Univerzita Palackeho V Olomouci

Ustav Experimentalni Botaniky Av Cr, V.v.i.

Institute of Experimental Botany of the Academy of Sciences of the Czech Republic

Institute of Experimental Botany

Biopatterns, S.r.o.

Institute of Experimental Botany Ascr

Palacky University Olomouc

Bioapex, S.r.o.

Libor Havlicek

Miroslav Strnad

Vladimir Krystof

Radek Jorda

Karel Dolezal

Marian Hajduch

Marek Zatloukal

Antonin Sturc

Borivoj Vojtesek

Igor Popa

René Lenobel

Eva Reznickova

Rene Lenobel

Stefan Zahler

Daniela Moravcová

Kveta Fuksova

Angelika Vollmar

Tomas Pospisil

Ladislava Vymetalova

5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidine derivatives of formula I that are effective inhibitors of kinases and exhibit strong antiproliferative and proapoptotic properties on lymphoma cells. Derivatives in the treatment of blood hyperproliferative diseases, such as Non-Hodgkin lymphomas are also disclosed.

5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidines for treatment of lymphoma

5-substituted-7-[4-(2-pyridyl)phenylmethylamino]-3-isopropylpyrazolo[4,3-d]pyrimidines are potent inhibitors of protein kinases, especially cyclin-dependent kinases such as CDK2 and CDK5, and display antileukemic, pro-apoptotic, antiangiogenic and anticancer activities. The invention also relates to processes for their preparation, to pharmaceutical compositions and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation, apoptosis, angiogenesis and inflammation, such as leukemia and metastatic solid cancer.

5-substituted 7- [4-(2-pyridyl)phenylmethylamino] -3-isopropylpyrazolo4,3-D]pyrimidine derivatives, use thereof as medicaments, and pharmaceutical compositions

The invention relates to new substituted 6-(2-aminobenzylamino)purines, represented by the general formula I, which can be used in CDK inhibition, in particular, in the treatment of viral infections and diseases involving cell proliferation. The invention further includes pharmaceutical preparations containing substituted 6-(2-aminobenzylamino)purines.

Substituted 6-(2-aminobenzylamino)purine derivatives, their use as medicaments and preparations containing these compounds

The invention relates to substituted 6-(2-hydroxybenzylamino)purines of general formula I, to their activity as cyclin-dependent kinases 2, 5, 7 and 9 inhibitors and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation or inflammation. The invention further includes pharmaceutical compositions containing the substituted 6-(2-hydroxybenzylamino)purines. 

Substituted 6-(2-hydroxybenzylamino)purine derivatives, their use as medicaments and compositions containing these derivatives

The present invention relates to a compound of formula I, or a pharmaceutically acceptable acid salt thereof.  The invention further relates to the use of such compounds in the treatment of hyperproliferative skin disorders, viral infections, cancer, rheumatoid arthritis, lupus, type I diabetes, multiple sclerosis, restenosis, polycystic kidney disease, graft rejection, graft versus host disease and gout, or for psoriasis, parasitoses such as those caused by fungi or protists, or Alzheimer's disease. Further aspects of the invention relate to the use of such compounds in the inhibition of cell proliferation, in the induction of apoptosis, to modulate the activity of adrenergic and/or purinergic receptors or to suppress immunostimulation. The invention also relates to the use of 2,6,9-trisubstituted 8-azapurines in maintaining mammalian ooctyes at the germinal vesicle stage.

Substituted [1,2,3] triazolo[4,5-D]pyrimidines as cdk inhibitors

The invention relates to 3-, 5-, 7-trisubstituted pyrazolo[4,3-d]pyrimidines represented by the general formula I and pharmaceutically acceptable salts thereof, whereinR3 is an optionally substituted alkyl, cycloalkyl, cycloheteroalkyl, cycloalkyl alkyl, aryl or alkylaryl group;R5 is halogen, &#x2014;NHNH, &#x2014;NHOH, NHCONH, guanylo (NH&#x2014;C(NH)NH) an optionally substituted C-Calkyl, alkenyl, alkynyl, C-Ccycloalkyl, R(C-Ccycloalkyl), heterocyclyl, heteroalkyl, aryl, heteroaryl, arylalkylene, arylalkenylene, arylalkynylene, cycloheteroalkyl, cycloheteroalkyl alkyl, heteroarylalkylene, heteroarylalkenylene, heteroarylalkynylene group, the group &#x2014;C(O)&#x2014;R, &#x2014;C(O)NRR, &#x2014;SOR, or &#x2014;NHC(O)R, wherein Rand Rare an optionally substituted C-Calkyl, alkenyl, or alkynyl group, R, R, and Rare independently selected from the group consisting of H, optionally substituted C-Calkyl, alkenyl, or alkynyl group, and Ris a hydroxy, amino, alkoxy, alkylamino, optionally substituted C-Calkyl, alkenyl or alkynyl group; or the group &#x2014;X&#x2014;R, wherein X is &#x2014;NH&#x2014;, &#x2014;O&#x2014;, &#x2014;S&#x2014; or &#x2014;N(alkyl)- and R' is hydrogen, an optionally substituted C-Calkyl, alkenyl, alkynyl, C-Ccycloalkyl, Rf(C-Ccycloalkyl), aryl, heterocyclyl, hetero C-Calkyl, arylalkylene, arylalkenylene, arylalkynylene, heteroaryl, cycloheteroalkyl, cycloheteroalkyl alkyl, or heteroarylalkylene, heteroarylalkenylene, heteroarylalkynylene group, the group &#x2014;C(O)&#x2014;R, &#x2014;C(O)NRR, &#x2014;SOR, or &#x2014;NHC(O)R, wherein R, R, R, R, Rand Rhave the above meaning, andR7 is halogen, &#x2014;NHNH, NHOH, NHCONH, guanylo (NH&#x2014;C(NH)NH) or the group &#x2014;X&#x2014;R, wherein X has the above meaning and the meaning of Ris as defined for R.

Pyrazolo[4,3-d]pyrimidines, processes for their preparation and methods for therapy

The present invention is based on the method of treating a patient suffering from leukemia comprising administering a therapeutically effective amount of the compound 2-(&lsqb;(3-hydroxypropyl)amino&rsqb;-6-benzylamino)-9-isopropylpurine or a pharmaceutically acceptable salt thereof.

Cyclin dependent kinase inhibitor

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Prague, Czechia

Libor Havlicek