Supervisors info:
Ιωάννης Παπαναστασίου, Επίκουρος Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Summary:
The present dissertation refers to the design and synthesis of novel 4-fluoro-3(thiazol-2 & 4-yl)aniline derivatives I-IV, as well as the pharmacological evaluation of their antimycobacterial activity.
The scaffold of the aforementioned compounds includes a 2,4-disubstituted 1,3-thiazole ring as the main core, while the 2,4-substituents of the thiazole have their positions switched in these derivatives. Subsequently, a phenol or 2-pyridine ring consists the aromatic pole, at C-2 or C-4 position and the aniline ring, at C-4 or C-2 position, respectively, is the aniline pole. The latter is attached by an amide bond with a side chain.
Structure-activity relationships have been developed concerning the functionalization of the side chain. Initially, benzamides 5,27,48 and 61, the aroyl-substituted compounds 6,28,49 and 62 with a para-fluorine atom, or adducts 7,29 and 63, with a meta-fluorine atom, were synthesized, respectively. At the same substituted position, a cyano group was used in the corresponding derivatives 8, 30, 50 and 64. The cyano group was replaced by a primary amino group, in compounds 21 and 40. Moreover, we have synthesized acetylphenyl derivatives 9,31,51 and 61 with less steric hindrance due to the acetoxy group interposed between the two rings, the thiazole and benzene. We have synthesized, next, derivatives with heterocycle substituents, such as 3-thiophenyl-, 5-nitrofuran-2-yl-, 3-methylfuran-2-yl-, 2-pyridinyl- and 1H-indol-2-yl -group and adducts with aliphatic rings from 3 to 10 carbon atoms. Finally, the amide bond of the side was replaced chain with an urea bond and we have proceeded on the synthesis of the respective derivatives 15, 16, 35 and 66, which bear a five-membered / six-membered heterocycle ring and para-chloro-aniline.
The pharmacological evaluation of the compounds of the present work is in progress. Preliminary screening has shown encouraging results in terms of the antimycobacterial activity of the current derivatives, which require further analysis and evaluation.
Keywords:
tuberculosis, mycobacterium, treatment, thiazole, aniline
