66186-85-4Relevant academic research and scientific papers
Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood
Thoma, Gebhard,Baenteli, Rolf,Lewis, Ian,Jones, Darryl,Kovarik, Jiri,Streiff, Markus B.,Zerwes, Hans-Guenter
, p. 4745 - 4749 (2011)
The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC50 values below 10 nM in both ligand binding and Ca2+-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC50 values below 10 nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.
ERGOLINE DERIVATIVES AND THEIR USE AS CHEMOKINE RECEPTOR LIGANDS
-
Page/Page column 12, (2008/06/13)
Disclosed are ergoline derivatives, Formula (I), wherein either each of R1 and R2, independently, is H; optionally R10 and/or R11-substituted-phenyl or - phenyl-C1-4alkyl; optionally R10 and/or R11-substituted-heteroaryl or -heteroaryl-C1-4alkyl; optionally R10 and/or R11-substituted heteroaryl N-oxide; optionally R10-substituted C1-C8 alkyl; optionally R10-substituted C2-C8 alkenyl, optionally R10-substituted C2-C8 alkynyl; optionally R10-substituted C3-C8 cycloalkyl, or optionally R10-substituted C4-C8 cycloalkenyl; or R1 and R2 form together with the nitrogen atom to which they are attached an optionally R10-substituted 3-8 membered ring containing in addition to the nitrogen atom up to 2 heteroatoms selected independently from N, O and S; R3 is H; OR1; CH2R1R2; (CH2)1-2NR1R2; CH2-CH2-OR1; CH2-CO-NR1R2; or CO-CH2R1R2; R4 is F; CI; Br; I; OR1; NR1R2 or has one of the significances given for R1; and R5 has one of the significances given for R1, in free form or in salt form for preventing or treating disorders or diseases mediated by interactions between chemokine receptors and their ligands.
