, T LFTs Interactions T Effects Wf probenecid T effects OF diazepam, theophylline, caffeine, metoprolol, propranolol, phenytoin, warfarin effects W/ antacids, didanosine, Fe salts. Mg, sucralfate, Na bicarbonate,... 

Fig. 4.1 Correlation of permeability and total hydrogen-bonding capacity for a series of structural heterogeneous compounds corticosterone (Co), testosterone (Te), propranolol (Pr), alprenolol (Al), warfarin (Wa), metoprolol (Me), felodipine (Fe), hydrocortisone (Hy),...

There is some anecdotal evidence that atrioventricular nodal blockade with verapamil or a beta-blocker can also be effective. However, in two cases the addition of a beta-blocker (either atenolol or metoprolol) to treatment with class I antidysrhythmic drugs (cibenzoline in one case and flecainide in the other) did not prevent the occurrence of atrial flutter with a 1 1 response (47). However, the author suggested that in these cases, although the beta-blockers had not suppressed the dysrhythmia, they had at least improved the patient s tolerance of it. In both cases the uses of class I antidysrhythmic drugs was contraindicated by virtue of structural damage, in the first case due to mitral valvular disease and in the second due to an ischemic cardiomyopathy. 

Figure 6-7 Structure-toxicity relationships with -adrenoceptor antagonists practolol, atenolol, and metoprolol.

Siegers C., Maquille A., Deridder V., Sonveaux E., Jiwan J.L.H., Tilquin B., LC-MS analysis in the e-beam and gamma radiolysis of metoprolol tartrate in aqueous solution Structure elucidation and formation mechanism of radiolytic products, Radiat. Phys. Chem., 2006,75,977-989. 

A list of 3-blockers indicating their structure and developmental status and the absence or presence of S-receptor selectivity, partial agonist activity and non-specific cardiac depressant property, is presented in Table I for reference. In addition to propranolol, two new 3-blockers have now been approved for use in man in the U.S. Metoprolol has been approved for use in hypertension, timolol has been approved for use in glaucoma.In other parts of the world, there are at least 17 3-blockers available for use. ... 

F igure 15.4. Comparison of the metabolism of metoprolol (3) with that of the soft drugs (8)designed starting from one of its inactive metabolites (7).The dashed line in structures (8)and (9)denotesthe possibility of having either isopropyl- or iert-butyl-substituted amines. 

Table 10-6 represents a summary of empirically arrived at structure-activity relationships, The exception of para-aryl substitutions for cardioselective P-blockers (IIB 1 and 4) should be noted but cannot be satisfactorily explained. In fact, not all the para substituents are as lipophilic as the amide ones in practolol, acebutolol (No. 11), atenolol (No. 12), or the ester group in esmolol (No. 14). The methoxyethyl group of metoprolol (No. 15) and the large hydrocarbon nature of the cyclopropylmethoxyethyl function of betaxolol (No. 13) would hardly be expected to increase aqueous solubility of these compounds (see Table 10-4). Still, all the -selective compounds are much less lipophilic than propranolol. Such apparent data correlations may have contributed to a belief that a cardioselectivity-hydrophilicity relationship exists due to some putative hydrophilic site on the Pj receptor. This notion, however, was dispelled by a study comparing hydrophilicity, substituent positions, and cardioselectivity in three sets of l-(2-propylamino)-3-phenoxy-2-propanols. The data clearly show that for each set of compounds even with identical lipophilicities (log P) the Pi-activity resided primarily in the para isomer.

Dronedarone is structurally related to amiodarone, which is known to inhibit the cytochrome P450 isoenzyme CYP2D6, by which metoprolol is metabolised (see Amiodarone + Beta blockers , p.246). This study also shows that dronedarone inhibits CYP2D6, effectively making extensive metabolisers into poor metabolisers. For more information on metaboliser status see Genetic factors , (p.4). 

In addition, iPSC-CMs have been used to model structural heart diseases, including familial dilated cardiomyopathy (DCM) (Sun et al., 2012) and hypertrophic cardiomyopathy (HCM) (Lan et al., 2013) caused by mutations in cardiac troponin T (cTnT) and myosin heavy chain 7 (MYH7), respectively. In both studies, iPSC-CMs recapitulated the disease phenotype at the cellular level with pharmacological rescue by chronic treatment with p-adrenergic blocker (propranolol or metoprolol) or the L-type Ca channel blocker (verapamil) (Sun et al., 2012 Lan et al., 2013) (Table 22.1). Collectively, these studies reinforce the ability of iPSC-CMs to model channelopathies and cardiomyopathies as well as to test the clinical efficacy of drugs. 

Figure 3.14 Structures of selected P-blockers dichloroisoprenaline (1), propranolol (2), atenolol (3), bisoprolol (4), metoprolol (5), and bupranolol (6).

Due to the need of extensive derivatization for GC-MS analysis (see Chapter 3), P-receptor blocking agents such as atenolol, bupranolol, metoprolol, and propranolol (Fig. 4.23,1-4) have been early subjects of LC-MS/MS analysis. The presence of a secondary amino function in all P-blockers provides sufficient proton affinity for positive ESI, and core structure-specific as well as individual product ions are derived from target analytes using low energy CID as summarized in Table 4.7. 

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