1,4-Dihydropyridine: A Dependable Heterocyclic Ring with the Promising and the Most Anticipable Therapeutic Effects

Author(s): Abhinav Prasoon Mishra*, Ankit Bajpai, Awani Kumar Rai.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 15 , 2019

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Graphical Abstract:


Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.

Keywords: 1, 4-Dihydropyridine, pyridine, Ca++channel blocker, voltage-gated calcium channel, antihypertension, therapeutic effects.

Sharma, V.K.; Singh, S.K. Synthesis, utility and medicinal importance of 1,2 & 1,4 dihydropyridines. RSC Adv, 2017, 7, 2682-2732.
Khedkar, S.A.; Auti, P.B. 1,4-Dihydropyridines: A class of pharmacologically important molecules. Mini Rev. Med. Chem., 2014, 14(3), 282-290.
Mansoor, S.S.; Aswin, K.; Logaiya, K.; Sudhan, S.P.N. Bismuth nitrate as an efficient recyclable catalyst for the one-pot multi component synthesis of 1, 4-dihydropyridine derivatives through unsymmetrical hantzsch reaction. J. Saudi Chem. Soc., 2016, 20(1), S001-S008.
Kappe, C.O. Biologically active dihydropyrimidones of the Biginelli-type -a literature survey. Eur. J. Med. Chem., 2000, 35(12), 1043-1052.
Swarnalatha, G.; Prasanthi, G.; Sirisha, N.; Chetty, C.M. 1,4-Dihydropyridines: A multtifunctional molecule- A review. Int. J. Chemtech Res., 2011, 3, 75-89.
Stout, D.M.; Meyers, A.I. Recent advances in the chemistry of dihydropyridines. Chem. Rev., 1982, 82(2), 223-243.
Eisner, U.; Kuthan, J. The chemistry of dihydropyridines. Chem. Rev., 1972, 72(1), 1-42.
Kuthan, J.; Kurfurst, A. Development in dihydropyridine chemistry. Ind. Eng. Chem. Prod. Res. Dev., 1882, 21(2), 191-261.
Hofmann, H.J.; Cimiraglia, R. Conformation of 1, 4- dihydropyridine- planar or boat-like? FBBS Lett., 1988, 241(1,2), 38-40.
Fossheim, R. Crystal structure of the dihydropyridine ca++ antagonist felodipine. Dihydropyridine binding prerequisites assessed from crystallographic data. J. Med. Chem., 1986, 29(2), 305-307.
Franckowiak, G.; Bechem, M.; Schramm, M.; Thomas, G. The optical isomers of the 1,4-dihydropyridine bay k 8644 show opposite Effects on ca channels. Eur. J. Pharmacol., 1985, 114(2), 223-226.
Goldmann, S.; Born, L.; Kazda, S.; Pittel, B.; Schramm, M. Synthesis, pharmacological effects, and conformation of 4,4-disubstituted 1,4-dihydropyridines. J. Med. Chem., 1990, 33(5), 1413-1418.
Goldmann, G.; Stoltefuss, J. 1,4-Dihydropyridines: Effects of chirality and conformation on the calcium antagonist and calcium agonist activities. Angew. Chem. Int. Ed. Engl., 1991, 30(12), 1559-1578.
Rovnyak, G.C.; Kimball, S.D.; Beyer, B.; Cucinotta, S.G.; DiMarco, J.D.; Gougoutas, J.; Hedberg, A.; Malley, M.; McCarthy, J.P.; Zhang, R.; Morelande, S. Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators. J. Med. Chem., 1995, 38(1), 119-129.
Aronow, W.S. Treatment of systemic hypertension. Am. J. Cardiovasc. Dis., 2012, 2(3), 160-170.
Zhang, L.; Song, Z.; Dong, Y.; Wang, Y.; Li, X.; Long, H.; Xu, K.; Deng, C.; Meng, M.; Yin, Y.; Xi, R. Enantiomeric separation of 1, 4-dihydropyridines by liquid-phase microextraction with supercritical fluid chromatography. J. Supercrit. Fluids, 2016, 107, 129-136.
Yu, F.; Zhou, B.; Xu, H.; Chang, K.; Shen, Y. An atom-economic green approach: Oxidative synthesis of functionalized 1,4-dihydropyridines from N,N-dimethylenaminones and amines. Tetrahedron Lett., 2015, 56(6), 837-841.
Cataldi, M.; Bruno, F. 1,4-Dihydropyridines: The multiple personalities of a blockbuster drug family. Transl. Med. UniSa, 2012, 4(2), 12-26.
Shaldam, M.A.; Elhamamsy, M.H.; Esmat, E.A.; El-moselhy, T.F. 1,4-Dihydropyridine calcium channel blockers: Homology modeling of the receptor and assessment of structure-activity relationship. ISRN Med. Chem, 2014, 2014, 1-14.
Schaller, D.; Gunduz, M.G.; Zhang, F.X.; Zamponi, G.W.; Wolber, G. Binding mechanism investigations guiding the synthesis of a novel condensed 1,4- dihydropyridine derivatives with L-/T-type calcium channel blocking activity. Eur. J. Med. Chem., 2018, 155, 1-12.
Wang, A.L.; Iadecola, C.; Wang, G. New generations of dihydropyridines for treatment of hypertension. J. Geriatr. Cardiol., 2017, 14(1), 67-72.
Fleckenstein, A.; Tritthart, H.; Flackenstein, B.; Herbst, A.; Grun, G. A new group of competitive divalent Ca-antagonists (iproveratril, D 600, prenylamine) with potent inhibitory effects on electromechanical coupling in mammalian myocardium. Pflugers Arch., 1969, 307(2), R25. [Article in German].
Coca, A.; Mazon, P.; Redon, J.; Divison, J.A.; Martínez, J.; Calvo, C.; Galceran, M.; Bareios, V.; Coll, A.R. Role of dihydropyridine calcium channel blockers in the management of hypertension. Expert Rev. Cardiovasc. Ther., 2013, 11(1), 91-105.
Wang, J.; Kario, K.; Lau, T.; Wei, Y.Q.; Park, C.G.; Kim, C.H.; Huang, J.; Zhang, W.; Li, W. Use of dihydropyridine calcium channel blockers in the management of hypertension in Eastern Asians: A scientific statement from the Asian pacific heart association. Hypertens. Res., 2011, 34(4), 423-430.
Liau, C. Barnidipine: A new calcium channel blocker for hypertension treatment. Exp. Revi. Cardio. Ther, 2005, 3(2), 207-213.
Van Zwieten, P.A. The pharmacological properties of lipophilic calcium antagonists. Blood Press. Suppl., 1998, 7(2), 5-9.
Chandra, K.S.; Ramesh, G. The fourth-generation calcium channel blocker: Cilnidipine. Ind Heart J., 2013, 65(6), 691-695.
Salazar, T.; Gonzalez, A.; Bandyopadhaya, D. Dihydropyridines as calcium channel blockers: An overview. J. Anal. Pharm. Res, 2017, 5(4), 00148.
Ozer, E.K. MiyaseGunduz, M.G.; El-Khouly. A.; Sara, Y.; Simsek, R.; Iskit, A.B.; Safak, C. Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Turk. J. Biochem, 2017, 43(6), 1-9.
Mohajeri, S.A.; Hosseinzadeh, H.; Salami, S.; Motamedshariaty, V.; Hadizadeh, F. Synthesis of novel 4-[1-(4-fluorobenzyl) -5-imidazolyl] dihydropyridines and studying their effects on rat blood pressure. Iran. J. Basic Med. Sci., 2011, 14(5), 451-457.
Zhou, K.; Zhao, Y.; Wang, X.; Cao, Y.; Fu, Q.; Zhang, S. Synthesis and antihypertensive activity evaluation in spontaneously hypertensive rats of nitrendipine analogs. Med. Chem. Res., 2011, 20(8), 1325-1330.
Balaev, A.N.; Eleev, A.F.; Eremin, O.G.; Fedorov, V.E. Synthesis and antihypertensive activity of 1,4-dihydropyridines containing 3-dialkylamino-2,2-dimethyl propyl fragments. Pharm. Chem. J., 2010, 44(2), 56-57.
Nekooeian, A.A.; Khalili, A.; Javidnia, K.; Mehdipour, A.R.; Miri, R. Antihypertensive effects of some new nitroxyalkyl 1, 4-dihydropyridine derivatives in the rat model of two-kidney, one-clip hypertension. Iran. J. Pharm. Res., 2009, 8(3), 193-199.
Hadizadeh, F.; Fatehi-Hassanabad, Z.; Fatehi-Hassanabad, M.; Beheshtizadeh, A.; Nabati, F. Synthesis and antihypertensive activity of novel 4-[1-(4-X-benzyl)-5-imidazolyl] dihydropyridines in the rat. Res. Pharm. Sci., 2007, 2(2), 85-90.
Liang, J.; Yeh, J.; Wang, C.; Liou, S.; Tsai, C.; Chen, I. The new generation dihydropyridine type calcium blockers, bearing 4-phenyl oxypropanolamine, display ∝-/β-adrenoceptor antagonist and long-acting antihypertensive activities. Bioorg. Med. Chem., 2002, 10, 719-730.
Ogawa, T.; Nakazato, A.; Tsuchida, K.; Hatayama, K. Synthesis and antihypertensive activity of new 1,4-dihydropyridine derivatives containing nitrooxyalkylester moieties at the 3- and 5- position. Chem. Pharm. Bull., 1993, 41(6), 1049-1054.
Bossert, B.F.; Meyer, H.; Wehinger, E. 4-Aryldihydropyridines, a new class of highly active calcium antagonists. Angew. Chem. Int. Ed. Engl., 1981, 20(9), 762-769.
Matos, H.L.S.; Masson, F.T.; Simeoni, L.A. Homem-de-mello, M. biological activity of dihydropyrimidinone (DHPM) derivatives: A systematic review. Eur. J. Med. Chem., 2018, 143, 1779-1789.
Freedman, D.D.; Waters, D.D. Dihydropyridine calcium antagonists greater vascular selectivity and some unique applications. Drugs, 1987, 34(5), 578-598.
Datar, P.A.; Auti, P.B. Design and synthesis of novel 4-substituted 1, 4-dihydropyridine derivatives as hypotensive agents. J. Saudi Chem. Soc., 2016, 20(5), 510-516.
Razzaghi-asl, N.; Miri, R.; Firuzi, O. Assessment of the cytotoxic effect of a series of 1, 4-dihydropyridine derivatives against human cancer cells. Iran. J. Pharm. Res., 2016, 15(3), 413-420.
Al-Said, M.S.; Bashandy, M.S.; Al-qasoumi, S.I.; Ghorab, M.M. Anti-breast cancer activity of some novel 1, 2-dihydropyridine, thiophene and thiazole derivatives. Eur. J. Med. Chem., 2011, 46(1), 137-141.
Goto, R.N.; Sobral, L.M.; Sousa, L.O.; Garcia, C.B.; Lopes, N.P.; Marin-Prida, J.; Ochoa-Rodriguez, E.; Verdecia-Reyes, Y.; Pardo-Andreu, G.L.; Curti, C.; Leopoldino, A.M. Anti-cancer activity of a new dihydropyridine derivative, VdiE-2N, in head and neck squamous cell carcinoma. Eur. J. Pharmacol., 2018, 819, 198-206.
Kumar, R.; Gahlyan, P.; Verma, A.; Jain, R.; Das, S.; Konwar, R.; Prasad, A.K. Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent anti-breast cancer agents. Synth. Commun., 2018, 48(7), 778-785.
Viradiya, D.; Mirza, S.; Shaikh, F.; Kakadiya, R.; Rathod, A.; Jain, N.; Rawal, R.; Shah, A. Design and synthesis of 1,4-dihydropyridine derivatives as anti-cancer agent. Anticancer. Agents Med. Chem., 2017, 17(7), 1003-1013.
Bazargan, L.; Fouladdel, S.; Shafiee, A.; Amini, M.; Ghaffari, S.M.; Azizi, E. Evaluation of anticancer effects of newly synthesized dihydropyridine derivatives in comparison to verapamil and doxorubicin on T47D parental and resistant cell lines in vitro. Cell Biol. Toxicol., 2008, 24(2), 165-174.
Dhinakaran, I.; Padmini, V.; Bhuvanesh, N. One-pot synthesis of N-aryl 1,4-dihydropyridine derivatives and their biological activities. J. Chem. Sci., 2015, 127(12), 2201-2209.
Aziz, H.M.; Gomha, S.M. Synthesis and in vitro anti-breast cancer activity of some novel 1,4-dihydropyridine derivatives. Int. J. Pharm. Pharm. Sci., 2013, 5(3), 183-189.
Sirisha, K.; Achaiah, G.; Reddy, V.M. Facile synthesis and antibacterial, antitubercular and anticancer activities of novel 1, 4-dihydropyridines. Arch. Pharm. Chem. Life Sci, 2010, 343(6), 342-352.
Foroughinia, F.; Javidnia, K.; Amirghofran, Z.; Mehdipour, A.; Miri, R. Design and synthesis of new symmetrical derivatives of dihydropyridine containing a pyridyl group on the 3, 5-positions and evaluation of their cytotoxic and multidrug resistance reversal activity. J. Pharm. Pharmacol., 2008, 60(11), 1481-1489.
Saponara, S.; Ferrara, A.; Gorelli, B.; Shah, A.; Kawase, M.; Motohashi, N.; Molnar, J.; Sgaragli, G.; Fusi, F. 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1, 4-dihydro-2,6-dimethylpyridine (DP7): A new multidrug resistance inhibitor devoid of effects on langendorff-perfused rat heart. Eur. J. Pharmacol., 2007, 563(1-3), 160-163.
Kawase, M.; Shah, A.; Gaveriya, H.; Motohashi, N.; Sakagami, H.; Varga, A.; Molna, J. 3,5-dibenzoyl-1,4-dihydropyridines: Synthesis and MDR reversal in tumor cells. Bioorg. Med. Chem., 2002, 10(4), 1051-1055.
Marquez, B.; Neuville, L.; Moreau, N.J.; Genet, J.; dos Santos, A.F.; Cano-de-Andrade, M.C. Sant, Ana A.E.G. Multidrug resistance reversal agent from jatropha elliptica. Phytochemistry, 2005, 66(15), 1804-1811.
Arentz, M.; Hawn, T.R. Tuberculosis infection: Insight from immunogenomics. Drug Discov. Today Dis. Mech., 2007, 4(4), 231-236.
Janin, Y.L. Antituberculosis drugs: Ten years of research. Bioorg. Med. Chem., 2007, 15(7), 2479-2513.
Lentz, F.; Reiling, N.; Martins, A.; Molnar, J.; Hilgeroth, A. Discovery of novel enhancers of isoniazid toxicity in mycobacterium tuberculosis. Molecules, 2018, 23(4)E825
Rasouli, Y.; Davood, A. Hybrid docking-QSAR studies of 1, 4-dihydropyridine-3, 5-dicarboxamides as potential antitubercular agents. Curr. Comput. Aided Drug Des, 2018, 14(1), 35-53.
Hilgeroth, A.; Reiling, N.; Hemmer, M.; Lentz, F. Discovery of novel N-phenyl 1,4 dihydropyridines with a dual mode of antimycobacterial activity. Bioorg. Med. Chem. Lett., 2016, 26(24), 5896-5898.
Iman, M. Davood, A.; Lotfinia, M.; Dehqani, G.; Sardari, S.; Azerang, P.; Amini, M. design, synthesis and anti-tubercular activity of novel 1, 4-dihydropyrine-3,5 dicarboxamide containing 4(5)-chloro-2-ethyl- 5(4)-imidazolyl moiety. Iran. J. Pharmaceut. Res., 2016, 15(4), 791-799.
Trivedi, A.R.; Dodiya, D.K.; Dholariya, B.H.; Kataria, V.B.; Bhuva, V.R.; Shah, V.H. Synthesis and biological evaluation of some novel N-aryl-1,4-dihydropyridines as potential antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21(18), 5181-5183.
Fassihi, A.; Azadpour, Z.; Delbari, N.; Saghaie, L.; Memarian, H.R.; Sabet, R.; Alborzi, A.; Miri, R.; Pourabbas, R.; Mardanehe, J.; Mousavi, P.; Moeinifardf, B.; Sadeghi-Ali, A.H. Synthesis and antitubercular activity of novel 4-substituted imidazolyl-2,6-dimethyl-N3,N5-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides. Eur. J. Med. Chem., 2009, 44(8), 3253-3258.
Khoshneviszadeh, M.; Edraki, N.; Javidnia, K.; Alborzi, A.; Pourabbas, B.; Mardanehc, J.; Miri, R. Synthesis and biological evaluation of some new 1, 4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents. Bioorg. Med. Chem., 2009, 17(4), 1579-1586.
Shafii, B.; Amini, M.; Akbarzadeh, T.; Shafiee, A. Synthesis and antitubercular activity of N3, N5-diaryl-4- (5-aryl isoxazole-3-yl)-1,4-dihydropyridine- 3,5-dicarboxamide. J. Sci. I.R. Iran, 2008, 19(4), 323-328.
Nasrollahi, S.M.H.; Ghasemzadeh, M.A.; Zolfaghari, M.R. Synthesis and antibacterial evaluation of somenew 1,4 dihydropyridines in the presence of Fe3O4@silica sulfonic acid nanocomposite as catalyst. Acta. Chem. Slov., 2018, 65(1), 199-207.
Ahamed, A.; Arif, I.A.; Mateen, M.; Kumar, R.S.; Idhayadhulla, A. Antimicrobial, anticoagulant, and cytotoxic evaluation of multidrug resistance of new 1,4-dihydropyridine derivatives. Saudi J. Biol. Sci., 2018, 25(6), 1227-1235.
Narsinghani, T.; Soni, L.K.; Chourey, S. Synthesis and antimicrobial activity of 1,4-dihydropyridine derivative. J. Drug Deliv. Ther., 2017, 7(7), 142-145.
Moradi, L.; Mahinpour, R.; Zahraei, Z.; Pahlevanzadeh, N. New synthetic method for the Synthesis of 1,4-dihydropyridine using aminated multiwalled carbon nanotubes as high efficient catalyst and investigation of their antimicrobial properties. J. Saudi Chem. Soc., 2018, 22(7), 876-885.
Elumalai, K.; Elumalai, M.; Eluri, K. Facile synthesis, spectral characterization, antimicrobial and in vitro cytotoxicity of novel N3, N5-diisonicotinyl-2,6-dimethyl-4-phenyl-1, 4-dihydropyridine-3,5-dicarbohydrazide derivatives. Bull. Fac. Pharm., 2016, 54(1), 77-86.
Mehta, P.; Verma, P. Antimicrobial activity of some derivatives of 1,4-dihydropyridines. J. Chem., 2013, 2013, 1-4.
Kumar, R.S.; Idhayadhulla, A.; Nasser, A.J.A.; Selvin, J. Synthesis and antimicrobial activity of a new series of 1,4-dihydropyridine derivatives. J. Serb. Chem. Soc., 2011, 76(1), 1-11.
Kumar, A.; Maurya, R.A.; Sharma, S.; Kumar, M.; Bhatia, G. Synthesis and biological evaluation of N-aryl-1,4-dihydropyridines as novel antidyslipidemic and antioxidant agents. Eur. J. Med. Chem., 2010, 45(2), 501-509.
Velena, A.; Zarkovic, N.; Troselj, K.G.; Bisenieks, E.; Krauze, A.; Poikans, J.; Duburs, G. 1,4-Dihydropyridine derivatives: Dihydronicotinamide analogues - model compounds targeting oxidative stress. Oxid. Med. Cell. Longev., 2016, 2016, 1-35.
Cabreraa, D.D.C.; Santa-Helenab, E.; Leala, H.P.; Mouraa, R.R.D.; Neryb, L.E.M.; Goncalvesb, C.A.N.; Russowskyc, D.; D’Ocaa, M.A.M. Synthesis and antioxidant activity of new lipophilic dihydropyridines. Bioorg. Chem., 2019, 84, 1-16.
Yang, G.; Bowei, W.; Shang, G.; Ruhui, Z.; Chunying, Y.; Zheng, S.; Zhihui, L. Design and synthesis of 1,4-dihydropyridine and cinnamic acid esters and their antioxidant properties. Chem. Res. Chin. Univ., 2016, 32(4), 594-599.
Rucins, M.; Kaldre, D.; Pajuste, K.; Fernandes, M.A.S.; Vicente, J.A.F.; Klimaviciusa, L.; Jaschenko, E.; Kanepe-Lapsa, I.; Shestakova, I.; Plotniece, M.; Gosteva, M.; Sobolev, A.; Jansone, B.; Muceniece, R.; Klusa, V.; Plotniece, A. Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1, 4-dihydropyridine derivatives. Comptes Rendus Chem, 2014, 17, 69-80.
Vijesh, A.M.; Isloor, A.M.; Peethambar, S.K.; Shivananda, K.N.; Arulmoli, T.; Isloor, N.A. Hantzsch reaction: Synthesis and characterization of some new 1, 4-dihydropyridine derivatives as potent antimicrobial and antioxidant agents. Eur. J. Med. Chem., 2011, 46(11), 5591-5597.
Tirzitis, G.; Tirzite, D.; Hyvonen, Z. Antioxidant Activity of 2,6-Dimethyl-3,5-dialkoxycarbonyl -1,4-dihydropyridines in metal-ion catalyzed lipid peroxidation. Czech J. Food Sci., 2001, 19(3), 81-84.
Teleb, M.; Zhang, F.; Huang, J.; Gadotti, V.M.; Farghaly, A.M.; Aboulwafa, O.M.; Zamponi, G.W.; Fahmy, H. Synthesis and biological evaluation of novel N3-substituted dihydropyrimidine derivatives as T-type calcium channel blockers and their efficacy as analgesics in mouse models of inflammatory pain. Bioorg. Med. Chem., 2017, 26(6), 1926-1938.
Nangare, A.K.; Kakad, S.B.; Chavan, A.N.; Bole, S.S. Synthesis and signification of 1, 4-dihydropyridines analogs in different pharmaceutical drug. World J. Pharm. Res, 2015, 4(12), 738-749.
Mishra, B.; Mishra, R. Synthesis of some new 1,4-dihydropyridine derivatives for anti-inflammatory activity. Pharmacist, 2007, 2, 13-16.
Indumathi, S.; Karthikeyan, R.; Nasser, A.J.A.; Idhayadhulla, A.; Kumar, R.S. Anticonvulsant, analgesic and anti-inflammatory activities of some novel pyrrole and 1,4-dihydropyridine derivatives. J. Chem. Pharm. Res., 2015, 7(2), 434-440.
Pattan, S.R.; Dighe, N.S.; Musmade, D.S.; Tambe, S.K.; Kale, S.H.; Gaware, V.M.; Chavan, P.A. Synthesis and evaluation of some new substituted 1,4-dihydro pyridine derivatives and their anticonvulsant activity. J. Chem. Pharm. Res., 2010, 2(1), 246-252.
Samzadeh-Kermani, A.; Shafaroodi, H.; Miri, R.; Mirkhani, H.; Vosooghi, M.; Shafie, A. Lipo philic 2-(4-chlorophenyl)-4-thiazolyl-1,4-dihydropyridines: Synthesis, calcium channel antagonist activity, and protection against pentylenetetrazole-induced seizure. Med. Chem. Res., 2009, 18(2), 112-126.
Shafiee, A.; Rastkari, N.; Sharifzadeh, M. Anticonvulsant activities of new 1,4-dihydropyridine derivatives containing 4-nitroimidazolyl substituents. DARU-J. Facul. Pharm, 2004, 12(2), 81-86.
Subudhia, B.B.; Pandab, P.K.; Bhatta, D. Synthesis and antiulcer activity study of 1, 4- dihydropyridines and their Mannich bases with sulfanilamide. Ind J. Chem., 2009, 48, 725-728.
Kumar, R.S.; Idhayadhulla, A.; Nasser, A.J.A.; Selvin, J. Synthesis and anticoagulant activity of a new series of 1,4-dihydropyridine derivatives. Eur. J. Med. Chem., 2011, 46, 804-810.
Budriesi, R.; Ioan, P.; Leoni, A.; Pedemonte, N.; Locatelli, A.; Micucci, M.; Chiarini, A.; Galietta, L.J.V. Cystic Fibrosis: A new target for 4-imidazo[2,1-b]thiazole-1, 4-dihydropyridines. J. Med. Chem., 2011, 54, 3885-3894.
Cateni, F.; Zacchigna, M.; Pedemonte, N.; Galietta, L.J.V.; Mazzei, M.T.; Fossa, P.; Giampieri, M.; Mazzei, M. Synthesis of 4-thiophen-20-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel. Bioorg. Med. Chem., 2009, 17, 7894-7903.
Pandey, V.P.; Bisht, S.S.; Mishra, M.M.; Kumar, A.A.; Siddiqi, M.I.; Verma, A.; Mittal, M.; Sane, S.A.; Gupta, S.; Tripathi, R.P. Synthesis and molecular docking studies of 1-phenyl-4-glycosyl-dihydropyridines as potent antileishmanial agents. Eur. J. Med. Chem., 2010, 45, 2381-2385.
Leon, R.; Rios, C.L.; Marco-Contelles, J.; Huertas, O.; Barril, X.; Luque, F.J.; Lopez, M.G.; Garcia, A.G.; Villarroya, M. New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection propertie. Bioorg. Med. Chem., 2008, 16, 7759-7769.
Contelles, J.M.; Leon, R.; Rios, C.L.; Samadi, A.L.; Bartolini, M.; Andrisano, V.; Huertas, O.; Barril, X.; Luque, F.J.; Guez-Franco, M.R.; Lopez, B.; Lopez, A.G.; Garcia, A.G.; Carreiras, M.C.; Villarroya, M. Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of alzheimer’s disease. J. Med. Chem., 2009, 52, 2724-2732.
Milkovic, L.; Vukovic, T.; Zarkovic, N.; Tatzber, F.; Bisenieks, E. Kalme, Z.; Bruvere, I.; Ogle, Z.; Poikans, J.; Velena, A.; Duburs, G. Antioxidative 1,4-dihydropyridine derivativesmodulate oxidative stress and growth of human osteoblast-like cells in vitro. Antioxidants, 2018, 7(9), 123.
Burges, R.A.; Dodd, M.G. Amlodipine. Cardiovasc. Drug Rev., 1990, 8(1), 25-44.
Ohashi, K.; Ebihara, A. Aranidipine (MPC- 1304), A new dihydropyridine calcium antagonist: A review of its antihypertensive action. Cardiovasc. Drug Rev., 1996, 14(1), 1-16.
Wellington, K.; Scott, L.J. Azelnidipine. Drugs, 2003, 63(23), 2613-2621.
Malhotra, H.S.; Plosker, G.L. Barnidipine. Drugs, 2001, 61(7), 989-996.
Yao, K.; Nagashima, K.; Miki, H. New drugs and recent techniques pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel. J. Pharmacol. Sci., 2006, 261, 243-261.
Buchiya, F.V.; Jain, V.; Raj, H. A reviewα : analytical methods for determination of cilnidipine in biological fluid and pharmaceutical dosage forms. Pharmatutor, 2014, 2(11), 22-29.
Keating, G.M. Clevidipine: A review of its use for managing blood pressure in perioperative and intensive care settings. Drugs, 2014, 74, 1947-1960.
Kastron, V.V.; Vitolin, R.O.; Dubur, G.Y. Synthesis and pharmacological activity of 1,4-dihydropyridine. Translated from Khimiko-farmatsevticheskii Zhurnal, 1991, 24(6), 14-21.
Vega, J.A.; Sabbatini, M.; Del, M.E.; Amenta, F. Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of neurofilament protein immunoreactivity in the cerebellar cortex of aged rats. Mech. Ageing Dev., 1994, 75, 169-177.
Amenta, F.; Ferrantea, F.; Mancini, M.; Sabbatinia, M.; Vegab, A.; Zaccheoc, D. Effect of long term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats. Mech. Ageing Dev., 1995, 78, 27-37.
Masuda, Y.; Tanaka, S. Efonidipine Hydrochloride: A new calcium antagonist. cardiovasc. Drug Rev, 1994, 12(2), 123-135.
Kuhn, A.; Carlsson, J.; Miketic, S.; Tebbe, U. Hemodynamic and antiischemic effects of intravenous elgodipine, a new dihydropyridine calcium channel blocker, in patients with chronic stable angina. Cardiovasc. Drugs Ther., 1995, 9, 595-600.
Mannhold, R.; Jablonkaz, B.; Voigtl, W.; Schgnafinger, K. Calcium- and calmodulin-antagonism of elnadipine derivatives: Comparative SAR. Eur. J. Med. Chem., 1992, 27, 229-235.
Prisant, M.; Bottini, B.; Dipiro, J.T. Novel drug-delivery systems for hypertension. The Am. J. Med., 1992, 93, 2A-45S-2A-55S.
Leonetti, G.; Gradnik, R.; Terzoli, L.; Fruscio, M.; Rupoli, L.; Zanchetti, A. Felodipine a new vasodilating drug: Blood pressure, cardiac, renal and humoral effects in hypertensive patients. J. Cardiovasc. Pharmacol., 1984, 6, 392-398.
Kritchevsky, D.; Tepper, S.A.; Klurfeld, D.M. Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits. Atheroscler, 1988, 69, 89-92.
Alajarin, R.; Vaquero, J.J.; Alvarez-builla, J.; Pastor, M.; Sunkel, C.; Casa-juana, M.F.; Priego, J.; Statkow, P.R.; Sanz-Aparicio, J.; Fonsecall, I. Synthesis, structure, and pharmacological evaluation of the stereoisomers of furnidipine. J. Med. Chem., 1995, 38(15), 2830-2841.
Krzemi, T.F.; Grzyb, J.; Porc, M.P.; Chatterjee, S.S. Anti-arrhythmic and cardio-protective effects of furnidipine in a rat model: A dose response study. Cardiovasc. Drug Rev., 2006, 549(1-3), 91-97.
Yamada, S.; Kimura, R. Pharmacodynamics and pharmacokinetics of iganidipine. Cardiovasc. Drug Rev., 1996, 14(3), 213-230.
Brogden, R.N.; Sorkin, E.M. Mild to moderate hypertension isradipine. Drugs, 1995, 49(4), 618-649.
Mccormack, P.L.; Wagstaff, A.J.; Meredith, P.A.; Infirmary, W. Lacidipine a review of its use in the management of hypertension. Drugs, 2003, 63(21), 2327-2356.
Lee, C.R.; Bryson, H.M. Lacidipine: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of hypertension. Drugs, 1994, 48(2), 274-296.
Mcclellan, K.J.; Jarvis, B. Lercanidipine review of its use in hypertension. Drugs, 2000, 60(5), 1123-1140.
Bang, L.M.; Chapman, T.M.; Goa, K.L. Lercanidipine a review of its efficacy in the management of hypertension. Drugs, 2003, 63(22), 2449-2472.
Dalal, J.; Mohan, J.C.; Iyengar, S.S.; Hiremath, J. Sathyamurthy, I. Bansal, S. Kahali D Dasbiswas A. S-amlodipine: An isomer with difference - time to shift from racemic amlodipine. Int. J. Hypertens., 2018, 2018(1999), 1-14.
Cheer, S.M.; Clellan, K.M. Manidipine: A review of its use in hypertension. Drugs, 2001, 61(12), 1777-1799.
Roca-cusachs, A.; Triposkiadis, F. Antihypertensive effect of manidipine. Drugs, 2005, 65, 2-, 11-19.
Mckeage, K.; Scott, L.J. Manidipine a review of its use in the management of hypertension. Drugs, 2004, 64(17), 1923-1940.
Sorkin, E.M.; Clissold, S.P. Nicardipine a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in the treatment of angina pectoris, hypertension and related cardiovascular disorders nicardipine. Drugs, 1987, 345, 296-345.
Frampton, J.E.; Faulds, D. Nicardipine a review of its pharmacology and therapeutic efficacy in older patients. Drugs Aging, 1993, 3(2), 165-187.
Michael, J.; Groshong, T.; Tobias, J.D. Nicardipine for hypertensive emergencies in children with renal disease. Pediatr. Nephrol., 1998, 12, 40-42.
Dollery, C.T.; Murphy, M.B.; Scriven, A.J.I. Role of nifedipine in treatment of hypertension. Br. Med. J., 1983, 287, 257-259.
Macgregor, G.A. Nifedipine and hypertensionα : Roles of vasodilation and sodium balance. Cardiovasc. Drugs Ther., 1989, 3, 295-301.
Brennan, F.; Flanagan, M.; Blake, S.; Cannon, P. Nifedipine in the treatment of hypertension. Eur. J. Clin. Pharmacol., 1983, 25, 7-9.
Romanin, C.; Seyd, K.; Glossmann, H.; Schindler, H. The dihydropyridine niguldipine inhibits T-type Ca2+ currents in atrial myocytes. Eur. J. Physiol., 1992, 420(3-4), 410-412.
Kreiner, G.; Roman, A.; Zelek-molik, A.; Kowalska, M.; Nalepa, I. Lack of α 1A -adrenergic receptor-mediated antidepressant-like effects of S-(+)- niguldipine and B8805-88033 in the forced swim test. Behav. Pharmacol., 2016, 27(4), 397-401.
Ishida, S.; Koto, T.; Nagai, N.; Oike, Y. Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular infl ammation in endotoxin-induced uveitis. Jpn. J. Ophthalmol., 2010, 54(6), 594-601.
Brogden, R.N.; Mctavish, D. Nilvadipine a review of its pharmacodynamic and pharmacokinetic properties, therapeutic use in hypertension and potential in cerebrovascular disease and angina. Drugs Aging, 1995, 6(2), 150-171.
Hanyu, H.; Hirao, K.; Shimizu, S.; Sato, T.; Kiuchi, A.; Iwamoto, T. Nilvadipine prevents cognitive decline of patients with mild cognitive impairment. Int. J. Geriatr. Psychiat, 2007, 22(12), 1264-1266.
Langley, M.S.; Sorkin, E.M. Nimodipine a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cerebrovascular disease. Drugs, 1989, 37(5), 669-699.
Muck, W.; Ahr, G.; Kuhlmann, J. Nimodipine potential for drug-drug interactions in the elderly. Drugs Aging, 1995, 6(3), 229-242.
Goa, K.L.; Sorkin, E.M. Nitrendipine a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. Drugs, 1987, 155, 123-155.
Byyny, R.L.; Loverde, M.; Mitchell, W.; Denver, P.D. Treatment of hypertension in the elderly with a new calcium channel blocking drug, nitrendipine. Am. J. Med., 1989, 86(1), 49-55.
Knorr, A. The pharmacology of nisoldipine. Cardiovasc. Drugs Ther., 1987, 1(4), 393-402.
Fodor, J.G.; Nisoldipine, C.C. Efficacy and tolerability in hypertension and ischemic heart disease. Cardiovasc. Drugs Ther., 1997, 10(3), 873-879.
Galan, L.; Talavera, K.; Vassort, G.; Alvarez, J.L. Characteristics of Ca 2 channel blockade by oxodipine and elgodipine in rat cardiomyocytes. Eur. J. Pharmacol., 1998, 357, 93-105.
Karpova, M.N.; Antonikov, I.M.; Pankov, O.Y.; Glebov, R.N. Organic calcium antagonists verapamil and riodipine prevent elevation of free calcium level in rat brain synaptosomes during metrazol kindling. Bull. Exp. Biol. Med., 1992, 114(9), 252-254.
Tirzite, A.J.; Tirzite, G.D.; Dubur, G.J. Effect of nifedipine and riodipine on biochemical processes in intact erythrocytes. Bull. Exp. Biol. Med., 1991, 110(4), 1358-1360.
Karpova, M.N.; Abrosimov, I.Y.; Kryzhanovskii, G.N. Effectiveness of combined application of calcium blockers and antiepileptic drugs. Bull. Exp. Biol. Med., 1997, 124(7), 1-4.
Karpova, M.N.; Kryzhanovskii, G.N.; Abrosimov, I.Y. Antiseizure and neurotoxic effects of various combinations of phenobarbital, diazepam, sodium valproate and 1, 4-dihydropyridine riodipin. Bull. Exp. Biol. Med., 1994, 118(7), 692-695.
Kim, C.S.; Matsumori, A.; Goldberg, L.; Doye, A.A.; Mccoy, Q.; Gwathmey, J.K. Effects of pranidipine, a calcium channel antagonist, in an avian model of heart failure. Cardiovasc. Drugs Ther., 1999, 13, 455-463.
Rosenthal, J.; Hittel, N.; Stumpe, K.O. Pranidipine, a novel calcium antagonist, once daily, for the treatment of hypertension: A multicenter, double-blind, placebo-controlled dose-finding study. Cardiovasc. Drugs Ther., 1996, 10(1), 59-66.
Galletti, F. Luchowski, E. Triggle, D.J. 1,4-Dihydropyridine activators in the tiamdipine series. Eur. J. Pharmacol., 1990, 185, 157-161.
Galletti, I.F.; Zheng, W.; Gopalakrishnan, M. Rutledge, Triggle, D.J. Interaction of analogs of the 1,4 dihydropyridine tiamdipine in cardiac and smooth muscle. Eur. J. Pharmacol., 1991, 195, 125-129.

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Year: 2019
Page: [1219 - 1254]
Pages: 36
DOI: 10.2174/1389557519666190425184749
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