Alam Mohammad Mumtaz, Akhter Mymoona, Husain Asif, Marella Akranth, Tanwar Om Prakash, Ali Rahmat, Hasan Syed Misbahul, Kumar Harish, Haider Rashiduddin, Shaquiquzzaman Mohammad
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi - 110062, India.
Acta Pol Pharm. 2012 Nov-Dec;69(6):1077-85.
Thirteen new 6-(1-H-indole-2-yl)-4-oxo-2-[2-(substituted-benzylidene)-hydrazinyl]-4,5-dihydropy-rimidine-5-carbonitrile derivatives were synthesized. The title compounds, hydrazones, were synthesized by reaction of hydrazine group of 2-hydrazinyl-4-(1-H-indole-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes using a mixture (2:8, v/v) of glacial acetic acid and alcohol. The required intermediate compound 2 was synthesized from 2-mercapto-4-(1-H-indole-2-yl)-6-oxo-1,6-dihy-dropyrimidine-5-carbonitrile 1 upon nucleophilic attack by the hydrazine hydrate. Compound 1 was synthesized by modified Biginelli condensation method using indole-3-carbaldehyde, ethyl cyanoacetate and thiourea. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial actions. Among the newer derivatives, one compound i.e., 6-(1-H-indole-2-yl)-4-oxo-2-[2-(2,6-dichlorobenzylidene)-hydrazinyl]-4,5-dihydropyrimidine-5-carbonitrile (7) emerged as lead compound having 71.14% inhibition of edema and 12.5 microg/mL MIC against both bacterial and fungal strains.
合成了13种新型的6-(1-H-吲哚-2-基)-4-氧代-2-[2-(取代亚苄基)-肼基]-4,5-二氢嘧啶-5-腈衍生物。通过2-肼基-4-(1-H-吲哚-2-基)-6-氧代-1,6-二氢嘧啶-5-腈(2)的肼基与不同取代的芳香醛在冰醋酸和乙醇的混合液(2:8, v/v)中反应合成了标题化合物腙。所需的中间体化合物2是由2-巯基-4-(1-H-吲哚-2-基)-6-氧代-1,6-二氢嘧啶-5-腈1在水合肼的亲核进攻下合成的。化合物1通过改良的Biginelli缩合方法，使用吲哚-3-甲醛、氰基乙酸乙酯和硫脲合成。对这些化合物的抗炎、镇痛、致溃疡和抗菌作用进行了评估。在这些新衍生物中，一种化合物即6-(1-H-吲哚-2-基)-4-氧代-2-[2-(2,6-二氯亚苄基)-肼基]-4,5-二氢嘧啶-5-腈(7)成为先导化合物，对水肿的抑制率为71.14%，对细菌和真菌菌株的最低抑菌浓度为12.5 μg/mL。
