Annexure-I COMPLETE DESCRIPTION
BACKGROUND OF THE PRESENT INVENTION:
(i) Field of Present Invention:
Pyrimidine is well known biologically active nitrogen containing heterocyclic compound. In recent years researchers are much interested on the synthesis of pyrimidine analogues. Pyrimidine derivatives posses fungicidal [1], herbicidal [2], antidepressant [3], and antitumor properties [4, 5]. Synthetically prepared amino pyrimidine derivatives display a wide range of biological activities such as antibacterial [6], antitumor [7] and antiviral [8, 9]. Therefore, the substituted amino pyrimidine structure can be found in diverse clinically approved drugs. Interestingly, a substituted amino pyrimidine moiety was also suggested to account for the antioxidant activity [10]. Among those amino pyrimidine heterocycle, 2-aminopyrimidines have been widely used as pharmacophore for drug discovery. 2-Aminopyrimidines constitute a part of the DNA base pair molecules [11]. Compounds having potent anticancer activity, CDK inhibitory activity, / [12-14], anti-proliferative activity [15], kinase inhibitor, // [16], antibacterial agents [17], antitumor, /// antidiabetic activity [18], antimalarial, IV anti-plasmodial agents [19], antimicrobial activity, V [20] and anti-inflammatory, VI [21]. Due to numerous biological applications of 2-Aminopyrimidine, we have focused our research on synthesis of 2-Aminopyrimidine by using pharmacologically important structural scaffold acridine pharmacophore.
Protein-ligand interaction is comparable to the lock-and-key principle, in which the lock encodes the protein and the key is ensemble with the ligand. The major driving force for binding appears to be hydrophobic interaction [22]. In silico techniques helps identifying drug target via bioinformatics tools. They can also be used to explore the target structures for possible active sites, generate candidate molecules, dock these molecules with the target, rank them according to their binding affinities, further optimize the molecules to improve binding characteristics [23]. Diabetes Mellitus (DM) is a leading non-communicable disease which affects more than 100 million people worldwide and is considered as one of the fine leading disease which causes death in the world [24]. Type-2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Management of type 2 diabetes by conventional therapy involves in the inhibition of degradation of dietary starch by glycosidase such as a-amylase and a-glycosidase [25]. The pathogenesis of type-2 diabetes involves progressive development in insulin resistance associated with a defect in insulin secretion, leading to overt hyperglycaemia. However, compounds which improve insulin sensitivity and glucose intolerance are somewhat limited warranting the discovery and characterization of novel molecules targeting various pathways involved in the pathogenesis of type-2 diabetes [26]. Currently, there are few drugs that are able to counteract the development of the associated pathologies. Therefore, the need to search for new drug

candidates in this field appears to be critical. Aromatic amines and thiazolidinones nuclei would produce new compounds with significant antidiabetic properties [27]
In our research group, we have already reported larvicidal activity of 7-chloro-3,4-dihydro-9-
phenylacridin-1 (2//)-one and (£)-7-chloro-3,4-dihyro-phenyl-2-[(pyridin-2-
yl)methylene]acridin-l(2//)-ones [28]. In continuation of our research work on acridine
moiety, presently we focus on the synthesis of 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-
dihydropyrimido[4,5-a]acridin-2-amine, 3a-f derivatives. All the synthesized
dihydropyrimido[4,5-a]acridin-2-amines analogues, 3a-f were evaluated for docking and in vitro antidiabetic activity.
(ii) Description and related art:
There are numerous biologically active fused heterocyclic rings [29]. Among these acridone is one of scaffold known to associate with several biological activities [30]. Acridone derivatives are also found in natural plant sources, which are provids various disorders. Many plants, particularly plants pertaining to Rutaceae species possess maximum number of acridone derivatives [31]. Taking into account of these facts and our experience in the synthesis and Characterization of acridine core, we focused our attention on new synthesis of acridine and its derivatives [32]. Based on extensive investigations, it has been revealed that the efficient preparation of the desired compounds (3a-f).
The present invention provides a novel compounds (3a-f). This invention also provides biological importance of synthesized derivatives (3a-f) to be used in this process. To verify the practicability of the projected route as shown in Fig. 1, synthesized derivatives and physical data's are summarized in table 1.
SUMMARY OF THE PRESENT INVENTION
In the preceding study, a series of novel 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amincs, 3a-f have been synthesized. Structures of these synthesized molecules were studied by FT-IR, 'H NMR, nC NMR, EI-MS and single crystal X-ray structural analysis data. An in silico molecular docking was performed on derivatives of highest in vitro activity on a-amylase and a-glucosidase. Overall data indicate that the compound 3e is a promising lead compound for the development of selective inhibition of a-amylase and a-glucosidase. The synthesized compounds were screened for their antidiabetic activity by in vitro methods.
DETAILED DESCRD7TION OF THE PRESENT INVENTION
Accordingly the present invention provides a process for the synthesis of 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amines, 3a-f have been synthesized. Structures of these synthesized molecules were studied by FT-IR, *H NMR, 13C NMR, EI-MS and single crystal X-ray structural analysis data. An in silico molecular docking was performed on derivatives of highest in vitro activity on a-amylase and a-glucosidase.

The following exemplary embodiments are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention.
EXEMPLARY EMBODIMENT 1:
Synthesis o/10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5- ajacridin-2-amines (3a-f)
10-chloro-4,12-diphenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amines, 3a-f were synthesized via., fE)-2-benzylidene-7-choloro-3,4-dihydro-9-phenylacridin-l(2//)-ones, la-f were mixed with guanidine carbonate 2 (0.9008 g, 0.01 mol) and 10 % ale. NaOH (1 g in 10 ml ethanol) and then heated under reflux condition for 5 h. After the completion of the reaction, reaction mixture was cooled and poured into crushed ice. The crude product was separated by column chromatography using ethyl acetate and pet ether solvent to get the target compounds, 3a-f. The synthetic scheme was explained in scheme 1 and all synthesized derivatives and physical data were summarized in table 1.
EXEMPLARY EMBODIMENT 2:
An in silico molecular docking was performed on derivatives of highest in vitro activity on a-amylase and a-glucosidase.
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I/WE CLAIM(S)
1. A process for the synthesis of 10-chloro-4,12-diphenyl-5,6-dihydropyrimido[4,5-fl]acridin-2-amines, 3a-f were synthesized via., (£)-2-benzylidene-7-choloro-3,4-dihydro-9-phenylacridin-l(2//)-ones, la-f were mixed with guanidine carbonate 2 (0.9008 g, 0.01 mol) and 10 % ale. NaOH (1 g in 10 ml ethanol) and then heated under reflux condition for 5 h.
2. A process according to claim 1 Synthesized compounds were evaluated for an in silico molecular docking was performed on derivatives of highest in vitro activity on a-amylase and a-glucosidase. Overall data indicate that the compound 3e is a promising lead compound for the development of selective inhibition of a-amylase and a-glucosidase. The synthesized compounds were screened for their antidiabetic activity by in vitro methods.