Abstract:
:Metalloproteinases of the astacin family are drawing ever increasing attention as potential drug targets. However, knowledge regarding inhibitors thereof is limited in most cases. Crucial for the development of metalloprotease inhibitors is high selectivity, to avoid side effects brought about by inhibition of off-target proteases and interference with physiological pathways. In this study we aimed at the design of novel selective inhibitors for the astacin proteinase meprin α. Based on a recently identified tertiary amine scaffold, a series of compounds was synthesized and evaluated. The compounds exhibit reasonable inhibitory activity with high selectivity over other metalloproteases. The isoenzyme meprin β is only slightly inhibited. Hence, the present study revealed a novel class of selective meprin α inhibitors with improved selectivity over known compounds.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Tan K,Jäger C,Schlenzig D,Schilling S,Buchholz M,Ramsbeck Ddoi
10.1002/cmdc.201800300subject
Has Abstractpub_date
2018-08-20 00:00:00pages
1619-1624issue
16eissn
1860-7179issn
1860-7187journal_volume
13pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::Natural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total synt...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500246
更新日期:2015-10-01 00:00:00
abstract::An alternative method to prepare 2-organylchalcogenopheno[2,3-b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2-chloro-3-(organylethynyl)pyridines by using the NaBH4 /PEG-400 reducing system, followed by an intramolecular cyclization. It was poss...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000358
更新日期:2020-09-16 00:00:00
abstract::A small set of aggrecanase inhibitors based on the pyrrolo[3,4-c]quinolin-1-one or oxoisoindoline frameworks bearing a 4-(benzyloxy)phenyl substituent and different zinc binding groups were rationally designed and evaluated in silico by docking studies using the crystal structure of the ADAMTS-5 catalytic domain (PDB ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900523
更新日期:2010-05-03 00:00:00
abstract::The present work describes some recent approaches to novel 3-oxabicyclo[3.2.0]heptane-type nucleosides structurally similar to the potent anti-HIV agent stavudine (d4T). To gain knowledge at the molecular level relevant for further synthetic designs, the lack of activity of these compounds was investigated by computat...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200059
更新日期:2012-06-01 00:00:00
abstract::Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000858
更新日期:2020-12-06 00:00:00
abstract::The in silico design, synthesis, and biological evaluation of ten potent type II dehydroquinase inhibitors are described. These compounds contain an anhydroquinate core, incorporated as a mimic of the enolate reaction intermediate. This substructure is attached by a variety of linking units to a terminal phenyl group ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700032
更新日期:2007-07-01 00:00:00
abstract::Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900242
更新日期:2009-11-01 00:00:00
abstract::The three databases of PubChem, ChemSpider, and UniChem capture the majority of open chemical structure records with February 2018 totals of 95, 63, and 154 million, respectively. Collectively, they constitute a massively enabling resource for cheminformatics, chemical biology, and drug discovery. As meta-portals, the...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700724
更新日期:2018-03-20 00:00:00
abstract::TIBO- and TBO-like sulfone derivatives 1 and 2 were designed, synthesized, and tested for their ability to block the replication cycle of HIV-1 in infected cells. The anti-HIV-1 activities of sulfones 3, which were intermediates in the syntheses of 1 and 2, were also evaluated. Surprisingly, the sulfone analogues of T...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200500020
更新日期:2006-01-01 00:00:00
abstract::From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and n...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200403
更新日期:2013-02-01 00:00:00
abstract::The ferrocenyl diphenol complexes 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (1) and 1,2-bis(4'-hydroxyphenyl)-1-ferrocenyl-but-1-ene [(Z)-2], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 is far more cytotox...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900430
更新日期:2019-10-04 00:00:00
abstract::Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prep...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800238
更新日期:2018-08-10 00:00:00
abstract::Recently we reported on aryl-fluorosulfates as possible stable and effective electrophiles for the design of lysine covalent, cell permeable antagonists of protein-protein interactions (PPIs). Here we revisit the use of aryl-sulfonyl fluorides as Lys-targeting moieties, incorporating these electrophiles in XIAP (X-lin...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000355
更新日期:2020-11-18 00:00:00
abstract::Herein we report the design, synthesis, X-ray structural, and biological studies of an exceptionally potent HIV-1 protease inhibitor, compound 5 ((3S,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl ((2S,3R)-4-((2-(cyclopropylamino)-N-isobutylbenzo[d]thiazole)-6-sulfonamido)-1-(3,5-difluorophenyl)-3-hydroxybutan-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700824
更新日期:2018-04-23 00:00:00
abstract::The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, h...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900593
更新日期:2020-01-17 00:00:00
abstract::Some hybrid foldamers of various length, all containing the (4R,5S)-4-carboxy-5-methyloxazolidin-2-one (d-Oxd) moiety alternating with an l-amino acid (l-Val, l-Lys, or l-Ala), were prepared in order to study their preferred conformations and to evaluate their biological activity. Surprisingly, only the longer oligome...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600597
更新日期:2017-02-20 00:00:00
abstract::We report the synthesis of trifluoromethylated metallocenes (M=Fe, Ru) and related metal-free compounds for comparison of their biological properties with the aim to establish structure-activity relationships toward the anti-proliferative activity of this compound class. All new compounds were comprehensively characte...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402001
更新日期:2014-06-01 00:00:00
abstract::In the present study the importance of the active site histidine residue (His) for the activity of epoxide- or aziridine-based cysteine protease inhibitors is examined theoretically. To account for all important effects, QM/MM hybrid approaches are employed which combine quantum mechanical (QM) methods that are necess...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600159
更新日期:2007-01-01 00:00:00
abstract::Herbal medicines (HMs) are an important source of drugs. In this study, an efficient strategy integrating ultrafiltration LC-MS, microplate bioassays, and molecular docking was proposed to screen high-potency enzyme inhibitors from HMs. Using this strategy, the structure-activity relationships (SARs) including binding...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600489
更新日期:2016-12-06 00:00:00
abstract::Cyclic RGD-containing functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe the synthesis and in vitro screening of these RGD derivatives, as well as the determination of thei...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800422
更新日期:2009-04-01 00:00:00
abstract::Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at nontoxic doses in mice. An...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100271
更新日期:2011-10-04 00:00:00
abstract::Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential thera...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000839
更新日期:2020-12-04 00:00:00
abstract::A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the desi...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200054
更新日期:2012-05-01 00:00:00
abstract::Cancer cells express high levels of CK2, and its inhibition leads to apoptosis. CK2 has therefore emerged as a new drug target for cancer therapy. A biligand inhibitor ARC-772 was constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and a carboxylate-rich peptoid. ARC-772 was found to bind CK2 with a Kd...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700457
更新日期:2017-10-20 00:00:00
abstract::A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000346
更新日期:2010-11-08 00:00:00
abstract::Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300144
更新日期:2013-07-01 00:00:00
abstract::Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700271
更新日期:2017-07-06 00:00:00
abstract::3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives were synthesized, and their structures were confirmed by single-crystal X-ray diffraction. This reaction yields the 1,4-dicarboxamide derivatives rather than the 1,2-dicarboxamide derivatives. Their in vitro antitumor activities were evaluated against SGC-79...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200109
更新日期:2012-06-01 00:00:00
abstract::Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and β-amyloid inhibition, acting as a...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201800196
更新日期:2018-07-06 00:00:00
abstract::Serine- and metallo-β-lactamases present a threat to the clinical use of nearly all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. Efforts to develop metallo-β-lactamase (MBL) inhibitors require suitable screening platforms to allow the rapid determination of β-lactamase activity and eff...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300350
更新日期:2013-12-01 00:00:00