- A scalable oxidation for the final stage of synthesis of cathepsin K inhibitor SB-462795
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In developing the manufacturing route for the cathepsin K inhibitor SB-462795, the oxidation of a secondary alcohol for the final chemical stage is described. Prospective conditions were limited by several factors, particularly general safety concerns of oxidation reactions, the requirement to control impurities and transition metals isolated in the final product, and the desire to reduce the environmental impact. Two N-oxy free radical approaches (TEMPO and PIPO) and Moffatt conditions were evaluated in depth for their potential to achieve the targets. For reasons of robustness, scalability, and cost-effectiveness, the Moffatt conditions were the best manufacturing option.
- Goodman, Steven N.,Dai, Qunying,Wang, Jun,Clark, William M.
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- Large-scale synthesis of SB-462795, a cathepsin K inhibitor: the RCM-based approaches
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Two stereoselective syntheses of SB-462795, a highly potent cathepsin K inhibitor, are described. Both routes feature a C5-C6 disconnection by ring closing metathesis to construct an azepane ring and are amenable to large-scale manufacturing.
- Wang, Huan,Matsuhashi, Hayao,Doan, Brian D.,Goodman, Steven N.,Ouyang, Xi,Clark Jr., William M.
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scheme or table
p. 6291 - 6303
(2009/12/04)
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- Method of Preparation of Benzofuran-2-Carboxylic Acid -Amide
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This invention relates to a method of preparation of benzofuran-2-carboxylic acid {(S)-3-methyl-1-[(4S,7R)-7-methyl-3-oxo-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-butyl}-amide.
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Page/Page column 7; 14
(2008/12/04)
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- Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors
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The syntheses, in vitro characterizations, and rat and monkey in vivo pharmacokinetic profiles of a series of 5-, 6-, and 7-methyl-substituted azepanone-based cathepsin K inhibitors are described. Depending on the particular regiochemical substitution and
- Yamashita, Dennis S.,Marquis, Robert W.,Xie, Ren,Nidamarthy, Sirishkumar D.,Oh, Hye-Ja,Jeong, Jae U.,Erhard, Karl F.,Ward, Keith W.,Roethke, Theresa J.,Smith, Brian R.,Cheng,Geng, Xiaoliu,Lin, Fan,Offen, Priscilla H.,Wang, Bing,Nevins, Neysa,Head, Martha S.,Haltiwanger, R. Curtis,Sarjeant, Amy A. Narducci,Liable-Sands, Louise M.,Zhao, Baoguang,Smith, Ward W.,Janson, Cheryl A.,Gao, Enoch,Tomaszek, Thaddeus,McQueney, Michael,James, Ian E.,Gress, Catherine J.,Zembryki, Denise L.,Lark, Michael W.,Veber, Daniel F.
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p. 1597 - 1612
(2007/10/03)
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- Protease inhibitors
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The present invention provides C1-6alkyl-4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease; and parasitic diseases, including malaria, by administering to a patient in need thereof one or more compounds of the present invention.
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