Rajasekaran Aiyalu, Rajamanickam Velayuthem, Darlinquine Sabarimuthu
Department of Pharmaceutical Chemistry, KMCH College of Pharmacy, Coimbatore, India.
Yakugaku Zasshi. 2011;131(7):1079-84. doi: 10.1248/yakushi.131.1079.
A series of 3-substituted-2-thioxoquinazolin-4(3H)-one derivatives have been synthesized and their structures have been elucidated on the basis of IR, (1)H-NMR, elemental analysis and mass spectroscopic studies. Anti-inflammatory and analgesic activity of the synthesized compounds was evaluated by Carrageenan induced rat paw edema method and Eddy's hot plate method respectively. Among the synthesized compounds N-(4-hydroxyphenyl)-N-(4-oxo-3-phenyl-2-thioxo-3,4-dihydroquinazolin-1(2H)methyl)acetamide (PTQ01) showed excellent anti-inflammatory activity. N-(4-ethoxyphenyl)-N-(3-(naphthalen-2yl)-4-oxo-2-thioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)acetamide (NTQ02), N-(4-Hydroxyphenyl)-N-((3-naphthalen-2-yl)-4-oxo-2-thioxo-3,4-dihydorquinazolin-1(2H)-ylmethyl)acetamide (NTQ01), N-((3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)-N-(4-hydroxyphenyl)acetamide (ETQ01) N-(3-(4-ethoxyphenyl)-4-oxo-2thioxo-3,4-dihydroquinazolin-1(2H)-ylmethyl)-N-(4-hydroxyphenyl)acetamide (ETQ04), N-(4-ethoxyphenyl)-N-((4-oxo-3-phenyl-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide (PTQ02) and N-(4-ethoxyphenyl)-N-(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide (ETQ02) at a dose of 20 mg/kg exhibited significant anti-inflammatory activity compared to that of standard drug diclofenac sodium. The compound 2-(2,3-dimethylphenyl)(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydroquinazolin-1-2H)-1ylmethylamino)benzoic acid PTQ03 and sodium 2-(2-((2,6-dichlrophenyl)(3-(4-oxo-2-thioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)amino)phenylacetate (PTQ04) showed moderate anti-inflammatory activity. The compounds PTQ01, PTQ02, PTQ04, ETQ01 and ETQ02 showed significant analgesic activity compared with that of standard drug pentazocin.
合成了一系列3-取代-2-硫代喹唑啉-4(3H)-酮衍生物，并通过红外光谱、(1)H-核磁共振、元素分析和质谱研究对其结构进行了确证。分别采用角叉菜胶诱导的大鼠足跖肿胀法和Eddy热板法对合成化合物的抗炎和镇痛活性进行了评价。在合成的化合物中，N-(4-羟基苯基)-N-(4-氧代-3-苯基-2-硫代-3,4-二氢喹唑啉-1(2H)甲基)乙酰胺(PTQ01)表现出优异的抗炎活性。N-(4-乙氧基苯基)-N-(3-(萘-2-基)-4-氧代-2-硫代-3,4-二氢喹唑啉-1(2H)-基)甲基)乙酰胺(NTQ02)、N-(4-羟基苯基)-N-((3-萘-2-基)-4-氧代-2-硫代-3,4-二氢喹唑啉-1(2H)-基甲基)乙酰胺(NTQ01)、N-((3-(4-乙氧基苯基)-4-氧代-2-硫代-3,4-二氢喹唑啉-1(2H)-基)甲基)-N-(4-羟基苯基)乙酰胺(ETQ01)、N-(3-(4-乙氧基苯基)-4-氧代-2硫代-3,4-二氢喹唑啉-1(2H)-基甲基)-N-(4-羟基苯基)乙酰胺(ETQ04)、N-(4-乙氧基苯基)-N-((4-氧代-3-苯基-2-硫代-3,4-二氢喹唑啉-1(2H)-基)甲基)乙酰胺(PTQ02)和N-(4-乙氧基苯基)-N-(3-(4-乙氧基苯基)-4-氧代-2-硫代-3,4-二氢喹唑啉-1(2H)-基)甲基)乙酰胺(ETQ02)在剂量为20 mg/kg时，与标准药物双氯芬酸钠相比表现出显著的抗炎活性。化合物(2-(2,3-二甲基苯基)(3-(4-乙氧基苯基)-4-氧代-2-硫代-3,4-二氢喹唑啉-1-2H)-1基甲基氨基)苯甲酸PTQ03和2-(2-((2,6-二氯苯基)(3-(4-氧代-2-硫代-3,4-二氢喹唑啉-1(2H)-基)甲基)氨基)苯基乙酸钠(PTQ04)表现出中等抗炎活性。与标准药物喷他佐辛相比，化合物PTQ01、PTQ02、PTQ04、ETQ01和ETQ02表现出显著的镇痛活性。
