Benzyl 2-{[2,8-bis­(trifluoro­meth­yl)quinolin-4-yl](hy­droxy)meth­yl}piperidine-1-carboxyl­ate

The title mol­ecule, C25H22F6N2O3, adopts an open conformation whereby the quinoline and carboxyl­ate ester groups are orientated in opposite directions but to the same side of the piperidine ring so that the mol­ecule has an approximate U-shape. The piperidine ring adopts a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(14) loops

tert-Butyl 2-{[2,8-bis­(trifluoro­meth­yl)quinolin-4-yl](hy­droxy)meth­yl}piperidine-1-carboxyl­ate

The title mol­ecule, C22H24F6N2O3, adopts a folded conformation whereby the carboxyl­ate residue lies over the quinolinyl residue, with the dihedral angle between the carbamate and quinoline planes being 41.64 (7)°. Helical supra­molecular C(7) chains sustained by O—H⋯O hydrogen bonds propagating along the a-axis direction feature in the crystal packing. The F atoms of one of the CF3 groups are disordered over two orientations; the major component has a site occupancy of 0.824 (7)

2-{1-[2,8-Bis(trifluoro­meth­yl)quinolin-4-yl]-3,5,6,7,8,8a-hexa­hydro-1H-1,3-oxazolo[3,4-a]pyridin-3-yl}phenol

In the title mefloquine–oxazolidine derivative, C24H20F6N2O2, the oxazoline ring adopts an envelope conformation (the flap atom is N) and the piperidine ring has a chair conformation. The oxazoline and benzene residues lie away from the C6 ring of the quinoline group and, to a first approximation, to one side of the plane through the ten atoms (r.m.s. deviation = 0.025 Å). An intra­molecular O—H⋯N(piperidine) hydrogen bond is present. The crystal packing features C—H⋯O, C—H⋯F and C—H⋯π(hy­droxy­benzene) inter­actions

(R*,S*)-(±)-1-(2-{[2,8-Bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidin-1-yl)ethanone methanol monosolvate

The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C19H18F6N2O2·CH3OH. Each of the meth­ine­hydroxyl residue [the C—C—C—O torsion angle is −16.35 (17) °] and the piperidinyl group [distorted chair conformation] lies to one side of the quinolinyl ring system. The hydroxyl and carbonyl groups lie to either side of the mol­ecule, enabling their participation in inter­molecular inter­actions. Thus, the hydroxyl and carbonyl groups of two centrosymmetrically related mol­ecules are bridged by two methanol mol­ecules via O—H⋯O hydrogen bonds, leading to a four-mol­ecule aggregate. These are linked into a supra­molecular chain along the a axis via C—H⋯O inter­actions involving the hydroxyl-O atom. The chains assemble into layers that inter­digitate along the c axis being connected by C—H⋯F inter­actions

Synthesis, Solubility, Permeability, and In Vitro Activity against Mycobacterium tuberculosis

Funding Information: This work was supported by FCT-MCTES (PTDC/QUI-QOR/32406/2017, PEst-C/LA0006/2013, RECI/BBBBQB/0230/2012) and by the Associate Laboratory for Green Chemistry-LAQV (FCT-MCTES UIDB/50006/2020 and UIDP/50006/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC). Publisher Copyright: © 2022 by the authors.The development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis. Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with organic anions as chemical adjuvants. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride ([MFLH][Cl]) and several organic acid sodium salts in high yields. One of the salts, mefloquine mesylate ([MFLH][MsO]), presented increased water solubility in comparison with [MFLH][Cl]. Moreover, all salts with the exception of mefloquine docusate ([MFLH][AOT]) showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1R)-CSA], [MFLH][(1S)-CSA]) and mefloquine HEPES ([MFLH][HEPES]).publishersversionpublishe