Gd-Complexes of 1,4,7,10-Tetraazacyclododecane-N,N鈥?/i>,N鈥测€?N鈥测€测€?1,4,7,10-tetraacetic Acid (DOTA) Conjugates of Tranexamates as a New Class of Blood-Pool Magnetic Resonance

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• 作者：Sungwook Gu ; Hee-Kyung Kim ; Gang Ho Lee ; Bong-Seok Kang ; Yongmin Chang ; Tae-Jeong Kim
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 13, 2011
• 年：2011
• 卷：54
• 期：1
• 页码：143-152
• 全文大小：987K
• 年卷期：v.54,no.1(January 13, 2011)
• ISSN：1520-4804

文摘

Gd-complexes of the type [Gd(L)(H₂O)]路xH₂O (5a鈭?b>c), where L is DOTA conjugates of tranexamic acid (4a) and tranexamic esters (4b,c), have been prepared as a new class of MRI blood-pool contrast agents (BPCAs). Thermodynamic stability (K_GdL) and pharmacokinetic inertness of 5 compare well with or better than those of analogous MRI contrasting agents (CAs) such as Gd-DOTA and Gd-DTPA-BMA. Their R₁-relaxivities are significantly higher than those of any of the clinically used MRI CAs. T₁-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver. The structural uniqueness of 5c lies in the fact that it adopts macrocyclic DOTA instead of acyclic DTPA. In addition, 5c is nonionic and makes no resort to aromatic substituent(s) in the chelate backbone for the blood-pool enhancement. The nature of hepatobiliary uptake demonstrated by 5c may be explained in terms of lipophilicity of tranexamate in the chelate (4c). The cell cytotoxicity test shows no toxicity found with 5, suggesting their use as a practical MRI BPCAs.