Derivatives 4a-f Research Articles

Synthesis of Novel Amide Functionalized Pyrido[2,3-d]pyrimidine Derivatives and their Anticancer Activity

A series of novel amide functionalized pyrido[2,3-d]pyrimidine derivatives were synthesized from 2-amino-6-(thiophen-2-yl)-4-(trifluoro-methyl)nicotinonitrile (1), which on reaction with trifluoroacetic acid to get pyridopyrimidine (2). Compound 2 when treated with bromoethyl acetate followed by hydrazine hydrate to get hydrazide derivatives 4. Compound 4 on reaction with different substituted aromatic aldehydes to obtain Schiff base derivatives 5a-f. In another way, compound 3 treated with different substituted amines and amino acids to obtain amide derivatives 6a-f, 7a-d and 8a-c. All the compounds evaluated for anti-cancer activity against four human cancer cell lines such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-prostate cancer (HTB-81) and HeLa-cervical cancer (CCL-2) and among the sythesized compounds, only 5d, 7d and 8a were identified as the potent compounds against the anticancer activity.

Synthesis and Characterization of New Dihydronaphthalene Candidates as Potent Cytotoxic Agents against MCF-7 Human Cancer Cells.

In the present work, a new series of dihydronaphthalene derivatives were synthesized starting with 6-methoxy-1-tetralone 1, and the corresponding hydrazine derivative 2. Reaction of compound 2 with aryl isothiocyanates produced thiosemicarbazides 3a-d, which were reacted with ethyl chloroacetate to give thiazolidinone derivatives 4a-d. Pyrano thiazolecarbonitrile derivatives 5a-f were prepared by heating a mixture of compounds 4a or 4c, aryl aldehydes, and malononitrile utilizing distilled water in the presence of catalytic amount of potassium hydrogen phthalate. Also, treatment of 4a with DMF-DMA under solvent-free conditions gave enaminone derivative 6, which condensed with ethyl acetoacetate or acetylacetone or malononitrile or cyanothioacetamide to give compounds 7-10, respectively. Finally, reaction of the enaminone 6 with 2-aminoimidazol or 2-aminothiazol in the presence of glacial acetic acid produced derivatives 11 and 12, respectively. Cytotoxic evaluation of eleven compounds, against MCF-7 (human breast adenocarcinoma) cell lines, was estimated. Results revealed that five of the examined compounds 5a, 5d, 5e, 10, and 3d showed potent cytotoxic activities recording, IC50 values; 0.93 ± 0.02, 1.76 ± 0.04, 2.36 ± 0.06, 2.83 ± 0.07, and 3.73 ± 0.09 μM, respectively, which were more potent than the reference used (Saturosporin, IC506.08 ± 0.15 μM). The new products were also examined towards normal epithelial breast cells (MCF10A). All of them showed very good safety profile with different degrees and were safer than the reference drug used. Compound 5a was the most effective against MCF-7 cells and was less toxic than Saturosporin by about 18.45-folds towards MCF01A normal cells. All the new compounds were fully characterized by the different spectral and analytical tools. Herein, detailed syntheses, spectroscopic, and biological data are reported.

Design, synthesis, PASS prediction, in-silico ADME and molecular docking studies of substituted-(Z)-3-benzylidine-5-aza-2-oxindole derivatives (Part-1)

Abstract In this research article we report a simple protocol for the synthesis of series novel of substituted (Z)-3-benzylidine-5-aza-2-oxindole derivatives (5a-f) by employing optimized reaction condition of Knoevenagel condensation. Among the reaction conditions attempted, the reaction in ethanol and piperidine at 80 °C afforded the desired products (5a-f) in satisfactory yields and enhanced purity via trituration and recrystallization. The physicochemical as well as spectroscopic evidences established the assigned structures of the compounds without any ambiguity. The anti-inflammatory proficiency assessment for the synthesized compounds has been carried out on the basis of Prediction of Activity Spectra for Substances (PASS) technique and compared with standard tenidap. Furthermore, to validate the results of PASS prediction, molecular docking studies of the synthesized compounds (5a-f) were carried out on the TNF-α target protein (PDB ID: 2AZ5 ). The compounds displayed less docking energies in the range of -6.9 to -7.5 Kcal/mol than tenidap (-8.8 Kcal/mol). Additionally, in silico ADME analysis was carried out to check drug ability and toxicity issues.

Microwave-assisted Synthesis of Novel Pyrazole Derivatives and their Biological Evaluation as Anti-Bacterial Agents.

Microwave-assisted condensation of acetophenone 1 and aromatic aldehydes 2 gave chalcone analogs 3, which were cyclized to pyrazole derivatives 6a-f via the reaction with hydrazine hydrate and oxalic acid in the presence of the catalytic amount of acetic acid in ethanol. The structural features of the synthesized compounds were characterized by melting point, FT-IR, 1H, 13C NMR and elemental analysis. The antibacterial activities of the synthesized pyrazoles were evaluated against three gram-positive bacteria, such as Enterococcus durans, Staphylococcus aureus, Bacillus subtilis and two gram-negative bacteria such as Escherichia coli and Salmonella typhimurium. All the synthesized pyrazoles showed relatively high antibacterial activity against S. aureus strain, and none of them demonstrated antibacterial activity against E. coli.

Comparative Evaluation of the Inhibitory Potential of Synthetic N-Heterocycles, Cu/Fe3O4@SiO2 Nanocomposites and Some Natural Products against Non-Resistant and Antibiotic-Resistant Acinetobacter baumannii

Background: Acinetobacter baumannii is a common infectious agent in hospitals. New antimicrobial agents are identified and prepared to combat these bacterial pathogens. In this context, the blocking potentials of a series of synthesized N-heterocyclic compounds, Cu/Fe3O4@SiO2 nanocomposites, glycine, poly-L-lysine, nisin and hydroalcoholic extracts of Trachyspermum ammi, Curcuma longa and green tea catechins were evaluated against non-resistant and multidrug-resistant strains of A. baumannii. Methods: Solutions of heterocyclic derivatives and hydroalcoholic extracts of Trachyspermum ammi, Curcuma longa and green tea catechins were prepared at initial concentration of 10240 μg ml-1 in 10% DMSO. Other compounds were dissolved in water at the same concentrations. Their in vitro inhibitory activity was assessed by determination of IZD, MIC and MBC values. Results: Glycine, poly-L-lysine, nisin, Curcuma longa and green tea catechins extracts, and thiazoles 3a, 3d and 3f were ineffective at their initial concentrations. Heterocyclic derivatives 7a-f, 3c, 3e and 3h, Cu/Fe3O4@SiO2 nanocomposites and Trachyspermum ammi extract could block the growth of bacterial strains with IZDs (7.40-15.51 mm), MICs (32-1024 µg ml-1) and MBCs (128-2048 µg ml-1). Conclusion: Among synthetic chemicals and natural products, the best antimicrobial effects were recorded with (E)-2-(5-acetyl-4-methylthiazol-2-yl)-2-(thiazolidin-2-ylidene)acetonitrile (7b) and the extract of Trachyspermum ammi. It is imperative that their toxic and histopathologic effects were assessed in future researches. It is predicted that the essential oil of Trachyspermum ammi will improve its antibacterial activities.

Synthesis and antiproliferative activities of polymethoxyflavones aminoalkyl and amino acid derivatives

Abstract Twelve novel aminoalkyl derivatives 3a-3f, 4a-4f and four novel amino acid derivatives 5a, 5b, 6a and 6b of polymethoxyflavones 1 and 2 were synthesized through regioselective demethylation, etherification, amination, EDCl-mediated amide condensation and alkaline hydrolysis, using tangeretin and nobiletin as starting materials. Their antiproliferative activities against four different human cancer cell lines (Aspc-1, SUN5, HepG-2 and HCT116) were evaluated by in vitro CCK-8 assay. The results show that the majority of the synthetic compounds exhibited moderate to good antiproliferative activity. In particular, the antiproliferative activity of compound 5b against HepG-2 cells (IC50 0.057 μM) was equal to the positive control drug Staurosporine (IC50 0.0575 μM).

Heterocyclization of 2-Arylidenecyclohexan-1,3-dione: Synthesis of Thiophene, Thiazole, and Isoxazole Derivatives with Potential Antitumor Activities.

Thiophene, thiazole, and isoxazole derivatives are present in a wide range of natural and synthetic compounds with heterogeneous pharmacological activity. Due to their structural diversity, they are some of the most versatile classes of compounds for anticancer drug design and discovery. Thiophene, thiazole, and isoxazole derivatives were herein designed with a dual purpose: as antiproliferative agents and kinase inhibitors. The test compounds were synthesized in moderate to high yields through a simple methodology. Tetrahydrobenzo[b]thiophen-5-one derivatives 5a-f were prepared from the reaction of 2-arylidencyclohexan- 1,3-dione 3a-c with elemental sulfur and either of malononitrile (4a) or ethyl cyanoacetate (4b) in 1,4-dioxan in the presence of triethylamine. Compounds 5a,b were used for the synthesis of thiophene, thiazole, and isoxazole derivatives through their reactions with different chemical reagents. Antiproliferative evaluations, c-Met kinase, and Pim-1 kinase inhibitions were performed where some compounds revealed high activities. In all cases, antiproliferative activity and the kinase inhibitions were performed against six cancer cell lines and five tyrosine kinases, respectively. Where the most cytotoxic compounds were 3c, 5d, and 16c with IC50's 0.29, 0.68, and 0.42μM, respectively, against the A549 cell line. The anti-proliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines (A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460). The most potent compounds toward the cancer cell lines (3a, 3c, 5d, 7c, 11c, 16a, and 16c) were further investigated towards the five tyrosine kinases (c-kit, FIT-3, VEGFR-2, EGFR, and PDGFR). Compounds 3c, 5d, and 16c were selected for testing of their inhibition for the Pim-1 kinase due to their anti-proliferation activities against the cancer cell lines and their high activities against the tyrosine kinases.

Some 1,3,5-trisubstituted pyrazoline derivatives targeting breast cancer: Design, synthesis, cytotoxic activity, EGFR inhibition and molecular docking.

Different 1,3,5-trisubstituted pyrazoline derivatives 2a-c, 3-c, 4a-f, 6a-c, 7a-f and 8a-d were prepared via condensation reaction of the appropriate chalcone 1a-c or 5a-c with various hydrazine derivatives. All compounds were screened for their cytotoxicity against breast MCF-7 cancer cell line and the normal fibroblasts WI-38. Thirteen compounds 2a, 3a, 3c, 4a-d, 6c, 7d, 7e, 8b, 8d and 8f revealed promising cytotoxicity against MCF-7 compared to the reference standard staurosporine and they were safe to the normal fibroblasts WI-38. In addition, compounds 3c, 6c, 7d, 8b and 8d elicited higher cytotoxicity than erlotinib and exhibited promising EGFR inhibitory activity at submicromolar level comparable to that of erlotinib except for compound 8b that may exert its cytotoxicity via another mechanism besides EGFR inhibition. Molecular docking of 3c, 6c, 7d, 8b and 8d in the active site of EGFR confirmed the obtained results.

Synthesis, Characterization and in vitro Antimicrobial Screening of Some Novel Series of 2-Azetidinone Derivatives Integrated with Quinoline, Pyrazole and Benzofuran Moieties

A series of 5-(benzofuran-2-yl)-N-(3-chloro-4-(2-(p-tolyloxy) substituted quinolin-3-yl)-2-oxoazetidin-1-yl)-1-phenyl-1H-pyrazole-3-carboxamide derivatives (4a-f) were synthesized with excellent yields by cyclocondensation reaction of 5-(benzofuran-2-yl)-N′-(2-(p-tolyloxy) substituted quinolin-3-yl)methylene)-1-phenyl-1H-pyrazole-3-carbohydrazide (3a-f) with chloroacetyl chloride in presence of triethylamine in DMF. One pot condensation of 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide (1) with 2-(p-tolyloxy) substituted quinoline-3-carbaldehyde (2a-f) in ethanol solvent in presence of catalytic amount of acetic acid gave intermediate compounds (3a-f). The structures of newly synthesized compounds have been substantiated through elemental analysis and spectral studies viz. 1H NMR, 13C NMR, IR and mass spectra. All the synthesized compounds were screened for their in vitro antibacterial activity against pathogenic bacteria such as S. aureus and E. coli at different concentrations.

Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives.

Synthesis of bioactive heterocyclic compounds having effective biological activity is an essential research area for wide-ranging applications. In this study, a conventional methodology has been developed for the synthesis of a series of new 3-mercapto-1,2,4-triazole derivatives 4a-f. The purity and structure of the synthesized molecules were confirmed by 1H NMR, 13C NMR and elemental analysis. In addition, the prepared compounds were screened for their anti-proliferative activity against three human cancer cell lines including A549 (lung cancer), MCF7 (breast cancer) and SKOV3 (ovarian cancer) using MTT reduction assay. All the tested compounds demonstrated remarkable cytotoxic activity with IC50 values ranging from 3.02 to 15.37µM. The heterocyclic compound bearing 3,4,5-trimethoxy moiety was found to be the most effective among the series displaying an IC50 of 3.02µM specifically against the ovarian carcinoma cancer cell line (SKOV3). Moreover, Annexin V-FITC/propidium iodide staining assay indicated that this compound can induce apoptosis in SKOV3 cells. Furthermore, cell cycle assay showed a significant cell cycle arrest at the G2/M phase in a dose-dependent manner for this compound. The molecular docking results was showed binding modes of potent compound 4d perfectly corroborated the suggestion of binding to the colchicine site. The entire results conclude that 3-mercapto-1,2,4-triazole derivatives can be synthesized by a green method for biological and pharmacological applications. New analogs of 3-mercapto-1,2,4-triazole potential derivatives for anti-proliferative activity were synthesized. Cytotoxic activity of all synthesized compounds was evaluated against tree human cancer cell lines: lung (A549), breast (MCF7) and ovarian (SKOV3).

Synthesis, Characterization, and Antimicrobial Evaluation of Some New 1,4-Dihydropyridines-1,2,4-Triazole Hybrid Compounds

Many 1,4-dihydropyridines hybrid with 1,2,4-triazole 4a-l were synthesized by the reaction of 5,5′-(2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-diyl)bis(4-amino-4H-1,2,4-triazole-3-thiol) (2) with various substituted aldehydes. The target compounds 4 were cyclized using bromine in acetic acid to give 1,4-dihydropyridine-bis-triazolothiadiazoles hybrid derivatives 8a-f. The chemical structure of the newly synthesized derivatives was examined by elemental and spectral analysis (IR, NMR, and MS). The antimicrobial activity of the synthesized hybrids was assessed using the Agar diffusion well method. The obtained results indicated that many derivatives have more effective inhibition than Amphotericin B, Ampicillin, and Gentamicin.

KF/CP NPs as an efficient nanocatalyst for the synthesis of 1,2,4-triazoles: Study of antioxidant and antimicrobial activity

In this research, a green procedure and conventional methodology have been developed for the synthesis of a series of 3-mercapto-1,2,4-triazole derivatives (4a-f) in the presence of KF/Clinoptilolite nanoparticles (KF/CP NPs) as catalyst in water at 80 oC. Also, diphenyl-picrylhydrazine (DPPH) radical trapping and ferric reduction activity potential (FRAP) assays are used for evaluation of antioxidant activity of some synthesized compounds (4a-4d). Besides, the antimicrobial activity of some synthesized compounds was studied employing the disk diffusion test on Gram-positive bacteria and Gram-negative bacteria. This procedure has some advantages such as short time of reaction, simple and green procedure, using low-cost catalyst, excellent yield of product and employing different substrate.

Anti-proliferate Activity and 5α-reductase Inhibitors of Chiral Macrocyclic (Nα-di-nicotinoyl)[L-phenylalaninyl-L-leucinyl]Pentapeptide Candidates Against LNCaP and PC-3 Prostate Cancer Cell Lines

A series of macrocyclic derivatives 2-6 were prepared using N α -dinicotinoyl-bis[L-phenylalaninyl-L-leucyl]hydrazide 1 and cyclo pentapeptide hydrazide 2 as starting materials. The hydrazide 1 was cyclized with diaminoalkanes to macrocyclic hezaazahexaamide derivatives 3a-c , respectively. Finally, compound 2 was condensed with 3,5-diacetylpyridine gave the corresponding macrocyclic Schiff base 4 . Finally, condensation of 2 with substituted aromatic or heterocyclic aldehyde derivatives gave the corresponding Schiff base derivatives 5a-f and 6a-c , respectively. The synthesized compounds were screened as 5α-reductase inhibitors and anti-proliferative activity against prostate cancer cell lines.

Semi-synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of β-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The β-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC50 values of 29.7 μM (3a), 16.4 μM (3b), 17.8 μM (3c), 20.4 μM (3d), 28.1 μM (3e) and 28.2 μM (3f). The semi-synthetic β-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]D.

Design, Synthesis and Anti-tuberculosis Activity of Hydrazones and N-acylhydrazones Containing Vitamin B6 and Different Heteroaromatic Nucleus

Background: The term vitamin B6 refers to a set of six compounds, pyridoxine,pyridoxal ,and pyridoxamine and their phosphorylated forms, among which pyridoxal 5´-phosphate (PLP) is the most important and active form acting as a critical cofactor. These compounds are very useful in medicinal chemistry because of their structure and functionalities and are also used in bioinorganic chemistry as ligands for complexation with metals. Methods: In this study, a series of hydrazones 1a-g and N-acylhydrazones 2a-f containing vitamin B6 have been synthesized from commercial pyridoxal hydrochloride and the appropriate aromatic or heteroaromatic hydrazine or N-acylhydrazine. All synthesized compounds have been fully characterized and tested against Mycobacterium tuberculosis. Results: Among the N-acylhydrazones derivatives 2a-f, 2d (para- pyridine substituted Nacylhydrazone; MIC = 10.90 µM) exhibited the best activity. The ortho-pyridine derivative 2b exhibited intermediate activity (MIC = 87.32 µM), and the meta-pyridine derivative 2c was inactive. In case of the hydrazone series 1a-g, 7-chloroquinoxaline derivative 1f (MIC = 72.72 µM) showed the best result, indicating that the number of nitrogen and chlorine atoms in the radical moiety play an important role in the anti-tuberculosis activity of the quinoxaline derivatives (1f and 1g). Conclusion: The data reported herein indicates that the isoniazid derivative 2d (MIC = 10.90 µM) exhibited the best activity in the N-acylhydrazone series and; the quinoxaline nucleus derivative 1f (MIC = 72.72 µM) was the most active compound in the hydrazone series.

Synthesis and in vivo Anti-inflammatory Evaluation of Piperazine Derivatives Containing 1,4-Benzodioxan Moiety

Six piperazine derivatives 6a-f containing 1,4-benzodioxan moiety have been synthesized and characterized by 1H NMR, ESI-MS and elemental analysis. The structure of 6d was further confirmed by single crystal X-ray diffraction. All these novel compounds were screened for their in vivo anti-inflammatory activity employing classical para-xylene-induced mice ear-swelling model. The results revealed that most of the target compounds showed significant anti-inflammatory activities, especially compound 6a with ortho-substituted methoxy group on the phenylpiperazine ring exhibited the best activity among the designed compounds.

Silica sulfuric acid / ethylene glycol: An Efficient Eco-friendly Catalyst for One-pot Synthesis of Tricyclic and Tetarcyclic Dihydropyrimidine Derivatives.

A simple and efficient eco-friendly chemical procedures were developed for the synthesis of series of tricyclic and tetarcyclic dihydropyrimidine derivatives in excellent yields via a one-pot, multi-component reaction in the presence of silica sulfuric acid / ethylene glycol catalyst. The Tricyclic dihydropyrimidine derivatives 1a-g (benzo[4,5]imidazo[1,2-a]pyrimidine derivatives) were synthesized in high yields and high purity with short reaction times by reacting 2-aminobenzimidazole, aldehydes and ethyl acetoacetate. Also, the tetracyclic dihydropyrimidine derivatives 3a-f (benzo[4,5]imidazo[1,2-a]pyrimido[4,5-d]pyrimidin-4(1H)-one derivatives) were synthesized by the reaction of 2-aminobenzimidazole, aldehydes and cyanoacetamide. This present new protocol offers shorter reaction time, high yields and low cost. This method provides much improved protocol over the existing methods.

Assessment of quinazolinone derivatives as novel non-nucleoside hepatitis B virus inhibitors

Hepatitis B virus (HBV) infection is a worldwide public health issue. Search for novel non-nucleoside anti-HBV agents is of great importance. In the present study, a series of quinazolinones derivatives (4a-t and 5a-f) were synthesized and evaluated as novel anti-HBV agents. Among them, compounds 5e and 5f could significantly inhibit HBV DNA replication with IC50 values of 1.54 μM and 0.71 μM, respectively. Interestingly, the selective index values of 5f was higher than that of lead compound K284–1405, suggesting 5f possessed relatively safety profile than K284–1405. Notably, 5e and 5f exhibited remarkably anti-HBV activities against lamivudine and entecavir resistant HBV strain with IC50 values of 1.90 and 0.84 μM, confirming their effectiveness against resistant HBV strain. In addition, molecular docking studies indicated that compounds 5e and 5f could well fit into the dimer-dimer interface of HBV core protein dominated by hydrophobic interactions. Notably, their binding modes were different from the lead compound K284–1405, which may be attributed to the additional substituent groups in the quinazolinone scaffold. Taken together, 5e and 5f possessed novel chemical structure and potent anti-HBV activity against both drug sensitive and resistant HBV strains, thus warranting further research as potential non-nucleoside anti-HBV candidates.

Synthesis and evaluation of novel GSK-3β inhibitors as multifunctional agents against Alzheimer's disease

To target the multi-facets of Alzheimer's disease (AD), a series of novel GSK-3β inhibitors containing the 2,3-diaminopyridine moiety were designed and synthesized. The amide derivatives 5a-f showed moderate potency against GSK-3β with weak Cu2+, Zn2+ and Al3+ chelating ability. The imine derivatives 9a, 9b and 9e were potent GSK-3β inhibitors and selective Cu2+and Al3+ chelators. The 1,2-diamine derivatives 10a-e were strong metal-chelators, but decreased or lost their GSK-3β inhibitory potency. In vitro, compounds 9a, 9b and 9e, especially 9b, exhibited good Cu2+-induced Aβ aggregation inhibition, Cu2+-Aβ complex disaggregation, ROS formation inhibition, and antioxidant activities. In cells, compounds 9a, 9b and 9e can inhibit tau protein phosphorylation and protect neuro cells against Cu2+-Aβ1–42 and H2O2-induced cell damage. Furthermore, compound 9b was predicted to have the ability to pass the BBB with drug likeness properties. Therefore, compound 9b might be a good lead for the development of novel GSK-3β inhibitors targeting multi-facets of AD.

Microwave Assisted Synthesis of Pyrazolo[1,5-a]pyrimidine, Triazolo[1,5-a]pyrimidine, Pyrimido[1,2-a]benzimdazole, Triazolo[5,1-c][1,2,4]triazine and Imidazo[2,1-c][1,2,4]triazine

Background: This paper describes the synthesis of novel fused heterocycles, from the reaction 2-cyano-N-cyclohexyl-3-acrylamide derivatives 5a-f with nitrogen nucleophilic reagents, which carried out under microwave irradiation. Reactivity of 3 towards diazonium amines salts to afford hydrazones undergo cyclization to give amino pyrazole and the fused heterocyclic compounds incorporating cyclohexyl moiety. The synthesized compounds excellently utilized microwave irradiation in short time and high yield. Methods: Synthesis of Fused heterocycles derivatives from 2-cyano-N-cyclohexyl acetamide utilizing Microwave irradaition. Results: Regioselective facile synthesis of innovative heterocycles from the reaction of 2-cyano-Ncyclohexyl acetamide (3) with appropriate aldehydes to afford the corresponding acrylamide derivatives 5a-f under microwave irradiation. Acrylamides 5 reacts with hydrazine derivatives affording the corresponding pyrazole derivatives 7a and 7b, furthermore the treatment of acrylamides 5 with 2-amino benzimidazole, amino pyrazole, and aminotriazole derivatives to gives corresponding pyrimido[1,2-a]benzimdazole 10, pyrazolo[1,5-a]pyrimidine 12 and triazolo[1,5-a]pyrimidine 14; respectively in good yield. Reactivity of 3 towards diazonium amines salts afforded hydrazones derivatives, which undergo cyclization to give the corresponding derivatives 19a and the fused pyrazolo[5,1-c][1,2,4]triazine 22, triazolo[5,1-c][1,2,4]triazine 24 and imidazo[2,1-c][1,2,4]triazine 28 incorporating cyclohexyl moiety. Conculsion: In this investigation, we have synthesized innovative pyrimido[1,2-a]benzimdazole, and triazolo[1,5-a]pyrimidine, pyrazolo[1,5-a]pyrimidine, 2-amino benzimidazole, amino pyrazole, aminotriazole, fused pyrazolo[5,1-c][1,2,4]triazine, triazolo[5,1-c][1,2,4]triazine and imidazo[2,1- c][1,2,4]triazine derivatives incorporating cyclohexyl moiety utilizing microwave irradiation. The compounds were obtained under microwave reaction in excellent yield in a short reaction time.