Application of a mathematical topological pattern of antihistaminic activity for the selection of new drug candidates and pharmacology assays.
Molecular topology was used to achieve a mathematical model capable of classifying compounds according to their antihistaminic activity and low sedative effects. By application of this model of activity to databases containing chemical reagents and drugs exhibiting other pharmacological activity, we selected 30 compounds with possible antihistaminic activity. After those with possible sedative effects were discarded, activity tests were performed with five chemical reagents and three drugs searching for in vivo antihistaminic activity. The obtained results indicate that compounds such as 4-[(E)-2-(1,3-benzothiazol-2-yl)vinyl]-N,N-dimethylaniline (AH2), 2-ethyl-9,10-dimethoxyanthracene (AH4), and 2,4-bis(alpha,alpha-dimethylbenzyl)phenol (AH5) showed antihistaminic activity above terfenadine, the reference drug, whereas others, for instance, pergolide, miconazole, trihexyphenidyl, 2-(dibenzylamino-3-phenyl-1-propanol (AH1), and N-benzylquininium chloride (AH3), were less active than terfenadine.
Duart
María J
MJ
Departamento de Ingeniería, División de al Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernandez, Alicante, Spain.
García-Domenech
Ramón
R
Galvez
Jorge
J
Aleman
Pedro A
PA
Martín-Algarra
Rafael V
RV
Antón-Fos
Gerardo M
GM
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D003872:Dermatitis / Q000276:immunology / Q000517:prevention & control; D015195:Drug Design; D005260:Female; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000494:pharmacology; D016014:Linear Models; D008433:Mathematics; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D016593:Terfenadine / Q000737:chemistry / Q000494:pharmacology
C512081:2,4-bis(alpha,alpha-dimethylbenzyl)phenol; C512082:2-ethyl-9,10-dimethoxyanthracene; C512080:4-(2-(1,3-benzothiazol-2-yl)vinyl)-N,N-dimethylaniline; D000814:Aniline Compounds; D000873:Anthracenes; D052160:Benzothiazoles; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D010636:Phenols; D016593:Terfenadine; D006632:Histamine