Abstract：
:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. The classification rates were calculated to be 87% and 81% for sweet and bitter peptides, respectively. The SIMCA method has also suggested that two factors, shape and size, of the C-terminal amino acid moiety R in the dipeptides are extremely important to model their taste qualities.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Miyashita Y,Takahashi Y,Takayama C,Sumi K,Nakatsuka K,Ohkubo T,Abe H,Sasaki Sdoi
10.1021/jm00156a006subject
Has Abstractpub_date
1986-06-01 00:00:00pages
906-12issue
6eissn
0022-2623issn
1520-4804journal_volume
29pub_type
杂志文章abstract：:Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 μM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were depende...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301121j
更新日期：2012-09-27 00:00:00
abstract：:In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980656r
更新日期：1999-04-22 00:00:00
abstract：:A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a sca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049279a
更新日期：2005-05-05 00:00:00
abstract：:It is presently known that the long-term failure in the treatment of AIDS with the currently available nucleotide reverse transcriptase inhibitors (NRTIs) is related to the development of resistance by reverse transcriptase (RT) at the binding or incorporation level or both, or subsequent to the nucleotide incorporati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060698c
更新日期：2006-12-28 00:00:00
abstract：:Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00021
更新日期：2020-05-28 00:00:00
abstract：:As part of a continuing search for specific inhibitors of the enzymes involved in polyamine biosynthesis, we have designed and synthesized a multisubstrate adduct inhibitor, S-adenosyl-1,12-diamino-3-thio-9-azadodecane (AdoDATAD), in which critical portions of the nucleophilic aminopropyl acceptor are covalently linke...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00126a026
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abstract：:A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0497489
更新日期：2004-12-30 00:00:00
abstract：:Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00049a008
更新日期：1994-11-11 00:00:00
abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070336k
更新日期：2007-08-09 00:00:00
abstract：:G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,随机对照试验
doi：10.1021/jm2010964
更新日期：2012-04-26 00:00:00
abstract：:On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenocepto...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a001
更新日期：1985-02-01 00:00:00
abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070593p
更新日期：2007-12-27 00:00:00
abstract：:Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two r...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0311036
更新日期：2004-06-17 00:00:00
abstract：:The fumagillin family of natural products inhibits angiogenesis through the irreversible inhibition of the type 2 methionine aminopeptidase (MetAP2). Herein is reported a novel fumagillin analogue named fumarranol. It is shown that, like fumagillin, fumarranol selectively inhibits MetAP2 and endothelial cell prolifera...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060559v
更新日期：2006-09-21 00:00:00
abstract：:Quantitative structure-activity relationships of the Hansch-type were developed to account for inhibition of thymidine kinases from Herpes simplex viruses types 1 and 2 (HSV1,2) by N2-phenylguanines. Derivatives with meta and/or para substituents on the phenyl ring display a wide range of overlapping, but not identica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00094a007
更新日期：1992-08-07 00:00:00
abstract：:We previously have reported four possible binding conformation of dynorphin A (Dyn A) for the central kappa opioid receptors, induced by the address sequence, using a molecular mechanics energy minimization approach. The lowest energy conformation was found to exhibit an alpha-helical conformation in the cyclized addr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950369c
更新日期：1996-03-01 00:00:00
abstract：:Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970232h
更新日期：1997-08-01 00:00:00
abstract：:A variety of dicarboxylic acid linkers introduced between the alpha-amino group of Pro(6) and the -amino group of Lys(10) of the cyclic lactam alpha-melanocyte-stimulating hormone (alpha-MSH)-derived Pro(6)-D-Phe(7)/D-Nal(2')(7)-Arg(8)-Trp(9)-Lys(10)-NH2 pentapeptide template lead to nanomolar range and selective hMC3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070461w
更新日期：2008-01-24 00:00:00
abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9504870
更新日期：1996-03-29 00:00:00
abstract：:A new technique for using receptor surface models in quantitative structure-activity relationship (QSAR) analysis is described. Receptor surface models provide compact, quantitative descriptors which capture three-dimensional information about putative receptor/ligand interactions. Receptor surface models can be const...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00012a008
更新日期：1995-06-09 00:00:00
abstract：:A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100506y
更新日期：2010-08-26 00:00:00
abstract：:Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00166
更新日期：2016-05-26 00:00:00
abstract：:The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an "in-house" collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01031
更新日期：2017-09-28 00:00:00
abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...
journal_title：Journal of medicinal chemistry
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更新日期：1999-07-15 00:00:00
abstract：:Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors...
journal_title：Journal of medicinal chemistry
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更新日期：2008-09-25 00:00:00
abstract：:A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC₅₀ = 2.3 ± 0.8 μM) with marginal cy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300612z
更新日期：2012-10-25 00:00:00
abstract：:The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resist...
journal_title：Journal of medicinal chemistry
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doi：10.1021/acs.jmedchem.9b01937
更新日期：2020-05-14 00:00:00
abstract：:Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801389m
更新日期：2009-02-26 00:00:00
abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040215+
更新日期：2005-09-08 00:00:00
abstract：:Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a functional assay, resulting in the identification of an isothiourea h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901472u
更新日期：2010-02-11 00:00:00
