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Research Paper

Synthesis and biological evaluation of novel (E)-N'-benzylidene hydrazides as novel c-Met inhibitors through fragment based virtual screening

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Pages 468-477 | Received 13 Sep 2019, Accepted 02 Dec 2019, Published online: 06 Jan 2020

Figures & data

Figure 1. Structure of the kinase domain of c-Met bind to GSK1363089, (a) 3D-view image; (b) pose-view image.

Figure 1. Structure of the kinase domain of c-Met bind to GSK1363089, (a) 3D-view image; (b) pose-view image.

Figure 2. (a) Fragment growing based virtual screening; (b) the hit compound docked into c-Met.

Figure 2. (a) Fragment growing based virtual screening; (b) the hit compound docked into c-Met.

Scheme 1. Reagents and conditions: (i) CuSO4, Vitamin C, EtOH/H2O, 40 °C, 5–10 h; (ii) NaOH, 6 h, HCl; (iii) hydrazine hydrate, rt, 5 h; (iv) EDCI, HOBt, Et3N, 35 °C, 8–10 h.

Scheme 1. Reagents and conditions: (i) CuSO4, Vitamin C, EtOH/H2O, 40 °C, 5–10 h; (ii) NaOH, 6 h, HCl; (iii) hydrazine hydrate, rt, 5 h; (iv) EDCI, HOBt, Et3N, 35 °C, 8–10 h.

Table 1. Novel compounds and their activities against c-Met.

Table 2. Descriptors and relative importance of descriptors.

Figure 3. Important structural requirements of (E)-N'-benzylidene hydrazides by means of the ligand based 3D-QSAR.

Figure 3. Important structural requirements of (E)-N'-benzylidene hydrazides by means of the ligand based 3D-QSAR.

Table 3. The inhibitory activities of the five compounds against VEGFR-2 and c-Met.

Figure 4. (a) The superposing of c-Met and VEGFR-2 kinase; (b) the active sites of the two kinases; (c) the RMSD value of the superposing conformation.

Figure 4. (a) The superposing of c-Met and VEGFR-2 kinase; (b) the active sites of the two kinases; (c) the RMSD value of the superposing conformation.
Supplemental material

Supplemental Material

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