Isoproterenol synthesis

Isoproterenol, chemiluminescence, 647 (—)-Isopulegol, artemisinin synthesis, 277, 278 Isothermal microcalorimetry, oxidation stability evaluation, 672 Isotopomers... 

These results show that acipimox acts to inhibit cAMP-stimulated hpolysis through suppression of intracellular cAMP levels, with a subsequent decrease in PKA activity. The anti-lipolytic activity of acipimox is associated with a quantitative shift of HSL from the LD to the cytosol in rat adipocytes, suggesting that, by decreasing intracellular cAMP levels, acipimox can reduce the association of HSL with TAG substrate of the LD. Pharmacokinetic studies show that the plasma concentration of acipimox in man after a single 250 mg oral dose reaches 33 gM, and remains above 7 gM for 6-8 h [448]. In comparison, acipimox is a potent anti-lipolytic agent at a concentration of 10 gM and above, in human adipose tissue stimulated maximally and sub-maximally by isoproterenol [449]. Thus, plasma acipimox levels correlate well with its in vitro effect on hpolysis and cAMP synthesis in rat adipocytes. 

Several papers have described the synthesis and biologic activity of cyclic phenethanolamines (i.e. tetrahydronaphthalenes, ex. 4o).°° °° some of which have 2 selectivity of up to 120 X that of Isoproterenol. 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

Forskolln stimulation of cyclic AMP synthesis in C6-2B rat astrocytoma cells is decreased after the cells are grown In the presence of cyclohexlmide, a protein synthesis inhibitor. 0 This occurs without the loss of isoproterenol or cholera toxin stimulated adenylate cyclase. It was suggested that the cyclohexlmide blocks the synthesis of a protein which has a high turnover rate and is required for forskolln stimulation of adenylate cyclase. 

In the second example, we will imprint a chiral template, (R)-isoproterenol (as depicted in Fig. 9), which is another common asthma medication [41]. The synthesis of materials that can discriminate between enantiomers [24] demonstrates the vast potential of the imprinting technique. Because the chemical and physical properties of enantiomers are identical in anonchiral environment, the observation of enantios-electivity in MIPs can only be attributed to the three-dimensional arrangement of the functional monomers around the template molecule. Chiral selectivity in MIPs can be readily observed in batch-mode binding and competition studies [31] similar to the one described in the theophylline MIP protocol. In this case, however, we will present a procedure for evaluating the MIP as a HPFC packing material in order to... 

Arnett, C.D., Wright, (., and Zenker, N. (1978) Synthesis and adrenergic activity of benzimidazole bioisosteres of norepinephrine and isoproterenol. Journal of Medicinal Chemistry, 21 (1), 72-78. 

In applying this approach to the catecholamines 13-C we first considered functionalization of the aromatic ring. > However, none of our derivatives had the potency or efficacy as 3-adrenergic agonists that isoproterenol does. The most promising approach has proven to be derivatization through the amine function in the side chain of the molecules. These studies have led to the synthesis... 

In view of these findings and the increased potency of several model derivatives compared to isoproterenol, we undertook the synthesis of a series of congener derivatives in which the length of the spacer group was kept constant (at the equivalent of 4... 

Optically active halohydrins or styrene oxide derivatives obtained by the reduction of a-halo ketones followed by treatment with base have been widely used as key intermediates in the synthesis of many chiral drugs containing the p-amino alcohol moiety. Examples of such drugs include (R)-denopamine (13) [46a], (R)-isoproterenol (14) [46b], d-solatol (15) [47], (R)-fluoro(nor)epinephrine (16) [48], (R)-salmeterol (17) [49], and (R,R)-formoterol (18) [50] (Scheme 11.4). Most OABs were effective for the reduction of 2-bromo- or 2-chloroacetophenone derivatives (22), providing the corresponding halohydrins with high enantioselectivities (Table 11.4). 

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