Patent
Triptolide analogs for the treatment of autoimmune and inflammatory disorders
| العنوان: | Triptolide analogs for the treatment of autoimmune and inflammatory disorders |
|---|---|
| Patent Number: | 8,193,249 |
| تاريخ النشر: | June 05, 2012 |
| Appl. No: | 12/474305 |
| Application Filed: | May 29, 2009 |
| مستخلص: | The present invention provides synthetic methods and compositions for treatment of autoimmune and anti-inflammatory disorders comprising administering an effective amount of a derivative of triptolide alone or in combination or alternation with other anti-autoimmune or anti-inflammatory compounds. |
| Inventors: | Wang, Susheng (Clarkston, GA, US); Liotta, Dennis C. (Atlanta, GA, US); Snyder, James P. (Atlanta, GA, US); Venkatesan, Hariharan (San Diego, CA, US) |
| Assignees: | Emory University (Atlanta, GA, US) |
| Claim: | 1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula (II), (IV) or (III): [chemical expression included] or its pharmaceutically acceptable salt or prodrug thereof, wherein: (a) the dotted line indicates the presence of either a single or double bond, wherein the valances of a single bond are completed by hydrogens; (b) A, B, D and E are O; and R 1 , R 2 , R 3 , R 4 , R 5 and R 6 , are independently hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkynyl, aryl, alkaryl, or arylalkyl, wherein the pharmaceutical composition is a tablet, troche, or capsule. |
| Claim: | 2. The pharmaceutical composition of claim 1 further comprising another active agent. |
| Claim: | 3. A compound of formula (II), (IV) or (III): [chemical expression included] or its pharmaceutically acceptable salt or prodrug thereof, wherein: (a) the dotted line indicates the presence of either a single or double bond, wherein the valances of a single bond are completed by hydrogens; (b) A, B, D and E are O; and R 5 and R 6 are independently hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, alkaryl, or arylalkyl; R 1 , R 2 and R 4 are alkyl; and R 3 is hydrogen. |
| Claim: | 4. A compound of formula (II), (IV) or (III): [chemical expression included] or its pharmaceutically acceptable salt or prodrug thereof, wherein: (a) the dotted line indicates the presence of either a single or double bond, wherein the valances of a single bond are completed by hydrogens; (b) A, B, D and E are O; and R 5 and R 6 are independently hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, alkaryl, or arylalkyl; R 1 is t-butyl; R 4 is methyl; and R 2 and R 3 are hydrogen or methyl. |
| Claim: | 5. A compound having the following formula, [chemical expression included] or salt thereof. |
| Current U.S. Class: | 514/691 |
| Patent References Cited: | 3563741 February 1971 Delzenne et al. 3816437 June 1974 Houlihan 3917652 November 1975 Pawson et al. 3932430 January 1976 Habeck et al. 3957816 May 1976 Habeck et al. 4522811 June 1985 Eppstein et al. 5216175 June 1993 Avery et al. 5294443 March 1994 Lipsky et al. 5430054 July 1995 Qian et al. 5581004 December 1996 Rieke et al. 5648382 July 1997 Billington et al. 5856580 January 1999 McMorris 6127396 October 2000 Cordi et al. 6538105 March 2003 Drauz et al. 6777441 August 2004 Wang et al. 7557139 July 2009 Venkatesan et al. 2004/0204394 October 2004 Minaskanian 2032285 June 1991 3440826 May 1985 3913310 October 1990 095098 November 1999 2104516 March 1983 54073766 June 1979 61197573 September 1986 WO 90/02744 March 1990 WO 94/02540 February 1994 WO 94/26265 November 1994 WO 95/03272 February 1995 WO 95/16672 June 1995 WO 95/25718 September 1995 WO 98/22442 May 1998 WO 99/19298 April 1999 WO 99/29642 June 1999 WO 00/39094 July 2000 WO 01/04089 January 2001 WO 02/28862 April 2002 |
| Other References: | Katsuhara (Journal of Organic Chemistry, 1967, vol. 32, pp. 797-799). cited by examiner Abstract of Gierer et al, (Acta Chemica Scandinavica, 1977, vol. B31, pp. 546-560). cited by examiner U.S. Appl. No. 12/831,672, filed Jul. 7, 2010, Liotta, et al. cited by other Adam, W., et al., “Thermal and Bromide Ion-catalyzed Rearrangement of Benzofuran Dioxetanes to 1-oxaspira(2.5.)octa-5,7-dien-4-ones,” J. Am. Chem. Soc., 1994, vol. 116, No. 15, pp. 6713-6718. cited by other Arenz, C., et al., “Synthesis of the First Selective Irreversible Inhibitor of Neutral Sphingomyelinase,” Angew. Chem. Int. Ed., 2000, vol. 39, No. 8, pp. 1440-1442. cited by other Baldwin, J., et al., “Phenoxathiins From Spiroepoxycyclohexadienones,” Tetrahedron Lett., 1980, vol. 21, pp. 4971-4972. cited by other Blewer, R., et al., “Dimensional Expansion and Surface Microstructure in Helium-implanted Erbium-hydride Films,” J. Nuclear Materials, 1972, vol. 4, No. 2, pp. 260-278 (abstract only). cited by other Briggs, J., et al., “A critical review of Immunosuppressive therapy,” Immunology Lett., 1991, vol. 29, Nos. 1-2, pp. 89-94. cited by other Connors, T., “The Choice of Prodrugs for Gene Directed Enzyme Prodrug Therapy of Cancer,” Gene Therapy, 1995, vol. 2, pp. 707-709. cited by other Gesson, J., et al., “Diels-Alder Reaction of Cyclopentadiene and Spiroepoxy-2,4-cyclohexadienones,” Tetrahedron Lett., 1993, vol. 34, No. 2941-2944. 18, pp. 2941-2944. cited by other Keown, P., et al., “Annual Review of Transplantation,” Clin. Transplants, 1991, pp. 205-223. cited by other Platt, J., et al., “Transplantation of Discordant Xenografts: A Review of Progress,” Immunology Today, 1990, vol. 11, No. 2, pp. 450-456. cited by other Qui, X., et al., Immunosuppressant PG490 (Triptolide) Inhibits T-cell Interleukin-2 Expression at the Level of Purine-box/Nuclear-Factor of Activated T-cells and NF-kB Transcriptional Activity, J. Biol. Chem., vol. 274, No. 19, pp. 13443-13450. cited by other Roberts, J., et al., “Liver Transplantation Today,” Ann. Rev. Med., 1989, vol. 40, pp. 287-303. cited by other Sierra, M. and De La Torre, M., “Dead Ends and Detours En Route to Total Synthesis of the 1990s,” Angew. Chem. Int. Ed., 2000, vol. 39, pp. 1538-1599. cited by other Yang, D., et al., “Studies on Triepoxide Analogs of Triptolide,” Tetrahedron Letters, 1997, vol. 38, No. 39, pp. 6865-6868. cited by other |
| Primary Examiner: | Canella, Karen |
| Attorney, Agent or Firm: | Mason, James C. Hollinger, Susanne Emory Patent Group |
| رقم الانضمام: | edspgr.08193249 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |