Variolin derivatives and their use as antitumor agents

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S293000, C544S242000

Reexamination Certificate

active

07495000

ABSTRACT:
Variolin derivatives of formula (5) are provided, wherein the substituent groups defined by X2, R1, R2, R3, R6, R7and R12are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, NO2, NH2, NHR′, N(R′)2, NHCOR′, NHSO2R′, CN, halogen, ═O, C(═O)H, C(═O)R′, CO2H, CO2R′, carboxyalkyl, C1-C12alkyl, C2-C12alkenyl, C2-C12alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; wherein each of the R′ groups is independently selected from the group consisting of H, OH, SH, NO2, NH2, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, CO2CH3, C1-C12alkyl, C2-C12alkenyl, C2-C12alkynyl, aryl, aralkyl and heteroaromatic; wherein the pairs of groups R1and R2, R2and R3, R3and R12, R12and R6, or R6and R7may be joined into a carbocyclic or heterocyclic ring system.

REFERENCES:
patent: 2004/0058939 (2004-03-01), Alvarez et al.
patent: 2005/0014778 (2005-01-01), Morris et al.
patent: WO 02/04447 (2002-01-01), None
patent: WO 02/12240 (2002-02-01), None
patent: WO 03/006457 (2003-01-01), None
Alvarez et al., “Synthesis of Deoxyvariolin B”, Tetrahedron Letters, vol. 42, No. 8, Jan. 2001, pp. 315-317.
Alvarez et al., “Synthesis of 1, 2-dihydropyrrolo[1,2-c]primidin-1-ones”, J. Chem. Soc. Perkins Trans. I, pp. 249-255 (1999).
Alvarez et al., “Synthesis of 3-Aryl- and 3-Heteroaryl-7-azaindoles”, Synthesis, pp. 615-620 (1999).
Anderson et al., Studies toward the total synthesis of the variolins: rapid entry to the core structure: Tetrahedron Letters, vol. 42, No. 8, Jan. 2001, pp. 311-313.
Anderson et al., “Total Synthesis of Variolin B”, Tetrahedron Letters, vo. 42, No. 3, Dec. 2001, pp. 8697-8699.
Calabresi et al., “Chemotherapy of Neoplastic Diseases”, Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9thed., New York: McGraw-Hill, 1996, , pp. 1225-1229.
Capuano, Lilly et al., “(Heterocyclizations, XIII) New Polycyclic Pyrimidines with Bridge-Head Nitrogen”, Chem. Ber., 107, pp. 929-936 (1974).
Charya et al., “Wynthesis and Evaluation of Sulphonylhydrazones of Phthalimido Acetaldehyde as Anticancer Agents”, J. Indian Chem Soc., vol. 75, Jan. 1998, pp. 46-48.
Desarbre et al., “Synthesis of 2-Substituted-1H-Pyrrolo[2,3-b] Pyridines: Preparation of 7-Azaolivacine Analogue and 7-Azaindolopyridopyrimidine Derivatives”, Tetrahedron, 53(10), pp. 3637-3648 (1997).
Erba et al., “Cell cycle phase perturbation and apoptosis induced by Variolin B, a novel antitumor agent of marine origin”, Proc. Am. Assoc. Can. Res. Annual Meeting, vol. 27, #198 pp. 28-29 (1996).
Fresenda et al., “Synthetic studies towards the 2-aminopyrimidine alkaloids variolins and meridianins from marine origin”, Tetrahedron Letters, vol. 41, 2000, pp. 4777-4780.
Girgis et al., “The Synthesis of 5-Azaindoles by Substitution-Rearrangement of 7-Azaindoles upon Treatment with Certain Primary Amines”, J. Heterocyclic Chem., vol. 26, No. 2, pp. 317-325 (1989).
Katritzky et al., Comprehensive Heterocyclic Chemistry, Pergamon Press, Oxford, vol. 3, p. 111 (1984).
Katritzky, Alan R. et al., “Activation of the 2-Alkyl Group of a 2-Alkylindole toward Proton Loss and Subsequent Electrophilic Substitution”, J. Am. Chem. Soc., vol. 108, No. 21, pp. 6808-6809 (1986).
Lorenz et al. “A New Indole Synthesis”, J. Org. Chem., vol. 30, pp. 2531-2533 (1965).
Majeed et al., “Stannylation Reactions and Cross-Couplings in Pyrimidines”, Tetrahedron, vol. 45, No. 4, pp. 993-1006 (1989).
Mendiola et al., “Reaction of 2-Bromomethylazoles and TosMIC: A Domino Process to Azolopyrimidines. Synthesis of Core Tricycle of the Variolins Alkaloids”, Organic Letters, vol. 2, No. 21, pp. 3253-3256 (2000).
Molina et al., “Synthesis of the potent antitumoral marine alkaloid variolin B”, Tetrahedron Letters, vol. 43, Feb. 2002, pp. 1005-1007.
Perry et al., “Alkaloids from the Antarctic sponge Kirkpatrickia Varialosa—Part 1: Variolin B, A New Antitumour and Antiviral Compound”, Tetrahedron, vol. 50, No. 13, 1994, pp. 3987-3992.
Sawayama et al., “Displacement Reactions of 2-Alkylsulfonyl-4-Chloropyrimidine Derivatives with Nucleophiles”, Heterocycles, vol. 8, pp. 299-305 (1977).
Simone, “Oncology: Introduction”, Cecil Textbook of Medicine, 20thEdition, vol. 1, pp. 1004-1010, 1996.
Trimurtulu et al., “Alkaloids from the Antarctic Sponge Kirkpatrickia varialosa—Part 2: Variolin A and N(3?) methyl tratrhydrovariolin B” Tetrahedron, vol. 50, No. 13, 1994, pp. 3993-4000.
Vorbrüggen et al., Syntheses of Nucleosides—Amination of Heterocycles—A New Simple Synthesis of Cytidines, Liebigs Annalen Der Chemie, pp. 988-1002 (1975).

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