Synthesis and antithyroid activity of pyridine, pyrimidine and pyrazine derivatives of thiazole-2-thiol and 2-thiazoline-2-thiol.
A series of compounds was synthesized by linking various derivatives of pyridine, pyrimidine or pyrazine to thiazole-2-thiol or to its partially hydrogenated derivative 2-thiazoline-2-thiol. The reactions of the compounds with molecular iodine and lactoperoxidase were examined in vitro. Their antithyroid activity was also examined in vivo in the rat. T4 and TSH levels were determined, and the thyroid gland was examined histologically. 2-(3-Hydroxy-2-pyridyl)-2-thiothiazoline had the highest antithyroid activity of the compounds tested (Kc = 14931.mol(-1),IC(50)0.65 x 10(-4) M, activity of thyroid gland).
Lagorce
J F
JF
Department of Chemical Pharmacy, Faculty of Pharmacy, Limoges Cedex, France.
Comby
F
F
Rousseau
A
A
Buxeraud
J
J
Raby
C
C
D000818:Animals; D013956:Antithyroid Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D011719:Pyrazines / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D013956:Antithyroid Agents; D011719:Pyrazines; D011725:Pyridines; D011743:Pyrimidines; D013844:Thiazoles; C083339:2-(3-hydroxy-2-pyridyl)-2-thiothiazoline; D013972:Thyrotropin; C030986:pyrimidine; C023666:pyridine; D013974:Thyroxine