解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Into the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc ) of the cellular prion protein (PrPC ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a li...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700302
更新日期:2017-08-22 00:00:00
abstract::Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has li...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700220
更新日期:2017-08-22 00:00:00
abstract::Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700259
更新日期:2017-08-22 00:00:00
abstract::Together with estrogen receptors ERα and ERβ, the G protein-coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER-negative (ER-) and triple-negative (TN) breast cancer. Only a few selective GPER modulators h...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700145
更新日期:2017-08-22 00:00:00
abstract::Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channe...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700162
更新日期:2017-08-22 00:00:00
abstract::The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700170
更新日期:2017-07-20 00:00:00
abstract::Herein we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric chemokine receptor 2 (CXCR2) inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2, with IC50 values less than 10 μm ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700229
更新日期:2017-07-06 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::Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs ...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700216
更新日期:2017-06-07 00:00:00
abstract::The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700113
更新日期:2017-05-09 00:00:00
abstract::The natural product acivicin inhibits the glutaminase activity of cytidine triphosphate (CTP) synthetase and is a potent lead compound for drug discovery in the area of neglected tropical diseases, specifically trypanosomaisis. A 2.1-Å-resolution crystal structure of the acivicin adduct with the glutaminase domain fro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700118
更新日期:2017-04-20 00:00:00
abstract::Identification of potent agonists of odorant receptors (ORs), a major class of G protein-coupled receptors, remains challenging due to complex receptor-ligand interactions. ORs are present in both olfactory and non-chemosensory tissues, indicating roles beyond odor detection that may include modulating physiological f...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600612
更新日期:2017-04-06 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::Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and β-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interp...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600570
更新日期:2017-01-20 00:00:00
abstract::Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-wi...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600497
更新日期:2016-12-16 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::Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600427
更新日期:2016-11-07 00:00:00
abstract::The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the ...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201600288
更新日期:2016-10-19 00:00:00
abstract::We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdraw...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600343
更新日期:2016-10-06 00:00:00
abstract::Intraoperative imaging technologies recently entered the operating room, and their implementation is revolutionizing how physicians plan, monitor, and perform surgical interventions. In this work, we present a novel surgical imaging reporter system: intraoperative chemiluminescence imaging (ICI). To this end, we have ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600301
更新日期:2016-09-20 00:00:00
abstract::Blocking the 2-C-methyl-d-erythrithol-4-phosphate pathway for isoprenoid biosynthesis offers new ways to inhibit the growth of Plasmodium spp. Fosmidomycin [(3-(N-hydroxyformamido)propyl)phosphonic acid, 1] and its acetyl homologue FR-900098 [(3-(N-hydroxyacetamido)propyl)phosphonic acid, 2] potently inhibit 1-deoxy-d...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600249
更新日期:2016-09-20 00:00:00
abstract::A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 μg mL(-1) ; 2.55-5.09 μm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 μm] ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600250
更新日期:2016-09-06 00:00:00
abstract::Abnormally high corticosteroid levels are responsible for the onset of serious hormone-related diseases, and the inhibition of their biosynthesis by targeting cytochrome P450 (CYP) isoforms CYP11B1 and CYP11B2 has emerged as a promising strategy to restore healthy physiological levels of corticosteroids. With the aim ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600078
更新日期:2016-08-19 00:00:00
abstract::Over the years, the 2-substituted imidazoline nucleus has been demonstrated to be a bioversatile structural motif. In this study, novel imidazoline derivatives bearing a 3- and/or 4-hydroxy- or methoxy-substituted phenyl ring, linked by an ethylene bridge to position 2 of an N-benzyl- or N-phenethyl-substituted imidaz...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600022
更新日期:2016-08-19 00:00:00
abstract::The clinical use of N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) has been hindered by its lack of bioavailability. N,N'-bis(2-boronic pinacol ester benzyl)ethylenediamine-N,N'-diacetic acid methyl, ethyl, and isopropyl esters 7 a-c, respectively, and their dimesylate salts 8 a-c, are double prodr...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600197
更新日期:2016-08-05 00:00:00
abstract::Myotonic dystrophy is the most common form of adult-onset muscular dystrophy, originating in a CTG repeat expansion in the DMPK gene. The expanded CUG transcript sequesters MBNL1, a key regulator of alternative splicing, leading to the misregulation of numerous pre-mRNAs. We report an RNA-targeted agent as a possible ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600081
更新日期:2016-07-05 00:00:00
abstract::The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget-directed ligand named ARN2508 (2-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500507
更新日期:2016-06-20 00:00:00
abstract::Two acyclic cucurbit[n]uril (CB[n])-type molecular containers that differ in the length of the (CH2 )n linker (M2C2: n=2, M2C4: n=4) between their aromatic sidewalls and sulfonate solubilizing groups were prepared and studied. The inherent solubilities of M2C2 (68 mm) and M2C4 (196 mm) are higher than the analogue wit...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600090
更新日期:2016-05-06 00:00:00
abstract::Protein-protein interactions (PPIs) control many cellular processes in cancer and tumour growth. Of significant interest is the role PPIs play in regulating apoptosis. The overexpression of the antiapoptosis regulating Bcl-2 family of proteins is commonly observed in several cancers, leading to resistance towards both...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500488
更新日期:2016-04-19 00:00:00
abstract::The disruption of aberrant protein-protein interactions (PPIs) with synthetic agents remains a challenging goal in contemporary medicinal chemistry but some progress has been made. One such dysregulated PPI is that between the anti-apoptotic Bcl-2 proteins, including myeloid cell leukemia-1 (Mcl-1), and the α-helical ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500461
更新日期:2016-04-19 00:00:00
abstract::The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global p...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500483
更新日期:2016-04-19 00:00:00
abstract::The CXCR3 receptor, a class A G protein-coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure-b...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500573
更新日期:2016-03-17 00:00:00
abstract::Uropathogenic E. coli (UPEC) employ the mannose-binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half-life in vivo. In a rational design strategy, we obtained an X-ra...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600006
更新日期:2016-02-17 00:00:00
abstract::Structural preorganization to fix bioactive conformations at protein binding sites is a popular strategy to enhance binding affinity during late-stage optimization. The rationale for this enhancement relates to entropic advantages assigned to rigidified versus flexible ligands. We analyzed a narrow series of peptidomi...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500531
更新日期:2016-02-04 00:00:00
abstract::Nanoscale materials hold great promise in the therapeutic field. In particular, as carriers or vectors, they help bioactive molecules reach their primary targets. Furthermore, by themselves, certain nanomaterials-regarded as protective-can modulate particular metabolic pathways that are deregulated in pathological sit...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201500233
更新日期:2016-01-19 00:00:00
abstract::There has been significant interest in spleen tyrosine kinase (Syk) owing to its role in a number of disease states, including autoimmunity, inflammation, and cancer. Ongoing therapeutic programs have resulted in several compounds that are now in clinical use. Herein we report our optimization of the imidazopyrazine c...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500333
更新日期:2016-01-19 00:00:00
abstract::Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide he...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500442
更新日期:2015-12-01 00:00:00
abstract::A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500300
更新日期:2015-11-01 00:00:00
abstract::A hybrid approach was applied for the design of an inhibitor of trypsin-like serine proteases. Compound 16 [(R,R)- and (R,S)-diphenyl (4-(1-(4-amidinobenzylamino)-1-oxo-3-phenylpropan-2-ylcarbamoyl)phenylamino)(4-amidinophenyl)methylphosphonate hydrochloride], prepared in a convergent synthetic procedure, possesses a ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500319
更新日期:2015-10-01 00:00:00
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