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
Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2007
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology

Özet:
Antidiyabetik Etkili Bazı Bilesikler Üzerinde ArastırmalarBu çalısmada, 2,4-tiyazolidindion bilesiginin 3. ve 5. konumundan sübstitüe yeni bazı 2,4-tiyazolidindion türevlerinin sentezleri ve bunların antidiyabetik aktivitelerinin incelenmesiamaçlandı.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 sentezi2) 3-(p- ve/veya o- sübstitüe benzil)-1,3-tiyazolidin-2,4-dion sentezi3) 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 6orijinal bilesik sentez edildi.Ia:3-benzil-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIb:3-(4-florobenzil)-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIc:3-(4-klorobenzil)- 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionId:3-(4-bromobenzil)- 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dionIe:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-(2,4-diklorobenzil)-1,3-tiyazolidin-2,4-dionIf:3-(4-nitrobenzil)-5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-1,3-tiyazolidin-2,4-dion5-({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 sentezi2) 3-[2-( p- ve/veya o- sübstitüe fenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion sentezi3) 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-tiyazolidindiontürevi 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-dionIIb:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-florofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIc:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-klorofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIId:5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-bromofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dionIIe: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-dionIIf: 5-({4-kloro-2-[(2-feniletil)tiyo]-1,3-tiyazol-5-il}metilen)-3-[2-(4-nitrofenil)-2-oksoetil]-1,3-tiyazolidin-2,4-dion3-[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 sentezigerçeklestirildi.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 orijinalbilesik sentez edildi.IIIa:3-(2-fenil-2-okso-etil)-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIb:3-[2-(4-floro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIc:3-[2-(4-kloro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)- tiyazolidin-2,4-dionIIId:3-[2-(4-bromo-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionIIIe:3-[2-(2,4-dikloro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)- tiyazolidin-2,4-dionIIIf:3-[2-(4-nitro-fenil)-2-okso-etil]-5-(2,4-dikloro-tiyazol-5-il-metilenil)-tiyazolidin-2,4-dionElde edilen bilesiklerin saflıkları TK ile kontrol edildikten sonra ergime noktaları saptandı veyapıları 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. Bunagöre IIIc bilesiginin Z izomer yapısında oldugu görülmüstür.Anahtar sözcükler: Antidiyabetik aktivite, 2,4-tiyazolidindion, tiyazol,tiyazoliltiyazolidindion.

Abstract:
Studies on Some Chemical Compounds With Antidiabetic ActivityIn this study, it was aimed to investigate the synthesis and the antidiabetic activity of some new2,4-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 osubstituebenzyl)-1,3-thiazolidine-2,4-dione:1) Synthesis of 2,4-TZD2) 3-(p- and/or o- substitute benzyl)-1,3- thiazolidine-2,4-dione3) 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 osubstitutebenzyl)-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-dioneIb:3-(4-fluorobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneIc:3-(4-chlorobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneId:3-(4-bromobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-tiyazolidine-2,4-dioneIe:5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-(2,4-dichlorobenzyl)-1,3-tiyazolidine-2,4-dioneIf:3-(4-nitrobenzyl)-5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl} methylene)-1,3-thiazolidine-2,4-dioneSynthesis 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-dione1) Synthesis of 2,4-TZD2) 3-[2-( p- and/or o- substitute phenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dione3) 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-dioneIIb: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-fluorophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIIc: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-chlorophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIId: 5-({4-chloro-2-[(2- phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-bromophenyl)-2- oxoethyl]-1,3- thiazolidine-2,4-dioneIIe: 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-dioneIIf: 5-({4-chloro-2-[(2-phenylethyl)thio]-1,3-thiazole-5-yl}methylene)-3-[2-(4-nitrophenyl)-2-oxoethyl]-1,3- thiazolidine-2,4-dioneSynthesis of 3-[2-(p- and/or o-substitute phenyl)-2-oxo-ethyl]-5-(2,4-dichloro-thiazole-5-ylmethylenyl)-thiazolidine-2,4-dione1) Synthesis of 2,4-TZD2) Synthesis of 2,4-dichloro-1,3-thiazole-5-carbaldehyde3) 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-dioneIIIb:3-[2-(4-fluoro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIc:3-[2-(4-chloro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIId:3-[2-(4-bromo-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIe:3-[2-(2,4-dichloro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneIIIf:3-[2-(4-nitro-phenyl)-2-oxo-ethyl)-5-(2,4-dichloro-thiazole-5-yl-methylenyl)-thiazolidine-2,4-dioneBy using these three different general methods, 18 original compounds were synthesized whichare substitute at 3. and 5. positions of 2,4-TZD.The purity were controlled by TLC and then melting points were determined. The chemicalstructure of the synthesizen compounds were elucidated by their IR, 1H NMR, Mass, andElemantary 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