Patent
Methods and compositions for the treatment of cancer and related hyperproliferative disorders
| العنوان: | Methods and compositions for the treatment of cancer and related hyperproliferative disorders |
|---|---|
| Patent Number: | 9,713,613 |
| تاريخ النشر: | July 25, 2017 |
| Appl. No: | 14/940584 |
| Application Filed: | November 13, 2015 |
| مستخلص: | The present invention relates to methods of treating a disease related to cell hyper-proliferation via administration of a therapeutically effective amount of a compound having a general tripartite structure A-B-C. In the tripartite structure 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. The methods may utilize particular compounds, for example, having a piperidinyl, a pyrrolinyl or pyridinyl A ring, a thiazole B ring, and a phenyl C ring which may be further substituted independently. |
| Inventors: | Uesugi, Motonari (Osaka, JP); Wakil, Salih J. (Houston, TX, US); Abu-Elheiga, Lutfi (Houston, TX, US); Watanabe, Mizuki (Kyoto, JP) |
| Claim: | 1. A method for treating a cancer in a patient in need thereof, comprising the step of administering to the patient, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound according to the chemical structure: [chemical expression included] wherein R is H, isopropyl, benzyl, cyclohexyl, cyclopropylmethyl, —COMe, tert-butyloxycarbonyl, or methylsulfonyl, or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof; wherein the cancer is a cancer of the respiratory tract, brain, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, or parathyroid, or the cancer is lymphoma, sarcoma, melanoma, leukemia, multiple myeloma, or a distant metastasis of a solid tumor. |
| Claim: | 2. The method of claim 1 , wherein the chemical structure of the compound is: [chemical expression included] |
| Claim: | 3. The method of claim 1 , wherein the compound is: N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide, 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)phenylacetamide, N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine, N-benzyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine, or N-cyclohexyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine. |
| Claim: | 4. A method for treating a disease related to cell hyper-proliferation in a patient in need thereof, comprising the step of administering to the patient, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound that is: 4-(4-bromophenyl)-2-(pyrrolidin-2-yl)thiazole, 4-(4-bromophenyl)-2-(1-propylpyrrolidin-2-yl)thiazole, tert-butyl 2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate, benzyl 2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate, benzyl (R)-2-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)pyrrolidine-1-carboxylate, 3-(4-(4-bromophenyl)thiazol-2-yl)-1-propylpiperidine, tert-butyl 3-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate, benzyl 3-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate, benzyl 4-(4-(4-bromophenyl)thiazol-2-yl)piperidine-1-carboxylate, benzyl 3-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)piperidine-1-carboxylate, benzyl 4-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)piperidine-1-carboxylate, 3-chloro-4-methyl-N-(6-(4-(3-(trifluoromethyl)benzyl)piperazin-1-yl)pyridin-3-yl)benzenesulfonamide, (4-(5-chloro-2-methylphenyl)piperazin-1-yl)(4-(tosylamino)phenyl) methanone, 4-(4-((1-methyl-1H-benzo[d]imidazole-2-yl)methyl)piperazin-1-yl)-N-tosylbenzenamine, 4-chloro-N-(4-(4-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)piperazin-1-yl)phenyl) benzenesulfonamide; or 4-(3-(pyridin-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-N-tosylbenzenamine; (Z)-4-(3-cyano-3-(4-(2,4-dimethylphenyl)thiazol-2-yl)allyl)-N-(thiazol-2-yl)benzenesulfonamide. |
| Claim: | 5. The method of claim 4 , wherein the disease related to cell hyper-proliferation is cancer. |
| Claim: | 6. The method of claim 5 , wherein the cancer is a cancer of the breast, respiratory tract, brain, reproductive organs, prostate, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, or parathyroid, or the cancer is lymphoma, sarcoma, melanoma, leukemia, multiple myeloma, or a distant metastasis of a solid tumor. |
| Claim: | 7. The method of claim 2 , where the cancer is liver cancer. |
| Claim: | 8. The method of claim 2 , where the cancer is leukemia. |
| Claim: | 9. The method of claim 2 , where the cancer is multiple myeloma. |
| Patent References Cited: | 4153703 May 1979 Harrison et al. 4791200 December 1988 Press et al. 5643932 July 1997 Chihiro et al. 5792783 August 1998 Tang 7151196 December 2006 Wilkening et al. 7153889 December 2006 Altenbach et al. 7786143 August 2010 Nettekoven et al. 8207196 June 2012 Uesugi et al. 8927578 January 2015 Uesugi et al. 9187485 November 2015 Uesugi 2003/0069223 April 2003 Jacobs et al. 2004/0267017 December 2004 Bierer 2006/0148722 July 2006 Lewis et al. 2006/0229363 October 2006 Hamanaka 2009/0318436 December 2009 Albrecht 2013/0005768 January 2013 Uesugi et al. 2014/0038984 February 2014 Uesugi et al. 2014/0045845 February 2014 Hoegberg et al. 2014/0235646 August 2014 Uesugi et al. 2014/0303213 October 2014 Uesugi et al. 2015/0307501 October 2015 Uesugi et al. 2016/0128985 May 2016 Uesugi et al. 2016/0136164 May 2016 Uesugi et al. 3406329 August 1985 0513387 November 1992 1092711 April 2001 1348706 October 2003 H04-282326 October 1992 11 079993 March 1999 11186479 June 1999 2000-080086 March 2000 WO 94/22846 October 1994 WO 96/01825 January 1996 WO 96/23783 August 1996 9814191 April 1998 WO 99/15524 April 1999 01006261 January 2001 WO 02/46186 June 2002 02068417 September 2002 WO 03/027085 April 2003 WO 2004/014903 February 2004 WO 2004/091610 October 2004 WO 2004/103959 December 2004 WO 2005/016323 February 2005 WO 2005/049033 June 2005 WO 2005/051932 June 2005 2006017384 February 2006 WO 2006/024642 March 2006 2006080406 August 2006 WO 2006/133559 December 2006 2007001973 January 2007 WO 2007/005785 January 2007 WO 2007/020194 February 2007 WO 2007/052843 May 2007 WO 2007/062222 May 2007 WO 2008/026046 March 2008 WO 2008/090382 July 2008 WO 2008/097835 August 2008 WO 2009/027346 March 2009 WO 2009/055917 May 2009 WO 2010/013975 February 2010 WO 2010/059611 May 2010 WO 2010/090716 August 2010 WO 2011/085128 July 2011 WO 2012/129562 September 2012 WO 2013/052585 April 2013 2013110007 July 2013 WO 2016/073826 May 2016 WO 2016/105491 June 2016 |
| Other References: | STN—14940584—Preliminary search—04222016. cited by examiner Choi et al., Journal of Biological Chemistry, (2003), 278(9), p. 7320-24. cited by examiner Merck Manual, (2016). 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 locument. 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 Abu-Elheiga et al., Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2 Science 2001. 291:2613-2616. cited by applicant Abu-Elheiga et al., Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets Proc. Natl. Acad. Sci. USA 2003. 100:10207-10212. cited by applicant Abu-Elheiga et al., The subcellular localization of acetyl-CoA carboxylase 2 Proc. Nat Acad. Sci. 2000. 97:1444-1449. cited by applicant Abu-Elheiga et al., Human Acetyl-CoA Carboxylase 2, Journal of Biological Chemistry, 1997. 272:10669-10677. cited by applicant Abu-Elheiga et al., Human acetyl-CoA carboxylase: Characterization, molecular cloning, and evidence for two isoforms Proc. Natl. Acad. Sci. USA, 1995. 92: 4011-401. cited by applicant Boden et al., Mechanisms of Fatty Acid-induced Inhibition of Glucose Uptake The American Society for Clinical Investigation, Inc. 1994. 93: 2438-2446. cited by applicant Boizard et al., Obesity-related Overexpression of Fatty-acid Synthase Gene in Adipose Tissue Involves Sterol Regulatory Element-binding Protein Transcription Factors Journal of Biological Chemistry, 1998. 273: 29164-29171. cited by applicant Brown et al. , The SREBP Pathway: Regulation Review of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor Cell 1997. 89:331-40. cited by applicant Chalkley et al., Five-Hour Fatty Acid Elevation Increases Muscle Lipids and Impairs Glycogen Synthesis in the Rat, Metabolism,1998: 47:1121-1126. cited by applicant Cohen et al, Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss, Science, 2002. 297: 240-243. cited by applicant Goldstein et al., Protein Sensors for Membrane Sterols, Cell 2006. 124: 35-46. cited by applicant Grand-Perret et al., SCAP ligands are potent new lipid-lowering drugs, Nature Medicine 2001. 7: 1332-1338. cited by applicant Hastings et al., A vertebrate fatty acid desaturase with Δ5 and Δ6 activities, Proc. Natl. Acad. Sci. USA, 2001. 98: 14304-14309. cited by applicant Hookman et al., Current Biochemical Studies of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Suggest a New Therapeutic Approach The American Journal of Gastroenterology, 2003. 98: 2093-97. cited by applicant Horton et al., Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice, Proc. Natl. Acad. Sci. USA, 1998. 95: 5987-5992. cited by applicant Horton et al., Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes, Proc. Natl. Acad. Sci. USA, 2003. 100: 12027-12032. cited by applicant Horton et al., Overexpression of Sterol Regulatory Element-binding Protein-1a in Mouse Adipose Tissue Produces Adipocyte Hypertrophy, Increased Fatty Acid Secretion, and Fatty Liver, Journal of Biological Chemistry, 2003. 278: 36652-36660. cited by applicant Hua et al., Sterol Resistance in CHO Cells Traced to Point Mutation in SREBP Cleavage—Activating Protein, Cell, 1996. 87: 415-426. cited by applicant Hua et al., Hairpin Orientation of Sterol Regulatory Element-binding Protein-2 in Cell Membranes as Determined by Protease Protection, Journal of Biological Chemistry, 1995. 270: 29422-29427. cited by applicant Kim et al., ADD 1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism, Genes & Development, 1996. 10:1096-110. cited by applicant Kubota et al., PPARg Mediates High-Fat Diet-Induced Adipocyte Hypertrophy and Insulin Resistance. Molecular Cell, 1999. 4: 597-609. cited by applicant Liang et al., Diminished Hepatic Response to Fasting/Refeeding and Liver X Receptor Agonists in Mice with Selective Deficiency of Sterol Regulatory Element-binding Protein-1c, Journal of Biological Chemistry, 2002. 2779520-9528. cited by applicant Mao et al., Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis, Proc. Natl. Acad. Sci. USA, 2006. 103: 8552-8557. cited by applicant Marquardt et al., cDNA Cloning, Genomic Structure, and Chromosomal Localization of Three Members of the Human Fatty Acid Desaturase Family Genomics, 2000. 66:175-183. cited by applicant Matsusue et al., Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes, The Journal of Clinical Investigation, 2003. 111: 737-47. cited by applicant Miyazaki et al., The Biosynthesis of Hepatic Cholesterol Esters and Triglycerides Is Impaired in Mice with a Disruption of the Gene for Stearoyl-CoA Desaturase 1, Journal of Biological Chemistry, 2000. 275: 30132-30138. cited by applicant Moller et al., Metabolic Syndrome: A Clinical and Molecular Perspective Annu. Rev. Med. 2005. 56:45-62. cited by applicant Nakamura et al., Structure, Function, and Dietary Regulation of Δ6, Δ5, and Δ9 Desaturases. Annu. Rev. Nutr. 2004. 24:345-76. cited by applicant Oh et al., Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice, Proc. Natl. Acad. Sci. USA, 2005. 102: 1384-1389. cited by applicant Osborne et al., Sterol Regulatory ElementbindingProteins (SREBPs): Key Regulators of Nutritional Homeostasis and Insulin Action, Journal of Biological Chemistry, 2000. 275:. 32379-32382. cited by applicant Rader et al., A new feature on the cholesterol-lowering landscape, Nature Medicine, 2001. 7: 1282-84. cited by applicant Sakai et al., Sterol-Regulated Release of SREBP-2 from Cell Membranes Requires Two Sequential Cleavages, One Within a Transmembrane Segment, Cell, 1996. 85,1037-1046. cited by applicant Sakai et al., Molecular Identification of the Sterol-Regulated Luminal Protease that Cleaves SREBPs and Controls Lipid Composition of Animal Cells, Molecular Cell, 1998. 2: 505-514. cited by applicant Zambrowicz et al., Knockouts Model the 100 Best-Selling Drugs—Will They Model the Next 100?, Nat. Rev. Drug Discovery, 2002. 2: 38-51. cited by applicant Yahagi et al., Absence of Sterol Regulatory Element-binding Protein-1 (SREBP-1) Ameliorates Fatty Livers but Not Obesity or Insulin Resistance in Lepob/Lepob Mice. Journal of Biological Chemistry, 2002. 277: 19353-19357. cited by applicant Tontonoz et al., ADDi: a Novel Helix-Loop-Helix Transcription Factor Associated with Adipocyte Determination and Differentiation, Molecular and Cellular Biology, 1993. 13: 4753-4759. cited by applicant Ntambi et al., Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity, Proc. Natl. Acad. Sci. USA, 2002. 99: 11482-11486. cited by applicant Shimano et al., Sterol Regulatory Element-binding Protein-1 as a Key Transcription Factor for Nutritional Induction of Lipogenic Enzyme Genes, Journal of Biological Chemistry, 1999. 274: 35832-35839. cited by applicant Sheng et al., Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver, Proc. Natl. Acad. Sci. USA, 1995. 92: 935-938. cited by applicant Sato et al., Polyproline-Rod Approach to Isolating Protein Targets of Bioactive Small Molecules: Isolation of a New Target of Indomethacin, J. Am. Chem. Soc. 2007. 129: 873-880. cited by applicant Bellale, Eknath et al., “Diarylthiazole: an antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system”, Journal of Medicinal Chemistry Jun. 26, 2014, vol. 57, No. 15, pp. 6572-6582. cited by applicant Chen, Y et al., “Copper catalyzed synthesis of 1-aryl-1,2,3-triazoles from aryl iodides, alkynes, and sodium azide,” Journal of Organometallic Chemistry 2014, 749(31):215-218. cited by applicant Colah et al., Bulletin of Haffkine Institute 1997, 5(1), pp. 20-22. cited by applicant Cotugno et al., Organic & Biomolecular Chemistry 2012, vol. 10, pp. 808-813. cited by applicant Demirayak et al., Synthesis of some 4-pyrrolylphenylthiazole derivatives and investigation of their antimicrobial activities, Acta Pharmaceutica Turicica 1997, 39(3), pp. 133-136. cited by applicant Eckenstein, J. et al., “Uber die Eigenschaften einiger Phenyl-azol-Derivate,” Helvetica Chimica Acta, vol. XXXIII, No. 178, 1950, pp. 1353-1365. Machine translation included. cited by applicant El-Shukry, Gaber, Journal of the Iraqi Academy (1980), 31(4), 93-110 Research in organic chemistry. cited by applicant Hämmerle et al. Tetrahedron 2010, vol. 66, pp. 8051-8059. cited by applicant Ingalls, A. M. Dickie, M. M., and Snell, G. D., J. Hered. 1950, 41, 317-318. cited by applicant International Search Report and Written Opinion mailed Dec. 25, 2014 in International Patent Application No. PCT/US2014/053334, 13 pages. cited by applicant Jin et al. Chem. Eur. J. 2012, vol. 18, pp. 446-450. cited by applicant Khadse, B. G. et al., Bulletin of Haffkine Institute (1977), 5(2), 56-9 Synthesis and study of 2-[p-(2-substituted-4-thiazolyl)arylannino]pyrido(3,2-d)thiazoles as possible anthelmintic agents. cited by applicant Kowluru et al. Diabetes 2004, vol. 53, pp. 775-791. cited by applicant Ktorza A, B. C., Parent V, Penicaud L, Froguel P, Lathrop M, Gauguier D., Diabetes Metab. Suppl 2 1997, 38-46. cited by applicant Lee et al., Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of lnsig-1, J Biol Chem. Oct. 22, 2004; vol. 279(43), pp. 45257-45265. cited by applicant Maeda et al. Cell Metabolism 2005, 1(2), p. 107-119. cited by applicant Mullican, Michael, Search Report prepared for Mr. Gino Catena of Fulbright & Jaworski L.L.P. Science IP: scienceIPgcas.org, N. Narasimhamurthy et al., “Thiocarbonyl to carbonyl group transformation using CuCl and NaOH,” Tetrahedron Letters 1986, vol. 27, Issue 33, pp. 3911-3912. cited by applicant Narender et al., Tetrahedron Letters 2005, 46 (35), pp. 5953-5955. cited by applicant Richardson, C et al. J. Org. Chern. 2007, 72, 4750. cited by applicant Shimano, H. (2000) Trends Cardiovasc Med 10, 275-8. cited by applicant STN—14052074A—Preliminary—10—11—2014. cited by applicant The compound CAS RN 116227-98-6 entered STN database and accessible to public on Sep. 3, 1988. cited by applicant The compound CAS RN 1246471-51-1 entered STN database and accessible to public on Oct. 18, 2010. cited by applicant The compound CAS RN 1256384-71-0 entered STN database and accessible to public on Dec. 13, 2010. cited by applicant The compound CAS RN 1282016-56-1 entered STN database and accessible to public on Apr. 18, 2011, provided by Aurora Fine Chemicals. cited by applicant The compound CAS RN 1310695-72-7 entered STN database and accessible to public on Jun. 29, 2011. cited by applicant The compound CAS RN 298197-07-6 entered STN database and accessible to public on Oct. 23, 2000. cited by applicant The compound CAS RN 352656-48-5 entered STN database and accessible to public on Aug. 27, 2001. cited by applicant The compound CAS RN 361199-89-5 entered STN database and accessible to public on Oct. 9, 2001, provided by ChemBridge Corporation. cited by applicant The compound CAS RN 457943-97-4 entered STN database and accessible to public on Oct. 2, 2002, provided by Ambinter. cited by applicant The compound CAS RN 501914-24-5 entered STN database and accessible to public on Apr. 7, 2003, provided by Interchim. cited by applicant The compound CAS RN 831231-54-0 entered STN database and accessible to public on Feb. 15, 2005, provided by ChemBridge Co. cited by applicant The compound CAS RN 850301-38-1 entered STN database and accessible to public on May 11, 2005, provided by Enamine. cited by applicant The compound CAS RN 850338-20-4 entered STN database and accessible to public on May 12, 2005, provided by Enamine. cited by applicant The compound CAS RN 850373-62-5 entered STN database and accessible to public on May 12, 2005, provided by Enamine. cited by applicant The compound CAS RN 878666-16-1 entered STN database and accessible to public on Mar. 31, 2006, provided by AsInEx. cited by applicant The compound CAS RN 879343-52-9, entered STN database in 2006. cited by applicant The compound CAS RN 921110-77-2 entered STN database and accessible to public on Feb. 15, 2007, provided by Aurora Fine Chemicals. cited by applicant The compound CAS RN 921134-76-1 entered STN database and accessible to public on Feb. 15, 2007, provided by Aurora Fine Chemicals. cited by applicant The compound CAS RN 924137-63-3 entered STN database and accessible to public on Mar. 1, 2007, provided by Aurora Fine Chemicals. cited by applicant The compound CAS RN 930490-25-8 entered STN database and accessible to public on Apr. 17, 2007, provided by Enamine. cited by applicant The compound CAS RN 940754-80-3 entered STN database and accessible to public on Jul. 2, 2007, provided by Enamine. cited by applicant The compound CAS RN 941053-08-3 entered STN database and accessible to public on Jul. 4, 2007, provided by Enamine. cited by applicant The compound CAS RN 941087-30-5 entered STN database and accessible to public on Jul. 4, 2007, provided by Enamine. cited by applicant The compound CAS RN 941140-28-9 entered STN database and accessible to public on Jul. 4, 2007, provided by Enamine. cited by applicant The compound CAS RN 941206-37-7 entered STN database and accessible to public on Jul. 4, 2007, provided by Enamine. cited by applicant Turner, GL et al. Angew. Chern. Int. Ed. 2007, 42, 7996. cited by applicant Ueda, S. et al. Angew. Chern. Int. Ed. 2011, 38, 8944. cited by applicant Varma et al., J. Chem. Soc., Perkin Trans 1998, vol. 1, pp. 4098-4096. cited by applicant |
| Primary Examiner: | Chu, Yong |
| Attorney, Agent or Firm: | Squire Patton Boggs (US) LLP |
| رقم الانضمام: | edspgr.09713613 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |