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Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2018-10-27 , DOI: 10.1007/s00044-018-2256-z
Selvakumar Balaraman , Nagaraj Nayak , Madhuri Subbiah , Kuppanagounder P. Elango

A series of ten new compounds (7a–j) has been synthesized by absolutely replacing the glutamic acid part of Pemetrexed drug, chemically known as N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid, with primary, secondary, and aryl amines in high yields using diethylphosphorocyanidate (DEPC) as a peptide coupling agent. All the synthesized compounds are characterized by 1H and 13C NMR, LCMS, and FT-IR spectral techniques. All the synthesized novel non-glutamate 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives showed 4- to 7-folds higher antiviral activity than its structurally similar commercial drug Pemetrexed against Newcastle disease virus, an avian paramyxovirus. Among the lot, compounds possessing carboxamide synthesized using five-membered heteroaryl amines (7i and 7j) exhibited the highest antiviral activity.


中文翻译:

新型4-(2-(6-(4-氨基-4-氧代-4,5-二氢-1H-吡咯并[2,3-d]嘧啶-3-基)乙基)苯甲酰胺衍生物的合成及抗病毒研究

通过绝对替代培美曲塞药物的谷氨酸部分(化学名称为N- {4- [2-(2-(2-氨基-4-氧代-4,7-二氢])),合成了一系列十个新化合物(7a–j) -3H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酰基} -1-谷氨酸,具有伯胺,仲胺和芳基胺,使用二乙基磷腈基氰酸酯(DEPC)作为肽偶联剂可以高收率。所有合成的化合物的特征在于1 H和1313 C NMR,LCMS和FT-IR光谱技术。所有合成的新型非谷氨酸4-(2-(6-氨基-4-氧代-4,5-二氢-1H-吡咯并[2,3-d]嘧啶-3-基)乙基)苯甲酰胺衍生物均显示4-其抗病毒活性比其结构相似的商业药物Pemetrexed抗禽副粘病毒新城疫病毒高7倍。其中,具有使用五元杂芳基胺(7i7j)合成的具有羧酰胺的化合物表现出最高的抗病毒活性。
更新日期:2018-10-27
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