886362-07-8Relevant articles and documents
COMPOUND, PREPARATION METHOD THEREFOR, AND USE THEREOF
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Paragraph 0047-0048, (2021/03/19)
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.
Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists
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
, p. 1946 - 1960 (2013/05/09)
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.
INDAZOLE COMPOUNDS
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Page/Page column 31, (2012/03/26)
Indazole compounds, processes for their preparation, pharmaceutical compositions containing such compounds and their use in therapy.
CC.CHEMOKINE RECEPTOR 4 ANTAGONISTS
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Page/Page column 32-33, (2012/03/26)
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.
Lead optimisation of the N1 substituent of a novel series of indazole arylsulfonamides as CCR4 antagonists and identification of a candidate for clinical investigation
Procopiou, Panayiotis A.,Ford, Alison J.,Graves, Rebecca H.,Hall, David A.,Hodgson, Simon T.,Lacroix, Yannick M.L.,Needham, Deborah,Slack, Robert J.
scheme or table, p. 2730 - 2733 (2012/05/31)
Synthesis and preliminary SAR of the N1 substituent of a novel series of indazole sulfonamide chemokine receptor 4 (CCR4) antagonist is reported. Compound 7r was identified for further development.
3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α2-adrenoceptor compared to the imidazoline I1 receptor
Sczewski, Franciszek,Kornicka, Anita,Hudson, Alan L.,Laird, Shayna,Scheinin, Mika,Laurila, Jonne M.,Rybczyńska, Apolonia,Boblewski, Konrad,Lehmann, Artur,Gdaniec, Maria
experimental part, p. 321 - 329 (2011/02/26)
A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective α2-adrenoceptor ligand. Parent compound 4a and its 4-chloro (4c) and 4-methyl (4d) derivatives display α2-adrenoceptor affinity at nanomolar concentrations (Ki = 39.4, 15.9 and 22.6 nM, respectively) and relatively high α2/I1 selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at α2A-adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01 mg/kg iv.
INDAZOLYL-PYRIMIDINES AS KINASE INHIBITORS
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Page/Page column 64, (2011/10/13)
Disclosed are compounds having the formula: or a salt thereof, wherein A, n, R1, R1A, and R2 are as defined herein, and methods of making and using the same.
NOVEL COMPOUNDS
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Page/Page column 13, (2010/09/05)
Indazole compounds, processes for their preparation, intermediates usable in these processes, pharmaceutical compositions containing such compounds and their use in therapy.