218962-33-5Relevant academic research and scientific papers
The design, synthesis, and evaluation of organ-specific iron chelators
Bergeron, Raymond J.,Wiegand, Jan,McManis, James S.,Bharti, Neelam
, p. 7032 - 7043 (2007/10/03)
A series of iron chelators, three (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4- methyl-4-thiazolecarboxylic acid (DADFT) and three (S)-4,5-dihydro-2-(2- hydroxyphenyl)-4-thiazolecarboxylic acid (DADMDFT) analogues are synthesized and assessed for their lipophilicity (log Papp), iron-clearing efficiency (ICE) in rodents and iron-loaded primates (Cebus apella), toxicity in rodents, and organ distribution in rodents. The results lead to a number of generalizations useful in chelator design strategies. In rodents, while log Papp is a good predictor of a chelator's ICE, chelator liver concentration is a better tool. In primates, log Papp is a good predictor of ICE, but only when comparing structurally very similar chelators. There is a profound difference in toxicity between the DADMDFT and DADFT series: DADMDFTs are less toxic. Within the DADFT family of ligands, the more lipophilic ligands are generally more toxic. Lipophilicity can have a profound effect on ligand organ distribution, and ligands can thus be targeted to organs compromised in iron overload disease, for example, the heart.
Quinolines and quinazolines useful in therapy
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, (2008/06/13)
Compounds of formula I, wherein R1 represents C1-4 alkoxy optionally substituted by one or more fluorine atoms; R2 and R3 independently represent H or C1-6 alkoxy (which is optionally substituted); R4 represents a 4-, 5-, 6- or 7-membered heterocyclic rin
