Background: This research project is designed to identify the anti-diabetic effects of the newly synthesized compounds to conclude the perspective of consuming one or more of these new synthetic compounds for diabetes management.

Introduction: A series of dihydropyrimidine (DHPM) derivative bearing electron releasing and electron-withdrawing substituent’s on phenyl ring (a-j) were synthesized and screened for antihyperglycemic( anti-diabetic) activity on streptozotocin (STZ) induced diabetic rat model. The newly synthesized compounds were characterized by using FT-IR, melting point, 1H and 13C NMR analysis. The crystal structure and supramolecular features were analyzed through single-crystal X-ray study. Anti-diabetic activity testing of newly prepared DHPM scaffolds was mainly based on their relative substituent on the phenyl ring along with urea and thiourea. Among the synthesized DHPM scaffold, the test compound c having chlorine group on phenyl ring at the ortho position to the hydropyrimidine ring with urea and methyl acetoacetate derivative shows moderate lowering of glucose level. However, the title compounds methyl 4-(4-hydroxy-3-methoxyphenyl)- 6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate(g) and ethyl 4-(3-ethoxy-4- hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate(h) having methoxy and ethoxy substituents on phenyl ring show significant hypoglycemic activity compared to the remaining compounds from the Scheme 1.

Methods: The experimental rat models for the study were divided into 13 groups (n = 10); group 1 animals were treated with 0.5% CMC (0.5mL) (vehicle); group 2 were considered the streptozotocin (STZ)/nicotinamide diabetic control group (DC) and untreated, group 3 diabetic animals were administered with gliclazide 50 mg/kg and act as a reference drug group. The remaining groups of the diabetic animals were administered with the newly synthesized dihydropyrimidine compounds in a single dose of 50 mg/kg orally using the oral gavage, daily for 7 days continuously. The blood glucose level was measured before and 72 hrs after nicotinamide-STZ injection, for confirmation of hyperglycemia and type 2 diabetes development.

Results: Blood glucose levels were significantly (p<0.05) reduced after treatment with these derivatives. The mean percentage reduction for gliclazide was 50%, while that of synthesized compounds were approximately 36%.

Conclusion: Our result suggests that the synthesized new DHPM derivative containing alkoxy group on the phenyl ring shows a significant lowering of glucose level compared to other derivatives.

背景：本研究项目旨在确定新合成化合物的抗糖尿病作用，从而总结出食用一种或多种这些新合成化合物来治疗糖尿病的观点。

简介：合成了一系列在苯环（aj）上带有电子释放和吸电子取代基的二氢嘧啶（DHPM）衍生物，并筛选了链脲佐菌素（STZ）诱导的糖尿病大鼠模型的抗高血糖（抗糖尿病）活性。通过FT-IR，熔点，1H和13C NMR分析对新合成的化合物进行表征。通过单晶X射线研究分析了晶体结构和超分子特征。新制备的DHPM支架的抗糖尿病活性测试主要是基于它们在苯环上的相对取代基以及脲和硫脲。在合成的DHPM支架中，在具有尿素和乙酰乙酸甲酯衍生物的对氢嘧啶环的邻位的苯环上的邻位具有氯基的受试化合物c显示出葡萄糖水平的适度降低。然而，标题化合物4-（4-羟基-3-甲氧基苯基）-6-甲基-2-硫代-1,2,3,4-四氢嘧啶-5-羧酸酯（g）和乙基4-（3-乙氧基）与该方案中的其余化合物相比，在苯环上具有甲氧基和乙氧基取代基的-4-羟基苯基）-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸盐（h）显示出明显的降血糖活性1。

方法：将实验的大鼠模型分为13组（n = 10）。第1组动物用0.5％CMC（0.5mL）（载体）治疗；第2组被认为是链脲佐菌素（STZ）/烟酰胺类糖尿病对照组（DC），未经治疗，第3组糖尿病动物被给予格列齐特50 mg / kg并作为参考药物组。其余组的糖尿病动物每天用口服管饲法以50mg / kg的单剂量口服新合成的二氢嘧啶化合物，每天连续7天。在注射烟酰胺-STZ之前和之后72小时测量血糖水平，以确认高血糖和2型糖尿病的发展。

结果：用这些衍生物治疗后，血糖水平显着降低（p <0.05）。格列齐特的平均减少百分比为50％，而合成化合物的平均减少百分比约为36％。

结论：我们的结果表明，与其他衍生物相比，在苯环上含有烷氧基的合成新DHPM衍生物显示出葡萄糖水平的显着降低。