Patent
Compositions and methods for the treatment of metabolic disorders
| العنوان: | Compositions and methods for the treatment of metabolic disorders |
|---|---|
| Patent Number: | 9,212,179 |
| تاريخ النشر: | December 15, 2015 |
| Appl. No: | 14/310339 |
| Application Filed: | June 20, 2014 |
| مستخلص: | The present invention relates to the compound for treatment and/or prevention of one or more metabolic disorders utilizes an A-B-C tripartite structure, wherein A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. Also provided are methods for the treatment and/or prevention of one or more metabolic disorders, for example, obesity or diabetes, utilizing fatostatin A and/or a derivative and/or analog thereof and/or the A-B-C tripartite compounds. |
| Inventors: | Uesugi, Motonari (Osaka, JP); Wakil, Salih J. (Houston, TX, US); Abu-Elheiga, Lutfi (Houston, TX, US); Watanabe, Mizuki (Kyoto, JP) |
| Assignees: | Baylor College of Medicine (Houston, TX, US) |
| Claim: | 1. A compound having the chemical structure: [chemical expression included] wherein X is CH or C-OMe; R 1 is H, Et, OMe or n-propyl; Y is CH or [chemical expression included] R 2 is OH, OMe, OEt, or -NHR 3 ; R 3 is H, methyl, ethyl, or isopropyl; R 4 is H, Me, F, or Cl; and R 5 is Cl, Br, OBz, OH, OCH 2 COOMe, F, Me, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, [chemical expression included] OMe, NHBoc, [chemical expression included] NHTs, [chemical expression included] wherein when R 4 is H, R 5 is OBz, OH OCH 2 COOMe NH-i-Pr, NHCOMe, NHSO Me NHBn, [chemical expression included] OMe, NHBoc, [chemical expression included] NHTs, [chemical expression included] |
| Claim: | 2. The compound of claim 1 , wherein R 3 is isopropyl. |
| Claim: | 3. The compound of claim 1 , wherein R 4 is H. |
| Claim: | 4. The compound of claim 1 , wherein R 5 is Cl, F, or Me. |
| Claim: | 5. The compound of claim 1 , wherein Y is CH. |
| Claim: | 6. The compound of claim 1 , wherein the chemical structure is: [chemical expression included] wherein X is CH or C-OMe; R 1 is H, Et, OMe or n-propyl; R 4 is H, Me, F, or Cl; and R 5 is Cl, Br, OBz, OH, OCH 2 COOMe, F, Me, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, [chemical expression included] OMe, NHBoc [chemical expression included] NHTs [chemical expression included] wherein when R 4 is H, R 5 is OBz, OH, OCH 2 COOMe NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, [chemical expression included] OMe,NHBoc, [chemical expression included] NHTs [chemical expression included] |
| Claim: | 7. The compound of claim 6 , wherein X is C-OMe and R 1 is OMe. |
| Claim: | 8. The compound of claim 6 , wherein X is CH and R 1 is H. |
| Claim: | 9. The compound of claim 6 , wherein R 5 is Cl, F, or Me. |
| Claim: | 10. The compound of claim 1 , wherein the chemical structure is: [chemical expression included] wherein Y is CH or [chemical expression included] R 2 is OH, OMe, OEt, or -NHR 3 ; R 3 is H, methyl, ethyl, or isopropyl; R 4 is H, Me, F, or 01 ; and R 5 is Cl, Br, OBz, OH, OCH 2 COOMe, F, Me, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, [chemical expression included] OMe, NHBoc [chemical expression included] NHTs, [chemical expression included] wherein when R 4 is H, R 5 is OBz, OH, OCH 2 COOMe NH-i-Pr, NHCOMe,NHSO 2, NHBn, [chemical expression included] OMe, NHBoc, [chemical expression included] NHTs, [chemical expression included] |
| Claim: | 11. The compound of claim 10 , wherein R 3 is isopropyl. |
| Claim: | 12. The compound of claim 10 , wherein R 5 is Cl, F, or Me. |
| Claim: | 13. The compound of claim 10 , wherein Y is CH. |
| Claim: | 14. The compound of claim 1 , wherein the chemical structure is: [chemical expression included] wherein R 2 is OH, OMe, OEt, or -NHR 3 ; R 3 is H, methyl, ethyl, or isopropyl; R 4 is H, Me, F, or Cl; and R 5 is Cl, Br, OBz, OH, OCH 2 COOMe, OCH 2 COOH, F, Me, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, OMe, NHBoc, [chemical expression included] OMe, NHBoc, [chemical expression included] NHTs, [chemical expression included] |
| Claim: | 15. The compound of claim 14 , wherein R 3 is isopropyl. |
| Claim: | 16. The compound of claim 14 , wherein R 5 is Cl, F, or Me. |
| Claim: | 17. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient. |
| Claim: | 18. A kit comprising: the compound of claim 1 ; and a container housing the compound. |
| Patent References Cited: | 4791200 December 1988 Press et al. 5643932 July 1997 Chihiro et al. 7151196 December 2006 Wilkening et al. 7153889 December 2006 Altenbach et al. 8778976 July 2014 Uesugi et al. 2006/0229363 October 2006 Hamanaka 0513387 November 1992 1092711 April 2001 1348706 October 2003 11186479 June 1999 9814191 April 1998 0106261 January 2001 02068417 September 2002 2006017384 February 2006 2006080406 August 2006 2007001973 January 2007 2013110007 July 2013 |
| Other References: | Colah et al., Bulletin of Haffkine Institute, (1977), 5(1), p. 20-22. cited by examiner Narender et al., Tetrahedron Letters, (2005), 46(35), p. 5953-5955. cited by examiner CAS RN 879343-52-9, CAS-STN database—2006. cited by examiner Bilgin, et al. 2-Pyridylthiazoles II synthesis and structure elucidations, Acta Pharmaceutical Turcica, 1999; vol. 30: pp. 133-137; entire document. cited by applicant Choi, et al. Identification of bioactive molecules by adipogenesis profiling of organic compounds, J Biol Chem, Feb. 28, 2003; vol. 278(9): pp. 7320-7324; entire document. cited by applicant Ide, et al. Sesamin, a sesame lignin, decreases fatty acid synthesis in rat liver accompanying the down-regulation of sterol regulatory element binding protein-1, Biochemica et Biophysica Acta, 2001; vol. 1534: pp. 1-13; entire document. cited by applicant Kamisuki, et al. A small molecule that blocks fat synthesis by inhibiting the activation of SREBP, Chemistry & Biology, 2009; vol. 16: pp. 882-892; entire document. cited by applicant Kamisuki, et al. Synthesis and elevation of diarylthiazole derivatives that inhibit activation of sterol regulatory element-binding proteins, J Med Chem, 2011; vol. 54(13): pp. 4923-4927; entire document. cited by applicant Sanfillippo, et al. Synthesis of (aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity, J Med Chem, 1988; vol. 31: pp. 1778-1785; entire document. cited by applicant Vachal, et al. Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor, Bioorg Medchem Lett, 2006; vol. 16: pp. 3684-3687; entire document. cited by applicant Reilly, et al. Proceedings of the Nutritioin Society 2003; vol. 62: pp. 611-619; entire document. cited by applicant Pinent, et al. Int J Obesity, 2005; vol. 29: pp. 934-941; entire document. cited by applicant Das, et al. A rapid and high-yielding synthesis of thiazoles and aminothiazoles using ammonium-12- molybdophosphate, J Mol Catal A, Jun. 2006; vol. 252: pp. 235-237; entire document. cited by applicant Uesugi, M Organic compounds that control Srebp activities, Ikagaku Oyo Kenkyu Zaidan Kenkyu Hokoku, 2006; vol. 25: pp. 168-172; entire document. cited by applicant Chihiro, et al. Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: synthesis and structure-activity relationships, J Med Chem 1995; vol. 38: pp. 353-358; entire document. cited by applicant |
| Primary Examiner: | Chu, Yong |
| Attorney, Agent or Firm: | Adler, Benjamin Aaron |
| رقم الانضمام: | edspgr.09212179 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |