Introduction of Peripheral Carboxylates to Decrease the Charge on Tm3+ DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents
A series of structurally modified Tm3+ DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm3+ DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal. (Figure Presented).
Suchy, Mojmír,Milne, Mark,Elmehriki, Adam A. H.,McVicar, Nevin,Li, Alex X.,Bartha, Robert,Hudson, Robert H. E.
p. 6516 - 6532
(2015/09/08)
Serine protease inhibitors
Serine protease inhibitors, prodrugs thereof and pharmaceutically acceptable salts thereof are disclosed. The serine protease inhibitors exhibit anticoagulant activity and are useful for treating or preventing thrombin related diseases.
The current invention discloses halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors, and pharmaceutically acceptable salts thereof.
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Page column 19
(2010/02/04)
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