32852-81-6Relevant articles and documents
1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors
Boshoff, Helena I. M.,Caljon, Guy,Forbes, He Eun,Hulpia, Fabian,Jian, Yanlin,Munier-Lehmann, Hélène,Risseeuw, Martijn D. P.,van Calenbergh, Serge
, (2020/07/07)
A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).
Substrate-selective inhibition of cyclooxygenase-2: Development and evaluation of achiral profen probes
Windsor, Matthew A.,Hermanson, Daniel J.,Kingsley, Philip J.,Xu, Shu,Crews, Brenda C.,Ho, Winnie,Keenan, Catherine M.,Banerjee, Surajit,Sharkey, Keith A.,Marnett, Lawrence J.
, p. 759 - 763 (2012/10/29)
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 μM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.
Esters and amides of substituted phenyl acetic acids
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, (2008/06/13)
Esters and amides of substituted phenyl acetic acids having the formula wherein Q is a deprotonated residue of a polymer or macromolecular structure having a molecular weight of at least 1000 containing at least two primary and/or secondary amino groups and/or hydroxy groups;, n is an integer of at least 2;, R1 and R2 are independently selected from, hydrogen, halogen, alkyl, alkenyl, alkinyl or halo alkyl;, R3 is one or more substituents selected from halogen, alkyl, alkenyl or alkinyl, cycloalkyl, oxo-substituted alkylcycloalkyl, haloalkyl, alkoxy, alkenyloxy, alkinyloxy, alkylamino, alkenylamino, alkinylamino, alkysulfonyl, alkenylsulfonyl, alkinylsulfonyl, alkylsulfinyl, alkenylsulfinyl, alkinylsulfinyl, alkylsulfenyl, alkenylsulfenyl, alkinylsulfenyl, pyrrolyl, piperidinyl, benzoyl, imidazolpyridinyl, isoindolyl, oxo-substituted isoindolyl, thionylcarbonyl, phenyl, phenoxy and halo-substituted phenoxy, are useful in the treatment of colonic polyps.
