1.
Graffner-Nordberg, Malin, et al.
(författare)
Computational predictions of binding affinities to dihydrofolate reductase: synthesis and biological evaluation of methotrexate analogues
2000
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 43:21, s. 3852-3861
Tidskriftsartikel (refereegranskat) abstract
The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.
2.
Bertozzi, Fabio, et al.
(författare)
Temporary in situ aluminum and zinc tethering in Diels-Alder reactions
2000
Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 2:9, s. 1283-1286
Tidskriftsartikel (refereegranskat) abstract
(formula presented) Temporary tethering using aluminum or zinc in Diels-Alder reactions made possible the use of otherwise "noncompatible" combinations of dienes and dienophiles, resulting in the one-step formation of substituted cyclohexene 1,2-bis-methanols. Excellent regioselectivity and also significant stereoselectivity were obtained.
3.
4.
Zygmunt, Peter M., et al.
(författare)
The anandamide transport inhibitor AM404 activates vanilloid receptors
2000
Ingår i: European Journal of Pharmacology. - 0014-2999. ; 396:1, s. 39-42
Tidskriftsartikel (refereegranskat) abstract
The possibility that the anandamide transport inhibitor N-(4-hydroxyphenyl)-5,8,11,14-eicosatetraenamide (AM404), structurally similar to the vanilloid receptor agonists anandamide and capsaicin, may also activate vanilloid receptors and cause vasodilation was examined. AM404 evoked concentration-dependent relaxations in segments of rat isolated hepatic artery contracted with phenylephrine. Relaxations were abolished in preparations pre-treated with capsaicin. The calcitonin-gene related peptide (CGRP) receptor antagonist CGRP-(8-37) also abolished relaxations. The vanilloid receptor antagonist capsazepine inhibited vasodilation by AM404 and blocked AM404-induced currents in patch-clamp experiments on Xenopus oocytes expressing the vanilloid subtype 1 receptor (VR1). In conclusion, AM404 activates native and cloned vanilloid receptors. Copyright (C) 2000 Elsevier Science B.V.
