Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors

Rheault, Tara R.; Caferro, Thomas R.; Dickerson, Scott H.; Donaldson, Kelly H.; Gaul, Michael D.; Goetz, Aaron S.; Mullin, Robert J.; McDonald, Octerloney B.; Petrov, Kimberly G.; Rusnak, David W.; Shewchuk, Lisa M.; Spehar, Glenn; Truesdale, Anne T.; Vanderwall, Dana E.; Wood, Edgar R.; Uehling, David

doi:10.1016/j.bmcl.2008.12.011

Cited by 74 publications

(34 citation statements)

References 16 publications

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“…Tumour growth arrest by lapatinib was shown in human tumour xenografts [142], and the compound was approved for the treatment of breast cancer in 2007. Other groups have also investigated dual Erb-2/EGFR inhibitors [119,139].…”

Section: The Importance Of Determining Selectivitymentioning

confidence: 99%

Measuring and interpreting the selectivity of protein kinase inhibitors

2009

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Protein kinase inhibitors are a well-established class of clinically useful drugs, particularly for the treatment of cancer. Achieving inhibitor selectivity for particular protein kinases often remains a significant challenge in the development of new small molecules as drugs or as tools for chemical biology research. This review summarises the methodologies available for measuring kinase inhibitor selectivity, both in vitro and in cells. The interpretation of kinase inhibitor selectivity data is discussed, particularly with reference to the structural biology of the protein targets. Measurement and prediction of kinase inhibitor selectivity will be important for the development of new multi-targeted kinase inhibitors.

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Section: The Importance Of Determining Selectivitymentioning

confidence: 99%

Measuring and interpreting the selectivity of protein kinase inhibitors

2009

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“…-A solution of 15 in acetic anhydride (30 mL) was refl uxed for 8 h, the reaction mixture was concentrated under reduced pressure and the solid obtained was crystallized from ethanol to give 16 as a white powder. (17). -A mixture of 15 (4.19 g, 10 mmol) and succinic anhydride (1.10 g, 10 mmol) was fused at 220 °C in an oil bath for 15 min.…”

Section: -{mentioning

confidence: 99%

“…Among these active compounds, thieno [3,2-d]pyrimidines have generated wide-spread interest due to their remarkable antitumor activities (3,4,14). Thus, substituted thieno [3,2-d]pyrimidines exert pronounced activity as PI3K inhibitors (GDC-0941) and EGFR and VEGFR dual inhibitors, which are used in the treatment of cancers (15)(16)(17). As a part of our continuing program on the synthesis of antimicrobial and antitumor compounds, we have earlier reported on a series of heterocyclic moieties that have biological activities (11)(12)(13).…”

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confidence: 99%

Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents

2017

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A novel series of carbamothioylamino-benzene-sulfonamidethiophene-carboxylates 4a-c and thieno [3,2-d]pyrimidin-2-yl-amino-benzene-sulfonamides 5a-c were synthesized in a series of synthetic steps and were used as key intermediates for the synthesis of thienotriazolopyrimidine-benzene-sulfonamide derivatives 6a-c and 7a-c. Thieno[3,2-d]pyrimidinones (8 and 9) were also prepared. Compound 9 was used as an intermediate for the synthesis of imidazole/1,2,4-triazole and tetrazine functionalized thieno[3,2-d]pyrimidine derivatives (10-12). Pyrrole derivatives/pyrrolopyrimidine/pyrrolotriazolopyrimidine functionalized thiophenes (15-19) were also synthesized. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Most of the newly synthesized compounds were evaluated for their in vitro activity against three human tumor cell lines, namely, liver cancer (HepG-2), colon cancer (HT-29) and lung cancer (NCI-H460), using doxorubicin as standard. , resp.) showed higher activity against all cell lines than doxorubicin. Most of the compounds were also screened for antibacterial activity using ciprofl oxacin as standard drug. Compounds 4b and 6b, both containing benzenesulfonamide linked to N-, 10 bearing imidazole moiety, and 15 and 19b,c with a thiophene-2-carboxylic acid chain, exhibited high activity against Gram-positive and Gram-negative bacteria.

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“…Pyrimidine and thienopyrimidine derivatives display a broad variety of biological activities, such as anticancer, [1][2][3][4][5][6] antiviral, [7][8][9] antitumor, [10][11][12][13][14][15] anti-inflammatory, 16,17 antimicrobial, [18][19] antimalarial 20 and antioxidant activities. 21,22 Also thienopyrimidines have long been the subject of chemical and biological research.…”

Section: Introductionmentioning

confidence: 99%