Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation.
Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation.
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DOI：
10.1016/j.bmcl.2010.12.085
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发表时间：
2011-02
影响因子：
2.7
通讯作者：
I. Vlahov;Fei You;H. Santhapuram;Yu Wang;Jeremy F. Vaughn;Spencer J. Hahn;Paul J. Kleindl;Mingjin Fan;C. Leamon
中科院分区：
文献类型：
--
作者：
I. Vlahov;Fei You;H. Santhapuram;Yu Wang;Jeremy F. Vaughn;Spencer J. Hahn;Paul J. Kleindl;Mingjin Fan;C. Leamon
描述了叶酸受体（FR）靶向抗炎药氨基蝶呤肼偶联物的高效合成。以市售的4-[（2-氨基-4-亚胺-3,4-二氢蝶啶-6-甲基）氨基]-苯甲酸为原料合成了2-{4-苯甲酰氨基}-5-氧-5-{N ' -[2-（吡啶-2-基二磺胺基）-乙氧羰基]-肼基}-戊酸。这种新型的、活化的氨蝶呤肼通过半胱氨酸末端（c端）、肽/碳水化合物间隔物与叶酸偶联，产生高度水溶性的偶联物，允许在靶细胞的核内体内释放游离的氨蝶呤肼。
Efficient syntheses of folate receptor (FR) targeting conjugates of the anti-inflammatory, aminopterin hydrazide, are described. 2-{4-Benzoylamino}-5-oxo-5-{N′-[2-(pyridin-2-yldisulfanyl)-ethoxycarbonyl]-hydrazino}-pentanoic acid is synthesized from commercially available 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid. Conjugation of this novel, activated aminopterin hydrazide to folic acid through cysteine-terminating (C-terminus), peptide/carbohydrate spacers results in highly water soluble conjugates which allow for the release of free aminopterin hydrazide within the endosomes of targeted cells.