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Molecules 2017, 22(6), 913; doi:10.3390/molecules22060913

Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors

1
Graduate Institute of Medical Sciences, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan
2
School of Pharmacy, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Pierre Koch
Received: 29 March 2017 / Revised: 21 May 2017 / Accepted: 29 May 2017 / Published: 31 May 2017
(This article belongs to the Special Issue Kinase Inhibitors)
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Abstract

Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ. The molecular modeling results showed that, in terms of VEGFR-2 binding, the synthesized products had a similar binding mode to sunitinib but with tighter interaction. View Full-Text
Keywords: multi-target kinase inhibitor; VEGFR-2 inhibitor; PDGFRβ inhibitor angiogenesis; (2-oxoindolin-3-ylidene)methylpyrrole multi-target kinase inhibitor; VEGFR-2 inhibitor; PDGFRβ inhibitor angiogenesis; (2-oxoindolin-3-ylidene)methylpyrrole
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Yang, T.-H.; Lee, C.-I.; Huang, W.-H.; Lee, A.-R. Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors. Molecules 2017, 22, 913.

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