Abstract:
:[This corrects the article DOI: 10.1021/acsmedchemlett.8b00507.].
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
De Simone A,La Pietra V,Betari N,Petragnani N,Conte M,Daniele S,Pietrobono D,Martini C,Petralla S,Casadei R,Davani L,Frabetti F,Russomanno P,Novellino E,Montanari S,Tumiatti V,Ballerini P,Sarno F,Nebbioso A,Altuccidoi
10.1021/acsmedchemlett.9b00316subject
Has Abstractpub_date
2019-08-06 00:00:00pages
1357issue
9issn
1948-5875journal_volume
10pub_type
已发布勘误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
pub_type: 杂志文章
doi:10.1021/ml300429p
更新日期:2013-01-17 00:00:00
abstract::The phenethylamine backbone is a privileged substructure found in a wide variety of G protein-coupled receptor (GPCR) ligands. This includes both endogenous neurotransmitters and active pharmaceutical agents. More than 20 structurally unique heterocyclic phenethylamine derivatives were broadly evaluated for GPCR affin...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00225
更新日期:2019-09-23 00:00:00
abstract::Multitarget anti-inflammatory drugs interfering with the arachidonic acid cascade exhibit superior efficacy. In this study, a prototype dual inhibitor of soluble epoxide hydrolase (sEH) and LTA4 hydrolase (LTA4H) with submicromolar activity toward both targets has been designed and synthesized. Preliminary structure-a...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00330
更新日期:2019-10-30 00:00:00
abstract::We report the synthesis of a novel heat shock protein 90 (hsp90) inhibitor conjugated to a star polymer. Using reversible addition-fragmentation chain-transfer (RAFT) polymerization, we prepared star polymers comprised of PEG attached to a predesigned functional core. The stars were cross-linked using disulfide linker...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml400082b
更新日期:2013-07-25 00:00:00
abstract::Specific abrogation of cyclin-dependent kinase 5 (CDK5) activity has been validated as a viable approach for the development of anticancer agents. However, no selective CDK5 inhibitor has been reported to date. Herein, a structure-based in silico screening was employed to identify novel scaffolds from a library of com...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00029
更新日期:2019-03-20 00:00:00
abstract::The atypical chemokine receptor CXCR7 has been studied in various disease settings including immunological diseases and heart disease. Efforts to elucidate the role of CXCR7 have been limited by the lack of suitable chemical tools with a range of pharmacological profiles. A high-throughput screen was conducted to disc...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00163
更新日期:2020-05-14 00:00:00
abstract::A protein structure-guided drug design approach was employed to develop small molecule inhibitors of the BET family of bromodomains that were distinct from the known (+)-JQ1 scaffold class. These efforts led to the identification of a series of substituted benzopiperazines with structural features that enable interact...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00191
更新日期:2017-07-14 00:00:00
abstract::General control nonderepressible 2 (GCN2) is a master regulator kinase of amino acid homeostasis and important for cancer survival in the tumor microenvironment under amino acid depletion. We initiated studies aiming at the discovery of novel GCN2 inhibitors as first-in-class antitumor agents and conducted modificatio...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00400
更新日期:2019-09-19 00:00:00
abstract::A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical candidate INCB050465 (20, parsaclisib). The unique structure of 20 contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in o...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00334
更新日期:2019-10-17 00:00:00
abstract::In light of the biomedical significance of metallo-β-lactamases (MβLs), ten new mercaptoacetic acid thioester amino acid derivatives were synthesized and characterized. Biological activity assays indicated that all these synthesized compounds are very potent inhibitors of L1, exhibiting an IC50 value range of 0.018-2....
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00098
更新日期:2015-04-23 00:00:00
abstract::This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significantly induced typica...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml400162g
更新日期:2013-10-18 00:00:00
abstract::Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionali...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500030p
更新日期:2014-03-21 00:00:00
abstract::Inhibitors of the protein methyltransferase Enhancer of Zeste Homolog 2 (EZH2) may have significant therapeutic potential for the treatment of B cell lymphomas and other cancer indications. The ability of the scientific community to explore fully the spectrum of EZH2-associated pathobiology has been hampered by the la...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00037
更新日期:2015-03-04 00:00:00
abstract::In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt1-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml4004765
更新日期:2014-04-10 00:00:00
abstract::Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor 1 to reduce its clearance by cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 (2) with improved physicochemical properties and a mixed m...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00343
更新日期:2018-01-04 00:00:00
abstract::A series of 1,4-disubstituted piperazine-based compounds were designed, synthesized, and evaluated as dopamine D2/D3 receptor ligands. The synthesis relies on the key multicomponent split-Ugi reaction, assessing its great potential in generating chemical diversity around the piperazine core. With the aim of evaluating...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00131
更新日期:2015-06-23 00:00:00
abstract::The effects of opioids in the central nervous system (CNS) provide significant benefit in the treatment of pain but can also lead to physical dependence and addiction, which has contributed to a growing opioid epidemic in the United States. Gastrointestinal dysfunction is an additional serious consequence of opioid us...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00406
更新日期:2019-11-26 00:00:00
abstract::Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desm...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml200254h
更新日期:2012-03-08 00:00:00
abstract::Pyxinol, the main metabolite of 20S-protopanaxadiol in human liver, was chosen as a novel skeleton for the development of anti-inflammatory agents. Pyxinol derivatives modified at C-3, C-12, or C-25 and selected stereoisomers were designed, prepared, and investigated for in vitro anti-inflammatory activities. Structur...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00562
更新日期:2020-02-12 00:00:00
abstract::Translational readthrough-inducing drugs (TRIDs) rescue the functional full-length protein expression in genetic diseases, such as cystic fibrosis, caused by premature termination codons (PTCs). Small molecules have been developed as TRIDs to trick the ribosomal machinery during recognition of the PTC. Herein we repor...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00609
更新日期:2020-02-18 00:00:00
abstract::This report describes the discovery of RAD140, a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). The characterization of RAD140 in several preclinical models of anabolic androgen action is also described. ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml1002508
更新日期:2010-12-02 00:00:00
abstract::A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocy...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500464f
更新日期:2015-02-06 00:00:00
abstract::A series of N-(3-ethynyl-2,4-difluorophenyl)sulfonamides were identified as new selective Raf inhibitors. The compounds potently inhibit B-Raf(V600E) with low nanomolar IC50 values and exhibit excellent target specificity in a selectivity profiling investigation against 468 kinases. They strongly suppress proliferatio...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00039
更新日期:2015-03-18 00:00:00
abstract::Nonsense mutations introduce a premature termination codon (PTC) and are the underlying cause of multiple rare genetic diseases and cancers. Although certain aminoglycosides bind to eukaryotic ribosomes enabling incorporation of an amino acid at the PTC and formation of full-length protein, they are inefficient and to...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.8b00610
更新日期:2019-04-09 00:00:00
abstract::Imidazopyridine 1 was identified from a phenotypic screen against P. falciparum (Pf) blood stages and subsequently optimized for activity on liver-stage schizonts of the rodent parasite P. yoelii (Py) as well as hypnozoites of the simian parasite P. cynomolgi (Pc). We applied these various assays to the cell-based lea...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500244m
更新日期:2014-07-06 00:00:00
abstract::The attachment of lipids to C- or N-terminally positioned lysine side-chain amino groups increases the activity of a short synthetic (Arg-Trp)3 antimicrobial peptide significantly, making these peptides even active against pathogenic Gram-negative bacteria. Thus, a peptide with strong activity against S. aureus (1.1-2...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300148v
更新日期:2012-09-04 00:00:00
abstract::Water-soluble cyclodextrin (CyD) complexed with porphyrin derivatives with different substituents in the meso-positions showed different photodynamic activities toward cancer cells under illumination at wavelengths over 600 nm, the most suitable wavelengths for photodynamic therapy (PDT). In particular, aniline- and p...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00098
更新日期:2017-04-19 00:00:00
abstract::The identification and lead optimization of a series of pyridopyrimidinone derivatives are described as a novel class of efficacious dual PI3K/mTOR inhibitors, resulting in the discovery of 31. Compound 31 exhibited high enzyme activity against PI3K and mTOR, potent suppression of Akt and p70s6k phosphorylation in cel...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.8b00002
更新日期:2018-02-27 00:00:00
abstract::Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300188t
更新日期:2012-12-11 00:00:00
abstract::The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A series of molecules that feature both an N-phenylsulfonamide and tertiary amide were not only very potent at LIMK2 but also were extremely selective against a panel of other kinases. Enzymatic kinetic studies showed these molecules to be n...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500242y
更新日期:2014-08-07 00:00:00