4‐Substituted Thioquinolines and Thiazoloquinolines: Potent, Selective, and Tween‐80 in vitro Dependent Families of Antitubercular Agents with Moderate in vivo Activity

Abstract

Two new families of closely related selective, non-cytotoxic, and potent antitubercular agents were discovered: thioquinolines and thiazoloquinolines. The compounds were found to possess potent antitubercular properties in vitro, an activity that is dependent on experimental conditions of MIC determination (resazurin test and the presence or absence of Tween-80). To clarify the therapeutic potential of these compound families, a medicinal chemistry effort was undertaken to generate a lead-like structure that would enable murine efficacy studies and help elucidate the in vivo implications of the in vitro observations. Although the final compounds showed only limited levels of systemic exposure in mice, modest levels of efficacy in vivo at nontoxic doses were observed.

Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure–activity relationships

“…The resulting suspension was poured into ice. The solids were isolated by filtration washed with cold water and dried under vacuum to yield the product as a yellow solid (12 mg, 0.04 mmol, 33%) [33], mp 258.0-259.…”

“…The warm mixture was filtered through a Celite patch and the remaining solids were washed several times with warm EtOH. The filtrates were combined and concentrated [33]. The residue was purified by preparative thin layer chromatography on silica gel (dichloromethane/methanol, 10/1) to give the product as a brown solid (13 mg, 0.05 mmol, 36%), mp 190.…”

Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides

“…In addition, three physicochemical properties were measured: artificial membrane permeability, kinetic aqueous solubility (CLND, chemiluminescent nitrogen detection) and ChromlogD. 21,22 Table 2 presents the results for the reference compound 1 and the first set of compounds possessing variations to the substitution pattern of the quinoline system (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The main goal was to investigate the contribution to anti-mycobacterial activity of the 6-methoxy and 2-methyl quinoline substituents.…”

Ultrasound-Assisted Synthesis of 4-Alkoxy-2-methylquinolines: An Efficient Method toward Antitubercular Drug Candidates

“…Additionally, electronic variations of the substituents did not significantly alter the observed results. In addition, the methods described in the literature have reported the synthesis of compounds from quinoline and benzyl bromide derivatives in the presence of K 2 CO 3 in DMF under conventional conditions with reaction times ranging from 5 to 8 h [20,21]. These procedures have led to products with 17-76% yields, one of which described the use of chromatography in the purification of compounds.…”