Camptothecin analogs and methods of preparation thereof

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C546S116000

Reexamination Certificate

active

10919068

ABSTRACT:
A compound has the formulain racemic form, enantiomerically enriched form or enantiomerically pure form. R6is preferably —Si(R8R9R10) or —(R7)Si(R8R9R10), wherein R7is an alkylene group, an alkenylene group, or an alkynylene group; and R8, R9and R10are independently a C1-10alkyl group, a C2-10alkenyl group, a C2-10alkynyl group, an aryl group or a —(CH2)NR11group, wherein N is an integer within the range of 1 through 10 and R11is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SRcor a nitro group. R1–R4can be broadly substituted. R5is preferably a C1-10alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R13is preferably H, F or —CH3. R16is R16is —C(O)Rfor H. The E-ring (the lactone ring) may be opened. A method of synthesis of compound (1) and intermediates in the synthesis thereof are provided.

REFERENCES:
patent: 5468859 (1995-11-01), Fortunak
patent: 5700939 (1997-12-01), Fortunak
patent: 5744605 (1998-04-01), Curran
patent: 5910491 (1999-06-01), Hausheer
patent: 5935967 (1999-08-01), Hausheer
patent: 5981542 (1999-11-01), Bigg
patent: 6057303 (2000-05-01), Haridas
patent: 6136978 (2000-10-01), Curran
patent: 6150343 (2000-11-01), Curran
patent: WO 97/00876 (1997-01-01), None
patent: WO9700876 (1997-01-01), None
patent: WO 98/07727 (1998-02-01), None
patent: WO 98/28305 (1998-07-01), None
patent: WO9828304 (1998-07-01), None
patent: WO 98/35940 (1998-08-01), None
patent: WO 99/11646 (1999-03-01), None
patent: WO 00/50427 (2000-08-01), None
Homocamptothecis J. Med . Chem 1998 vol. 41 pp. 5410-5419.
Curran, D.P. and Liu, H., “New 4+1 Radical Annulations—A Formal Total Synthesis of (+/−)-Camptothecin,” J. Am. Chem Soc., 114, 5863-5864 (1992). Published Jul. 1, 1992.
Curran, D.P., “The Camptothecins—A reborn Family of Antitumor Agents”, J. Chin. Chem. Soc., 40, 1-6 (1993). Published Feb. 1993.
Curran, D.P. et al., “Recent Applications of Radical Reactions in Natural Product Synthesis,” Pure Appl. Chem., 65, 1153-1159 (1993). Published Jun. 1993.
Curran, D.P. et al., “Cascade Radical Reactions of Isonitriles: A Second-Generation Synthesis of (20S)-Camptothecin, Topotecan, Irinotecan, and Gl-147211C,” Angew. Chem. Int. Ed, 34, 2683-2684 (1995). Published Jan. 5, 1996.
Curran, D.P., Liu, H.; Josien, H; Ko, S.B., “Tandem Radical Reactions of Isonitriles with 2-pyrdonyl and other aryl radicals: Scope and Limitations, and a First Generation Sunthesis of (+/−)-Camptothecin,” Tetrahedron, 52, 11385-11404 (1996). Published Aug. 1996.
Josien, H. et al., “Synthesis of (S)-mappicine and Mappicine Ketone Via Radical Cascade Reaction of Isonitirles,” Tetrahedron, 53, 8881-8886 (1997). Published Jun. 30, 1997.
Josien, H. et al., “7-Silylcamptothecins (Silatecans): A New Family of Camptothecin Antitumor Agents,” Bioorg. Med. Chem. Lett. 7, 3189-3295 (1997).
Josien, H. et al., “A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles,” Chem. Eur. J. 4, 67-83 (1998). Published Jan. 1998.
Zihou, M. et al., “Reduced Albumin Binding Promotes the Stability and Activity of Topotecan in Human Blood,” Biochemistry, 34, 13722-13727 (1995).
Burke, T.G. and Zihou, M., “The Structural Basis of Camptothecin Interaction with Human Serum Albumin: Impact on Drug Stability,” J. Med. Chemistry, 37, 40-46 (1994).
Zihou, M. and Burke, T.G., “Marked Interspecies Variations Concerning the Interactions of Camptothecin with Serum Albumins: A Frequency-Domain fluorescence Spectroscopic Study,” Biochemistry, 33, 12540-12545 (1994).
Zihou, M. and Burke, T.G., “Differential Interactions of Camptothecin Lactone and Carboxylate Forms with Human Blood Components,” Biochemistry, 33, 10325-10336 (1994).
Burke, T.G., and Zihou, M., “Ethyl Substitution at the 7 Position Extends the Half-Life of 10-Hydroxycamptothecin in the Presence of Human Serum Albumin,” J. Med. Chemistry, 37:17, 2580-2582 (1993).
Burke, T.G. et al., “Lipid Bilayer Partitioning and Stability of Camptothecin Drugs,” Biochemistry, 32:20, 5352-5364 (1993).
Zihou, M. and Burke, T.G., Preferential Binding of the Carboxylate Form of Camptothecin by Human Serum Albumin, Anal. Biochem., 212, 285-287 (1993).
Burke, T.G. and Tritton, T.R., “Structural Basis of Anthracycline Selectivity for Unilamellar Phosphatidylcholine Vesicles: An Equilibrium Binding Study,” Biochemistry, 24, 1768-1776 (1985).
Burke, T.G. and Tritton, T.R., “Location and Dynamics of Anthracycline Bound to Unilamellar Phosphatidylcholine Vesicles,” Biochemistry, 24, 5972-5980 (1985).
Burke, T.G. et al., “The Important Role of Albumin in Determing the Relative Human Blood Stabilities of the Camptothecin Anticancer Drugs,” J. Parm. Sciences, 84:4 (1995).

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