| Sonstiges: |
- Nachgewiesen in: USPTO Patent Grants
- Sprachen: English
- Patent Number: 9,597,325
- Publication Date: March 21, 2017
- Appl. No: 13/879106
- Application Filed: September 30, 2011
- Assignees: Trustees of Boston University (Boston, MA, US)
- Claim: 1. A method of inhibiting LSF in a subject, the method comprising administering to the subject an effective amount of a compound of formula (III), wherein the formula (III) has the structure: [chemical expression included] wherein: R 1 is aryl, wherein the aryl can be optionally substituted with C 1 -C 6 alkoxyl at ortho-position; R 2 and R 3 are hydrogen or R 2 and R 3 together form a second bond between the carbons to which they are attached; R 4 is hydrogen; R 5 is selected from the group of hydrogen and C 1 -C 6 alkyl; R 6 and R 7 are hydrogen; R 10 and R 11 are hydrogen; or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
- Claim: 2. The method of claim 1 , wherein the compound of formula (I) is of formula (IV), wherein formula (IV) has the structure: [chemical expression included] or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
- Claim: 3. The method of claim 1 , wherein the compound of formula (III) is selected from the group consisting of compounds of formulae (IV), (V), (VI), (VIII), (XII), (XIII) and (XXV): [chemical expression included] [chemical expression included] [chemical expression included] [chemical expression included] or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
- Claim: 4. The method of claim 1 , wherein the subject suffers from or is at risk of cancer.
- Claim: 5. The method of claim 4 , wherein the cancer is hepatocellular carcinoma (HCC).
- Claim: 6. The method of claim 4 , wherein the cancer is selected from the group consisting of: breast cancer, colon cancer, ovarian cancer, lung cancer, kidney cancer, cancers of the hematopoietic system, cancers of the endometrium, cervical cancer, cancers of the upper digestive tract, stomach cancer, liver cancers and cancers of the small intestine.
- Claim: 7. The method of claim 1 , wherein the subject suffers from or is at risk of HIV or is in need of lower inflammatory responses.
- Claim: 8. The method of claim 1 , wherein R 1 is aryl optionally substituted with C 1 -C 4 alkoxy.
- Claim: 9. The method of claim 1 , wherein R 1 is aryl optionally substituted with ethoxy, propyloxy, isopropyloxy, or butyloxy.
- Patent References Cited: 6713462 March 2004 Metcalf, III et al. ; 7081256 July 2006 Kubota et al. ; 2003/0130505 July 2003 Li et al. ; 2009/0081183 March 2009 Margolis et al. ; 2010/0004277 January 2010 Bulawa et al. ; 101410384 April 2009 ; 98/36641 August 1998 ; 03/066630 August 2003 ; 2007/136592 November 2007 ; 2011/123427 October 2011
- Other References: Chang et al. J. Med. Chem. 2009, vol. 52, pp. 4883-4891. cited by examiner ; Chang et al., Journal of Medicinal Chemistry, 52(15):4883-4891 (2009). “Design and synthesis of 2-(3-Benzo[b] thienyl)-6,7-methylenedioxyquinolin-4-one analogues as potent antitumor agents that inhibit tubulin assembly.” cited by applicant ; Singh et al., Chemical & Pharmaceutical Bulletin, 58(2):242-246 (2010). “Design and synthesis of C-ring lactone- and lactam-based podophyllotoxin analogues as anticancer agents.” cited by applicant ; Bing et al., J Biol Chem., 275:31616-31623 (2000). “Nfkappa B interacts with serum amyloid A3 enhancer factor to synergistically activate mouse serum amyloid A3 gene transcription.” cited by applicant ; Bovolenta et al., J. Immunol., 163:6892-6897 (1999). “In vivo administration of recombinant IL-2 to individuals infected by HIV down-modulates the binding and expression of the transcriptioni factors Ying-Yang-1 and leader binding protein-1/late simian virus 40 factor.” cited by applicant ; Bruni et al., J Biol Chem, 277:35481-35488 (2002). “Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression.” cited by applicant ; Drouin et al., J Immunol, 168:2847-2856 (2002). “The ubiquitously expressed DNA-binding protein Late SV40 Factor binds Ig switch regions and represses class switching to IgA.” cited by applicant ; Haigh et al., J. Chem. Inf. Model, 45:673-684 (2005). “Small molecule shape-fingerprints.” cited by applicant ; Hansen et al., Cell Cycle, 8:2146-2151 (2009). “Transcriptions factors LSF and E2Fs: Tandem cyclists driving G0 to S?” cited by applicant ; Huang et al., Interferon Cytokine Res, 19:1403-1411 (1999). “Synergistic induction fo mouse serum amyloid A3 promoter by the inflammatory mediators IL-1 and IL-6.” cited by applicant ; Koehler et al., Curr. Opin. Chem. Biol., 14:331-340 (2010). “A complex task? Direct modulation of transcription factors with small molecules.” cited by applicant ; Li et al., J. Org. Chem., 70:2881-2883 (2005). “Trifluoroacetic acid-mediated hydroarylation: synthesis of dihydrocoumarins and dihydroquinolones.” cited by applicant ; Murata et al., Genes to Cells, 3:443-457 (1998). “Transcription factor CP2 is essential for lens-specific expression o fthe chicken alphaA-crystallin gene.” cited by applicant ; Porta-De-La-Riva et al., J. Biochem., 435:563-568 (2011). “TFCP2c/LSF/LBP-1c is required for Snail1-induced fibronectin gene expression”. cited by applicant ; Powell et al., EMBO J, 19:4665-4675 (2000). “Inhibition of the mammalian transcription factor LSF induces S-phase-dependent apoptosis by downregulating thymidylate synthase expression.” cited by applicant ; Saxena et al, Mol Cell Biol., 29:2335-2345 (2009). “Phosphorylation by cyclin C/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of LSF during G1 progression.” cited by applicant ; Sharma et al., Biochem. Pharmacol, 80:666-673 (2010). “Exploiting the balance between life and death: targeted cancer therapy and ‘oncogenic shock.’” cited by applicant ; Shirra et al., J Biol Chem., 273:19260-19268 (1998). “LSF and NTF-1 share a conserved DNA-recognition motif yet required different oligomerization states to form a stable protein-DNA complex.” cited by applicant ; Swendeman et al., J Biol Chem, 269:11663-11671 (1994). “Characterization of the genomic structure chromosomal location, promoter and developmental expression fo the alpha-globin transcription factor CP2.” cited by applicant ; Traylor-Knowles et al., BMC Evolutionary Biology, 10:101 (2010). The evolutionary diversification of LSF and Grainyhead transcription factors preceded the radiation of basal animal lineages. cited by applicant ; Veljkovic et al., Gene, 343:23-40 (2004). “Lineage-specific and ubiquitous biological roles of the mammalian transciption factor LSF.” cited by applicant ; Weinstein et al., Cancer Res, 68:3077-3080 (2008). “Oncogene Addiction.” cited by applicant ; Yoo et al., J Clin Invest, 119:465-477 (2009). “Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression.” cited by applicant ; Yoo et al., PNAS, 106:12938-12943 (2009). “Identification of genes conferring resistance to 5-fluorouracil.” cited by applicant ; Yoo et al., PNAS, 107:8357-8362 (2010). “Transcription factor late SV40 (LSF) functions as an oncogene in hepatocellular carcinoma.” cited by applicant ; Zhong et al., J Biol Chem, 269:21269-21276 (1994). “Evidence that levels of the dimeric cellular transcription factor CP2 play little role in the activation of the HIV-1 long terminal repeat in vivo or following superinfection with herpes simplex virus type 1.” cited by applicant
- Primary Examiner: Jean-Louis, Samira
- Attorney, Agent or Firm: Nixon Peabody LLP
|
