الفهرس 
Chemistry of 4-thiazolidinonesOnly 14 pages are availabe for public view
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Abstract
The original work of this thesis can be classified into two parts:
The first part deals with synthesis of 5-amino-2-(4-chlorobenzylidene)-7-(4-
chlorophenyl)-3-oxo-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-6,8-dicarbo
nitrile 1 by the one-pot multicomponent reactions (MCRs) of p-chloro
benzaldehyde, malononitrile and thioglycolicacid (2:2:1 molar ratio) in
absolute ethanol in the presence of a catalytic amount of piperidine in good
yields (Scheme 1).
(Compound 1 proved to be a useful key intermediate for synthesis of new
fused heterocyclic derivatives. Thus, treatment of 1 with hydrazine
derivatives (binucleophile) afford the corresponding pyrazolo
[3’,4’:4,5]thiazolo[3,2-a]pyridine derivatives 3, 4. On the other hand,
reaction of 1 with hydroxylamine hydrochloride afforded
isoxazolo[5’,4’:4,5]thiazolo[3,2-a] pyridine derivative 5. When compound 1
allowed to react with thiourea, 9-amino-4,7-bis(4-chlorophenyl)-2-thioxo-
1,2-dihydro-7H-pyrido[2’,1’:2,3]thiazolo[4,5-d]pyrimidine-6,8-dicarbonitrile
6 was obtained (Scheme 3).Thiazolo[3,2-a]pyridine derivative 1 when treated with
triethylorthoformate gave the corresponding ethyoxymethylene derivative 7,
which underwent hydrazonolysis and cyclization to give pyrazolo
[3’’,4’’:4’,5’]thiazolo[3’,2’:1,6]pyrido[2,3-d]pyrimidine-6-carbonitrile Furthermore, treatment of 1 with formamide and formic acid gave the
corresponding thiazolopyridopyrimidine derivatives 9 and 10 respectively.
On the other hand, the reaction of 1 with acetic anhydride afforded 2-methyl-
4,9-dioxo-3,5,8,9-tetrahydro-4H-thiazolo[3’,2’:1,6]pyrido [2,3-d]pyrimidine-
6-carbonitrile derivative 11. Alkylation of Thiazolo[3,2-a] pyridine
derivative 1 with alkylating reagent such as bromo cycloalkane gave 5-
(cyclohexylamino)-3-oxo-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-6,8-
dicarbonitrile derivative 12 (Scheme 4). Pyrano [2’,3’:4,5] thiazolo [3,2-a]pyridine derevatives 13, 14, 15, 16, 17
were obtaineded when compound 1 was reacted with different active
methylene compounds such as ethylacetoacetate, diethylmalonate,
benzylcyanide, ethylchloroacetate, cyanoaceticacid and/ or ethylcyanoacetate
respectively (Scheme 5).
(Reaction of pyrano[2’,3’:4,5]thiazolo[3,2-a]pyridine- derivative 2 with
benzoylchloride and formamide gave in a ‘one step reaction’
pyrimidino[3’’’,4’’’:5’’,6’’]pyrano[2’’,3’’:4’,5’]thiazolo[3’,2’:1,6]pyrido[2,3-
d]pyrimidine derivatives 18 and 19 respectively.
Furthermore, 4,7-bis(4-chlorophenyl)-2-((-4-nitrobenzylidene) amino)-9-
((4-nitrobenzylidene)amino)-4H, 7H- pyrano [2’,3’:4,5] thiazolo[3,2-
a]pyridine-3,6,8-tricarbonitrile 20 was obtained by reaction of 2 with pnitrobenzaldehyde
(Scheme 6).Anti-cancer activity:
Most of the synthesized compounds were tested for their anti-cancer
activity against two human anticancer cell lines (HePG2, MCF-7).
The results showed that compounds 3 and 8 have a very strong
cytotoxicity, while compounds 2, 15 and 19 possess a strong cytotoxicity;
however compounds 4, 5, 6, 9, 12 and 17 exerted a moderate cytotoxicity,
furthermore compounds 1, 11, 13, 16 and 20 showed a weak cytotoxicity
against HePG2.
In continuation, compounds 3 and 8 have a very strong cytotoxicity, while
compounds 2, 6, 15 and 19 possess a strong cytotoxicity; however
compounds 4, 5, 9, 12, 13 and 17 exerted a moderate cytotoxicity,
furthermore compounds 1, 11, 16, 18 and 20 showed a weak cytotoxicity
against MCF-7.