Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity

Jorda, Radek; Havlíček, Libor; McNae, I. W.; Walkinshaw, M. D.; Voller, Jiří; Šturc, Antonín; Navrátilová, Jana; Kuzma, Marek; Mistrik, M.; Bártek, J.; Strnad, Miroslav; Kryštof, Vladimír

doi:https://dx.doi.org/10.1021/jm200064p

Number of the records: 1

Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity

1.

SYSNO ASEP	0368592
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity
Author(s)	Jorda, Radek (UEB-Q)_{ORCID, RID} Havlíček, Libor (UEB-Q)_{RID, ORCID} McNae, I. W. (GB) Walkinshaw, M. D. (GB) Voller, Jiří (UEB-Q)_{RID, ORCID} Šturc, Antonín (UEB-Q) Navrátilová, Jana (UEB-Q) Kuzma, Marek (MBU-M)_{ORCID, RID} Mistrik, M. (CZ) Bártek, J. (CZ) Strnad, Miroslav (UEB-Q)_{RID, ORCID} Kryštof, Vladimír (UEB-Q)_{RID, ORCID}
Number of authors	12
Source Title	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 54, č. 8 (2011), s. 2980-2993
Number of pages	14 s.
Language	eng - English
Country	US - United States
Keywords	STRUCTURE-GUIDED DESIGN ; DNA-END RESECTION ; DOWN-REGULATION ; R-ROSCOVITINE ; CELL-CYCLE
Subject RIV	ED - Physiology
R&D Projects	GA301/02/0475 GA ČR - Czech Science Foundation (CSF)
	GA301/08/1649 GA ČR - Czech Science Foundation (CSF)
	ED0007/01/01 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
CEZ	AV0Z50380511 - UEB-Q (2005-2011)
	AV0Z50200510 - MBU-M (2005-2011)
UT WOS	000289697800033
DOI	10.1021/jm200064p
Annotation	Inhibition of cyclin-dependent kinases (CDKs) with. small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)-propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine.
Workplace	Institute of Experimental Botany
Contact	David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
Year of Publishing	2012

Number of the records: 1