Abstract:
:Tak-242 (resatorvid), a Toll-like Receptor 4 (TLR4) inhibitor, has been identified as a potent suppressor of innate inflammation. As a strategy to target Tak-242 to select tissue, four TLR4-inactive prodrugs were synthesized for activation via two different release mechanisms. Two nitrobenzyl Tak-242 prodrugs released the parent drug upon exposure to the exogenous enzyme nitroreductase, while the two propargyl prodrugs were converted to Tak-242 in the presence of Pd0.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Plunk MA,Alaniz A,Olademehin OP,Ellington TL,Shuford KL,Kane RRdoi
10.1021/acsmedchemlett.9b00518subject
Has Abstractpub_date
2020-01-03 00:00:00pages
141-146issue
2issn
1948-5875journal_volume
11pub_type
杂志文章abstract::Carbazoles represent a family of tricyclic compounds that widely appeared in nature. Numerous studies have revealed a diverse array of bioactivity associated with this scaffold. In the present study, a novel and highly efficient methodology for preparing 1,3-dihydroxy-2-carboxycarbazole from indole-3-acetic acid and M...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00158
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abstract::Tankyrases, an enzyme subfamily of human poly(ADP-ribosyl)polymerases, are potential drug targets especially against cancer. We have evaluated inhibition of tankyrases by known PARP inhibitors and report five cocrystal structures of the most potent compounds in complex with human tankyrase 2. The inhibitors include th...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml3001352
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abstract::Synthesis of a strict structural analogue of albaconazole in which the quinazolinone ring is fused by a thiazole moiety led to the discovery of a new triazole with broad-spectrum antifungal activity. Compound I exhibited high in vitro activity against pathogenic Candida species and filamentous fungi and showed prelimi...
journal_title:ACS medicinal chemistry letters
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abstract::Selective activation of the M1 muscarinic receptor via positive allosteric modulation represents an approach to treat the cognitive decline in patients with Alzheimer's disease. A series of amides were examined as a replacement for the carboxylic acid moiety in a class of quinolizidinone carboxylic acid M1 muscarinic ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300280g
更新日期:2012-10-13 00:00:00
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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更新日期:2014-05-14 00:00:00
abstract::Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of...
journal_title:ACS medicinal chemistry letters
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abstract::IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and p...
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abstract::EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functio...
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journal_title:ACS medicinal chemistry letters
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更新日期:2019-10-17 00:00:00