Synthesis and biological evaluation of novel 9-functional heterocyclic coupled 7-deoxy-9-Dihydropaclitaxel analogue

Cheng, Qi; Oritani, Takayuki; Horiguchi, Tohru; Yamada, Teiko; Mong, Yan

doi:10.1016/s0960-894x(00)00031-7

Cited by 19 publications

(11 citation statements)

References 29 publications

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“…After constructing 3D-QSAR models from the training sets, test sets containing twelve and ten compounds, respectively, for epothilone-18,48,49 and paclitaxel-derivatives, [50][51][52][53][54][55][56] were generated and used to predict activity values (Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Lee¹,

Lee²,

Briggs³

et al. 2013

Bulletin of the Korean Chemical Society

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Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol TM ) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two β-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone-and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five-and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.

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Section: Resultsmentioning

confidence: 99%

Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Lee¹,

Lee²,

Briggs³

et al. 2013

Bulletin of the Korean Chemical Society

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“…The synthesis of a series of novel 7-deoxy-9-dihydro-9-(v-nucleotidylsuccinyl)-paclitaxel analogs ( natural taxoid by Cheng and coworkers (Scheme 8.22) [70]. The natural taxoid 2.2.100 was first converted to 7-deoxy-9-dihydrobaccatin, to which the functional heterocyclic fragments were connected at the C9 position through succinyl linkers.…”

Section: New Chemistry Of Paclitaxelmentioning

confidence: 99%

“…They found that 5 (20) assembly; this is the first example of a modified D-ring taxoid showing equivalent activity to paclitaxel. Cheng and coworkers reported the synthesis of a series of novel 9-functional heterocyclic coupled 7-deoxy-9-dihydropaclitaxel analogs (2.3.62-2.3.65, Figure 8.20) [70]. These analogs were tested in a tubulin assembly assay and evaluated for their cytotoxicities against various human cancer cell lines.…”

Section: Simple Analogs In Clinical Developmentmentioning

confidence: 99%

Recent Progress in the Chemistry and Biology of Paclitaxel (TaxolTM) and Related Taxanes

Zhao

Kingston

2012

Plant Bioactives and Drug Discovery

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“…Among the structural analogues of taxol, a potentially bioactive taxoid docetaxol (Taxotere ® ) occupies a particular place. The NIRT derivatives with 7-deoxy-9-dihydrotaxol were synthesized, and their antitumor properties were studied [63].…”

Section: Other Systemsmentioning

confidence: 99%

“…Cheng et al [63] chose the succinic acid residue as a bridge connecting the taxoid and AZT molecules (Scheme 10). The derivative (XLIX) of the natural taxoid was treated with a succinic anhydride excess, and the resulting (L) was treated with AZT in the presence of DMAP to get (LI) (yield 85%).…”

Section: Other Systemsmentioning

confidence: 99%

Ester Derivatives of Nucleoside Inhibitors of Reverse Transcriptase: 2. Molecular Systems for the Combined Therapy with 3′-Azido-3′-Deoxythymidine and 2′,3′-Didehydro-3′-Deoxythymidine

Berezovskaya

Chudinov

2005

Russ J Bioorg Chem

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Synthesis and biological evaluation of novel 9-functional heterocyclic coupled 7-deoxy-9-Dihydropaclitaxel analogue

Cited by 19 publications

References 29 publications

Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Recent Progress in the Chemistry and Biology of Paclitaxel (TaxolTM) and Related Taxanes

Ester Derivatives of Nucleoside Inhibitors of Reverse Transcriptase: 2. Molecular Systems for the Combined Therapy with 3′-Azido-3′-Deoxythymidine and 2′,3′-Didehydro-3′-Deoxythymidine

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