A structure-activity relationship study of compounds with antihistamine activity.
A structure-activity relationship (SAR) analysis of H(1)-, H(2)- and H(3)-antihistamine activity was carried out and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol4-yl)ethanamine, 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole, 2-(1-piperazinyl)benzothiazole, 2-[4-(1-alkyl)piperidinyl]benzothiazole, 2-(N,N',N'-dimethylalkyl-1,2-ethanediamino)benzothiazole, 2[1-(4-aminopiperidinyl)]benzothiazole, 2-[2-phenyl-4-thiazolyl]ethanamine derivatives and selected H(1)- and H(2)-antihistamine drugs were obtained. NP TLC and RP2 TLC plates (silica gel NP 60F(254) and silica gel RP2 60F(254) silanized precoated), impregnated with a solution of aspartic acid (L-Asp) and a solution of an analogue of aspartic acid (propionic acid), were used in two developing solvents as H(1)-, H(2)- and H(3)-antihistaminic interaction models. The lipophilicity data of the examined compounds were obtained and used in the SAR assay. Biochromatographic tests using TLC plates impregnated with solutions of asparic acid or propionic acid were found to be a source of useful data for the qualitative analysis of compounds with different structures, demonstrating activity to histamine H(1)-, H(2)- and H(3)-receptors. The four presented discriminant models based on biochromatographic studies are an efficient tool in the SAR analysis for initial prediction of compound activity direction within histamine receptors.
Brzezińska
Elzbieta
E
Medical University of Łódź, Department of Analytical Chemistry, 1 Muszyńskiego Street, 90-151 Łódź, Poland. ebrzezinska@pharm.am.lodz.pl
Kośka
Grazyna
G
D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology; D002855:Chromatography, Thin Layer / Q000379:methods; D016002:Discriminant Analysis; D006633:Histamine Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D011968:Receptors, Histamine / Q000378:metabolism; D013329:Structure-Activity Relationship
D052160:Benzothiazoles; D006633:Histamine Antagonists; D011968:Receptors, Histamine; C005465:benzothiazole