Ring structure thiazole derivatives

Piroxicam (84, Feldene in the US), a non-selective COX inhibitor with both analgesic and antipyretic properties, is one of the most used NSAIDs and serves as prototype of the oxicam family. This drug is utilized to relieve the symptoms of arthritis, menstrual pains or cramps and fever. It is also used in veterinary medicine to treat certain neoplasias expressing COX receptors, such as bladder, colon and prostate cancers. Variation on the structure of piroxicam has produced several other analogues with the benzene ring replaced by a thiophene ring and/or derivatives of the amide moiety, including meloxicam (85, a thiazole amide), isoxicam (86, an isoxazole amide), tenoxicam (87a, a thiophene derivative) and lornoxicam (87b, a chlorothiophene derivative). 

The cyclamides are small cyclic peptides that characteristically contain multiple thiazole, thiazoline, oxazole, and oxazoline rings, which are derived from cysteine, serine, and threonine residues. Some of the first examples of this class to be described were the patellamides (53-55) from the tunicate Lissoclinum patella, although it was later determined they were produced by the symbiotic cyanobacterium Prochloron sp. The structures were solved by a combination of acid hydrolysis and GC analysis, coupled with 2D NMR. Smaller cyclic peptides from this class include the hexapeptides westiellamide (56) and microcyclamide (57) from M. aeruginosa Many members of the class possess cytotoxic properties, although their biological function or mechanism of action is not fully understood. In contrast to many cyanobacterial peptides, aside from the unusual heterocyclic residues, these peptides generally contain only ribosomal amino acids. 

Bacitracin contains a cyclic peptide as part of a complex structure of 12 amino acid residues (if one considers the thiazole ring as cysteine derived). Bacitracin-treated bacterial cultures accumulate precursor peptidoglycan chains, as do the penicillins. However, the mechanism is very different. Its prevention of lysine inclusion into the murein structure is probably of lesser significance. Later demonstration show that drug binding to the membrane-bound bactoprene phosphate and the metal ions (Zn2+ are particularly involved) is more likely to be important to the antibacterial mechanism, namely, inhibition of dephosphorylation of the phospholipid carrier. 

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

Rhodacyanines possess two chromophoric systems. They are at the same time neutrocyanine derivatives, which involves position 5 of the ketomethylene, and methine cyanine, which involves position 2. Following lUPAC s standard nomenclature rules, structure 7 is named 3-ethyl-4-phenyl-2- 4-oxo-3-ethyl-5-[2-(3-ethy]-2,3-dihydro-benzo-l,3-thiazo-lylidene)ethylidene]-tetrahydro-l,3-thiazolylidene-methyl -1.3-thiazolium iodide (Scheme 5). It implies that the 4-phenyl thiazole ring having the... 

The fused tetrazole 422 (Scheme 19) was originally assumed307" to be nitrated on the thiazole ring, but recent NMR studies have shown that a p-nitrophenyl derivative is formed.1836 Since 422 (and 424) display azide tetrazole tautomerism (Section IV,B,1), the exact structure of the reacting species is unknown, but the product exists predominantly as the azide. 

The work of Taddei et al.230 on imidazol2,1 -6]thiazole 337 and derivatives has interesting implications on the structure of azapen-talenes, and an important aspect of this study is that the molecular geometry used for calculations on 6-phenylimidazo[2,l-6]thiazole 417 was obtained from X-ray structure determinations130b (Section V,A). The reactivity of this system (Scheme 18, Section IV,C,4,b) is better correlated with Tr-electron densities than with total charges, and 7r-bond orders (by the PPP method) show that the thiazole part of the molecule is more localized than the imidazole part (Section VII). Proton chemical shifts, except that of the H2 proton a to sulfur (Section V,G,2), vary linearly with the total charge carried by the ring carbon atoms. 

---