The synthesis, preparation, chemical reactivities and biological activity of simple heterocyclic and heteropolycyclic nitrogen systems as small units as functional pyrazoles, pyridine and pyrimidine, and the related fused systems are reviewed. Among the various possible routes to the formation, isomeric structures have been cited because of patented reaching advanced phases of clinical trials, from 2000 to 2020.
Chellat, M.F., Raguz, L. and Riedl, R. (2016) Targeting Antibiotic Resistance. Angewandte Chemie International Edition, 55, 6600-6626. https://doi.org/10.1002/anie.201506818
Dinoiu, V.J.L. (2006) Synthesis of New Trifluoromethyl-Containing 1-(3,5-Dialkyl-4- hydroxybenzyl)-pyrazole and -pyrazol-5-one Derivatives and Their Corresponding Aroxyls Pyrazole. Journal of Serbian Chemical Society, 71, 323. https://doi.org/10.2298/JSC0604323D
Hanamoto, T., et al. (2007) N-Arylation of 4-Fluoro-5-trimethylsilyl-1H-pyrazole. Journal of Fluorine Chemistry, 128, 1126-1130. https://doi.org/10.1016/j.jfluchem.2007.04.019
Chaudhry, F., et al. (2013) Synthesis of Pyrazoleacrylic Acids and Their Derivatives. Asian Journal of Chemistry, 25, 7879-7882. https://doi.org/10.14233/ajchem.2013.14670
Abdel-Rahman, R.M., Angawi, R.F. and Al-Mehmadi, A.R. (2017) Synthesis and Biological Evaluation of Fluorine Substuted Pyrazolo[4,3-e][1,2,4]triazines as Purine Analoguesi. Chemical Society, 21, 495-503. https://doi.org/10.1016/j.jscs.2016.11.004
Bakhotmah, D. and Abdel-Rahman, R. (2016) A Review on the Synthesis and Chemistry of Bioactive Pyrazolines Bearing 1,2,4-Triazine Moieties. Mini-Reviews in Organic Chemistry, 13, 62-77. https://doi.org/10.2174/1570193X13666160225000114
McDermott, L.A., et al. (2006) Biological Evaluation of a Multi-Targeted Small Molecule Inhibitor of Tumor-Induced Angiogenesis. Bioorganic & Medicinal Chemistry Letters, 16, 1950-1953. https://doi.org/10.1016/j.bmcl.2005.12.092
Bakhotmah, D.A., et al. (2017) Synthesis of Some New Fluorinated Fused Heteropolycyclic Nitrogen Systems Containing Pyrazolo[3,4-d]pyrimidines Moiety and Their Effects on Cellobiase Activity Produced by Aspergillus nidulans Fungi. Modern Organic Chemistry Research, 2, 172. https://doi.org/10.22606/mocr.2017.24003
Khan, S.A., et al. (2017) Multistep Synthesis of Fluorine-Substituted Pyrazolopyrimidine Derivatives with Higher Antibacterial Efficacy Based on in Vitro Molecular Docking and Density Functional Theory. Journal of Heterocyclic Chemistry, 54, 3099-3107. https://doi.org/10.1002/jhet.2923
Brautigam, S., et al. (2009) Whole-Cell Biocatalysis: Evaluation of New Hydrophobic Ionic Liquids for Efficient Asymmetric Reduction of Prochiral Ketones. Enzyme and Microbial Technology, 45, 310-316. https://doi.org/10.1016/j.enzmictec.2009.06.015
Watanabe, T., et al. (1994.) Protective Effects of MCI-186 on Cerebral Ischemia: Possible Involvement of Free Radical Scavenging and Antioxidant Actions. Journal of Pharmacology and Experimental Therapeutics, 268, 1597-1604.
Li, Y.-J., et al. (2015) Evaluation of Sample Preparation and Chromatographic Separation for the Parallel Determination of Taurine and Edaravone in Rat Tissues Using HILIC-MS/MS. Analytical and Bioanalytical Chemistry, 407, 4143-4153. https://doi.org/10.1007/s00216-015-8635-0
Holzer, W., et al. (2004) On the Tautomerism of Pyrazolones: The Geminal 2J[pyrazole C-4,H-3(5)] Spin Coupling Constant as a Diagnostic Tool. Tetrahedron, 60, 6791-6805. https://doi.org/10.1016/j.tet.2004.06.039
Belmar, J., et al. (2005) Synthesis and Tautomeric Studies of Enamines from 1-(N-hexyl)-3-methyl-2-pyrazolin-5-one. Journal of the Brazilian Chemical Society, 16, 179-189. https://doi.org/10.1590/S0103-50532005000200009
Abdul-Rahman, R.M., Bakhotmah, D. and Fakhorji, M. (2017) Synthesis and Chemical Reactivity of Some New Fluorine Substituted Pyrazolopyrimidine Derivatives and Their Effect on Cellobiase Activity Produced by Fungi. World Journal of Organic Chemistry, 5, 1-5.
Abdel-Aziz, S. (1996) Fused Cyanopyrimidines: Part-I Synthesis and Reactions of Fused Cyanopyrimidine Derivatives and Their Effect on Cellobiase Activity. Phosphorus, Sulfur, and Silicon and the Related Elements, 116, 39-48. https://doi.org/10.1080/10426509608040467
Abdel-Hamide, S., et al. (1995) Synthesis of Some New Piperazine-nn’-bis-substituted Derivatives as Potential Biologically Active Agents. Chemical Papers, 49, 142-148.
Abdel-Rahman, R.M., et al. (2013) 1,2,4-Triazine Chemistry Part III: Synthetic Strategies to Functionalized Bridgehead Nitrogen Heteroannulated 1,2,4-Triazine Systems and Their Regiospecific and Pharmacological Properties. Current Organic Synthesis, 10, 136-160. https://doi.org/10.2174/157017913804810933
Bakhotmah, D. and Abdel-Rahman, R. (2017) Synthesis and Structural Determination of Novel Fluorinated Steroidal Spiro (Pyrazolo[4,3-e][1,2,4]Triazin-3’-yl) Derivatives as Affecting Enzymatic Agents. Letters in Organic Chemistry, 14, 134-140. https://doi.org/10.2174/1570178614666161230143228
Abdel-Rahman, R.M., Makki, M.S. and Al-Romaizan, A.N. (2014) Synthesis of Novel Fluorine Substituted Isolated and Fused Heterobicyclic Nitrogen Systems Bearing 6-(2’-Phosphorylanilido)-1,2,4-triazin-5-one Moiety as Potential Inhibitor towards HIV-1 Activity. International Journal of Organic Chemistry, 4, 247. https://doi.org/10.4236/ijoc.2014.44028
Abdelhamid, A.O., et al. (2005) Reactions of Hydrazonoyl Halides 41: Synthesis of 1,2,4-Triazoles, 2,3-Dihydro-1,3,4-thiadiazoles and Triazolo[4,3-a]pyrimidines. Phosphorus, Sulfur, and Silicon and the Related Elements, 180, 2097-2109. https://doi.org/10.1080/104265090917448
Bhardwaj, P. and Gupta, N. (2016) 1,2,4,5-Tetrazines as Platform Molecules for Energetic Materials and Pharmaceuticals. Iranian Journal of Organic Chemistry, 8, 1827-1831.
Bakhotmah, D.A. (2019) Synthesis of Fluorine and Phosphorus Compounds Bearing an Amino Pyrimidine-Substituted Pyrazolo[3,4-d]pyrimidine Moiety as Molluscicidal Agents against Some Snails. Polycyclic Aromatic Compounds, 1-9. https://doi.org/10.1080/10406638.2019.1684326
Abdel-Rahman, R.M., et al. (2010) 1,2,4-Triazine Chemistry Part I: Orientation of Cyclization Reactions of Functionalized 1,2,4-Triazine Derivatives. European Journal of Chemistry, 1, 236-245. https://doi.org/10.5155/eurjchem.1.3.236-245.54
Al-Hazme, B.D.A. and Al-Hazme, S.Y. (2019) Synthesis of Novel Heteropolycyclic Nitrogen Systems Bearing Fluorine Substituted Pyrazolo[3,4-d]pyrimidine Derived from Polyfunctional π-Acceptor Compounds and Guanidine as Fungicidal Probes. International Journal of Organic Chemistry, 9, 73-83. https://doi.org/10.4236/ijoc.2019.91007
Makki, M.S., Abdel-Rahman, R.M. and Alharbi, A.S. (2018) Synthetic Approach for Novel Fluorine Substituted α-Aminophosphonic Acids Containing 1,2,4-Triazin-5-one Moiety as Antioxidant Agents. International Journal of Organic Chemistry, 8, 1. https://doi.org/10.4236/ijoc.2018.81001
Makki, M.S., et al. (2012.) Designing and Synthesis of New fluorine Substituted Pyrimidine-thion-5-carbonitriles and the Related Derivatives as Photochemical Probe Agents for Inhibition of Vitiligo Disease. International Journal of Organic Chemistry, 2, 311. https://doi.org/10.4236/ijoc.2012.223043
Taib, L.A. and Adibani, S.A. (2018) Synthesis of New Fluorinated Fused Heteropolycyclic Nitrogen Systems Containing a Pyrazolotriazine Moiety as Antimicrobial Agents Part I. International Journal of Organic Chemistry, 8, 176. https://doi.org/10.4236/ijoc.2018.81013
Bawazir, W.A. and Abdel-Rahman, R.M. (2018) Synthesis of New Fluorinated Amino-Heterocyclic Compounds Bearing 6-Aryl-5-oxo-1,2,4-triazin-3-yl Moiety as Antimicrobial Agents. International Journal of Organic Chemistry, 8, 349. https://doi.org/10.4236/ijoc.2018.84027
Makki, M.S., Abdel-Rahman, R.M. and Alharbi, A.S. (2019) Synthesis and Anti-Inflammatory Effect of Some More New Fluorinated 3-Substituted Amino/3,5-Diamino-1,2,4-triazine Derivatives as Lamotrigine Analogs. Current Organic Synthesis, 16, 165-172. https://doi.org/10.2174/1570179415666181105142247
Bakhotmah, D.A. and Al-Hazme, S.Y. (2019) Behavior of 6-Amino-4(4’-fluorophenyl)-1- phenyl-3-methyl Pyrazolo[3,4-d]pyrimidine towards π-Acceptors Activated Carbonitrile and Carbonyl Compounds as Amylolytic Agents towards Some Fungi.
Al-Najjar, A.A., Amer, S.A., Riad, M., Elghamy, I. and Elnagdi, M.H. (1996) Studies with Polyfunctionally Substituted Heteroaromatic. A Routes for the Synthesis of Substituted 1,2,4-Triazolo[1,5-a]pyridines. Journal of Chemical Research, 296-297.
Abdel-Monem, W. (2004) Synthesis and Biological Evaluation of Some New Fused Heterobicyclic Derivatives Containing 1,2,4-Triazolo/1,2,4-Triazinopyridinone Moieties. Chemical Papers—Slovak Academy of Sciences, 58, 276-285. https://doi.org/10.1002/chin.200515138
Abdel-Monem, W.R. and Abdel-Rahman, R.M. (2005) 3-Dichloro/Dioxo Pyrido[1,2-b][1,2,4] triazine Derivatives towards Bi-Primary Nitrogen Agents and Their Biocidal Effects. Bollettino Chimico Farmaceutico, 144, 1-12.
Ibrahim, M.A., et al. (2009) Synthesis, Chemical Reactivity and Fungicidal Activity of Pyrido[1,2-b][1,2,4]triazine Derivatives. Journal of the Brazilian Chemical Society, 20, 1275-1286. https://doi.org/10.1590/S0103-50532009000700012
Ibrahim, M.A., et al. (2008) Synthesis and Antifungal Activity of Novel Polyheterocyclic Compounds Containing Fused 1,2,4-Triazine Moiety. Arkivoc, 16, 202-215. https://doi.org/10.3998/ark.5550190.0009.g19
Komarova, E., et al. (2007) 4,5-Diamino-1-phenyl-1,7-dihydro-6H-pyrazolo[3,4-b] pyridin-6-one in the Synthesis of Fused Tricyclic Systems. Russian Chemical Bulletin, 56, 2337-2343. https://doi.org/10.1007/s11172-007-0369-5
Katharkar, S.A. and Shinde, D.B. (2006) Synthesis of Antimicrobial 2,9,10- Trisubstitutcd-6-oxo-7,12-dihydro-chromcno[3,4-b]quinoxalines. Bioorganic & Medicinal Chemistry Letters, 16, 6181-6184. https://doi.org/10.1016/j.bmcl.2006.09.040
Zhang, G. and Chen, J. (2011) Synthesis and Cytotoxic Activities of 2-(4-(2- Heterocycloethoxy)phenyl)-1,2,4-triazolo[1,5-a]pyridines. Letters in Organic Chemistry, 8, 180-183. https://doi.org/10.2174/157017811795038377
Riedl, Z., et al. (2003) Ring Opening and Cycloadditions of Novel Fused 1,2,4-Triazines. Arkivoc, 62, 68. https://doi.org/10.3998/ark.5550190.0004.506
Rashad, A.E., et al. (2010) Synthesis, Reactions and Antimicrobial Evaluation of Some Polycondensed Thienopyrimidine Derivatives. Synthetic Communications, 40, 1149-1160. https://doi.org/10.1080/00397910903050954
Ali, T.E.-S. and Ibrahim, M.A. (2010) Synthesis and Antimicrobial Activity of Chromone-Linked 2-Pyridone Fused with 1,2,4-Triazoles, 1,2,4-Triazines and 1,2,4-Triazepines Ring Systems. Journal of the Brazilian Chemical Society, 21, 1007-1016. https://doi.org/10.1590/S0103-50532010000600010
Abdel-Megid, M. (2009) Synthesis of Some New Nitrogen Bridge-Head Pyrido[1,2,4]triazepines. Chemistry of Heterocyclic Compounds, 45, 1523-1531. https://doi.org/10.1007/s10593-010-0460-y
El-Kazak, A.M. and Ibrahim, M.A. (2013) Synthesis, Characterization and Antimicrobial Evaluation of the Novel Pyrido[1’,2’:2,3][1,2,4]triazolo[1,5-c]quinazolines and Thiazolo[3’,2’:2,3][1,2,4]triazolo[1,5-a]pyridines. ARKIVOC Online Journal of Organic Chemistry, 3, 282-293. https://doi.org/10.3998/ark.5550190.p007.884
Harb, A., Abbas, H. and Mostafa, F. (2005) Pyrazoles as Building Blocks in Heterocyclic Synthesis: Synthesis of Some New Substituted 1-Triazinylpyrazolo [3,4-d] pyrimidine and 1-Triazinylpyrazolo[3,4-b]pyridine Derivatives. Chemical Papers—Slovak Academy of Sciences, 59, 187. https://doi.org/10.1002/chin.200550154
Abdel-Rahman, R.M., et al. (2015) 1,2,4-Triazine Chemistry Part IV: Synthesis and Chemical Behavior of 3-Functionalized 5,6-Diphenyl-1,2,4-triazines towards Some Nucleophilic and Electrophilic Reagents. Journal of Heterocyclic Chemistry, 52, 1595-1607. https://doi.org/10.1002/jhet.2014
Elguero, J., et al. (2002) Pyrazoles as Drugs: Facts and Fantasies. Targets in Heterocyclic Systems, 6, 52-98.
Quiroga, J., et al. (2008) Regioselective Formylation of Pyrazolo[3,4-b]pyridine and Pyrazolo[1,5-a]pyrimidine Systems Using Vilsmeier-Haack Conditions. Tetrahedron Letters, 49, 2689-2691. https://doi.org/10.1016/j.tetlet.2008.02.166
Darwish, E.S., Mahmoud, F.F. and Farag, M. (2012) Synthesis and Antimicrobial Evaluation of Some New Pyrazole, Fused Pyrazolo[1,5-a]-pyrimidine and Pyrazolo[1,5-d]pyrimido[4,5-d]][1,2,3]triazine Derivatives. Asian Journal of Chemistry, 24, 2997.
Quiroga, J., et al. (2001) Synthesis and Structural Analysis of 5-Cyanodihydropyrazolo [3,4-b]pyridines. Journal of Heterocyclic Chemistry, 38, 53-60. https://doi.org/10.1002/jhet.5570380108
Hardy, C. (1984) The Chemistry of Pyrazolopyridines in Advances in Heterocyclic Chemistry. Elsevier, Amsterdam, 343-409. https://doi.org/10.1016/S0065-2725(08)60117-8
Wertalik, F. and Bonorden, R. (1968) Salivary Levels of Antibiotics from Use of Neomycin-Gramicidin Chewing Troches. Journal of Pharmaceutical Sciences, 57, 530-531. https://doi.org/10.1002/jps.2600570340
Elnagdi, M.H. and Wahba, E.A. (1990) Synthesis of Substituted Azaindenes: Synthesis of New Pyrazolo[1,5-a]pyrimidine Derivatives. Bulletin of the Chemical Society of Japan, 63, 1854-1856. https://doi.org/10.1246/bcsj.63.1854
Chavhan, N., et al. (2010) Synthesis and Biological Evaluation of Some Heterocycles from 1-Phenyl-3-(pyridine-3-yl)-1H-pyrazole-4-carbaldehyde. Asian Journal of Chemistry, 22, 4255.
Straub, A., et al. (2001) NO-Independent Stimulators of Soluble Guanylate Cyclase. Bioorganic & Medicinal Chemistry Letters, 11, 781. https://www.ncbi.nlm.nih.gov/pubmed/11277519
Elnagdi, M.H., Elmoghayar, M.R.H. and Elgemeie, G.E.H. (1987) Chemistry of Pyrazolopyrimidines. In: Advances in Heterocyclic Chemistry, Elsevier, Amsterdam, 319-376. https://doi.org/10.1016/S0065-2725(08)60164-6
Sekikawa, I., et al. (1973) Antituberculous Compounds; Synthesis of Pyrazolopyridines. Journal of Heterocyclic Chemistry, 10, 931-932. https://doi.org/10.1002/jhet.5570100607
Kuczyński, L., et al. (1979) Synthesis and Biological Activity of Pyrazo-[3,4-b]-pyridine Derivatives. Part I. Polish Journal of Pharmacology and Pharmacy, 31, 217-225.
Zeitschrift für El-Dean, A.K., et al. (1991) Synthesis of Some Pyrazolopyridine Sulphonamide Derivatives. Naturforschung B, 46, 541-546. https://doi.org/10.1515/znb-1991-0417
Chioua, M., et al. (2009) Synthesis and Biological Evaluation of 3,6-Diamino-1H- pyrazolo[3,4-b]pyridine Derivatives as Protein Kinase Inhibitors. Bioorganic & Medicinal Chemistry Letters, 19, 4566-4569. https://doi.org/10.1016/j.bmcl.2009.06.099
Dias, L.R., et al. (2007) Synthesis, in Vitro Evaluation, and SAR Studies of a Potential Antichagasic 1H-pyrazolo[3,4-b]pyridine Series. Bioorganic & Medicinal Chemistry, 15, 211-219. https://doi.org/10.1016/j.bmc.2006.09.067
Chebanov, V.A., et al. (2007) Cyclocondensation Reactions of 5-Aminopyrazoles, Pyruvic Acids and Aldehydes. Multicomponent Approaches to Pyrazolopyridines and Related Products. Tetrahedron, 63, 1229-1242. https://doi.org/10.1016/j.tet.2006.11.048
Lynch, B.M., et al. (1988) Pyrazolo[3,4-b]pyridines: Syntheses, Reactions, and Nuclear Magnetic Resonance Spectra. Canadian Journal of Chemistry, 66, 420-428. https://doi.org/10.1139/v88-074
Tensmeyer, L. and Ainsworth, C. (1966) Proton Magnetic Resonance Studies of Pyrazoles. The Journal of Organic Chemistry, 31, 1878-1883. https://doi.org/10.1021/jo01344a047
Maqbool, T., et al. (2013) Pyrazolopyridines I: Synthesis of Some Pyrazolo[3,4-b]pyridine-4-carboxylates. Asian Journal of Chemistry, 25, 7715-7718. https://doi.org/10.14233/ajchem.2013.14573A
El-Assiery, S.A., Sayed, G.H. and Fouda, A. (2004.) Synthesis of Some New Annulated Pyrazolo-Pyrido (or Pyrano) Pyrimidine, Pyrazolopyridine and Pyranopyrazole Derivatives. Acta Pharmaceutica (Zagreb), 54, 143-150.
El-Emary, T.I. (2007) Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4-b]pyridines Based on 5-Amino-3-methyl-1-phenylpyrazole. Journal of the Chinese Chemical Society, 54, 507-518. https://doi.org/10.1002/jccs.200700072
Acosta, P., et al. (2015) Annelation of Pyrrolo[1,2-a]pyrimidine and Pyrido[1,2-a]pyrimidine Systems to a Pyrazolopyridine Framework by a Cascade of Two Cyclization Reactions. Tetrahedron Letters, 56, 2917-2921. https://doi.org/10.1016/j.tetlet.2015.04.068
Quiroga, J., et al. (2015) Synthesis and Study of Fluorescence Properties of Novel Pyrazolo[4’,3’:5,6]pyrido[2,3-d]pyrimidin-5(6H)-one Derivatives. Journal of Molecular Structure, 1097, 69-75. https://doi.org/10.1016/j.molstruc.2015.05.019
Acosta, P., et al. (2017) Synthesis of Novel 7-Aryl and 7-Spiropyrazolo [4’,3’:5,6]pyrido[2,3-d]pyrimidine Derivatives and Their Study as AChE Inhibitors. Molecular Diversity, 21, 943-955. https://doi.org/10.1007/s11030-017-9774-3