By Gordon M. L. Cragg, David Kingston, David J. Newman

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5). These drugs include CA4P (discovered by George R. ; see appropriate references throughout), AVE806292,93,131 (discovered by Ajinomoto, Inc. [AC7700] and sponsored by Aventis), and ZD-6126132–135 (licensed from Angiogene Pharmaceuticals UK and sponsored by AstraZeneca). The similarity of CA4P and AVE8062 to the natural product CA4 is obvious. Likewise, the six, seven, six ring fusion in ZD-6126 is highly reminiscent of the six, seven, seven (tropolone) ring system of the natural product colchicine.

26. R. , Preparation of combretastatin A3 diphosphate prodrugs for the treatment of cancer, PCT Int. Application WO2002102766 A2, 2002. 27. R. B, Combretastatin A-4, US Patent 4,996,237, 1991. 28. R. , Isolation, structural elucidation and synthesis of novel antineoplastic substances denominated “combretastatins,” US Patent 5,569,786, 1996. 29. Pettit, G. , Combretastatin A-4 prodrug, US Patent 5,561,122, 1996. 30. Pinney, K. G. , Description of anti-mitotic agents which inhibit tubulin polymerization, US Patent 6,350,777, 2000.

Structure of the cytostatic macrocyclic lactone combretastatin D-2, J. Org. , 55, 2797, 1990. 55. , McGraw-Hill, New York, 1978. 56. , Structure of the α,β-tubulin dimer by electron crystallography, Nature, 391, 199, 1998. 57. , Direct photoaffinity labeling of tubulin with taxol, J. Natl. , 84, 785, 1992. 58. E. , Synthesis, photochemical reactions, and tubulin binding of novel photoaffinity labeling derivatives of colchicine, J. Org. , 58, 1589, 1993. 59. , Synthesis and evaluation of 2-diazo-3,3,3-trifluopropanoyl derivatives of colchicine and podophyllotoxin as photoaffinity labels: reactivity, photochemistry, and tubulin binding, Photochem.

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Anticancer Agents from Natural Products by Gordon M. L. Cragg, David Kingston, David J. Newman
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