Esmolol development

Esmolol Starting maintenance dose of 0.1 mg/kg/min IV, with titration in increments of 0.05 mg/kg/min every 10 to 15 minutes as tolerated by BP until the desired therapeutic response is obtained, limiting symptoms develop, or a dose of 0.2 mg/kg/min is reached. An optional loading dose of 0.5 mg/kg may be given by slow IV administration (2 to 5 minutes) for more rapid onset of action. Alternatively, the initial IV therapy may be omitted. 

The synthesis of esmolol was adopted from the classical procedures that had been developed for propranolol, 1 (see Chapter II-8). The synthetic route is depicted in Scheme 9.5 [12]. 

Pharmacokinetics Most of the systemic agents have been developed for chronic oral use, but bioavailability and duration of action vary widely (Table 10-2). Esmolol is a shortacting ester beta-blocker that is only used parenterally. Nadolol is the longest-acting beta-blocker. Acebutolol and atenolol are less lipid-soluble than the older beta-blockers and probably enter the CNS to a lesser extent. 

Besides aryl iodides, less reactive aryl bromides were also effective coupling partners in the Pd(ll)-catalyzed C(sp )-Hbond arylations (Scheme 1.14a) [36]. The good functional group compatibility and broad substrate scope enabled it attractive for concise s)mthesis of cardioselective (Tblocker drug molecule Esmolol. Later, Shi et al. developed a Pd(ll)-catalyzed monoarylation of P-methyl C(sp )-H of alanine derivatives with aryl iodides using 8-aminoquinoline auxiliary [37]. Almost at the same lime, a similar organic transformation was accomplished, with aryl iodides and bromides as aryl donors in the catalysis of Ni(OTf>2 [38]. One recent report demonstrated that the unactivated 3-posilion of proline derivatives could also be aiylated with 8-aminoquinoline auxiUaiy (Scheme 1.14b) [39]. 

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