Generic placeholder image

Current Organic Synthesis


ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Review Article

Dihydropyrimidinones Scaffold as a Promising Nucleus for Synthetic Profile and Various Therapeutic Targets: A Review

Author(s): Shaik Khasimbi, Faraat Ali, Kiran Manda, Anjali Sharma, Garima Chauhan and Sharad Wakode*

Volume 18, Issue 3, 2021

Published on: 07 December, 2020

Page: [270 - 293] Pages: 24

DOI: 10.2174/1570179417666201207215710

Price: $65


Background: This review elaborates the updated synthetic and pharmacological approaches of a known group of dihydropyrimidinones/thiones from the multi-component reaction like Biginelli reaction, which was named Pietro Biginelli in 1891. This review consists of the reaction of an aromatic aldehyde, urea and ethyl acetoacetate leading to dihydropyrimidinone/thione. Currently, the scientific movement to develop economically viable green methods using compounds that are reusable, non-volatile, easily obtained, etc.

Objective: This review covers the recent synthesis and pharmacological advancement of dihydropyrimidinones/ thiones moiety, along with covering the structure-activity relationship of the most potent compounds, which may prove to become better, more efficacious and safer agents. Thus, this review may help the researchers in drug designing and development of new Dihydropyrimidinones entities.

Conclusion: This review focuses on the wide application of dihydropyrimidinone/thione review reports the design, synthesis and pharmacological activities of nitrogen-sulphur containing dihydropyrimidinone moiety by using multi-component reaction. Dihydropyrimidinones (DHPM) pharmacophore is an important heterocyclic ring in medicinal chemistry. It is derived from multi-component reactions, “Biginelli reaction” and plays a critical role as anticancer, antioxidant, antimicrobial, anti-inflammatory, anti-HIV-1, antimalarial, anti-inflammatory, antihypertensive and anti-tubercular agents. Exhaustive research has led to its vast biological profile, with a wide range of therapeutic application.

Keywords: Dihydropyrimidinones, anti-microbial, anti-depressant, anti-cancer, antifungal, anthelmintic, anti-diabetic.

Graphical Abstract
Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P. Passerinii three-component and Ugi four-component condensation are the most popular among other reaction for their wide scope and synthetic utility. Chem. Eur. Jr., 2000, 6, 3321.
Domling, A.; Ugi Angew, I. Passerinii three-component and Ugi four-component condensation are the most popular among many other reaction for their scope and synthetic utility. Chem. Int. Eur., 2000, 39, 3168.
Biginelli, P. Synthesis of some hexahydroquinazolines using K3AIF6 (AI2O3/KF) as an efficient catalyst in some hexahydroquinazolinone derivatives. Chim Ital., 1893, 23, 360-413.
Biologically active dihydropyrimidone of the Biginelli type –a literature survey. Eur. J. Med. Chem., 2000, 12, 1043-1046.
Weber, L.; Illgen, K.; Almstetter, M. Discovery of new multi component reaction with combinatorial methods. Synlett, 1999, 3, 366.
Kappe, C.O. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron, 1993, 49, 6937.
Kappe, C.O. Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog. Acc. Chem. Res., 2000, 33(12), 879-888.
[] [PMID: 11123887]
Kaur, R.; Chaudhary, S.; Kumar, K.; Gupta, M.K.; Rawal, R.K. Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review. Eur. J. Med. Chem., 2017, 132, 108-134.
[] [PMID: 28342939]
Naidu, N.; Sorenson, M.E.; Patel, M.; Ueda, Y.; Banville, J.; Beaulieu, F.; Bollini, S.; Higley, H.; Lin, Z. Synthesis and evaluation of C2-carbon-likned eterocyclic-5-hydroxy-6-oxo-dihydropyrimidine-4-carboxamides as HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett., 2015, 25, 717-720.
Said, S.A.; Amr, A.E-G.E.; Sabry, N.M.; Abdalla, M.M. Synthesized of some heterocyclic system and their nucleoside of potent anti-inflammatory activities. Eur. J. Med. Chem., 2009, 44, 4787-4792.
[] [PMID: 19682771]
Lauro, G.M.; Strocchia, S. Terracciano, L. Bruno, K. Fischer, C. Pergola, O. Werz, R. Riccio, G. Bifulco, Structural-based design of Microsomal prostaglandin E2synthase-1 (mPGES-1) inhibitors using a virtual fragment growing optimization scheme. Eur. J. Med. Chem., 2017, 80, 407-415.
[] [PMID: 24794772]
Dragovich, P.S.; Fauber, B.P.; Corson, L.B.; Ding, C.Z.; Eigenbrot, C.; Ge, H.; Giannetti, A.M.; Hunsaker, T.; Labadie, S.; Liu, Y.; Malek, S.; Pan, B.; Peterson, D.; Pitts, K.; Purkey, H.E.; Sideris, S.; Ultsch, M.; VanderPorten, E.; Wei, B.; Xu, Q.; Yen, I.; Yue, Q.; Zhang, H.; Zhang, X. Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase. Bioorg. Med. Chem. Lett., 2013, 23(11), 3186-3194.
[] [PMID: 23628333]
Rovnyak, G.C.; Atwal, K.S.; Hedberg, A.; Kimball, S.D.; Moreland, S.; Gougoutas, J.Z.; O’Reilly, B.C.; Schwartz, J.; Malley, M.F. Dihydropyrimidine calcium channel blockers. 4. Basic 3-substituted-4-aryl-1,4-dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents. J. Med. Chem., 1992, 35(17), 3254-3263.
[] [PMID: 1387168]
Sondhi, S.M.; Goyal, R.N.; Lahoti, A.M.; Singh, N.; Shukla, R.; Raghubir, R. Synthesis and biological evaluation of 2-thiopyrimidine derivatives. Bioorg. Med. Chem., 2005, 13(9), 3185-3195.
[] [PMID: 15809154]
Bhosle, M.R.; Deshmukh, A.R.; Pal, S.; Srivastava, A.K.; Mane, R.A. Synthesis and antihyperglycemic evaluation of new 2-hydrazolyl-4-thiazolodinone-5-carboxylic acids having pyrazolyl pharmacophore. Bioorg. Med. Chem. Lett., 2015, 25, 2442-2446.
[] [PMID: 25937008]
Luszezki, J.J.; Glowniak, K.; Czuczwar, S.J. Time-curse and dose response relationship of imperatorin in the mouse maximal electroshock seizure threshold model. Neurosci. Res., 2007, 562, 53-59.
Diasio, R.B.; Harris, B.E. Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet., 1989, 16(4), 215-237.
[] [PMID: 2656050]
Dragunow, M. Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline. Pharmacol. Biochem. Behav., 1990, 36(4), 751-755.
[] [PMID: 2217501]
Trivedi, R.; Bhuva, V.R.; Dholariya, B.H.; Dodiya, D.K.; Kataria, V.B.; Shah, V.H. Synthesis and antitubercular evaluation of some novel 1, 2, 3, 6-tetrahydropyrimidne-5-carbonitile. Bioorg. Med. Chem. Lett., 2011, 20, 6100-6102.
[] [PMID: 20813528]
Russowsky, D.; Canto, R.F.; Sanches, S.A.; D’Oca, M.G.; de Fátima, A.; Pilli, R.A.; Kohn, L.K.; Antônio, M.A.; de Carvalho, J.E. Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues. Bioorg. Chem., 2006, 34(4), 173-182.
[] [PMID: 16765411]
Barton, D.H.; Hesse, R.H.; To, H.T.; Pechet, M.M. A convenient synthesis of 5-fluorouracil. J. Org. Chem., 1972, 37(2), 329-330.
[] [PMID: 5013354]
Vitreschak, A.G.; Rodionov, D.A.; Mironov, A.A.; Gelfand, M.S. Regulation of riboflavin biosynthesis and transport genes in bacteria by transcriptional and translational attenuation. Nucleic Acids Res., 2002, 30(14), 3141-3151.
[] [PMID: 12136096]
Prusoff, W.H. Synthesis and biological activities of iododeoxyuridine, an analog of thymidine. Biochim. Biophys. Acta, 1959, 32(1), 295-296.
[] [PMID: 13628760]
Ranise, A.; Bruno, O.; Bondavalli, F.; Schenone, S.; D’Amico, M.; Falciani, M.; Filippelli, W.; Rossi, F. 5-Substituted 2,3-dihydro-6-mercapto-1,3-diphenyl-2-thioxo-4(3H)-pyrimidinones and their 6-(acylthio) derivatives with platelet antiaggregating, antiinflammatory, antiarrhythmic, antihyperlipidemic and other activities. Farmaco, 1994, 49(9), 551-558.
Wamberg, M.; Pederson, E. B.; Nielsen, C. 2004.
Senthilkumar, P.; Long, J.; Swetha, R.; Shruthi, V.; Wang, R.R.; Preethi, S.; Yogeeswari, P.; Zheng, Y.T.; Sriram, D. Synthesis of zidovudine derivatives with anti-HIV-1 and antibacterial activities. Nucleosides Nucleotides Nucleic Acids, 2009, 28(2), 89-102.
[] [PMID: 19219739]
Ojo, B.; Findsen, L.A.; Igarashi, N.; Kong, B.; Chowdhury, B.K. Synthesis and bronchodilatory activity of four new derivatives of deoxyvasicine. Drug Des. Discov., 1996, 14(1), 1-14.
Keam, S.J. Telbivudine. Drugs, 2007, 67(13), 1917-1929.
[] [PMID: 17722961]
Mandala, D.; Watts, P. An improved synthesis of lamivudine and emtrictabine. ChemistrySelect, 2017, 2(3), 1102-1105.
Ciceri, S.; Ciuffreda, P.; Ferrabischi, P. Synthesis of the antitumor nucleoside capecitabine through a chemo-enzymatic approach. Tetrahedron Lett., 2015, 56(43), 5909-5913.
Mandala, D.; Chada, S.; Watts, P. Semi-continuous multi-step synthesis of lamivudine. Org. Biomol. Chem., 2017, 15(16), 3444-3454.
[] [PMID: 28362445]
Kim, J.; Cowan, A.; Lisek, R.; Raymondi, N.; Rosenthal, A.; Hirsch, D.D.; Rawls, S.M. Icilin-evoked behavioral stimulation is attenuated by alpha2-adrenoceptor activation. Brain Res., 2011, 1384, 110-117.
[] [PMID: 21315691]
Singh, V.; Sapehiyia, V.; Srivastava, V.; Kaur, S. ZrO2-pillared clay: An efficient catalyst for solventless. Catal. Commun., 2006, 7(8), 571-578.
Capparelli, E.V.; Holland, D.; Okamoto, C.; Gragg, B.; Durelle, J.; Marquie-Beck, J.; van den Brande, G.; Ellis, R.; Letendre, S. Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV. AIDS, 2005, 19(9), 949-952.
[] [PMID: 15905676]
Grover, GJ.; Dzwonczyk, S.; McMullen, DM.; Normandin, DE.; Parham, CS.; Sleph, PG.; Moreland, S. 1995.
Mayer, T.U.; Kapoor, T.M.; Haggarty, S.J.; King, R.W.; Schreiber, S.L.; Mitchison, T.J. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science, 1999, 286(5441), 971-974.
[] [PMID: 10542155]
Rami, C.; Patel, L.; Patel, C.N.; Parmar, J.P. Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine derivatives. J. Pharm. Bioallied Sci., 2013, 5(4), 277-289.
[] [PMID: 24302836]
Economou, C.; Romaire, J.P.; Scott, T.Z.; Parr, B.T.; Herzon, S.B. A convergent approach to batzelladine alkaloids. Total synthesis of (+)-batzelladine E,(-)-dehydrobatzelladineC, and (+)-batzelladine K. Tetrahedron Lett., 2018, 74(26), 3188-3197.
Huang, R.I.; Patel, P.; Walinsky, P.; Fischman, D.L.; Ogilby, J.D.; Awar, M.; Frankil, C.; Savage, M.P. Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention. Catheter. Cardiovasc. Interv., 2006, 68(5), 671-676.
[] [PMID: 17034064]
Busch, M; Jan, D 2015.
David, B; Hans, H 2014.
Colin, M. 1997.
Nussbaum, F V; Dagmar, K; Sonja, A; Martina, D. 2013.
Gnamm, C; Hoesch, H; Peters, S; Oost, T.J.R.U. 2019.
Nussbaum, FV; Dagmar, K; Sonja, A; Martina, D 2015.
Vincent, E; Claude, G 2015.
Masahirio, Y.; Noriyoshi, S.; Eiichi, W.; Shingo, F. 2020.
Gabriela, C; Tony, T; Anna, R 2016.
Scott, E. S; Lauren, B; John, C; Ken William, D. 2017.
Mashooq, A B; Mohamed, A. 2018.
Olcay, B; Jeffrey, L 2011.
Mark Joseph, T; Holly Victoria, A; Craig, A; Steven Mark, B; Mark, K; Adrian Kotei, K; Nathaniel, J. Heteroaryl derivatives as sepiapterin reductase inhibitors., 2018.
Ulrike, D. 2006.
Luiz, B A; Augusto Rocha, B F; Rafique, KJ; Faria Santos, C R; Saba, S; Do Nascimento, V. 2018.
Luther, J.M. Is there a new dawn for selective mineralocorticoid receptor antagonism? Curr. Opin. Nephrol. Hypertens., 2014, 23(5), 456-461.
[] [PMID: 24992570]
McDonald, T.F.; Pelzer, S.; Trautwein, W.; Pelzer, D.J. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol. Rev., 1994, 74(2), 365-507.
[] [PMID: 8171118]
Tajbakhsh, M.; Mohajerani, B.; Heravi, M.M.; Ahmadi, A.N. Natural HEU type zeolite catalyzed Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives. J. Mol. Catal. Chem., 2005, 236, 216-219.
Aswin, K.; Mansoor, S.S.; Logaiya, K.; Sudhan, P.N.; Ahmed, R.N. Facile synthesis of 3,4-dihydropyrimidin-2(1H)-ones and thiones and indeno[1,2-d]pyrimidines catalyzed by p-dodecylbenzenesulfonic acid. J. Taib. Uni. Sci., 2014, 8, 236-247.
Stefani, H.A.; Gatti, P.M. 3,4-dihydropyrimidin-2(1H)-ones: fast synthesis under microwave irradiation in solvent free conditions. Synth. Commun., 2000, 30, 2165-2173.
Patil, S.; Jadhavar, Sd.; Mane, S.Y. Pineapple juice as a natural catalyst: An excellent catalyst for Biginelli reaction. Int. J. Org. Chem. (Irvine), 2011, 11, 25-131.
Moosavifar, M.C.R. An appropriate one-pot synthesis of dihydropyrimidinones catalyzed by heteropoly acid supported on zeolite: An efficient and reusable for the Biginelli. C. R. Chim., 2012, 15, 444-447.
Silva, L.; Fernandes, S.A.; Fatima, A.A. A P-Sulfonic acid Calix[4]arene as an efficient catalyst for one-pot synthesis of pharmaceutically significant Coumarin derivatives under solvent-free condition. Tetrahedron Lett., 2011, 52, 6328-6330.
Chitra, S.; Pandiarajan, K. Calcium fluoride: an efficient and reusable catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and their corresponding 2(1H)-thione: an improved high yielding protocol for the Biginelli reaction. Tetrahedron Lett., 2009, 50(19), 2222-2224.
Ghotkar, N.S.; Der Phar, B.N. Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-one using layered double hydroxide(LDH) as a eco-friendly catalyst. Chemi., 2015, 7, 167-172.
Jain, S.L.; Joseph, J.K.; Singhal, S.; Mol, B.J. PEG-assisted solvent and catalyst free synthesis of 3,4-dihydropyrimidinone under mild reaction condition. Cat. A. Chem., 2007, 26, 8134-8138.
Raju, M. Kalaipriya, R. Uma, R. Sridhar, S. Ramakrishna, Pyridinium trifluoroacetate mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and Tetrazolo[1,5-a]pyrimid ine-6-carboxylates. Curr. Chem. Lett., 2012, 1, 27-34.
González-Olvera, R.; Román-Rodríguez, V.; Negrón-Silva, G.E.; Espinoza-Vázquez, A.; Rodríguez-Gómez, F.J.; Santillan, R. Multicomponent synthesis and evaluation of new 1,2,3-triazole derivatives of dihydropyrimidinones as acidic corrosion inhibitors for steel. Molecules, 2016, 21(2), 250-263.
[] [PMID: 26907242]
Kalita, H.R.; Phukan, P. CuI as reusable catalyst for the Biginelli reaction. Catal. Commun., 2007, 81, 179-182.
Khosropour, R.; Beygzadeh, M.M.; Jokar, M. A one-pot synthesis of 3,4-dihydro pyrimidin-2(1H)-one from primary alcohols promoted by Bi(NO3)3.5H2O in two different media: Organic solvent and ionic liquid. Heterocycles, 2005, 65, 767.
Zhou, H.; Hw, M.; Liu, C.; Luo, H.; Prep, G. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-one using CuBr2 as catalyst, Biochem. Biotechnol. 36 (2006) 375. (a).V. A. Chebanov, V. E. Desenko, S. M. Chernenko, V. N. Knyazeva, I. V. Groth, U. Glasnov, T. N. Kappe, C. O. Tuning of chemo and regioselectivities in multicomponent condensations of 5-aminopyrazoles dimedone and aldehyde. J. Org. Chem., 2008, 73, 5110.
Wipf, P.; Cunningham, A. A solid phase protocol of the Biginelli dihydropyrimidine synthesis suitable for combinatorial chemistry. Tetrahedron Lett., 1995, 36(43), 7819-7822.
Cepanec, L.; Litvic, M.; Bartolinčić, A.; Lovric, M. Ferric chloride/tetraethyl orthosilicate as an efficient system for synthesis of dihydropyrimidinones by Biginelli reaction. Tetrahedron, 2005, 61, 4275-4280.
Wan, J.P.; Wang, C.; Pan, Y. Solvent-free synthesis of 6-unsubstituted dihydropyrimidine using 2-pyrrolidonium bisulphate as effect catalyst. Tetrahedron, 2011, 67, 922.
Tu, S.; Zhang, J.; Zhu, X.; Xu, J.; Zhang, Y.; Wang, Q.; Jia, R.; Jiang, B.; Zhang, J. New potential inhibitors of cyclin-dependent kinase 4: design and synthesis of pyrido[2,3-d]pyrimidine derivatives under microwave irradiation. Bioorg. Med. Chem. Lett., 2006, 16(13), 3578-3581.
[] [PMID: 16621547]
Yadav, L.D.S.; Awasthi, C.; Rai, V.K.; Rai, A. Biorenewable and mercaptoacetylating building blocks in the Biginelli reaction: Synthesis of thiosugar-annulated dihydro pyrimidines. Tetrahedron Lett., 2007, 48(28), 4899-4902.
Hazarkhani, H.; Karimi, B. N-Bromosuccinimide as an almost neutral catalyst for efficient synthesis of dihydropyrimidinones under microwave irradiation. Synthesis, 2004, 1239-1242.
Hamid, N.; Hamid, R.K.; Ayoob, B.A. A novel and efficient synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione and pyrido[2,3-d,5-d]dipyrmidine-2,4,6,8-tetrone derivatives. Tetrahedron, 2007, 63, 1770-1774.
Shujian, T.; Shansha, W.U.; Zhengguo, H.; Chin, W. H. An efficient microwave-assisted synthesis of pyrido[2,3-d]pyrimidine derivatives. J. Chem., 2009, 27, 1148-1152.
Zonouzi, F. Hosseinzadeh, N. Karimi, R. Mirzazadeh, W. N. Seik, Novel approach for the synthesis of a library of fluorescent chromenopyrimidine derivatives. ACS Comb. Sci., 2013, 15, 240-246.
[] [PMID: 23547948]
Ryabukhin, S.V.; Plaskon, A.S.; Ostapchuk, E.N.; Volochnyuk, D.M.; Tolmachev, A.A. N-Substituted urea and thiourea in Biginelli reaction promoted by Chlorotrimethylsilane: convenient synthesis of N1-alkyl-, N-aryl- andN1,N3-dialkyl-3,4-dihydropyrimidin-2(1H)-(thio)ones. Synthesis, 2011, 2261-2267.
Sasada, T.; Kobayashi, F.; Sakai, N.; Konakahara, T. An unprecedented approach to 4,5-disubstituted pyrimidine derivatives by a ZnCl(2)-catalyzed three-component coupling reaction. Org. Lett., 2009, 11(10), 2161-2164.
[] [PMID: 19371078]
Davoodnia, M. 2006.
Ziarani, G.M.; Faramarzi, S.; Asadi, S.; Badiei, A.; Bazl, R.; Amanlou, M. Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H) and their docking and urease inhibitory activity. Daru, 2013, 21(1), 3.
[] [PMID: 23351402]
Aswin, K.; Sheik, S. Triphenylphosphine: An efficient catalyst for the synthesi of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione thermal condition. J. King Saud Univ. Sci., 2013, 26(2), 141-148.
Wang, C.; Liu, H.; Song, Z.; Ji, Y.; Xing, L.; Peng, X.; Wang, X.; Ai, J.; Geng, M.; Zhang, A. Synthesis and structure-activity relationship study of pyrazolo[3,4-d]pyrimidines as tyrosine kinase RET inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(11), 2544-2548.
[] [PMID: 28404375]
Huang, Y.Y.; Wang, L.Y.; Chang, C.H.; Kuo, Y.H.; Kaneko, K.; Takayama, H.; Kimura, M.; Juang, S.H.; Wong, F.F. Vilsmeier-Haack reagent-promoted formyloxylation of α–chloro-N-arylacetamides by formamide. Tetrahedron, 2012, 68(47), 9658-9664.
Hajipour, R.; Ghayeb, Y.; Sheikhan, N.; Ruoho, A.E. Supported Tetra methylammonium nitrate/silica sulphuric acid as a useful reagent for nitration aromatic compounds under solvent-free condition. Synth. Commun., 2011, 41, 2226-2233.
Tian, Z-Y.; Du, G-J.; Xie, S-Q.; Zhao, J.; Gao, W-Y.; Wang, C-J. Synthesis and bioevaluation of 5-fluorouracil derivatives. Molecules, 2007, 12, 2450-2457.
Lu, J.; Bai, Y. Catalysis of the Biginelli reaction by ferric and nickel chloride Hexahydrates one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-one. Synthesis, 2002, 466-470.
Sweet, F.; Fissekis, J.D. Synthesis of substituted 3,4-tetrahydro-2(1H)-pyrimidinones and mechanism of the Biginelli reaction. J. Am. Chem. Soc., 1973, 95, 8741.
Reilly, O.B.C.; Atwal, K.S. Synthesis of substituted 1,2,3,4-tetrahydro-6-methyl-2-oxo-5-pyrimidine carboxylic acid esters: Biginelli condensation revisited. Hetrocyclic., 1987, 26, 1185.
Atwal, K.S.; Reilly, B.C.O.; Gougoutas, J.Z.; Malley, M.F. Synthesis of substituted 1,2,3,4-tetrahydro-6-methyl-2-thioxo-5-pyrimidinecarboxylic acid esters. Hetrocyclic., 1987, 26, 1189.
Kappe, C.O. A re-examination of the mechanism of the Biginelli dihydropyrimidine synthesis support for N-acyliminium ion intermediate. J. Org. Chem., 1997, 62(21), 7201-7204.
[] [PMID: 11671828]
Cepanee, L.; Litvic, M.; Filipan-Litvic, M.; Grüngold, I. Antimony(III)chloride- catalyst Biginelli reaction a versatile method for the synthesis of dihydropyrimidinone through a different reaction mechanism. Tetrahedron, 2007, 63, 11822.
Schauble, J.H.; Trauffe, E.A.; Deshpande, P.P.; Evans, R.D. Trans Dialkoxylation of cyclic alkenes: A Prévost-type reaction. Synthesis, 2005, 1333-1339.
Heravi, M.M.; Motamedi, R.; Seifi, N.; Bamoharram, F.F. 12-Molybdophosphoric acid: A recyclable catalyst for the synthesis of Biginelli-type 3,4-dihydropyrimidine-2(1H)-ones. J. Mol. Catal. Chem., 2007, 6, 373-376.
Abdel-latif, E.; Abdel-fattah, S.; Gaffer, H.; Etman, H. Synthesis and antitumor activity of some pyrazolo[3,4-d] pyrimidine and pyrazolo[3,4-b]pyridine derivatives, Egyptian. J. Basic Appl. Sci., 2016, 3, 118-124.
Roy, S.R.; Jadhavar, P.S.; Seth, K.; Sharma, K.K.; Chakraborti, A.K. Organocatalytic appilication of ionic liquids [bmim][MeSO4] as a recyclable organocatalyst in the multicomponent reaction for the preparation dihydropyrimidinones and thiones. Synthesis, 2011, 2261-2267.
Brown, A.M.; Kunze, D.L.; Yatani, A. The agonist effect of dihydropyridines on Ca channels. Nature, 1984, 311(5986), 570-572.
[] [PMID: 6207438]
Colović, M.B.; Krstić, D.Z.; Lazarević-Pašti, T.D.; Bondžić, A.M.; Vasić, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11(3), 315-335.
[] [PMID: 24179466]
Inglis, F. The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. Int. J. Clin. Pract. Suppl., 2002, (127), 45-63.
Arun, S.; Khamkaew, A. Anan, A. Nuttapon, A. Suksamrarn, V. Ajavakom, Novel racemic tetrahydrocur cuminoid dihydropyrimidinone analogues as potent acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23, 2880-2882.
[] [PMID: 23583510]
Barbosa, F.A.R.; Canto, R.F.S.; Saba, S.; Rafique, J.; Braga, A.L. Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer’s disease. Bioorg. Med. Chem., 2016, 24(22), 5762-5770.
[] [PMID: 27681239]
Canto, R.F.S.; Barbosa, F.A.; Nascimento, V.; de Oliveira, A.S.; Brighente, I.M.; Braga, A.L. Design, synthesis and evaluation of seleno-dihydropyrimidinones as potential multi-targeted therapeutics for Alzheimer’s disease. Org. Biomol. Chem., 2014, 12(21), 3470-3477.
[] [PMID: 24752799]
Luthin, D.R. Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life Sci., 2007, 81(6), 423-440.
[] [PMID: 17655875]
Hervieu, G. Melanin-concentrating hormone functions in the nervous system: food intake and stress. Expert Opin. Ther. Targets, 2003, 7(4), 495-511.
[] [PMID: 12885269]
Goss, J.M.; Schaus, S.E. Enantioselective synthesis of SNAP-7941: chiral dihydropyrimidone inhibitor of MCH1-R. J. Org. Chem., 2008, 73(19), 7651-7656.
[] [PMID: 18767801]
Jiang, Y.; Chen, C.A.; Lu, K.; Daniewska, I.; De Leon, J.; Kong, R.; Forray, C.; Li, B.; Hegde, L.G.; Wolinsky, T.D.; Craig, D.A.; Wetzel, J.M.; Andersen, K.; Marzabadi, M.R. Synthesis and SAR investigations for novel melanin-concentrating hormone 1 receptor (MCH1) antagonists Part 1. The discovery of arylacetamides as viable replacements for the dihydropyrimidinone moiety of an HTS hit. J. Med. Chem., 2007, 50(16), 3870-3882.
[] [PMID: 17668921]
Morano, K.A. New tricks for an old dog: The evolving world of Hsp70. Ann. N. Y. Acad. Sci., 2007, 1113(1), 1-14.
[] [PMID: 17513460]
Luders, J.; Demand, J.; Hohfeld, J. The ubiquity-related BAG-1 provides a link between the molecular chaperones. Hsc70/Hsp70 and the proteansome. J. Biol. Chem., 2000, 275(7), 4613-4617.
Chaiang, A.N.; Valderramos, J-C.; Balachandran, R.; Chaovatiya, R.J.; Mead, B.P.; Schneider, C.; Bell, J.; Michael, G. K.; M. Donna, Huryn, S. Xiaojiang, Chen, W. Billy, Day, A. David, Fidock, Peter Wipf, L. Jeffrey, L.; Select pyrimidinones inhibit the propagation of the malaria parasite plasmodium falciparum. Bioorg. Med. Chem., 2009, 17(4), 1527-1533.
[] [PMID: 19195901]
Christine, M.; Wright, J. Raj, Chovatiya, E. Jameson, M. David, Turner, Guangyu Zhu, Stefan Werner, M, Donna, Hurny, M. James, Pipas, W. Billy, W. Day, Peter Wipfb, L. Jeffrey, L. Brodsky, Pyrimidinone-peptoid hybrid molecule with distinct effects on molecular chaperone function and cell proliferation. Bioorg. Med. Chem., 2008, 16, 3291-3301.
Vale, R.D. The molecular motor toolbox for intracellular transport. Cell, 2003, 112(4), 467-480.
[] [PMID: 12600311]
Goshima, G.; Vale, R.D. Cell cycle-dependent dynamics and regulation of mitotic kinesins in Drosophila S2 cells. Mol. Biol. Cell, 2005, 16(8), 3896-3907.
[] [PMID: 15958489]
Gerson-Gurwitz, A.; Thiede, C.; Movshovich, N.; Fridman, V.; Podolskaya, M.; Danieli, T.; Lakämper, S.; Klopfenstein, D.R.; Schmidt, C.F.; Gheber, L. Directionality of individual kinesin-5 Cin8 motors is modulated by loop 8, ionic strength and microtubule geometry. EMBO J., 2011, 30(24), 4942-4954.
[] [PMID: 22101328]
Klein, E.; DeBonis, S.; Thiede, B.; Skoufias, D.A.; Kozielski, F.; Lebeau, L. New chemical tools for investigating human mitotic kinesin Eg5. Bioorg. Med. Chem., 2007, 15(19), 6474-6488.
[] [PMID: 17587586]
Bose, D.S.; Kumar, R.K.; Fatima, L. A remarkable rate acceleration of the one-pot three-component cyclocondensation reaction at room temperature: An expedient synthesis of mitotic kinesin Eg5 inhibitor monastrol. Synlett, 2004, 2, 279-282.
Chang, M.H. Hepatitis B virus infection. Semin. Fetal Neonatal Med., 2007, 12(3), 160-167.
[] [PMID: 17336170]
Glebe, D.; Urban, S. Viral and cellular determinants involved in hepadnaviral entry. World J. Gastroenterol., 2007, 13(1), 22-38.
[] [PMID: 17206752]
Zhu, X.; Zhao, G.; Zhou, X.; Xu, X.; Xia, G.; Zheng, Z.; Wang, L.; Yang, X.; Li, S. 2,4-Diaryl-4,6,7,8-tetrahydroquinazolin-5(1H)-one derivatives as anti-HBV agents targeting at capsid assembly. Bioorg. Med. Chem. Lett., 2010, 20(1), 299-301.
[] [PMID: 19897363]
Hawn, T.R.; Day, T.A.; Scriba, T.J.; Hatherill, M.; Hanekom, W.A.; Evans, T.G.; Churchyard, G.J.; Kublin, J.G.; Bekker, L.G.; Self, S.G. Tuberculosis vaccines and prevention of infection. Microbiol. Mol. Biol. Rev., 2014, 78(4), 650-671.
[] [PMID: 25428938]
Singh, K.; Singh, K.; Wan, B.; Franzblau, S.; Chibale, K.; Balzarini, J. Facile transformation of Biginelli pyrimidin-2(1H)-ones to pyrimidines. In vitro evaluation as inhibitors of Mycobacterium tuberculosis and modulators of cytostatic activity. Eur. J. Med. Chem., 2011, 46(6), 2290-2294.
[] [PMID: 21450375]
Sankar, C.; Pandiarajan, K. Synthesis and anti-tubercular and antimicrobial activities of some 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one N-isonicotinoylhydrazone derivatives. Eur. J. Med. Chem., 2010, 45(11), 5480-5485.
[] [PMID: 20822833]
Trivedi, A.R.; Bhuva, V.R.; Dholariya, B.H.; Dodiya, D.K.; Kataria, V.B.; Shah, V.H. Novel dihydropyrimidines as a potential new class of antitubercular agents. Bioorg. Med. Chem. Lett., 2010, 20(20), 6100-6102.
[] [PMID: 20813528]
Geijselaers, S.L.C.; Sep, S.J.S.; Claessens, D.; Schram, M.T.; van Boxtel, M.P.J.; Henry, R.M.A.; Verhey, F.R.J.; Kroon, A.A.; Dagnelie, P.C.; Schalkwijk, C.G.; van der Kallen, C.J.H.; Biessels, G.J.; Stehouwer, C.D.A. The role of hyperglycaemia. Insulin resistance and blood pressure in diabetes-associated difference in cognitive performance-the Maastricht study. Diabetes Care, 2017, 40(11), 1537-1547.
[] [PMID: 28842522]
Umpierrez, G.E.; Pasquel, F.J. Management of inpatient hyperglcemia and diabetes in older adults. Diabetes Care, 2017, 40(4), 509-517.
[] [PMID: 28325798]
Walls, Ron John J, Ratey, Robert, Simon, Rosen’s emergency medicine expert consult premium edition-enhanced online feature and print (Rosen’s emergency medicine: Concepts &. Clin. Pract., 2017.
Dhumaskar, K.L.; Meena, S.N.; Ghadi, S.C.; Tilve, S.G. Graphite catalyzed solvent free synthesis of dihydropyrimidin-2(1H)-ones/thiones and their antidiabetic activity. Bioorg. Med. Chem. Lett., 2014, 24(13), 2897-2899.
[] [PMID: 24835627]
Wang, Z.; Peng, S.; Peng, M.; Wang, C. Isolation of polyphenol compounds from olive waste and inhibition of their derivatives for α-Glucosidase and α-amylase. Nat. Prod. Res., 2019, •••, 1-5.
Kingston, W. Irish contributions to the origins of antibiotics. Ir. J. Med. Sci., 2008, 177(2), 87-92.
[] [PMID: 18347757]
Tanwar, J.; Das, S.; Fatima, Z.; Hameed, S. Multidrug resistance: an emerging crisis. Interdiscip. Perspect. Infect. Dis., 2014, 2014541340
[] [PMID: 25140175]
Ashok, M.; Holla, B.S.; Kumari, N.S. Convenient one pot synthesis of some novel derivatives of thiazolo[2,3-b]dihydropyrimidinone possessing 4-methylthiophenyl moiety and evaluation of their antibacterial and antifungal activities. Eur. J. Med. Chem., 2007, 42(3), 380-385.
[] [PMID: 17070617]
Lal, J.; Gupta, S.K.D.; Thavaselvam, D. D, Agarwal, Design, Synthesis, Synergistic antimicrobial activity and cytotoxicity of 4-aryl substituted 3,4-dihydropyrimidinone of curcumin. Bioorg. Med. Chem. Lett., 2012, 22(8), 2872-2876.
[] [PMID: 22440624]
Attri, P.; Bhatia, R.; Gaur, J.; Arora, B.; Gupta, A.; Kumar, N.; Choi, E.H. Triethylammonium actetate ionic liquid assisted one-pot synthesis of dihydropyrimidinones and evaluation of their antioxidant and antibacterial activities. Arab. J. Chem., 2017, 10(2), 206-214.
Brands, M.; Endermann, R.; Gahlmann, R.; Krüger, J.; Raddatz, S. Dihydropyrimidinones--a new class of anti-staphylococcal antibiotics. Bioorg. Med. Chem. Lett., 2003, 13(2), 241-245.
[] [PMID: 12482431]
Soliman, A.M.; Mohamed, S.K.; El-Remally, M.A.E.A.A.A.; Abdel-Ghany, H. Synthesis of pyrimidine, dihydropyrimidinone and dihydroimdazole derivatives under free solvent condition and their antibacterial evaluation. J. Heterocycl. Chem., 2014, 51(4), 1202-1209.
Bhuiyan, M.H.; Nessa, H.; Mahmud, M.M. Multicomponent reaction: Microwave-assisted efficient synthesis of dihydropyrimidinones (thiones) and quinazolinones under green chemistry protocol as probes for antimicrobial activities. Jr. Sci. Research., 2012, 4(1), 143-153.
Tale, R.H.; Rodge, A.H.; Hatnapure, G.D.; Keche, A.P. The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea: synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation. Bioorg. Med. Chem. Lett., 2011, 21(15), 4648-4651.
[] [PMID: 21737269]
Anand, P.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Tharakan, S.T.; Lai, O.S.; Sung, B.; Aggarwal, B.B. Cancer is a preventable disease that requires major lifestyle changes. Pharm. Res., 2008, 25(9), 2097-2116.
[] [PMID: 18626751]
Hayden, E.C. Cutting off cancer’s supply lines. Nature, 2009, 458(7239), 686-687.
[] [PMID: 19360048]
Bagri, A.; Kouros-Mehr, H.; Leong, K.G.; Plowman, G.D. Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale. Trends Mol. Med., 2010, 16(3), 122-132.
[] [PMID: 20189876]
Mostafa, A.S.; Selim, K.B. Synthesis and anticancer activity of new dihydropyrimidinone derivatives. Eur. J. Med. Chem., 2018, 156, 304-315.
[] [PMID: 30015070]
Soumyanarayanan, U.; Bhat, V.G.; Kar, S.S.; Mathew, J.A. Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study. Org. Med. Chem. Lett., 2012, 2(1), 23.
[] [PMID: 22691177]
Nadjm, B.; Behrens, R.H. Malaria: an update for physicians. Infect. Dis. Clin. North Am., 2012, 26(2), 243-259.
[] [PMID: 22632637]
Chernin, E. Patrick Manson (1844-1922) and the transmission of filariasis. Am. J. Trop. Med. Hyg., 1977, 26(5 Pt 2)(Suppl.), 1065-1070.
[] [PMID: 20786]
Rogerio, K.R.; Carvalho, L.J.M.; Domingues, L.H.P.; Neves, B.J.; Moreira Filho, J.T.; Castro, R.N.; Bianco Júnior, C.; Daniel-Ribeiro, C.T.; Andrade, C.H.; Graebin, C.S. Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[3,4-d]-pyrimidinodiones as new antiplasmodial compounds. Mem. Inst. Oswaldo Cruz, 2018, 113(8)e170452
[] [PMID: 29924131]
Radini, I.A.; Elsheikh, T.M.; El-Telbani, E.M.; Khidre, R.E. New potential antimalarial agents: Design, synthesis and biological evaluation of some novel quinoline derivatives as antimalarial agents. Molecules, 2016, 21(7), 909.
[] [PMID: 27428939]
de Araujo Furtado, M.; Rossetti, F.; Chanda, S.; Yourick, D. Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy. Neurotoxicology, 2012, 33(6), 1476-1490.
[] [PMID: 23000013]
Lewis, R.W.; Mabry, J.; Polisar, J.G.; Eagen, K.P.; Ganem, B.; Hess, G.P. Dihydropyrimidinone positive modulation of δ-subunit-containing gamma-aminobutyric acid type A receptors, including an epilepsy-linked mutant variant. Biochemistry, 2010, 49(23), 4841-4851.
[] [PMID: 20450160]
Trelle, S.; Reichenbach, W.; Simon, H. pius, Tschannen, Beatrice, Villiger, Peter, M. Egger, Matthias, Juni, Peter, Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. Br. Med. J. (Clin. Res. Ed.), 2011, 342, 7086.
Bhateware, A.; Jetti, S.R.; Kadre, T.; Paliwal, P.; Jain, S. Microwave-assisted synthesis and biological evaluation of dihydropyrimidinone derivatives as anti-inflammatory, antibacterial and antifungal agents. Int. J. Med. Chem., 2013, •••, 1-5.
Mokale, S.N.; Shinde, S.S.; Elgire, R.D.; Sangshetti, J.N.; Shinde, D.B. Synthesis and anti-inflammatory activity of some 3-(4,6-disubtituted-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives. Bioorg. Med. Chem. Lett., 2010, 20(15), 4424-4426.
[] [PMID: 20594837]
Viveka, S.; Dinesha, G.K. Nagaraja, P. Shama, G. Baavarajaswamy, K.P. Rao, & M. Yanjarappa Sreenivasa, One pot synthesis of thiazolo[2,3-b]dihydropyrimidinone possessing pyrazole moiety and evaluation of their anti-inflammatory activities. Med. Chem. Res., 2017, 27(1), 171-185.
Musini, V.M.; Tejani, A.M.; Bassett, K.; Wright, J.M. Pharmacotherapy for hypertension in the elderly. Cochrane Database Syst. Rev., 2009, (4)CD000028
Hiren, M.; Maryvaniya, K. 2011.
Priya, N.; Singh, P.; Bhatia, S.; Medhi, B.; Prasad, A.K.; Parmar, V.S.; Raj, H.G. Characterization of a unique dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate, as an effective antithrombotic agent in a rat experimental model. J. Pharm. Pharmacol., 2011, 63(9), 1175-1185.
[] [PMID: 21827490]
Mansouri, M.; Movahedian, A.; Rosrami, M.; Fassihi, A. 2012.
Vijay Kotra, V. 2014.
Manos-Turvey, A.; Al-Ashtal, H.A.; Needham, P.G.; Hartline, C.B.; Prichard, M.N.; Wipf, P.; Brodsky, J.L. Dihydropyrimidinones and -thiones with improved activity against human polyomavirus family members. Bioorg. Med. Chem. Lett., 2016, 26(20), 5087-5091.
[] [PMID: 27624078]
Bhat, M. A.; Naglah, M. A.; Kalmouch, A.; Al-Dhfyan, A. Synthesis and characterization of novel Biginelli dihydropyrimidinones derivatives containing Imidazole moiety., 2019.
Kaur, A.; Pathak, D.P.; Sharma, V.; Wakode, S. Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorg. Med. Chem., 2018, 26(4), 891-902.
[] [PMID: 29373271]
Sarkar, K.; Khasimbi, S.; Mandal, S.; Dastidar, P. Rationally development Metallogelators derivatives from Pyridyl deriva-tives of NSAIDs display anti-inflammatory and anti-cancer activities. ACS Appl. Mater. Interfaces, 2018, 10(36), 30649-30661.
[] [PMID: 30118200]
Kaur, A.; Wakode, S.R.; Pathak, D.P.; Shakya, A.K. Synthesis COX-2 inhibition, anti-inflammatory evaluation and docking study of substituted-N-93,4,5-trimethoxypheny)-benzo[d]oxazole derivatives. Med. Chem., 2018, 14, 660-673.
[] [PMID: 29564981]
Dastidar, P.; Roy, R.; Parveen, P.; Sarkar, K. Supramolecular synthon approach in designing molecular gels for advanced therapeutics. Adv. Ther., 2018, •••1800061

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy