Isoproterenol structure

FIG. 17 Chemical structures of (a) epinephrine hydrochloride, (b) dopamine hydrochloride, (c) isoproterenol hydrochloride, (d) phenylephrine hydrochloride, (e) tolazoline hydrochloride, (f) oxyprenolol hydrochloride, (g) alprenolol hydrochloride, and (h) propranolol hydrochloride. 

The basic structure shared by most 3-sympatholytics is the side chain of 3-sympathomimetics (cf isoproterenol with the p-blockers propranolol, pindolol, atenolol). As a rule, this basic structure is linked to an aromatic nucleus by a methylene and oxygen bridge. The side chain C-atom bearing the hydroxyl group forms the chiral center. With some exceptions (e.g., timolol, penbuto-lol), all p-sympatholytics are brought as racemates into the market (p. 62). 

It should be mentioned that the substituted ethanolamine group in the structure of )3-adrenobIockers is similar to that of many compounds with agonistic adrenergic activity (isoproterenol (II.1.9), albuterol (11.1.21), and others), and therefore it is possible that it may be responsible for high affinity of the examined adrenoblockers with )3-adrenergic receptors. 

The CL emission of Scheme 3 catalyzed by HRP can be applied to the quantitative analysis of catecholamines, such as dopamine (68), epinephrine (132), L-DOPA (30), norepinephrine (133), deoxyepinephrine (134) isoproterenol (135) and dihydroxybenzy-lamine (136), in a FIA system, after undergoing the oxidation shown for dopamine (68) in equation 20. The mechanism of this process is not totally clear however, the CL yields of equation 20 depend upon the pH of the system (pH 9 is convenient and is achieved by adjusting the concentration of imidazole), the temperature (60 °C is adequate) and the structure of the analyte (a calibration curve is needed for each one). Taking 68 as reference (100%) the CL yields after 30 min incubation (achieved by controlling the flow through a long capillary mbe) are as shown in equation 42 A5i... 

While the inhibition of noradrenaline re-uptake exerts predominantly an a-adrenergic effect, a selective jS-adrenergic effect can not be obtained by such an indirect mechanism. All selective /3-sympathomi-metics activate the receptors, P -, P2- or both sub-types, directly. The first pure jS-sympathomimetic in clinical use was isoproterenol which is structurally identical to adrenaline except the methyl-moiety at the N-position in the side-chain is replaced by an isopropyl-group. All effects produced by isoproterenol are due to either P -or 62-adrenoceptor stimulation tachycardia, increased stroke volume, decreased vascular resistance, broncho dilatation and, in pregnancy, uterus relaxation. The metabolic effects of isoproterenol are less pronounced than those of adrenaline. 

The sympatholyfics of this type interfere with the /3i- and /S2-adrenoceptor subtypes. Via this mechanism the stimulating influence of the sympathetic nervous system on the heart and the metabolism and its inhibiting influence on smooth muscle is blocked. /3-Adrenoceptor blocking agents, or /3-blockers, mostly have a typical isoproterenol-like structure with an isopropylamine or a tertiary butylamine group and a substituted phenoxy moiety bound to the isopropanol backbone. The substituents determine the physicochemical properties of the particular drug and thereby its pharmacokinetic proflle. 

The adrenomimetic drugs can be divided into two major groups on the basis of their chemical structure the catecholamines and the noncatecholamines. The catecholamines include norepinephrine, epinephrine, and dopamine, all of which are naturally occurring, and several synthetic substances, the most important of which is isoproterenol (isopropyl norepinephrine). The skele-... 

The similarity in structure to (3-agonists is most certainly responsible for the finding that some (3-blockers activate (3-receptors that is, they have some intrinsic sympathomimetic activity. The intrinsic activity of these compounds is generally modest in comparison with an agonist, such as isoproterenol, and they are generally referred to as partial agonists (see Chapter 2). 

The similarity measure intuitively used by organic chemists is the number of structural features and their mutual arrangement which two compounds have in common. From this point of view adrenalin (1) and isoproterenol (2) would look rather similar and in fact both have similar biological properties as they are both agonists of P-adrenergic receptors. Both compounds are comparatively dissimilar to propranolol... 

Isoproterenol [eye soe proe TER a nole] is a direct-acting synthetic catecholamine that predominantly stimulates both pi and p2 adrenergic receptors. Its non-selectivity is one of its drawbacks. Its action on a receptors is insignificant. Its chemical structure is given in Figure 6.7. 

Figure 1.7. Structures of the natural adrenergic agonists, norepinephrine and epinephrine, and the synthetic p-selective agonist isoproterenol.

The first blocker was not reported until I9S8, when Powell and Slater described the activity of dichloroisoprotcrcnol (DCI). The structure of DCI is like that of isoproterenol, except that the catechol hydroxyl groups have been replaced by two chloFO groups. This simple structural modification, involving the replacement of the aromatic hydroxyl groups. 

Structure activity relationships for a series of sympathomimetic amines having a carbostyril moiety (11) have been reported.35 The most potent (11, R3=H, R4=t-butyl) is 22,400 x isoproterenol in relaxation of guinea pig trachea, and is also more fi-2 selective than 4. Order of activity Rg H>Me>Et, R4 t-butyl>i-Pr>CMe2CH20> Bz>H.35 Another analog (11, R3=Et, R4=CHMe9) (OPC 2009) is claimed to be more active and more selective... 

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