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Improved synthesis and pharmacologic activity of the enantiomers of a new benzofurane type antiarrhythmic compound
Author(s) -
Ecker Gerhard,
Fleischhacker Wilhelm,
Helml Thomas,
Noe Christian R.,
Scasny Sonja,
LemmensGruber Rosa,
Studenik Christian,
Marei Hesham,
Heistracher Peter
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060417
Subject(s) - chemistry , enantiomer , chronotropic , diastereomer , stereochemistry , lactol , high performance liquid chromatography , derivative (finance) , chromatography , lactone , medicine , heart rate , blood pressure , financial economics , economics , radiology
An improved synthesis of the enantiomers of the new benzofurane‐type antiarrhythmic compound 1 is described, which makes use of the enantiomerically pure mbe‐lactol. Thus, acylation of the benzofurane 4 with acetic anhydride and subsequent bromination gave the bromoacetyl‐derivative 6 , which, after reduction with LiAlH 4 , was protected with mbe‐lactol to give a mixture of the diastereomers 8A and 8b . After separation via column chromatography assignment of absolute configuration was carried out using a well‐established NMR‐ method. Reaction with propylamine and cleavage of the protective group gave (R)‐ 1 and (S)‐ 1 , respectively. Enantiomeric purity was confirmed using a direct HPLC method with rsp‐cyclodextrine as stationary phase. Pharmacological investigations on isolated guinea pig heart muscle preparations showed that GE 68 and its two enantiomers did not significantly differ from each other with regard to their negative inotropic, negative chronotropic, and lack of β‐adrenoceptor blocking action. In contrast, the reference drug propafenone was equally potent in its negative inotropic and chronotropic activity as GE 68, but additionally showed a weak β‐adrenoceptor blocking activity. © 1994 Wiley‐Liss, Inc.