| Popis: |
Crystal structures of three class I antiarrhythmic agents: (1) iso-butyl 3-(1-pyrrolidinylmethyl)-4-(hydroxy)-methylphenylacetate hydrochloride, (2) 1,4-benzodioxan-2-methyl-3-(1-pyrrolidinylmethyl)-4-(hydroxy)-methylphenylacetate hydrochloride and (3) 1,4-benzodioxan-2-methyl-3-(1-pyrrolidinylmethyl)methylphenylacetate oxalate were determined. All three compounds are protonated at the N atom of the pyrrolidine ring. The protonated amine forms strong N-H...Cl or N-H...O intermolecular hydrogen bonds with the anions (either the chloride ion or the O atom of the hydrogen oxalate). The pyrrolidine rings are found in a similar orientation relative to the phenyl ring in all these compounds. The separations between the N atom of the pyrrolidine ring and the carbonyl O atom are observed in a range close to the N...O distance for class Ic antiarrhythmic agents found by Glowka, Dargie & Codding [J. Med. Chem. (1991), 34, 2678-2684]. Molecular mechanics calculations are used to identify the structural similarity of these antiarrhythmic agents, and to establish possible binding features required for class I agents. |
Plný text