Biyolojik etkili yeni bazı tiyazoliltiyazolidindion türevleri üzerine sentez çalışmaları
Synthesis studies on some novel thiazolylthiazolidinedione derivatives with biologic effect
Yazar: MELİS EZER
Danışman: PROF. DR. OYA BOZDAĞ DÜNDAR
Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2010
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology
Dizin: Biyolojik aktivite = Biological activity ; Biyolojik yararlılık = Biological availability ; Kimyasal yapı = Chemical structure ; Sentez = Synthesis ; Tiyazolidinon = Thiazolidinone ; Tiyazoller = Thiazoles

Özet:
Bu çalışmada, 2,4-tiyazolidindion bileşiğinin 3. ve 5. konumundan sübstitüe yeni bazı türevlerinin sentezleri ve bunların antidiyabetik aktivitelerinin incelenmesi amaçlandı.Bileşiklerin Sentezi:5-({4-kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il}metilen)-3-( p- ve/veya o- sübstitüe benzil/fenaçil)tiyazolidin-2,4-dion sentezi:1) 2,4-TZD (I) sentezi2) 2,4-Dikloro-1,3-tiyazol-5-karbaldehid (II) sentezi3) Etil 2-(2,5-dioksotiyazolidin-3-il) asetat (VI) sentezi4) 3-(p- ve/veya o- sübstitüe benzil/fenaçil)tiyazolidin-2,4-dion (IVa-f/Va-f) sentezi gerçekleştirildi.5) TZD (I) / N3 sübstitüe TZD (IVa-f, Va-f, VI) ve 4-kloro-2-(morfolino-4-il)-1,3-tiyazol-5-karbaldehid (III) başlangıç maddelerinden hareketle morfolino tiyazolil 2,4-TZD türevi 15 adet orijinal bileşik sentez edilmiştir.1. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)tiyazolidin-2,4-dion2. 3-Benzil-5-((4-kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)tiyazolidin-2,4-dion3. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)- 3-(4-fluorobenzil)-tiyazolidin-2,4-dion4. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen) )-3-(4-klorobenzil)-tiyazolidin-2,4-dion5. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen) )-3-(4-bromobenzil)-tiyazolidin-2,4-dion6. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen) )-3-(2,4-dikolorobenzil)-tiyazolidin-2,4-dion7. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(4-nitrobenzil)-tiyazolidin-2,4-dion8. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-okso-2-feniletil) tiyazolidin-2,4-dion9. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-(4-fluorofenil)-2-oksoetil) tiyazolidin-2,4-dion10. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-(4-klorofenil)-2-oksoetil) tiyazolidin-2,4-dion11. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-(4-bromofenil)-2-oksoetil) tiyazolidin-2,4-dion12. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-(2,4-diklorofenil)-2-oksoetil) tiyazolidin-2,4-dion13. 5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen))-3-(2-(2,4-nitrofenil)-2-oksoetil) tiyazolidin-2,4-dion14. (Z)-Etil 2-(5-((4-kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)-2,4-dioksotiyazolidin-3-il)asetat15. (Z)-2-(5-((4-Kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)-2,4-dioksotiyazolidin-3-il)asetik asitElde edilen bileşiklerin saflıkları İTK ile kontrol edildikten sonra ergime noktaları saptandı ve yapıları IR, 1H NMR, kütle ve elementel analiz verileri ile kanıtlandı.(Z)-Etil 2-(5-((4-kloro-2-(morfolino-4-il)-1,3-tiyazol-5-il)metilen)-2,4-dioksotiyazolidin-3-il)asetat (14) bileşiğinin konformasyonel yapısı X-Ray kristallografik analizi ile aydınlatılmıştır. Buna göre 14 nolu bileşiğin Z izomer yapısında olduğu görülmüştür.

Abstract:
In this study, synthesis of some new derivatives of 2,4-thiazolidinedion compound from 3rd and 5th location and their antidiabetic activities aimed to be investigated.Synthesis of Compounds:5-({4-chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl}methylene)-3-(p- and/or o-substituted benzyl/phenacyl)thiazolidin-2,4-dion synthesis:1) 2,4-TZD (I) synthesis2) 2,4-Dichloro-thiazol-5-carbaldehyde (II) synthesis3) Ethyl 2-(2,5-dioxothiazolidin-3-yl) acetate (IV) synthesis4) 3-(p- ve/veya o- sübstitüe benzyl/phenacyl)thiazolidine-2,4-dion (IVa-f/Va-f) synthesis was carried out.5) By setting out from starting materials TZD (I) / N3 substituted TZD (IVa-f, Va-f, VI) ve 4-chloro-2-(morpholino-4-yl)-1,3-thiazol-5-carbaldehyde (III); 15 pieces of original compounds were synthesized which are derivative of morpholino thiazolyl 2,4-TZD.1. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)thiazolidine-2,4-dion2. 3-Benzyl-5-((4-chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)thiazolidine-2,4-dion3. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)-3-(4-fluorobenzyl)thiazolidine-2,4-dion4. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(4-chlorobenzyl)thiazolidine-2,4-dion5. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(4-bromobenzyl)thiazolidine-2,4-dion6. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2,4-dichlorobenzyl)thiazolidine-2,4-dion7.5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(4-nitrobenzyl)thiazolidine-2,4-dion8. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-oxo-2-phenylethyl) thiazolidine-2,4-dion9. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-(4-fluorophenyl)-2-oxoethyl)thiazolidine-2,4-dion10. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-(4-chlorophenyl)-2-oxoethyl)thiazolidine-2,4-dion11. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-(4-bromophenyl)-2-oxoethyl)thiazolidine-2,4-dion12. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-(2,4-dichlorophenyl)-2-oxoethyl)thiazolidine-2,4-dion13. 5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene))-3-(2-(2,4-nitrophenyl)-2-oxoethyl)thiazolidine-2,4-dion14. (Z)-Ethyl 2-(5-((4-chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)-2,4-dioxothiazolidine-3-yl)acetate15. (Z)-2-(5-((4-Chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)-2,4-dioxothiazolidine-3-yl)acetic acidAfter purity of obtained compounds had been checked by TLC, the melting points of these compounds were decected and their structures were proved by IR, 1H NMR, mass and elemental analysis data.Conformational structure of (Z)-ethyl 2-(5-((4-chloro-2-(morpholino-4-yl)-1,3-thiazol-5-yl)methylene)-2,4-dioxothiazolidin-3-yl)acetate (14) compound has been revealed by X-Ray Crystallographic Analysis. According to this, compound 14 was observed in Z isomer structure.