- COMPOUND, PREPARATION METHOD THEREFOR, AND USE THEREOF
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The present disclosure provides a compound of formula I or a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, wherein M is a monovalent alkali metal. The present disclosure also provides a method for preparing the compound or its pharmaceutically acceptable salt, solvate, or prodrug, and further provides a pharmaceutical composition containing the compound and its use in the preparation of a medicine, which can be used for the treatment of CCR4-mediated diseases.
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Paragraph 0049-0050
(2021/03/19)
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- Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists
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A series of indazole arylsulfonamides were synthesized and examined as human CCR4 antagonists. Methoxy- or hydroxyl- containing groups were the more potent indazole C4 substituents. Only small groups were tolerated at C5, C6, or C7, with the C6 analogues being preferred. The most potent N3-substituent was 5-chlorothiophene-2-sulfonamide. N1 meta-substituted benzyl groups possessing an α-amino-3-[(methylamino)acyl]- group were the most potent N1-substituents. Strongly basic amino groups had low oral absorption in vivo. Less basic analogues, such as morpholines, had good oral absorption; however, they also had high clearance. The most potent compound with high absorption in two species was analogue 6 (GSK2239633A), which was selected for further development. Aryl sulfonamide antagonists bind to CCR4 at an intracellular allosteric site denoted site II. X-ray diffraction studies on two indazole sulfonamide fragments suggested the presence of an important intramolecular interaction in the active conformation.
- Procopiou, Panayiotis A.,Barrett, John W.,Barton, Nicholas P.,Begg, Malcolm,Clapham, David,Copley, Royston C. B.,Ford, Alison J.,Graves, Rebecca H.,Hall, David A.,Hancock, Ashley P.,Hill, Alan P.,Hobbs, Heather,Hodgson, Simon T.,Jumeaux, Coline,Lacroix, Yannick M. L.,Miah, Afjal H.,Morriss, Karen M. L.,Needham, Deborah,Sheriff, Emma B.,Slack, Robert J.,Smith, Claire E.,Sollis, Steven L.,Staton, Hugo
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p. 1946 - 1960
(2013/05/09)
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- INDAZOLE COMPOUNDS
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Indazole compounds, processes for their preparation, pharmaceutical compositions containing such compounds and their use in therapy.
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Page/Page column 31
(2012/03/26)
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- CC.CHEMOKINE RECEPTOR 4 ANTAGONISTS
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Indazole compounds, processes for their preparation, pharmaceutical compositions containina such compounds and their use in the treatment of a disease or condition for which a CCR4 receptor antagonist is indicated.
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Page/Page column 33
(2012/03/26)
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- NOVEL COMPOUNDS
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Indazole compounds, processes for their preparation, intermediates usable in these processes, pharmaceutical compositions containing such compounds and their use in therapy.
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Page/Page column 14
(2010/09/05)
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