Synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-thione derivatives as potential calcium channel blockers.
Biginelli reaction which involves condensation of methyl 3-oxopentanoate, aromatic aldehydes and thiourea with a catalytic amount of HCl at reflux temperature has been used for the synthesis of 4-aryl-6-ethyl-5-(methoxycarbonyl)-3,4-dihydropyrimidin-2(1H)-thiones (1-16). In addition, Lewis acids such as FeCl(3).6H(2)O and/or H(3)BO(3) were also used as catalysts for one-pot synthesis of the products. Compared to the classical Biginelli reaction conditions, the usage of Lewis acids has the advantage of good yields and short reaction times. The calcium channel blocker activities of 1-16 were screened by the tests performed on isolated rat ileum and thoracic aorta. Although product 11, 2-nitrophenyl-derivative, has potent antispasmodic activity on BaCl(2)-stimulated rat ileum, it does not have vasodilator activity on KCl-stimulated rat thoracic aorta. Product 15, 2-ethoxyphenyl-derivative, exhibited significant antispasmodic and vasodilator activities in both screening paradigms.
Zorkun
Inci Selin
IS
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye-Ankara, Turkey.
Saraç
Selma
S
Celebi
Semra
S
Erol
Kevser
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D017609:Barium Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000737:chemistry*; D002712:Chlorides / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D007082:Ileum / Q000187:drug effects; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D017609:Barium Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002712:Chlorides; D004095:Dihydropyridines; D010276:Parasympatholytics; D013871:Thiones; D014665:Vasodilator Agents; C024986:barium chloride; D011189:Potassium Chloride