From bradykinin B2 receptor antagonists to orally active and selective bradykinin B1 receptor antagonists.

The bradykinin (BK) B1 receptor is an attractive target for the treatment of chronic pain and inflammation. Starting from a dual B1 and B2 antagonist, novel antagonists were designed that display low-nanomolar affinity for human B1 receptor and selectivity over B2. Initially, potent imidazoline derivatives were studied, but these compounds suffered from low bioavailability.

Antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide, fumarate (LF22-0542), a novel nonpeptidic bradykinin B1 receptor antagonist.

The antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide fumarate (LF22-0542), a novel nonpeptidic B1 antagonist, was characterized. LF22-0542 showed high affinity for human and mouse B1 receptors with virtually no affinity for the human B2 receptor; a selectivity index of at least 4000 times was obtained when LF22-0542 was profiled throughout binding or cell biology assays on 64 other G-protein-coupled receptor, 10 ion channels, and seven enzymes. LF22-0542 was a competitive B1 receptor antagonist and elicited significant antinociceptive actions in the mouse acetic acid-induced writhing assay, as well as in the second phases of formalin-induced nociception in mice and in both the first and second phases of the formalin response in rats.

Synthesis, structures, and magnetic properties of tetranuclear CuII-LnIII complexes.

The copper(II)-gadolinium(III) and copper(II)-terbium(III) complexes studied in this report derive from disymmetric trianionic ligands abbreviated H3Li (i = 4-6). These ligands are obtained through reaction of different aldehydes with "half-units" having an amide function, the latter resulting from the monocondensation of different diamines with phenyl 2-hydroxy-3-methoxybenzoate. Upon deprotonation, the Li ligands (i = 4-10) possess an inner N2O2 coordination site with one amido, one imine, and two phenoxo functions, an outer O2O2 or O2O coordination site, and an amido oxygen atom positioned out of these two sites.

Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives.

2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoid of alkylating property towards the synthetic model of heme Mn(II)-TPP.

Synthesis and trichomonacidal activity of perketals and hydroperoxides.

Some perketals were synthesized by the Dussault procedure using simple bromides and 2-methoxyprop-2-yl hydroperoxide. Treatment with acetic acid gave the corresponding hydroperoxides. Both perketals and hydroperoxides were tested in vitro as trichomonacidal agents.