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Structure and Mechanism of Formation of Conversion Products of Caspase Inhibitors in Aqueous Media

机译:水性培养基中胱天冬酶抑制剂转化产物的结构和机制

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The caspases play an important role in the apoptosis process and are activated following ischemic injury. 3,4-dihydro-2H-pyrimido(1,2-a)indol-10-ones have been identified as potent, non-peptide inhibitors of the caspase family of enzymes (1). They have been explored for their therapeutic utility in caspase inhibition for the prevention of tissue damage following ischemic injury. However, the in vivo potency of many analogues in the pyrimido(1,2-a)indole-10-one series substantially decreased with time under physiological conditions owing to the instability of these compounds in aqueous media. Initial studies using NMR and LC/MS suggested that these analogues formed hydrated conversion products under physiological conditions (2). This poster describes the structure and mechanism of formation of the conversion products of two pyrimidoindolone analogues in aqueous media using LC/MS and LC/MS/MS.
机译:胱天蛋白酶在凋亡过程中发挥着重要作用,并在缺血性损伤后激活。 3,4-二氢-2H-嘧啶(1,2-A)吲哚-10- indol-10- in鉴定为Caspase系列酶(1)的有效的非肽抑制剂(1)。他们已经探讨了他们在胱天蛋白酶抑制中预防缺血性损伤后的组织损伤的治疗效用。然而,由于在水性介质中的这些化合物的不稳定性,嘧啶(1,2-A)吲哚-10-1串中许多类似物中的多种类似物的体内效力随着这些化合物的不稳定性而在生理条件下随时间减少。使用NMR和LC / MS的初始研究表明这些类似物在生理条件下形成了水合转化产物(2)。该海报描述了使用LC / MS和LC / MS / MS在水性介质中形成两种嘧啶吲哚酮类似物的转化产物的结构和机制。

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