Preparation and biological evaluation of a potential photoaffinity label for the prostaglandin H2/thromboxane A2 receptor.
Preparation and biological evaluation of a potential photoaffinity label for the prostaglandin H2/thromboxane A2 receptor.
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前列腺素 H2/血栓素 A2 受体潜在光亲和标记的制备和生物学评价。
DOI：
10.1021/jm00388a029
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发表时间：
1987
影响因子：
7.3
通讯作者：
Venton,DL
中科院分区：
文献类型：
--
作者：
Arora,SK;Kattelman,EJ;Lim,CT;LeBreton,GC;Venton,DL
制备了两种芳香叠氮化物（24和26）作为PGH2/TXA2受体的潜在光亲和探针。这些化合物是基于PGH2/TXA2受体拮抗剂13-氮杂素酸，其下侧链末端被苯氧基（24）或苄基（26）叠氮化物取代。这两种化合物在光解和重悬后对血小板功能有不可逆的抑制作用。然而，在这两种芳香叠氮化物中，只有苯基衍生物26对前列腺素途径具有选择性。后一种化合物也被制备为芳香的125I（29）衍生物，它可能最终被证明是一种有用的标记探针，用于鉴定和分离推测的TXA2/PGH2受体。前列腺素在血小板聚集中的作用的研究使我们更好地了解心血管疾病的状态，并为设计治疗血栓性疾病（如心肌梗死、中风和肺栓塞）的药物提供了理论依据。近年来，前列腺素PGI2、PGEj和PGD2对血小板功能的抑制机制的研究取得了重大进展。通过使用有标签的衍生品，它做到了
Two aromatic azides (24 and 26) were prepared as potential photoaffinity probes for the PGH2/TXA2 receptor. The compounds are based on the well-characterized PGH2/TXA2 receptor antagonist 13-azaprostanoic acid, with the terminus of its lower side chain replaced with phenoxy (24) or benzyl (26) azide functionality. The two compounds were shown toirreversibly inhibit platelet function after photolysis and resuspension. However, of thetwo aromatic azides, only the benzyl derivative 26 appeared to be selective for the prostaglandin pathway. The latter compound was also prepared as the aromatic 125I (29) derivative, which may ultimately prove useful as a labeled probe for the identification and isolationof the putative TXA2/PGH2 receptor.Research on the role of prostaglandins in platelet ag-gregation has provided us with a better understanding of cardiovascular disease states and a rationale for the design of drugs potentially useful in the treatment of thrombotic conditions such as myocardial infarction, stroke, and pulmonary embolism. 2 In recent years significant progress has been made in understanding the inhibitory mechanisms of the prostaglandins PGI2, PGEj, and PGD2 on platelet function. With use of labeled derivatives, it has