{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:54:39Z","timestamp":1778820879920,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Dihydropyridine calcium channel blockers have some disadvantages such as light sensitivity and relatively short plasma half-lives. Stability of dihydropyrimidines analogues could be of advantage, yet they remain less well characterized. We aimed to test four newly synthesized Biginelli-type dihydropyrimidines for their calcium channel blocking activity on rat isolated aorta.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Dihydropyrimidines (compounds A\u2013D) were prepared by the Biginelli-like three-component condensation of benzaldehydes with urea\/thiourea and dimethyl or diethyl acetone-1,3-dicarboxylate, and their physicochemical properties and effects on depolarization-induced and noradrenaline-induced contractions of rat isolated aorta were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Dihydropyrimidines A and C blocked KCl-induced contraction only weakly (\u2212log(IC50) = 5.03 and 3.73, respectively), while dihydropyrimidine D (\u2212log(IC50) = 7.03) was almost as potent as nifedipine (\u2212log(IC50) = 8.14). Washout experiments revealed that dihydropyrimidine D may bind strongly to the L-type calcium channel or remains bound to membrane. All tested dihydropyrimidines only marginally inhibited noradrenaline-induced contractions of rat isolated aorta (20% reduction of noradrenaline Emax), indicating a more selective action on L-type calcium channel than nifedipine with 75% inhibition of noradrenaline Emax at 10\u22124m nifedipine).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compounds A and, particularly, D are potent calcium channel blockers in vitro, with a better selectivity in inhibiting depolarization-induced arterial smooth muscle contraction than nifedipine.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/j.2042-7158.2012.01466.x","type":"journal-article","created":{"date-parts":[[2012,2,8]],"date-time":"2012-02-08T09:49:30Z","timestamp":1328694570000},"page":"735-741","source":"Crossref","is-referenced-by-count":2,"title":["Selective inhibitory action of Biginelli-type dihydropyrimidines on depolarization-induced arterial smooth muscle contraction"],"prefix":"10.1093","volume":"64","author":[{"given":"Hana","family":"Cernecka","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Comenius University , Bratislava,","place":["Slovakia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Veizerova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University , Bratislava,","place":["Slovakia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Mensikova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Comenius University , Bratislava,","place":["Slovakia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Svetlik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University , Bratislava,","place":["Slovakia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Krenek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Comenius University , Bratislava,","place":["Slovakia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,5,1]]},"reference":[{"key":"2024103013320774400_cit1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-0348-7859-3","volume-title":"Calcium Channel Blockers","author":"Godfraind","year":"2004"},{"key":"2024103013320774400_cit2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0014-827X(99)00076-2","article-title":"Synthesis and X-ray crystal structure of the calcium channel antagonist: dimetyl 1,4-dihydro-2,6-dimetyl-4-[4\u2032-(4H-4-oxo-1-benzopyran-2-yl)phenyl]-3,5-pyridine dicarboxylate","volume":"54","author":"Tun\u00e7bilek","year":"1999","journal-title":"Farmaco"},{"key":"2024103013320774400_cit3","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1021\/jm00112a030","article-title":"Active conformation of 1,4-dihydropyridine calcium entry blockers. Effect of size of 2-aryl substituent on rotameric equilibria and receptor binding","volume":"34","author":"Rovnyak","year":"1991","journal-title":"J Med Chem"},{"key":"2024103013320774400_cit4","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S0006-3495(84)84233-2","article-title":"Photoalteration of calcium channel blockade in the cardiac Purkinje fiber","volume":"45","author":"Sanguinetti","year":"1984","journal-title":"Biophys J"},{"key":"2024103013320774400_cit5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/S0014-827X(00)00004-5","article-title":"UV derivate spectrophotometric study of the photochemical degradation on nisoldipine","volume":"55","author":"Marinkovic","year":"2000","journal-title":"Farmaco"},{"key":"2024103013320774400_cit6","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.talanta.2009.06.009","article-title":"Prediction of photosensitivity of 1,4-dihydropyridine antihypertensive by quantitative structure-property relationship","volume":"79","author":"Ioele","year":"2009","journal-title":"Talanta"},{"key":"2024103013320774400_cit7","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1021\/jm00130a029","article-title":"Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity","volume":"32","author":"Cho","year":"1989","journal-title":"J Med Chem"},{"key":"2024103013320774400_cit8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0731-7085(03)00194-8","article-title":"Photochemical degradation of solid-state nisoldipine monitored by HPLC","volume":"32","author":"Marinkovic","year":"2003","journal-title":"J Pharm Biomed"},{"key":"2024103013320774400_cit9","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S0731-7085(97)00122-2","article-title":"Electrochemical study of nisoldipine: analytical application in pharmaceutical forms and photodegradation","volume":"16","author":"Alvarez-Lueje","year":"1998","journal-title":"J Pharm Biomed"},{"key":"2024103013320774400_cit10","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1139\/y92-148","article-title":"Inactivation of cytochrome P450 and inhibition of ferrochelatase by analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine with 4-nonyl and 4-dodecyl substituents","volume":"70","author":"McCluskey","year":"1992","journal-title":"Can J Physiol Pharmacol"},{"key":"2024103013320774400_cit11","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1111\/j.2042-7158.1972.tb08919.x","article-title":"Dihydropyridines with potent hypotensive activity prepared by the Hantzsch reaction","volume":"24","author":"Love","year":"1972","journal-title":"J Pharm Pharmacol"},{"key":"2024103013320774400_cit12","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0968-0896(00)82188-4","article-title":"Imidazo[1,5-\u03b1]pyrimidine and benzol[4,5]imidazo[1,2-\u03b1]pyrimidine derivates as calcium antagonists","volume":"2","author":"Alajarin","year":"1994","journal-title":"Bioorg Med Chem"},{"key":"2024103013320774400_cit13","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S0223-5234(00)01189-2","article-title":"Biologically active dihydropyridines of the Biginelli-type \u2013 a literature survey","volume":"35","author":"Kappe","year":"2000","journal-title":"Eur J Med Chem"},{"key":"2024103013320774400_cit14","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/0016-0032(45)90548-5","article-title":"Studies on the chemotherapy of experimental virus infections; the effect of certain organic arsenicals on the course of experimental murine poliomyelitis","volume":"240","author":"McKinstry","year":"1945","journal-title":"J Franklin Inst"},{"key":"2024103013320774400_cit15","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1074-5521(00)00101-0","article-title":"Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis","volume":"7","author":"Haggarty","year":"2000","journal-title":"Chem Biol"},{"key":"2024103013320774400_cit16","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/S0014-827X(99)00068-3","article-title":"Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivates","volume":"54","author":"Tozkoparan","year":"1999","journal-title":"Farmaco"},{"key":"2024103013320774400_cit17","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejphar.2006.04.043","article-title":"Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety","volume":"540","author":"Basso","year":"2006","journal-title":"Eur J Pharmacol"},{"key":"2024103013320774400_cit18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.bmcl.2007.11.027","article-title":"Chemical modulators of heat shock protein 70 (Hsp 70) by sequential, microwave-accelerated reactions on solid phase","volume":"18","author":"Wisen","year":"2007","journal-title":"Bioorg Med Chem Lett"},{"key":"2024103013320774400_cit19","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1126\/science.1077215","article-title":"Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids","volume":"299","author":"Deres","year":"2003","journal-title":"Science"},{"key":"2024103013320774400_cit20","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1016\/j.bmcl.2006.03.102","article-title":"Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4","volume":"16","author":"Blackburn","year":"2006","journal-title":"Bioorg Med Chem Lett"},{"key":"2024103013320774400_cit21","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1016\/j.tetlet.2008.03.136","article-title":"Biginelli-like reaction with dialkyl acetone-1,3-dicarboxylates: a remarkable case of steric control","volume":"49","author":"Svetlik","year":"2008","journal-title":"Tetrahedron Lett"},{"key":"2024103013320774400_cit22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-1-4419-9254-3_2","article-title":"Pharmacology of Cav1 (L-Type) channels","volume-title":"Calcium Channel Pharmacology","author":"Triggle","year":"2004"},{"key":"2024103013320774400_cit23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1023\/B:MODI.0000047521.70687.52","article-title":"Quantitative structure-activity relationship studies on some series of calcium channel blockers","volume":"8","author":"Gupta","year":"2004","journal-title":"Mol Divers"},{"key":"2024103013320774400_cit24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00005344-199508000-00015","article-title":"Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,946","volume":"26","author":"Grover","year":"1995","journal-title":"J Cardiovasc Pharmacol"},{"key":"2024103013320774400_cit25","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1021\/jm00171a044","article-title":"dihydropyrimidine calcium channel blockers. 2. 3-substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines","volume":"33","author":"Atwal","year":"1990","journal-title":"J Med Chem"},{"key":"2024103013320774400_cit26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/30100001","article-title":"4-aryldihydropyrimidines via the Biginelli condensation: aza-analogs of nifedipine-type calcium channel modulators","volume":"3","author":"Kappe","year":"1998","journal-title":"Molecules"},{"key":"2024103013320774400_cit27","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1016\/S0040-4020(97)00022-7","article-title":"Conformational analysis of 4aryl-dihydropyrimidine calcium channel modulators. A comparison of ab initio, semiempirical and X-ray crystallographic studies","volume":"53","author":"Kappe","year":"1997","journal-title":"Tetrahedron"},{"key":"2024103013320774400_cit28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1476-5381.1988.tb16558.x","article-title":"A comparison of the effects of the calcium entry blockers, verapamil, diltiazem and flunarizine against contractions of the rat isolated aorta and portal vein","volume":"95","author":"Marriott","year":"1988","journal-title":"Br J Pharmacol"},{"key":"2024103013320774400_cit29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0163-7258(94)90033-7","article-title":"Calcium antagonists and vasodilatation","volume":"64","author":"Godfraind","year":"1994","journal-title":"Pharmacol Ther"},{"key":"2024103013320774400_cit30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1042\/cs068s065","article-title":"Role of endothelium in the contractile response of rat aorta to \u03b1-adrenoceptor agonists","volume":"68","author":"Godfraind","year":"1985","journal-title":"Clin Sci"},{"key":"2024103013320774400_cit31","first-page":"350","article-title":"The place of the calcium antagonist verapamil in antihypertensive therapy","volume":"4","author":"Buhler","year":"1982","journal-title":"J Cardiovasc Pharmacol"},{"key":"2024103013320774400_cit32","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0960-894X(01)80810-6","article-title":"Dihydropyrimidine calcium channel blockers 51: bicyclic dihydropyrimidines as potent mimics of dihydropyridines","volume":"1","author":"Atwal","year":"1991","journal-title":"Bioorg Med Chem Lett"},{"key":"2024103013320774400_cit33","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/0306-3623(95)02145-0","article-title":"Pharmacological activity of the new calcium antagonists, lacidipine, on isolated preparations","volume":"27","author":"Raddino","year":"1996","journal-title":"Gen Pharmacol"},{"key":"2024103013320774400_cit34","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1016\/j.ejmech.2009.02.021","article-title":"Synthesis and pharmacological investigation of 3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylates","volume":"44","author":"Chikhale","year":"2009","journal-title":"Eur J Med Chem"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.2042-7158.2012.01466.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/64\/5\/735\/60238526\/j.2042-7158.2012.01466.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/64\/5\/735\/60238526\/j.2042-7158.2012.01466.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T19:06:39Z","timestamp":1730315199000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/64\/5\/735\/6135316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,1]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2012,5,1]]},"published-print":{"date-parts":[[2012,5,1]]}},"URL":"https:\/\/doi.org\/10.1111\/j.2042-7158.2012.01466.x","relation":{},"ISSN":["2042-7158","0022-3573"],"issn-type":[{"value":"2042-7158","type":"electronic"},{"value":"0022-3573","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,5]]},"published":{"date-parts":[[2012,5,1]]}}}