Analogs of indole-3-carbinol metabolites as chemotherapeutic...

Details Analogs of indole-3-carbinol metabolites as chemotherapeutic... Analogs of indole-3-carbinol metabolites as chemotherapeutic...

2008-09-30

2008-09-30

Shiao, Rei-Tsang (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C548S483000, C548S484000

Reexamination Certificate

active

11350232

ABSTRACT:
Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds have the structure of formula (III)wherein R1, R2, R3, R4, R5, R6, R7, R8, R11, R12, R20, and R21are defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

REFERENCES:
patent: 3527517 (1970-09-01), Hackmann
patent: 4636820 (1987-01-01), Schmidt et al.
patent: 5086171 (1992-02-01), Mathiaparanam
patent: 5116978 (1992-05-01), Mathiaparanam
patent: 5206377 (1993-04-01), McAfee
patent: 5266699 (1993-11-01), Naef et al.
patent: 5326879 (1994-07-01), Takahashi et al.
patent: 5380723 (1995-01-01), Takahashi et al.
patent: 5843607 (1998-12-01), Hu et al.
patent: 5942340 (1999-08-01), Hu et al.
patent: 5948808 (1999-09-01), Safe
patent: 6323233 (2001-11-01), Wright et al.
patent: 6407102 (2002-06-01), Mahboobi et al.
patent: 7078427 (2006-07-01), Jong et al.
patent: 0908787 (1999-04-01), None
patent: 2207670 (1989-02-01), None
patent: WO 99/57117 (1999-11-01), None
patent: WO 02/36561 (2002-05-01), None
patent: WO 02/36597 (2002-05-01), None
patent: WO 0236561 (2002-05-01), None
Marzi et al, 2002, CAS:136:369712.
Aygün et al. (2003), “Synthesis and Biological Evaluation of Structural Variants of Carbazoquinocin C,”J. Heterocyclic Chem. 40(3):411-417.
Biswas et al. (1998), “A Convenient Synthesis of 5,11-Dihydro-5,11-dimethyl-6-trifluoromethylindolo[3,2-b]carbazole,”Indian J. Chem. B37B(9):841-843.
Black et al. (1995), “Synthesis of Indolo[3,2-b]carbazoles from 4,6-Dimethoxyindole and Aryl Aldehydes,”Tetrahedron51(43):11801-11808.
Black et al. (1993), “Calix[3]indoles, New Macrocyclic Tris(indolylmethylene) Compounds with 2,7-Linkages,”J. Chem. Soc., Chem. Comm., 10:819-821.
Bonnesen et al. (2001), “Dietary Indoles and Isothiocyanates That Are Generated from Cruciferous Vegetables Can Both Stimulate Apoptosis and Confer Protection Against DNA Damage in Human Colon Cell Lines,”Cancer Res. 61:6120-6130.
Bradlow et al. (1991), “Effects of Dietary Indole-3-carbinol on Estradiol Metabolism and Spontaneous Mammary Tumors in Mice,”Carcinogenesis12(9):1571-1574.
Brieskorn and Huber (1979), “2,3-Bis(3-methylindolyl)methane from 3-methylindole and formaldehyde,”Archiv. Der Pharmazie312:1046-1051 (Abstract).
Chinni et al. (2001), “Indole-3-carbinol (I3C) Induced Cell Growth Inhibition, G1 Cell Cycle Arrest and Apoptosis in Prostate Cancer Cells,”Oncogene20:2927-2936.
Chu et al. (1984), A novel serotonin antagonist 2,2′-bis[3-(2-N′N-dimethylaminoethyl)indolyl]sulfide (BDIS)J. Heterocyclic Chem. 21:1901-1903 (Abstract).
Crowell (2005), “The chemopreventative agent development research program in the Division of Cancer Prevention of the US National Cancer Institute: An overview,”Eur. J. Cancer, 41:1889-1910.
Fuerstner et al. (1995), “Titanium-induced zipper reactions,”Angew. Chem. Intl. Ed. 34:678-681 (Abstract).
Grotta et al. (1961), “Preparation of Some Condensed Ring Carbazole Derivatives,”J. Org. Chem. 26:1509-1511.
Hill and Townend (1972), “Light-induced reactions of α-(N-alkylanilino) ketones. Formation of diindolylmethanes,”J. Chem. Soc. Perkin Trans. 9-10:1210-1219 (Abstract).
Hino et al. (1973), “Preparation of 3-Substituted 2-Indolinethiones via Diindolyl Disulfides. Reaction of 3-Substituted Indoles with Sulfur Monochloride,”Chem. Pharm. Bull. 21(12):2739-2748 (abstract only).
Hino et al. (1974), “Reaction of Skatole with Iodine in the Presence of Thiourea,”Chem. Pharm. Bull. 22(11):2728-2731 (abstract only).
Hünig et al. (1976), “Synthese Vinyloger und Azavinyloger Redoxsysteme Mit Indolylresten Als Endgruppen,”Liebigs Ann. Chem. 6:1039-1059.
Jackson et al. (1987), “Electrophilic Substitution in Indoles. Part 15. The Reaction Between Methylenedi-indoles andp-Nitrobenzenediazonium Fluoroborate,”J. Chem. Soc. Perkin Trans. I11:2543-2551.
Kim, and Milner (2005), “Targets for indole-3-carbinol in cancer prevention,”J. Nutritional Biochem. 16:65-73.
Kistenmacher et al. (1992), “A Direct Synthesis of Indolocarbazoles via New Dinitroterphenyl Precursors,”J. Heterocyclic Chem. 29:1237-1239.
Knölker et al. (1998), “Iron-Mediated Synthesis of Indolo[2,3-b]carbazole,”Tetrahedron Letters39:4007-4008.
Knölker et al. (2000), “Transition Metal Complexes in Organic Synthesis. Part 61: Convergent Synthesis of Indolo[2,3-b]carbazole by an Iron-Mediated Bidirectional Annulation of Two Indole Rings,”Tetrahedron56:4733-4737.
Kojima et al. (1994), “Chemoprevention of Spontaneous Endometrial Cancer in Female Donryu Rats by Dietary Indole-3-carbinol,”Cancer Res. 54:1446-1449.
Lau et al. (1986), “Reductive Deoxygenation of Aryl Aldehydes and Ketones and Benzylic, Allylic, and Tertiary Alcohols by ZnI2-NaCNBH3,”J. Org. Chem. 51(15):3038-3043.
Liu et al. (1994), “Indolo[3,2-b]carbazole: A Dietary-Derived Factor That Exhibits Both Antiestrogenic and Estrogenic Activity,”J. Natl. Cancer Institute86(23):1758-1765.
Manson et al. (2005), “Innovative agents in cancer prevention,”Recent Results Cancer Res. 166:257-75. (Abstract).
Marshall (2003), “Cervical Dysplasia: Early Intervention,”Alternative Medicine Rev. 8:156-170.
Michnovicz et al. (1997), “Changes in Levels of Urinary Estrogen Metabolites After Oral Indole-3-carbinol Treatment in Humans,”J. Natl. Cancer Institute89(10):718-723.
Napolitano et al. (1993), “Oxidation Chemistry of 5,6-Dihydroxy-2-methylindole,”Tetrahedron49(40):9143-9150.
Pindur et al. (1987), “Reaktivität und Reaktionswege von Methylsubstituierten Bisindolylcarbenium-Ionen,”J. Heterocyclic Chem. 24(1):159-163.
Swindells et al. (1956), “Preparation of Indolocarbazoles. VIII. Preparation of 1-Methylindolo[2′,3′-2,3]carbazole,”J. Chem. Soc., pp. 1135-1138.
Veronesi and Bonanni (2005), “Chemoprevention: From research to clinical oncology,”Eur. J. Cancer, 41:1833-1841.
Von Dobeneck et al. (1969), “α.β′-Diindolylmethane und -Methene. Der Urorosein-Chromophor,”Chem. Ber. 102(4):1347-1356.
Wille et al. (2001), “Malassezin—A Novel Agonist of the Arylhydrocarbon Receptor from the YeastMalassezia furfur,”Bioorganic&Medicinal Chem. 9:955-960.

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