24068-63-1Relevant academic research and scientific papers
3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models
Jorda, Radek,Havlí?ek, Libor,?turc, Antonín,Tu?ková, Diana,Daumová, Lenka,Alam, Mahmudul,?kerlová, Jana,Nekardová, Michaela,Pe?ina, Miroslav,Pospí?il, Tomá?,?iroká, Jitka,Urbánek, Lubor,Pachl, Petr,?ezá?ová, Pavlína,Strnad, Miroslav,Klener, Pavel,Kry?tof, Vladimír
, p. 4606 - 4623 (2019/05/06)
Cyclin-dependent kinases are therapeutic targets frequently deregulated in various cancers. By convenient alkylation of the 5-sulfanyl group, we synthesized 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with various substitutions at position 5 with potent antiproliferative activity in non-Hodgkin lymphoma cell lines. The most potent derivative 4.35 also displayed activities across more than 60 cancer cell lines. The kinase profiling confirmed high selectivity of 4.35 toward cyclin-dependent kinases (CDKs) 2, 5, and 9, and the cocrystal with CDK2/cyclin A2 revealed its binding in the active site. Cultured lymphoma cell lines treated with 4.35 showed dephosphorylation of CDK substrates, cleavage of PARP-1, downregulation of XIAP and MCL-1, and activation of caspases, which collectively confirmed ongoing apoptosis. Moreover, 4.35 demonstrated significant activity in various cell line xenograft and patient-derived xenograft mouse models in vivo both as a monotherapy and as a combination therapy with the BCL2-targeting venetoclax. These findings support further studies of combinatorial treatment based on CDK inhibitors.
5-ALKYLTHIO-7-[(4-ARYLBENZYL)AMINO]-1(2)H-PYRAZOLO[4,3-D]PYRIMIDINES FOR TREATMENT OF LYMPHOMA
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Page/Page column 17, (2019/08/26)
The present invention relates to 5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidine derivatives of formula I which are effective inhibitors of kinases and exhibit strong antiproliferative and proapoptotic properties on lymphoma cells. This invention further relates to use of said derivatives in the treatment of blood hyperproliferative diseases, such as Non-Hodgkin lymphomas.
Asymmetric alkyl-alkyl cross-couplings of unactivated secondary alkyl electrophiles: Stereoconvergent suzuki reactions of racemic acylated halohydrins
Owston, Nathan A.,Fu, Gregory C.
supporting information; experimental part, p. 11908 - 11909 (2010/11/04)
A method for asymmetric alkyl-alkyl Suzuki reactions of unactivated secondary alkyl electrophiles, specifically, cross-couplings of racemic acylated halohydrins with alkylborane reagents, has been developed. A range of protected bromohydrins, as well as a protected chlorohydrin and a homologated bromohydrin, are coupled in good ee by a catalyst derived from commercially available components.
Catalytic Asymmetric Cyclization of Some Bromohydrins with Chiral Cobalt Complex
Takeichi, Tsutomu,Takakura, Teruo,Ishimori, Michihiro,Tsuruta, Teiji
, p. 603 - 605 (2007/10/02)
Asymmetric cyclization of a variety of bromohydrins with base was examined in the presence of an optically active cobalt(salen) type complex.Optically active oxiranes of modest optical purities were obtained. erythro-3-Bromo-2-butanol and threo-3-bromo-2-butanol were cyclized similarly, and only trans-2,3-dimethyloxirane and cis-2,3-dimethyloxirane were obtained, respectively, indicating that the cyclization of bromohydrin proceeds by complete SN2 type reaction.
CONVERSION OF EPOXIDES TO BROMOHYDRINS BY B-BROMOBIS(DIMETHYLAMINO)BORANE
Bell, Thomas W.,Ciaccio, James A.
, p. 827 - 830 (2007/10/02)
Reaction of the title reagent with 1-alkene oxides regioselectively yields the corresponding 1-bromo-2-alkanols, while the more substituted bromide predominates in the cases of styrene oxide and 1-methylcyclohexene oxide.
