:10.1007/s12272-011-0502-8 30. Greve, H.; Schupp, P. J.; Eguereva, E.; Kehraus, S.; K ig, G. M. J. Nat. Prod. 2008, 71, 1651653. doi:ten.1021/np8003326 31. Sabitha, G.; Padmaja, P.; Reddy, P. N.; Jadav, S. S.; Yadav, J. S. Tetrahedron Lett. 2010, 51, 6166168. doi:10.1016/j.tetlet.2010.09.072 32. Das, T.; Nanda, S. Tetrahedron Lett. 2012, 53, 25658. doi:10.1016/j.tetlet.2011.11.059 33. Arlt, D.; Bieniek, M.; Karch, R. Novel Metathesis Catalysts. WO 2008/034552 A1, March 27, 2008. 34. Mutlu, H.; Montero de Espinosa, L.; T O.; Meier, M. A. R. Beilstein J. Org. Chem. 2010, 6, 1149158. doi:10.3762/bjoc.6.131 35. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 95356. doi:ten.1021/ol990909q 36. Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900923. doi:10.1002/anie.200200556 37. Connon, S. J.; Blechert, S. Best. Organomet. Chem. 2004, 11, 9324. doi:ten.1007/b94650 38. Bach, J.; Berenguer, R.; Garcia, J.; L ez, M.; Manzanal, J.; Vilarrasa, J. Tetrahedron 1998, 54, 149474962. doi:ten.1016/S0040-4020(98)00936-3 39. Forman, G. S.; McConnell, A. E.; Tooze, R. P.; van Rensburg, W. J.; Meyer, W. H.; Kirk, M. M.; Dwyer, C. L.; Serfontein, D. W. Organometallics 2005, 24, 4528542. doi:10.1021/om0503848 40. Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 3381391. doi:10.1039/A903662H 41. Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am. Chem. Soc. 1988, 110, 29193. doi:10.1021/ja00209a048 42. Baker, B. A.; Boskovi, Z. V.; Lipshutz, B. H. Org. Lett. 2008, 10, 28992. doi:10.1021/ol702689v 43.Dacarbazine Neises, B.Docetaxel ; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978, 17, 52224. doi:10.1002/anie.197805221 44. Deutsch, C.; Krause, N.; Lipshutz, B. H. Chem. Rev. 2008, 108, 2916927. doi:10.1021/cr0684321 45. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551553. doi:10.1021/ja00252aAcknowledgementsGenerous financial support by the Deutsche Forschungsgemeinschaft (DFG grant Schm 1095/6-2) is gratefully acknowledged. We thank Evonik Oxeno for generous donations of solvents, and Umicore for generous donations of metathesis catalysts.PMID:27641997
Regardless of initial guarantee and sound biologic rationale, anti-angiogenic therapies targeting vascular endothelial development factor (VEGF) have demonstrated only modest clinical effect and are prone to resistance in many illness contexts (1). In advanced non-small cell lung cancer (NSCLC), the anti-VEGF monoclonal antibody bevacizumab increases general survival from roughly ten to 12 months when added to carboplatin-paclitaxel chemotherapy (2), but conveys no survival benefit when added to cisplatin-gemcitabine chemotherapy (3). The addition of sorafenib, a VEGF receptor (VEGFR) tyrosine kinase inhibitor, to standard chemotherapy doesn’t improve clinical outcomes and is associated with inferior outcomes in tumors with squamous histology (4). In advanced pancreatic cancer, the addition of bevacizumab to gemcitabine doesn’t strengthen general survival (five). In tumors for example lung and pancreatic cancers, proliferation and development signaling by way of alternate angiogenic pathways, for example platelet-derived growth factor (PDGF) (6, 7) and fibroblast development issue (FGF) (eight), seems to take part in tumor escape from anti-VEGF therapy. The PDGF-PDGFR axis effects angiogenesis, fibroblast activation, and tumor interstitial stress (9). In NSCLC, expression of FGF and PDGF are related with poor prognosis (10). Similar associations happen to be observed in pancreatic ca.