翻译 The peak coincides with the landmark publication by Loveriny, who propose an “escape from flatland” and suggest that compounds with a higher fraction of sp3 (Fsp3 = number of sp3 hybridized carbons/total carbon count) have an increased probability to succeed in compound translation to the clinic. Very recently, the advantages of quarternary carbon structures leading to higher Fsp3 and enhanced three-dimensionality have been comprehensively reviewed. Following these observations, theintroduction of spirocycles into lead structures seems highly attractive; however, it is often associated with increased synthetic effort, resulting from an increased number of synthetic steps and stereocenters or unusual reaction procedures. Nevertheless, medicinal chemists accept the increased expenditure due to the expected favorable effects on potency, selectivity, physicochemical properties, and pharmacokinetic (PK) profile. Some of the expectations of spirocyclic compounds are fully justified.
峰值与Loveriny的标志性出版物相吻合，他提出了“逃离平面”的概念，并建议具有更高sp3比例（Fsp3 = sp3杂化碳的数量/总碳数）的化合物在转化为临床药物的过程中成功的概率更高。最近，关于四级碳结构的优势（导致更高的Fsp3和增强的三维性）已经得到了全面的综述。基于这些观察结果，将螺环引入先导结构显得非常有吸引力；然而，这通常伴随着合成难度的增加，因为需要更多的合成步骤和立体中心，或者需要进行不常见的反应过程。尽管如此，药物化学家们仍然接受了这种增加的投入，因为他们预期这会对药物的效力、选择性、物理化学性质和药代动力学（PK）特性产生有利影响。对于螺环化合物的一些期望是完全合理的。