Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry


Hyperglycedemia and hypertriglyceridemia activities of newly synthesized compounds derived from 3'-(4-halophenyl)-5'-arylidene spiro(cyclohexane-(1,2')-thiazolidin)-4'-one

Author(s): Eman M. Flefel ,Hayam H. Sayed, Ahmed I. Hashem, Dalia O. Saleh , Walaa El-Sofany and Farouk M.E. Abdel-Megeid

5-Arylidene spiro[cyclohexane-(1,2')-thiazolidin-4'-one derivatives 1a-d were treated with some nucleophiles. So, when 1b was treated with hydrazine hydrate or phenylhydrazine it gave the pyrazolothiazole derivatives 2a,b, respectively. Compounds 1b,c were reacted with thiourea to give the corresponding thiazolopyrimidine derivatives 3a,b, respectively. Compound 1b, d were reacted with active methylene compound, namely, acetoacetanilide to afford the thiazolopyridine derivatives 5a,b, respectively. The latter compound was confirmed chemically via reaction with p-chlorobenzaldehyde to afford the condensation product 6. The oxirano derivatives 7a and b were prepared via reaction of hydrogen peroxide with arylidene spirothiazole derivatives 1a and d. Compound 7b was reacted with different amine derivatives using different conditions to afford compounds 8a,b-14a-c through ring opening of the oxirane ring. Compound 7b was reacted with 2-(2-chloroethoxy)ethanol to afford compounds 16. Compounds 14a-c were reduced using zinc dust to afford compound 17a-c. The structure of compound 17a, b were confirmed chemically via alkylation with methyl iodide or treatment with chloroacetic acid in the presence of pchlorobenzaldehyde to give the corresponding S-methylpyrimidine or thiazolo-pyrimidine derivatives 18a,b and 19, respectively. Compound 19 was reacted with hydrazine hydrate or hydroxylamine to afford the thiazolo[5',4':4,5]}pyrazolo[3',4':4,5]thiazolo [3,2-a]pyrimidine derivative 20 or the thiazolo [5',4':4,5]} isoxazolo [5',4':4,5] thiazolo [3,2-a]pyrimidine] 21, respectively. Moreover, some of the newly prepared products were screened for determination of the serum glucose level and triglycerides level. Oral treatment of hyperglycaemic rats with compounds 7b, 13, 15, 18b and 21 (0.01 mM/kg/day) for 10 consecutive days caused a marked decrease in the elevated serum level of glucose reaching about 169%, 140%,151%, 135% and 110% of the normal values, respectively. Similar treatment of hyperglycaemic rats showed a prominent decrease in the serum level of triglycerides reaching about 190%, 344%, 211%, 126% and 147%, respectively.