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::A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimeth...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900179
更新日期:2019-06-18 00:00:00
abstract::Seasonal influenza infections are associated with an estimated 250-500 000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have pro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900084
更新日期:2019-06-18 00:00:00
abstract::The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900112
更新日期:2019-05-06 00:00:00
abstract::We developed new 10 B carriers for boron neutron capture therapy (BNCT) that can effectively transport and accumulate boron clusters into cells. These carriers consist of a lipopeptide, mercaptoundecahydrododecaborate (BSH), and a disulfide linker. The carriers were conceived according to the structure of pepducin, a ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800793
更新日期:2019-04-17 00:00:00
abstract::The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800815
更新日期:2019-03-22 00:00:00
abstract::The Pathogen Box is a 400-strong collection of drug-like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201800755
更新日期:2019-02-19 00:00:00
abstract::Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800724
更新日期:2019-02-05 00:00:00
abstract::Following the discovery of a type III allosteric modulator of cyclin-dependent kinase 2 (CDK2) characterized by a hexahydrocyclopenta[c]quinolone scaffold, three different series of its derivatives were synthesized and biologically evaluated. Docking of the synthesized compounds into the allosteric pocket of CDK2 allo...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800687
更新日期:2018-12-20 00:00:00
abstract::The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800638
更新日期:2018-12-06 00:00:00
abstract::The application of covalent inhibitors has experienced a renaissance within drug discovery programs in the last decade. To leverage the superior potency and drug target residence time of covalent inhibitors, there have been extensive efforts to develop highly specific covalent modifications to decrease off-target liab...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800592
更新日期:2018-12-06 00:00:00
abstract::Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800487
更新日期:2018-11-06 00:00:00
abstract::Despite significant advances made in the last decade in the understanding of molecular mechanisms of sepsis and in the development of clinically relevant therapies, sepsis remains the leading cause of mortality in intensive care units with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane pat...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800505
更新日期:2018-11-06 00:00:00
abstract::A small library of 17 organoruthenium compounds with the general formula [RuII (fcl)(chel)(L)]n+ (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compou...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800432
更新日期:2018-10-22 00:00:00
abstract::Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure-activity relationship study of a small library ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800388
更新日期:2018-09-06 00:00:00
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-tar...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800300
更新日期:2018-08-20 00:00:00
abstract::The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the antic...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800348
更新日期:2018-08-20 00:00:00
abstract::The histone methyltransferase SET7/9 methylates not only histone but also non-histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine recep...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800233
更新日期:2018-08-10 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::Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic-resistant threat, and has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acqu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800240
更新日期:2018-07-18 00:00:00
abstract::β-Lactamases (BLs) are important antibiotic-resistance determinants that significantly compromise the efficacy of valuable β-lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non-β-lactam BL inhibitor introduced into clinical practice. Ceftazidime-avibactam represe...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800213
更新日期:2018-07-18 00:00:00
abstract::A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection re...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800193
更新日期:2018-07-06 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::Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increas...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700783
更新日期:2018-05-23 00:00:00
abstract::The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report th...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800067
更新日期:2018-05-08 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 emergence and dissemination of multidrug resistant (MDR) pathogens resistant to nearly all available antibiotics poses a significant threat in clinical therapy. Among them, Klebsiella pneumoniae clinical isolates overexpressing KPC-2 carbapenemase are the most worrisome, extending bacterial resistance to last-reso...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700788
更新日期:2018-04-06 00:00:00
abstract::Efavirenz (EFV), an antiretroviral that interacts clinically with co-administered drugs via activation of the pregnane X receptor (PXR), is extensively metabolized by the cytochromes P450. We tested whether its primary metabolite, 8-hydroxyEFV (8-OHEFV) can activate PXR and potentially contribute to PXR-mediated drug-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700730
更新日期:2018-04-06 00:00:00
abstract::This is, to our knowledge, the most comprehensive analysis to date based on generative topographic mapping (GTM) of fragment-like chemical space (40 million molecules with no more than 17 heavy atoms, both from the theoretically enumerated GDB-17 and real-world PubChem/ChEMBL databases). The challenge was to prove tha...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700561
更新日期:2018-03-20 00:00:00
abstract::Digital Drug Discovery: Guest Editors Andreas Bender (University of Cambridge) and Nathan Brown (BenevolentAI) present the 20 articles included in this Special Issue on Cheminformatics in Drug Design. As they summarize each article, they also discuss the common themes within in silico drug discovery that these papers ...
journal_title:ChemMedChem
pub_type: 社论
doi:10.1002/cmdc.201800123
更新日期:2018-03-20 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::A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a n...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700689
更新日期:2018-03-20 00:00:00
abstract::Because only a few studies have investigated the affinity and functional activity of NMDA receptor open channel blockers under the same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activities of MK-801, phencyclidine (PCP), dexoxadrol, etoxadrol, (S)- ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700810
更新日期:2018-03-06 00:00:00
abstract::The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700731
更新日期:2018-02-20 00:00:00
abstract::Discovered as a modulator of the toxic response to environmental pollutants, aryl hydrocarbon receptor (AhR) has recently gained attention for its involvement in various physiological and pathological pathways. AhR is a ligand-dependent transcription factor activated by a large array of chemical compounds, which inclu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700669
更新日期:2018-02-06 00:00:00
abstract::Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein we describe a novel nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblast...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700629
更新日期:2018-01-22 00:00:00
abstract::γ-Glutamylcyclotransferase (GGCT) depletion inhibits cancer cell proliferation. However, whether the enzymatic activity of GGCT is critical for the regulation of cancer cell growth remains unclear. In this study, a novel diester-type cell-permeable prodrug, pro-GA, was developed based on the structure of N-glutaryl-l-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700660
更新日期:2018-01-22 00:00:00
abstract::Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Herein we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary N-substituted 7-amino...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700449
更新日期:2017-12-19 00:00:00
abstract::Despite various inhibitors targeting the zinc center(s) of enzymes, drugs that target zinc fingers have not been examined in detail. We previously developed a dithiol compound named SN-1 that has an inhibitory effect on the function of zinc finger transcription factors, but its mechanism of action has not yet been elu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700399
更新日期:2017-12-07 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 series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700446
更新日期:2017-10-09 00:00:00