Patent
Compositions and methods for the treatment of metabolic disorders
العنوان: | Compositions and methods for the treatment of metabolic disorders |
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Patent Number: | 8,778,976 |
تاريخ النشر: | July 15, 2014 |
Appl. No: | 13/484685 |
Application Filed: | May 31, 2012 |
مستخلص: | The present invention relates to treatment and/or prevention of one or more metabolic disorders utilizing fatostatin A and/or a derivative and/or analog thereof. In other aspects, 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 and are described in detail herein. In specific aspects, the metabolic disorder includes obesity or diabetes, for example. |
Inventors: | Uesugi, Motonari (Houston, TX, US); Wakil, Salih J. (Houston, TX, US); Abu-Elheiga, Lutfi (Houston, TX, US); Mao, Qian (Houston, TX, US); Kamisuki, Shinji (Chiba, JP); Kugimiya, Akira (Osaka, JP) |
Assignees: | Baylor College of Medicine (Houston, TX, US) |
Claim: | 1. A compound selected from the group consisting of: 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl benzoate; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; methyl 2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetate; 4-(4-chlorophenyl)-2-(3,4-dimethoxyphenyl)thiazole; 4-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-propylpyridine; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; N-isopropyl-4(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine; N-(4-(2-(2-propylpyridin-4yl)thiazol-4yl)phenyl)acetamide; N-(4-(2-(2-propylpyridin-4yl)thiazol-4yl)phenyl)methanesulfonamide; N-benzyl-4-(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine; N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine; 4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid; methyl 4-(4bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylate; 4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 3-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; 2-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; 4-(4-bromophenyl)-N-isopropyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxamide; a pharmaceutically acceptable salt thereof; a stereoisomer thereof; and any combination or mixture thereof. |
Claim: | 2. The compound of claim 1 wherein said compound is selected from the group consisting of N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine, and N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methane sulfonamide. |
Claim: | 3. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient. |
Claim: | 4. A kit comprising the compound of claim 1 , wherein the compound is housed in a suitable container. |
Claim: | 5. The kit of claim 4 , further comprising an additional therapy for a metabolic disorder. |
Claim: | 6. A composition or pharmaceutically acceptable salt or stereoisomer thereof, having the general formula: [chemical expression included] wherein X is N; R 1 is independently selected from H, Et, OMe or n-propyl; Y 3 is CH or [chemical expression included] wherein R 2 is independently selected from OH, OMe, or NH-i-Pr; R 3 is independently selected from H, F, or Cl; and R 4 is independently selected from Cl, Br, OBz, OH, OCH 2 COOMe, OCH 2 COOH, F, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn, [chemical expression included] OMe, NHBoc, [chemical expression included] NHTs, [chemical expression included] |
Claim: | 7. The composition of claim 6 , wherein R 1 is n-propyl. |
Claim: | 8. The composition of claim 7 , wherein Y 3 is CH. |
Claim: | 9. The composition of claim 8 , wherein R 3 is Cl and R 4 is Cl. |
Claim: | 10. The composition of claim 8 , wherein R 3 is H. |
Claim: | 11. The composition of claim 10 , wherein R 4 is selected from the group consisting of Br, NH-i-Pr, NHSO 2 Me, NHBn, [chemical expression included] NHBoc, NHTs, [chemical expression included] |
Claim: | 12. The composition of claim 11 , having the following formula: [chemical expression included] [chemical expression included] [chemical expression included] |
Claim: | 13. The composition of claim 6 , wherein said compound is selected from the group consisting of: 4-(4-(4-bromophenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-phenylthiazol-2-yl)-2-propylpyridine; 4-(4-(4-chlorophenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(4-ethylphenyl)thiazol-2-yl)pyridine; 4-(4-p-tolylthiazol-2-yl)pyridine; 4-(4-(4-methoxyphenyl)thiazol-2-yl)pyridine; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl benzoate; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; methyl 2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetate; 2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetic acid; 4-(4-(3,4-dichlorophenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(4-fluorophenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-propylpyridine; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)acetamide; N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide; N-benzyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid; methyl 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylate; 4-(4-(4-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine; 3-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; 2-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol; 4-(4-bromophenyl)-N-isopropyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxamide; 4-(4-(4-chlorophenyl)thiazol-2-yl)pyridine; 4-(4-(4-chlorophenyl)thiazol-2-yl)-2-ethylpyridine; 2-propyl-4-(4-(thiophen-2-yl)thiazol-2-yl)pyridine; 2-(2-propylpyridin-4-yl)-4-p-tolylthiazole-5-carboxylic acid; 2-ethyl-4-(4-p-tolylthiazol-2-yl)pyridine; 4-phenyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid; methyl 2-(2-propylpyridin-4-yl)-4-p-tolylthiazole-5-carboxylate; tert-butyl 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenylcarbamate; N-cyclohexyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)-N-tosylbenzenamine; N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)-8-quinolinesulfonamide; N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)-2-thiophenesulfonamide; and any combination thereof. |
Claim: | 14. The composition of claim 13 , wherein said at least one compound is selected from the group consisting of: 4-(4-(4-bromophenyl)thiazol-2-yl)-2-propylpyridine; N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; and N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide; a pharmaceutically acceptable salt; a stereoisomer thereof; and any combination thereof. |
Current U.S. Class: | 514/342 |
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. 2006/0229363 October 2006 Hamanaka 0 513 387 November 1992 1 092 711 April 2001 1 348 706 October 2003 11 079993 March 1999 11186479 June 1999 WO 98/14191 April 1998 WO 02/068417 September 2002 WO 2006/017384 February 2006 WO 01/06261 August 2006 WO 2006/080406 August 2006 WO 2007/001973 January 2007 |
Other References: | Choi et al, The journal of Biological Chemistry, 278(9), 2003, p. 7320-7324. cited by examiner International Search Report issued during the prosecution of International Application No. PCT/US08/52778. cited by applicant Written Opinion issued during the prosecution of International Application No. PCT/US08/52778. cited by applicant Bilgin, Altan, 2-Pyridylthiazoles II Syntesis and Structure Elucidations, Acta Pharmaceutical Turcica. 1999. vol. 30, pp. 133-137. 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. 7320-4. cited by applicant Lee et al., Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of Insig-1, J Biol Chem. Oct. 22, 2004; vol. 279(43), pp. 45257-65. cited by applicant Mullican, Michael, Search Report prepared for Mr. Gino Catena of Fulbright & Jaworski L.L.P. Science IP: scienceIP@cas.org International Preliminary Report on Patentability, issued Aug. 4, 2009 (published Aug. 14, 2008) during the prosecution of International Application No. PCT/US2008/52778. 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., 38:353-358, 1995. cited by applicant Extended European Search Report issued in European Application No. 08728809.8, mailed Aug. 29, 2011. 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,” Biochimica et Biophysica Acta, 1534:1-13, 2001. cited by applicant Kamisuki et al., “A small molecule that blocks fat synthesis by inhibiting the activation of SREBP,” Chemistry & Biology, 16:882-892, 2009. cited by applicant Kamisuki et al, “Synthesis and evaluation of diarylthiazole derivatives that inhibit activation of sterol regulatory element-binding proteins,” Journal of Medicinal Chemistry, 54(13):4923-4927, 2011. cited by applicant Sanfillippo et al., “Synthesis of (Aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity,” J. Med. Chem., 31:1778-1785, 1988. cited by applicant Vachal et al., “Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor,” Bioorganic & Medicinal Chemistry Letters, 16:3684-3687, 2006. cited by applicant Choi et al., The Journal of Biological Chemistry, (2003), vol. 278(9), p. 7320-24. cited by applicant Reilly et al., Proceedings of the Nutrition Society (2003), V.62, p. 611-619. cited by applicant Pinent et al. International Journal of Obesity, (2005), vol. 29, p. 934-941. 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;252:235-237. cited by applicant Uesugi, M Organic compounds that control SREBP activities, Ikagaku Oyo Kenkyu Zaidan Kenkyu Hokoku, 2006;25:168-172. 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;38:353-358. cited by applicant |
Primary Examiner: | Chu, Yong |
Attorney, Agent or Firm: | Adler, Benjamin Aaron |
رقم الانضمام: | edspgr.08778976 |
قاعدة البيانات: | USPTO Patent Grants |
الوصف غير متاح. |