Geometry of Lidocaine-like Molecules: 3. Structure of a Potent Antiarrhythmic Agent: 2-Methyl-2-(1-morpholinyl)-N-(2,6-dimethylphenyl) acetamide

• Autorzy: Główka M. , Olczak A. , Białasiewicz W. , Kwapiszewski W.
• Języki publikacji: EN

Abstrakty

EN

Crystal structure of an alanylyl analog of lidocaine with its amine function incorporated into morpholine ring and showing promising type I antiarrhythmic activity was studied in form of free base and hydrochloride. Crystal data: free base a = 9.498(2), b = 11.716(2), c = 13.497(2); hydrochloride a = 10.820(1), b = 11.971(3), c = 12.564(1); both P212121 (Z = 4); R1 = 0.039 and 0.037, respectively. Substitution at C alfa and incorporation of N amine atom into the aliphatic morpholinic ring significantly change conformational preference around C alfa-C(O) and C alfa-N(ring) bonds, as compared with parent lidocaine. The most interesting conformational change observed was that the title molecule in the protonated form (being probably the biologically active) has gauche orientation of _N-H(amine) bond in relation to C=O group, while all other structures have different orientations, either antiperiplanar or synperiplanar (unprotonated lidocaine only). And the two groups are crucial for hydrogen bonds formation with a perspective receptor of type I antiarrhythmics.

Słowa kluczowe

EN

type I antiarrhythmics; acyl-2,6-xylidines; lidocaine chiral analogs; crystal structure

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2005
• Tom: Vol. 79 / nr 6
• Strony: 1079--1085
• Opis fizyczny: Bibliogr. 17 poz., rys.

Twórcy

autor

Główka M.

• Institute of General and Ecological Chemistry, Technical University of Łódź, Żeromskiego 116, 90-924 Łódź, Poland

autor

Olczak A.

• Institute of General and Ecological Chemistry, Technical University of Łódź, Żeromskiego 116, 90-924 Łódź, Poland

autor

Białasiewicz W.

• Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Łódź, Muszyńskiego 1, 91-151 Łódź, Poland

autor

Kwapiszewski W.

• Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Łódź, Muszyńskiego 1, 91-151 Łódź, Poland

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