SYNTHESIS OF AMINO ACETYLENIC BENZOPHENONE DERIVATIVES AS H3-ANTAGONISTS

Objective: To synthesize new amino acetylenic benzophenone derivatives with significant H3-antagonist's activity.Methods: Amino acetylenic benzophenone derivatives were synthesized from the reaction of 2-hydroxybenzophenone with 3-bromoprop-1-in to generate 2-(prop-2-yn-1-yloxy)-1,3-benzophenone (AZ-1). A mixture of 2-(prop-2-yn-1-yloxy)-1,3-benzophenone, paraformaldehyde, cyclic amine, cuprous chloride (catalytic amount) in peroxide free dioane through Mannich reaction yielded the designed amino acetylenic benzophenone derivatives (AZ-2-7).Results: The IR, H1-NMR, 13C NMR, and elemental analysis were consistent with the assigned structures. The designers of these compounds as H3-antagonists were based on the nationalization of the important criteria that provide effective inhibitory binding with H3-receptor. Molecular docking results of compounds (AZ-2-7) showed a good H3-receptor antagonistic activity relative to thioperamide of-6 (kcal/mol) especially AZ-2 which has-8.6 (kcal/mol).Conclusion: Docking results provide a good lead to designing more effective H3 antagonists in managing many CNS diseases like Alzheimer, epilepsy, depression, schizophrenia and many others

DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

Objective: To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.Methods: Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, 1H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d6 as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.Results: The IR, 1H-NMR, 13C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.Conclusion: For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity.Â

Synthesis and Characterization of 2(2-Tetrahydropyranylthio) methyl cyclopropylamine

2(2-Tetrahydropyranylthio) methyl cyclopropyl amines were synthesized from allylmercaptan through several steps. The structures of the intermediates and the final products where confirmed through IR, NMR and elemental analysis, these compounds may be of value in the treatment of diseases  where free radicals are implicated in their pathogensis, since the thio and the amino groups of the synthesized compounds may act as free radical scavengers