| Reference | [1]. Cottet, F. and Schlosser, M., 2004.<br />
Logistic flexibility in the preparation of isomeric halopyridinecarboxylic acids.<br />
Abstract: Although there are many conceivable ways to funtionalize, and specifically carboxylate, 2-chloro-4-(trifluoromethyl)pyridine optionally at all three vacant positions, it is more straightforward to prepare only the 2-chloro-4-(trifluoromethyl)pyridine-3-carboxylic acid (1) from this precursor and the other 6-chloro-4-(trifluoromethyl)pyridine-2- and -3-carboxylic acids (2 and 3) from a different one, viz. 5-bromo-2-chloro-4-(trifluoromethyl)pyridine. In the same manner, it proved more convenient to convert 5-chloro-2-(trifluoromethyl)pyridine in only two of the corresponding acids (6 and 7) and to make the third one (8) from 3-bromo-5-chloro-2-(trifluoromethyl)pyridine as an alternative starting material. All model substrates for functionalization were readily accessible from the correspondingly substituted chloroiodopyridine through heavy halogen displacement by in situ generated (trifluoromethyl)copper.<br />
Tetrahedron, 60(51), pp.11869-11874.<br />
<br />
[2]. Newkome, G.R., Moorfield, C.N. and Sabbaghian, B., 1986.<br />
Chemistry of heterocyclic compounds series. Part 108. Reductive dehalogenation of electron-poor heterocycles: nicotinic acid derivatives.<br />
The Journal of Organic Chemistry, 51(6), pp.953-954.<br />
<br />
[3]. Chapter, B., 2016.<br />
3.2 Chapter B: Flexible-Fragment-Growing Boosts Potency of Quorum Sensing Inhibitors against Pseudomonas aeruginosa virulence.<br />
Abstract: Pseudomonas aeruginosa is the cause of nosocomial infections and recurrent pneumonia in cystic fibrosis patients. Antibiotic treatment becomes increasingly difficult due to the spreading of multi-drug resistant strains and its ability to grow in a biofilm. The virulence of this pathogen is mainly controlled by quorum sensing (QS) systems. This process enables bacteria to coordinate the expression of virulence factors and biofilm formation as a function of cell density. For this purpose, P. aeruginosa utilize among others the pqs (Pseudomonas Quinolone Signal) system. In this study anti-virulence agents were developed interfering with the pqs system. During a fragment-based drug discovery campaign antagonists of the Pseudomonas Quinolone Signal Receptor (PqsR) were synthesized. Based on hits identified in a surface plasmon resonance (SPR) screening, novel lead structures were generated. This development process involved selective synthetic modifications of the hit structures and structure-based design methods. Fragments were successfully merged with moieties of an alternative compound class. The optimized structures displayed potent reduction of virulence factors and signaling molecules in P. aeruginosa. During another fragment screening the first synthetic PqsE ligands were identified. The binding mode of these fragments was elucidated. Furthermore, it was shown that the inhibition of the enzymatic activity did not translate into an effect on its virulence regulatory role.<br />
PSEUDOMONAS AERUGINOSA, p.61.
|
