Title:
NOVEL ANTI-CANCER THIOPHENE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2013/190137
Kind Code:
A3
Abstract:
The present invention relates to compounds having cytostatic activity against tumor cells. The compounds of the invention are of formula (I), or derivatives hereof, wherein R0, R1, R2, A, and X have defined meanings as described in claim 1.
Inventors:
BALZARINI JAN (BE)
DEHAEN WIM (BE)
THOMAS JOICE (BE)
LIEKENS SANDRA (BE)
ROMAGNOLI ROMEO (IT)
BARALDI PIER GIOVANNI (IT)
DEHAEN WIM (BE)
THOMAS JOICE (BE)
LIEKENS SANDRA (BE)
ROMAGNOLI ROMEO (IT)
BARALDI PIER GIOVANNI (IT)
Application Number:
PCT/EP2013/063082
Publication Date:
February 27, 2014
Filing Date:
June 21, 2013
Export Citation:
Assignee:
UNIV LEUVEN KATH (BE)
UNIV FERRARA (IT)
UNIV FERRARA (IT)
International Classes:
A61K31/559; C07D333/36; A61P35/00; C07D333/38; C07D401/12; C07D405/12; C07D409/12
Domestic Patent References:
| WO2003104218A1 | 2003-12-18 | |||
| WO2005033102A2 | 2005-04-14 | |||
| WO2009109983A1 | 2009-09-11 |
Other References:
ROMEO ROMAGNOLI ET AL: "Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 21, no. 9, 1 May 2011 (2011-05-01), pages 2746 - 2751, XP055075559, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2010.11.083
ROSOWSKY: "2,4-Diaminothieno [ 2,3d]pyrimidines as Antifolates and Antimalarials. 3. Synthesis of 5,6-Disubstituted Derivatives and Related Tetracyclic Analogsf", J. MED. CHEM., 1 January 1973 (1973-01-01), XP055075605, Retrieved from the Internet [retrieved on 20130819]
ROSOWSKY A: "2,4-Diaminothieno[2,3-d]pyrimidine Analogues of Trimetrexate and Piritrexim as Potential Inhibitors of Pneumocystis carinii and Toxoplasma gondii Dihydrofolate Reductase", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 36, 1 January 1993 (1993-01-01), pages 3103 - 3112, XP002358211, ISSN: 0022-2623, DOI: 10.1021/JM00073A009
XIAN-GUI HUANG ET AL: "A facile and practical one-pot synthesis of multisubstituted 2-aminothiophenes via imidazole-catalyzed Gewald reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 67, no. 34, 21 June 2011 (2011-06-21), pages 6202 - 6205, XP028381863, ISSN: 0040-4020, [retrieved on 20110625], DOI: 10.1016/J.TET.2011.06.061
DONKOR I O ET AL: "Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 38, no. 6, 1 June 2003 (2003-06-01), pages 605 - 611, XP004433580, ISSN: 0223-5234, DOI: 10.1016/S0223-5234(03)00101-6
YIJUN DENG ET AL: "Synthesis and Biological Activity of a Novel Series of 6-Substituted Thieno[2,3- d ]pyrimidine Antifolate Inhibitors of Purine Biosynthesis with Selectivity for High Affinity Folate Receptors over the Reduced Folate Carrier and Proton-Coupled Folate Transporter for Cellular Entry +", JOURNAL OF MEDICINAL CHEMISTRY, vol. 52, no. 9, 14 May 2009 (2009-05-14), pages 2940 - 2951, XP055067210, ISSN: 0022-2623, DOI: 10.1021/jm8011323
KAN WANG ET AL: "Cyanoacetamide MCR (III): Three-Component Gewald Reactions Revisited", JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 12, no. 1, 11 January 2010 (2010-01-11), pages 111 - 118, XP055075595, ISSN: 1520-4766, DOI: 10.1021/cc9001586
ROSOWSKY: "2,4-Diaminothieno [ 2,3d]pyrimidines as Antifolates and Antimalarials. 3. Synthesis of 5,6-Disubstituted Derivatives and Related Tetracyclic Analogsf", J. MED. CHEM., 1 January 1973 (1973-01-01), XP055075605, Retrieved from the Internet
ROSOWSKY A: "2,4-Diaminothieno[2,3-d]pyrimidine Analogues of Trimetrexate and Piritrexim as Potential Inhibitors of Pneumocystis carinii and Toxoplasma gondii Dihydrofolate Reductase", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 36, 1 January 1993 (1993-01-01), pages 3103 - 3112, XP002358211, ISSN: 0022-2623, DOI: 10.1021/JM00073A009
XIAN-GUI HUANG ET AL: "A facile and practical one-pot synthesis of multisubstituted 2-aminothiophenes via imidazole-catalyzed Gewald reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 67, no. 34, 21 June 2011 (2011-06-21), pages 6202 - 6205, XP028381863, ISSN: 0040-4020, [retrieved on 20110625], DOI: 10.1016/J.TET.2011.06.061
DONKOR I O ET AL: "Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 38, no. 6, 1 June 2003 (2003-06-01), pages 605 - 611, XP004433580, ISSN: 0223-5234, DOI: 10.1016/S0223-5234(03)00101-6
YIJUN DENG ET AL: "Synthesis and Biological Activity of a Novel Series of 6-Substituted Thieno[2,3- d ]pyrimidine Antifolate Inhibitors of Purine Biosynthesis with Selectivity for High Affinity Folate Receptors over the Reduced Folate Carrier and Proton-Coupled Folate Transporter for Cellular Entry +", JOURNAL OF MEDICINAL CHEMISTRY, vol. 52, no. 9, 14 May 2009 (2009-05-14), pages 2940 - 2951, XP055067210, ISSN: 0022-2623, DOI: 10.1021/jm8011323
KAN WANG ET AL: "Cyanoacetamide MCR (III): Three-Component Gewald Reactions Revisited", JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 12, no. 1, 11 January 2010 (2010-01-11), pages 111 - 118, XP055075595, ISSN: 1520-4766, DOI: 10.1021/cc9001586
Attorney, Agent or Firm:
BOUNAGA, Sakina et al. (E. Gevaertdreef 10a, Sint-Martens-Latem, BE)
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