Tez No	İndirme	Tez Künye	Durumu
203027		Biyolojik etkili yeni bazı tiyazolidindion türevleri üzerinde sentez çalışmaları / Studies on the synthesis of some new thiazolidinedione derivatives possesing biological activity Yazar:ARZU MENTEŞE Danışman: DOÇ.DR. OYA BOZDAĞ DÜNDAR Yer Bilgisi: Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı Konu:Eczacılık ve Farmakoloji = Pharmacy and Pharmacology Dizin:	Onaylandı Yüksek Lisans Türkçe 2007 156 s.
Antidiyabetik Etkili Bazı Bilesikler Üzerinde ArastırmalarBu çalısmada, 2,4-tiyazolidindion bilesiginin 3. ve 5. konumundan sübstitüe yeni bazı 2,4-tiyazolidindion türevlerinin sentezleri ve bunların antidiyabetik aktivitelerinin incelenmesiamaçlandı.Bilesiklerin Sentezi:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-( p- ve/veya o- sübstitüe benzil)-1,3-tiyazolidin-2,4-dion sentezi:1) 2,4-TZD sentezi2) 3-(p- ve/veya o- sübstitüe benzil)-1,3-tiyazolidin-2,4-dion sentezi3) 4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-karbaldehid sentezi gerçeklestirildi.4) Daha sonra 3-( p- ve/veya o- sübstitüe benzil)-1,3-tiyazolidin-2,4-dion ve 4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-karbaldehid bilesiklerinden hareketle 2,4-tiyazolidindion türevi 6orijinal bilesik sentez edildi.Ia:3-benzil-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIb:3-(4-florobenzil)-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIc:3-(4-klorobenzil)- 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionId:3-(4-bromobenzil)- 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIe:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-(2,4-diklorobenzil)-1,3-tiyazolidin-2,4-dionIf:3-(4-nitrobenzil)-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dion5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion sentezi:1) 2,4-TZD sentezi2) 3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion sentezi3) 4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-karbaldehid sentezi gerçeklestirildi.4) Daha sonra 3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion ve 4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-karbaldehit bilesiklerinden hareketle 2,4-tiyazolidindiontürevi 6 orijinal bilesik sentez edildi.IIa:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-fenil-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIb:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-florofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIc:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-klorofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIId:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-bromofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIe:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(2,4-diklorofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIf: 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-nitrofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion3-[2-(p- ve/veya o-sübstitüe fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dion sentezi için:1) 2,4-TZD sentezi,2) 2,4-dikloro-1,3-tiyazol-5-karbaldehid sentezi,3) 3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion sentezigerçeklestirildi.4) Daha sonra 2,4-dikloro-1,3-tiyazol-5-karbaldehit ve 3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion bilesiklerinden hareketle 2,4-tiyazolidindion türevi 6 orijinalbilesik sentez edildi.IIIa:3-(2-fenil-2-okso-etil)-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIb:3-[2-(4-floro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIc:3-[2-(4-kloro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)- tiyazolidin-2,4-dionIIId:3-[2-(4-bromo-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIe:3-[2-(2,4-dikloro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)- tiyazolidin-2,4-dionIIIf:3-[2-(4-nitro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionElde edilen bilesiklerin saflıkları TK ile kontrol edildikten sonra ergime noktaları saptandı veyapıları IR, 1H NMR, Mass ve Elementel analiz verileri ile kanıtlandı.3-[2-(4-Kloro fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)- tiyazolidin-2,4-dion(IIIc) bilesiginin konformasyonel yapısı X-Ray kristallografik analizi ile aydınlatılmıstır. Bunagöre IIIc bilesiginin Z izomer yapısında oldugu görülmüstür.Anahtar sözcükler: Antidiyabetik aktivite, 2,4-tiyazolidindion, tiyazol,tiyazoliltiyazolidindion.
Studies on Some Chemical Compounds With Antidiabetic ActivityIn this study, it was aimed to investigate the synthesis and the antidiabetic activity of some new2,4-thiazolidinedione derivatives which are substituted at 3. and 5. positions of 2,4-TZD ring.Synthesis of the compounds:Synthesis of 5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-(p- and/or osubstituebenzyl)-1,3-thiazolidine-2,4-dione:1) Synthesis of 2,4-TZD2) 3-(p- and/or o- substitute benzyl)-1,3- thiazolidine-2,4-dione3) 4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-carbaldehyde was synthesized.4) 6 original 2,4-thiazolidinedione derivatives were synthesized with reaction of 3-(p- and/or osubstitutebenzyl)-1,3- thiazolidine-2,4-dione and 4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-carbaldehyde.Ia:3-benzyl-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-1,3-thiazolidine-2,4-dioneIb:3-(4-fluorobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneIc:3-(4-chlorobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneId:3-(4-bromobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneIe:5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-(2,4-dichlorobenzyl)-1,3-tiyazolidine-2,4-dioneIf:3-(4-nitrobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-thiazolidine-2,4-dioneSynthesis of 5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-( pand/or o- substitute phenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dione1) Synthesis of 2,4-TZD2) 3-[2-( p- and/or o- substitute phenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dione3) 4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-carbaldehyde was synthesized.4) 6 original 2,4-thiazolidinedione derivatives were synthesized with reaction of 3-[2-( pand/or o- substitute phenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dione and 4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-carbaldehyde.IIa:5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-phenyl-2-oxoethyl]-1,3- thiazolidine-2,4-dioneIIb: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-fluorophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIIc: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-chlorophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIId: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-bromophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIIe: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(2,4-dichlorophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIIf: 5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-nitrophenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dioneSynthesis of 3-[2-(p- and/or o-substitute phenyl)-2-oxo-ethyl]-5-(2,4-dichloro-thiazole-5-ylmethylenyl)-thiazolidine-2,4-dione1) Synthesis of 2,4-TZD2) Synthesis of 2,4-dichloro-1,3-thiazole-5-carbaldehyde3) 3-[2-( p- and/or o- substitute phenyl)-2-oxoethyl]-1,3-thiazolidine-2,4-dione was synthesized.IIIa:3-(2-phenyl-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIb:3-[2-(4-fluoro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIc:3-[2-(4-chloro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIId:3-[2-(4-bromo-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIe:3-[2-(2,4-dichloro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIf:3-[2-(4-nitro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneBy using these three different general methods, 18 original compounds were synthesized whichare substitute at 3. and 5. positions of 2,4-TZD.The purity were controlled by TLC and then melting points were determined. The chemicalstructure of the synthesizen compounds were elucidated by their IR, 1H NMR, Mass, andElemantary analysis data.Conformationally structure of compound 3-[2-(4-chloro phenyl)-2-oxo-ethyl]-5-(2,4-dichlorothiazole-5-yl-methylenyl)- thiazolidine-2,4-dione (IIIc) was performed by X-Ray analysis.According to this, it was seen that the compounds IIIc is structure of Z isomer.Key Words : Antidiabetic activity, 2,4-thiazolidinedione, thiazole, thiazolylthiazolidinedione