- Pyrazole-based arylalkyne Cathepsin S inhibitors. Part III: Modification of P4 region
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Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1′/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described.
- Wiener, John J.M.,Wickboldt, Alvah Tyson,Nguyen, Steven,Sun, Siquan,Rynberg, Raymond,Rizzolio, Michele,Karlsson, Lars,Edwards, James P.,Grice, Cheryl A.
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p. 1070 - 1074
(2013/03/13)
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- Practical synthesis of a cathepsin S Inhibitor: Route identification, purification strategies, and serendipitous discovery of a crystalline salt form
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Chemical Equation Presented A redox economical strategy resulted in a concise, modular synthesis of compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared, in a two-step sequence in high yield. Efficient purification of the crude drug substance was accomplished via the formation of an unusual monoethyl oxalate salt.
- Deng, Xiaoliu,Liang, Jimmy T.,Peterson, Matthew,Rynberg, Raymond,Cheung, Eugene,Mani, Neelakandha S.
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experimental part
p. 1940 - 1947
(2010/05/18)
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- Pyrazole-based arylalkyne cathepsin S inhibitors. Part II: Optimization of cellular potency
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Basic lipophilic substituents dramatically improved the cellular potency of a previously disclosed series of pyrazole-based arylalkyne cathepsin S inhibitors. The incorporation of substituted benzylamines in the para position of the arylalkyne maintained
- Ameriks, Michael K.,Cai, Hui,Edwards, James P.,Gebauer, Damara,Gleason, Elizabeth,Gu, Yin,Karlsson, Lars,Nguyen, Steven,Sun, Siquan,Thurmond, Robin L.,Zhu, Jian
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scheme or table
p. 6135 - 6139
(2010/06/16)
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- PROCESSES FOR THE PREPARATION OF CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
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Method of making carbon-linked tetrahydro-pyrazolo-pyridine compounds of the following Formula (I) and pharmaceutically acceptable salts thereof: comprising reacting a compound of formula (IX): with a compound of formula (X): to form a compound of Formula
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Page/Page column 21
(2009/10/09)
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- CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
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Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.
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Page/Page column 73
(2008/12/08)
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