947255-03-0Relevant articles and documents
From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators
Xie, Haibo,Yang, Ka,Winston-McPherson, Gabrielle N.,Stapleton, Donnie S.,Keller, Mark P.,Attie, Alan D.,Smith, Kerry A.,Tang, Weiping
, (2020/08/21)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3′-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties.
ACYCLIC CXCR4 INHIBITORS AND USES THEREOF
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Paragraph 00236; 00237, (2019/07/13)
The present invention relates to compounds and methods useful for modulation, e.g. inhibition, of C-X-C receptor type 4 (CXCR4). The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using the compositions in the treatment of various disorders.
Novel Enantiomeric Pure Beta Agonists, Manufacturing and Use as a Medicament Thereof
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Page/Page column 37, (2008/06/13)
The present invention relates to enantiomerically pure compounds of formula 1 wherein the groups m, n, B, X, R1, m and Ym- may have the meanings given in the claims and specification, methods for preparing them and their use as pharmaceutical compositions, particularly as pharmaceutical compositions for the treatment of respiratory complaints.
