"Pyrazolo[4,3-d]pyrimidines as a new generation of anticytokinines and inhibitors of cyclin-dependent kinases"@en . " anticytokinines" . . . . . "B\u011Bhem \u0159e\u0161en\u00ED bylo p\u0159ipraveno 16 3,7-disubstituovan\u00FDch a 18 3,5,7-trisubstituovan\u00FDch pyrazolo[4,3-d]pyrimidin\u016F. V\u011Bt\u0161inou se jedn\u00E1 o \u00FA\u010Dinn\u00E9 inhibitory CDK nebo polymerizace tubulinu. Jedna z p\u0159ipraven\u00FDch l\u00E1tek vykazuje du\u00E1ln\u00ED \u00FA\u010Dinek na uveden\u00E9 c\u00EDle."@cs . " apoptosis" . . . "KJB4038301" . " pyrazolo[4" . . "1"^^ . "2014-02-12+01:00"^^ . "3-d]pyrimidines" . "Pyrazolo[4,3-d]pyrimidiny jako nov\u00E1 generace anticytokinin\u016F a inhibitor\u016F cyklin-dependentn\u00EDch kinas" . "cyclin-dependent kinases; apoptosis; anticytokinines; pyrazolo[4,3-d]pyrimidines; synthesis"@en . . "0"^^ . "2"^^ . "We found a new specific activity of pyrazolo[4,3-d]pyrimidines, viz. the ability to inhibit kinases of the cell division cycle (CDK1, CDK2, CDK4) and induce the apoptosis of tumor cell lines. In this project we want to study the structure and activity of pyrazolo[4,3-d]pyramidine derivatives. We propose to use the detailed knowledge (general and our own) of isomeric compounds purines (e.g. roscovitine, which is currently in phase II clinical testing - Cyclacel Ltd., UK). The aim of this project is to develop the methodology of preparation of pyrazolo[4,3-d]pyrimidines labelled by 3H or 14C. We want to label the most potent derivative by one of the above mentioned isotopes and to accomplish basic pharmacokinetic study and assess the mechanism of effect of these compounds on both molecular and cellular level."@en . "2"^^ . . . "2"^^ . . . . . "U skupiny 3,7-disubstituovan\u00FDch pyrazolo[4,3-d]pyrimidin\u016F (\u00FA\u010Dinn\u00E9 rostlinn\u00E9 anticytokininy) jsme objevili jejich novou specifickou aktivitu - schopnost inhibovat kinasy cyklu bun\u011B\u010Dn\u00E9ho d\u011Blen\u00ED (CDK1, CDK2, CDK4) a indukovat tak apopt\u00F3zu n\u00E1dorov\u00FDch bun\u011B\u010Dn\u00FDch lini\u00ED. V tomto projektu chceme studovat vztah struktury a aktivity deriv\u00E1t\u016F pyrazolo[4,3/d]pyrimidin\u016F. Pr\u00E1ce bude zalo\u017Eena na detailn\u00EDch znalostech (liter\u00E1rn\u00EDch i vlastn\u00EDch) izomern\u00EDch slou\u010Denin purin\u016F - nap\u0159. roscovitinu (v sou\u010Dasnosti je ve f\u00E1zi II klinick\u00E9ho zkou\u0161en\u00ED, Cyclacel Ltd., UK). \u00DAst\u0159edn\u00EDm c\u00EDlem pr\u00E1ce je nal\u00E9zt metodiku pro p\u0159\u00EDpravu t\u011Bchto slou\u010Denin ve zna\u010Den\u00E9 form\u011B (3H nebo 14C). Cht\u011Bli bychom ozna\u010Dit biologicky nejzaj\u00EDmav\u011Bj\u0161\u00ED deriv\u00E1t, prov\u00E9st z\u00E1kladn\u00ED farmakokinetickou studii a p\u0159edb\u011B\u017En\u011B stanovit mechanismus jeho \u00FA\u010Dinku na molekul\u00E1rn\u00ED a bun\u011B\u010Dn\u00E9 \u00FArovni." . . . "cyclin-dependent kinases" . . . . "http://www.isvav.cz/projectDetail.do?rowId=KJB4038301"^^ . "Series of 16 3,7-disubstituted and 18 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines have been prepared. Most of the derivatives inhibited activity of CDKs or tubulin polymerization. One of prepared compound exerts a dual specificity on both targets."@en . .