IMPROVED SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF THE ENANTIOMERS OF A NEW BENZOFURANE TYPE ANTIARRHYTHMIC COMPOUND

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...

Full description

Saved in:
Bibliographic Details
Published inChirality (New York, N.Y.) Vol. 6; no. 4; pp. 329 - 336
Main Authors ECKER, G, FLEISCHHACKER, W, HELML, T, NOE, CR, SCASNY, S, LEMMENSGRUBER, R, STUDENIK, C, MAREI, H, HEISTRACHER, P
Format Journal Article
LanguageEnglish
Published HOBOKEN Wiley 01.01.1994
Subjects
Chemistry
Chemistry, Analytical
Chemistry, Medicinal
Chemistry, Organic
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
PHARMACODYNAMIC ACTIVITY
ANTIARRHYTHMIC AGENTS
PREPARATION OF ENANTIOMERS
GE 68
MBE-LACTOLE
RSP-CYCLODEXTRINE
CHIRAL LACTOLS
Online AccessGet more information

Cover

More Information
Summary: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 LiAlH4, 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 beta-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 beta-adrenoceptor blacking activity. (C) 1994 Wiley-Liss, Inc.
ISSN:0899-0042
1520-636X
DOI:10.1002/chir.530060417