Mandava Suresh, Ganganna Bogonda, Hwang Jungjoong, Jang Younchang, Hwang Jiho, Samala Mallesham, Kim Ki-Bbeum, Park Haeil, Lee Ji Hyun, Baek Sun Young, Lee Jongkook
College of Pharmacy, Kangwon National University.
Advanced Analysis Team, Toxicological Evalauation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety.
Chem Pharm Bull (Tokyo). 2017;65(5):498-503. doi: 10.1248/cpb.c17-00034.
A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.
一些已获当局批准的磷酸二酯酶5（PDE5）抑制剂已成功用于治疗勃起功能障碍。由于这些药物的副作用，必须谨慎开处方，但它们及其类似物正被非法添加到膳食补充剂中。这些非法膳食补充剂对公众健康构成重大风险。已合成了几种二聚体他达拉非类似物，用作主要宣传为性增强产品的功能性食品检测中的参考标准。在该合成过程中，1-[双（二甲氨基）亚甲基]-1H-1,2,3-三唑并[4,5-b]吡啶鎓3-氧化物六氟磷酸盐（HATU）被证明是用于酰胺偶联以生产这些二聚体他达拉非类似物的首选试剂。此外，膳食补充剂中发现的分离出的二聚体他达拉非类似物（双前高他达拉非和双前环戊基他达拉非）初步指定的反式异构体结构现被修订为顺式异构体结构。
