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::The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.12.005
更新日期:2019-01-15 00:00:00
abstract::A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.11.028
更新日期:2019-01-01 00:00:00
abstract::Based on the molecular modelling studies, a rational modification of the lead molecule was made to develop highly potent compounds showing anti-cancer activity against human breast cancer cell lines MCF 7, MDA-MB-468 and T-47D. The most potent compounds have Log P and total polar surface area 4.4-5.4 and 59.8 Å, respe...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.11.021
更新日期:2019-01-01 00:00:00
abstract::We report the discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by using a structure-based drug design (SBDD) based on a docking model. The work leads to the representative compound 4a with high CSF-1R inhibitory activity (IC50 = 9.1 nM). The obtained crystal ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.051
更新日期:2019-01-01 00:00:00
abstract::Beta-hemoglobinopathies such as sickle cell disease represent a major global unmet medical need. De-repression of fetal hemoglobin in erythrocytes is a clinically validated approach for the management of sickle cell disease, but the only FDA-approved medicine for this purpose has limitations to its use. We conducted a...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.032
更新日期:2018-12-15 00:00:00
abstract::A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.013
更新日期:2018-12-15 00:00:00
abstract::Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.036
更新日期:2018-12-15 00:00:00
abstract::A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier l...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.029
更新日期:2018-12-15 00:00:00
abstract::Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compo...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.003
更新日期:2018-12-15 00:00:00
abstract::Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahy...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.022
更新日期:2018-12-15 00:00:00
abstract::Our internal casein kinase 1ε lead inhibitor, compound 1 was partially cleared by the polymorphic cytochrome P450 2D6. CYP2D6 involvement in metabolism implies more extensive clinical trials. We therefore wanted to reduce the contribution to clearance by this enzyme. We utilized metabolism reports for compound 1 perfo...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.031
更新日期:2018-12-15 00:00:00
abstract::A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.07.038
更新日期:2018-12-01 00:00:00
abstract::The human epidermal growth factor receptor (EGFR) family is known to be involved in cell signaling pathways. The extracellular domain of EGFR consists of four domains, of which domain II and domain IV are known to be involved in the dimerization process. Overexpression of these receptors is known to play a significant...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.10.005
更新日期:2018-12-01 00:00:00
abstract::Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin wi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.08.038
更新日期:2018-11-01 00:00:00
abstract::The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C-N bond formation/reduction/diazotizat...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.09.021
更新日期:2018-11-01 00:00:00
abstract::A series of (E)-N-Aryl-2-oxo-2-(3,4,5-trimethoxyphenyl)acetohydrazonoyl cyanides have been synthesized and evaluated for their anticancer activity in human hepatocellular liver carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines. Among all the tested compounds, compound 3a, 3e and 3n displayed more activity tha...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.09.004
更新日期:2018-11-01 00:00:00
abstract::By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.08.025
更新日期:2018-10-15 00:00:00
abstract::The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on ac...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.08.006
更新日期:2018-10-15 00:00:00
abstract::The voltage gated sodium channel Nav1.7 plays an essential role in the transmission of pain signals. Strong human genetic validation has motivated extensive efforts to discover potent, selective, and efficacious Nav1.7 inhibitors for the treatment of chronic pain. This digest will introduce the structure and function ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2018.08.007
更新日期:2018-10-15 00:00:00
abstract::A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the desi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.03.031
更新日期:2018-10-15 00:00:00
abstract::A series of canthin-6-one analogues were designed and synthesized in order to study their antibacterial activity and structure-activity relationships. Compound 22 showed a broad spectrum of antibacterial activity and exhibited better bactericidal effect (8-fold superiority against Staphylococcus aureus and 2-fold supe...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.06.001
更新日期:2018-10-01 00:00:00
abstract::The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimenthoxyochalcone (named DK-139) exhibits anti-inflammatory and anti-tumor invasion properties. However, effects of DK-139 on tumor cell growth remain unknown. In the present study, we evaluated the inhibitory activity of DK-139 against human lung cancer cells. Tr...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.07.003
更新日期:2018-09-15 00:00:00
abstract::A convenient solid phase peptide synthetic (SPPS) route is reported for the preparation of antimycobacterial wollamides. The method is based on on-resin head-to-tail cyclization and is fast, efficient and amenable to automation. The in vitro antimycobacterial activities of the newly synthesized wollamides were evaluat...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.07.021
更新日期:2018-09-15 00:00:00
abstract::Estrogen receptor α (ERα) is a crucial target for ERα positive breast cancer treatment. Previous drug discovery efforts were focused on developing inhibitors that targeted the canonical ligand binding pockets of the ligand binding domain (LBD) of ERα. However, significant percentage of patients developed cancer relaps...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2018.05.062
更新日期:2018-09-15 00:00:00
abstract::KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.019
更新日期:2018-09-15 00:00:00
abstract::RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat cau...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.10.034
更新日期:2018-09-01 00:00:00
abstract::Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.01.065
更新日期:2018-09-01 00:00:00
abstract::Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synth...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.03.035
更新日期:2018-09-01 00:00:00
abstract::Surgical methods guided by exogenous fluorescent markers have the potential to define tissue types in real time. Small molecule dyes with efficient and selective renal clearance could enable visualization of the ureter during surgical procedures involving the abdomen and pelvis. These studies report the design and syn...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.02.040
更新日期:2018-09-01 00:00:00
abstract::We have developed versatile methods toward the synthesis of a variety of piperidine/piperazine bridged isosteres of pridopidine. The compounds were assessed against the D2 receptor in agonist and antagonist modes and against the D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.06.038
更新日期:2018-08-15 00:00:00
abstract::Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2018.06.021
更新日期:2018-08-15 00:00:00
abstract::A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-α-induced monocyte adhesion to colon epithelial cells (an in vitro model of colit...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.06.012
更新日期:2018-08-01 00:00:00
abstract::Chelerythrine, an isoquinoline alkaloid isolated from the herbaceous perennial Chelidonium majus, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A) with an IC50 value of 0.55 µM. Chelerythrine was a reversible competitive MAO-A inhibitor (Ki = 0.22 µM) with a pot...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.06.023
更新日期:2018-08-01 00:00:00
abstract::Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.058
更新日期:2018-08-01 00:00:00
abstract::Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 in...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.055
更新日期:2018-08-01 00:00:00
abstract::Aberrant expansion of GGGGCC (G4C2) hexanucleotide repeat (HNR) in the first intron of C9ORF72 has been found in frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALD). The non-canonical DNA structures of the expanded repeats are causative to repeat instability leading to contraction and expansion. We dem...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.06.032
更新日期:2018-08-01 00:00:00
abstract::Water is an essential part of protein binding sites and mediates interactions to ligands. Its displacement by ligand parts affects the free binding energy of resulting protein-ligand complexes. Therefore the characterization of solvation properties is important for design. Of particular interest is the propensity of l...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2018.05.061
更新日期:2018-08-01 00:00:00
abstract::In this study, affinities and activities of derivatized analogues of Dmt-dermorphin[1-4] (i.e. Dmt-d-Ala-Phe-GlyNH2, Dmt = 2',6'-dimethyl-(S)-tyrosine) for the µ opioid receptor (MOP) and δ opioid receptor (DOP) were evaluated using radioligand binding studies, functional cell-based assays and isolated organ bath expe...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.015
更新日期:2018-07-15 00:00:00
abstract::The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.040
更新日期:2018-07-15 00:00:00
abstract::Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2018.05.002
更新日期:2018-06-15 00:00:00