226070-69-5Relevant articles and documents
CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO
-
Page/Page column 173; 174; 175, (2018/09/19)
The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.
Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in Vitro ADMET Properties
Miller, Eric J.,Jecs, Edgars,Truax, Valarie M.,Katzman, Brooke M.,Tahirovic, Yesim A.,Wilson, Robert J.,Kuo, Katie M.,Kim, Michelle B.,Nguyen, Huy H.,Saindane, Manohar T.,Zhao, Huanyu,Wang, Tao,Sum, Chi S.,Cvijic, Mary E.,Schroeder, Gretchen M.,Wilson, Lawrence J.,Liotta, Dennis C.
, p. 946 - 979 (2018/02/17)
CXCR4 is a seven-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by (1) stimulating prosurvival signaling and (2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated prosurvival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis. Current small molecule CXCR4 antagonists suffer from poor oral bioavailability and off-target liabilities. Herein, we report a series of novel tetrahydroisoquinoline-containing CXCR4 antagonists designed to improve intestinal absorption and off-target profiles. Structure-activity relationships regarding CXCR4 potency, intestinal permeability, metabolic stability, and cytochrome P450 inhibition are presented.
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
supporting information, 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.
HISTONE DEACETYLASE INHIBITORS
-
, (2012/05/04)
The disclosure provides compounds of formula I and methods for preparation thereof. The compounds act as inhibitor of histone deacetylase.
HISTONE DEACETYLASE INHIBITORS
-
, (2011/04/13)
The disclosure provides compounds of formula I and methods for preparation thereof. The compounds act as inhibitor of histone deacetylase.
NOVEL COMPOUNDS
-
Page/Page column 33-34, (2010/09/05)
Indazole compounds, processes for their preparation, intermediates usable in these processes, pharmaceutical compositions containing such compounds and their use in therapy.
PYRIDINONYL PDK1 INHIBITORS
-
Page/Page column 56, (2008/06/13)
The present invention provides pyridinonyl PDKl inhibitors and methods of treating cancer using the same.
SUBSTITUTED PYRIDINONES
-
, (2008/06/13)
Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and R5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.
DIARYLMETHYL AND RELATED COMPOUNDS
-
Page 106, (2010/02/09)
This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, Ar1, Ar2, E, a, b, c, and z are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
Azabicycloalkane compounds
-
Page 35, (2008/06/13)
This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6 and R7 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
