Abstract:
:The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3-yl)-benzo[d][1,3]oxazin-4-one is described. A structure-activity relationship study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5-ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl-piperazin-1-yl)-pyridin-3-yl] derivatives of this core were shown to yield HNE inhibitors of similar potency with significantly different stabilities in rat plasma.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Shreder KR,Cajica J,Du L,Fraser A,Hu Y,Kohno Y,Lin EC,Liu SJ,Okerberg E,Pham L,Wu J,Kozarich JWdoi
10.1016/j.bmcl.2009.06.053subject
Has Abstractpub_date
2009-08-15 00:00:00pages
4743-6issue
16eissn
0960-894Xissn
1464-3405pii
S0960-894X(09)00886-5journal_volume
19pub_type
杂志文章abstract::Among a series of taxinine (1) and its designed derivatives (2-33), two taxoids (29 and 33) increased cellular accumulation of vincristine in multidrug-resistant tumor cells more potently than verapamil, while the activities of eight taxoids (11, 14-16, 22, and 30-32) were comparable with that of verapamil. These resu...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00009-8
更新日期:1999-02-08 00:00:00
abstract::The benzothiazole aniline (BTA) conjugated with monoamine-monoamide (MAMA) was synthesized and then labeled with (99m)Tc. Its corresponding rhenium analogue was synthesized, and the fluorescent staining was performed in brain sections of both Tg mouse and Alzheimer's disease (AD) patient. The fluorescent rhenium compl...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.12.071
更新日期:2008-02-15 00:00:00
abstract::A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so tha...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.08.141
更新日期:2010-11-15 00:00:00
abstract::Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy diff...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.03.002
更新日期:2014-04-15 00:00:00
abstract::The Golden Triangle is a visualization tool developed from in vitro permeability, in vitro clearance and computational data designed to aid medicinal chemists in achieving metabolically stable, permeable and potent drug candidates. Classifying compounds as permeable and stable and plotting molecular weight (MW) versus...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.08.045
更新日期:2009-10-01 00:00:00
abstract::A nucleopeptide was prepared in a convergent manner via segmental coupling of the protected biopolymers in solution. The resulting nucleopeptide (4b, 72%) containing the binding site of lambda repressor and a peptide containing the consensus sequence of the DNA binding helix of the helix turn-helix-proteins was obtain...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00051-7
更新日期:1999-02-22 00:00:00
abstract::The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the num...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.06.026
更新日期:2019-08-15 00:00:00
abstract::The high resolution crystal structure of 5-(2-thienylacetamido)-1,3,4-thiadiazole-2-sulfonamide complexed to human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoform hCA II is reported. The compound binds in a similar manner with acetazolamide when the sulfamoyl-thiadiazolyl-acetamido fragment of the two compounds is con...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.08.019
更新日期:2013-10-15 00:00:00
abstract::A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols, have been discovered by combining virtual and focused screening efforts with design techniques. Synthesis of the two diastereomeric isomers of the molecule followed by chiral resolution of each enantiomer revealed the ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.07.053
更新日期:2009-09-01 00:00:00
abstract::The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00487-4
更新日期:1999-10-04 00:00:00
abstract::A series of novel tetracyclic core-containing HCV NS5A inhibitors has been discovered. Incorporation of tetrahydropyran-substituted amino acid moiety improved their potency and yielded HCV NS5A inhibitors with a minimum potency shift from the GT1a strain compared to other genotypes and mutants. Compounds 53 and 54 sho...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.01.031
更新日期:2019-03-01 00:00:00
abstract::A 1,8-naphthalimide-Cu(II) ensemble was rationally designed and synthesized as a new turn-on fluorescent probe utilizing the 'chemosensing ensemble' method for detections of thiols (Cys, Hcy and GSH) with high selectivity over other α-amino acids at pH 7.4 in organic aqueous media (EtOH/HEPES, v/v=9:1). The recognitio...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.03.004
更新日期:2013-05-01 00:00:00
abstract::Caffeic acid derivatives are increasingly regarded as potential oncoprotective that could inhibit both the initiation and progression of cancer. Here we have synthesized seven 1-arylnaphthalene lignans and related compounds and tested their impact on breast cancer cell growth in tissue culture. The product of the oxid...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.11.009
更新日期:2013-01-15 00:00:00
abstract::We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.09.015
更新日期:2015-10-15 00:00:00
abstract::Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-6...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.02.037
更新日期:2007-05-01 00:00:00
abstract::We report (a) on the synthesis of a long-wavelength fluorescent coumarin containing an allyloxy acetate moiety, (b) the synthesis of two linkers containing an allyloxy acetate and an alkyne or azide function, respectively, and (c) the selective modification human serum albumin by a sequential method involving Pd(II) c...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.09.002
更新日期:2013-11-01 00:00:00
abstract::A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, repres...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.11.070
更新日期:2011-01-01 00:00:00
abstract::New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.07.080
更新日期:2015-09-15 00:00:00
abstract::β-carbolines from various natural and synthetic sources have been known to show diverse biological activities. As a part of our current ongoing project to search for potent natural product-derived anti-leishmanial compounds, we have synthesized a series of substituted 1-aryl-β-carboline derivatives. A total of 22 comp...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.04.115
更新日期:2012-06-15 00:00:00
abstract::A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.03.113
更新日期:2013-06-01 00:00:00
abstract::Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.02.024
更新日期:2013-04-01 00:00:00
abstract::Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This comp...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.10.070
更新日期:2008-12-15 00:00:00
abstract::The docking approach for the screening of designed small molecule ligands, led to the identification of a critical arginine residue in peptide deformylase for spiro cyclopropyl PDF inhibitor's extra hydrophobic binding, providing us a useful tool for searching more efficient PDF inhibitors to fight for horrifying anti...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.05.077
更新日期:2016-08-01 00:00:00
abstract::The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章,评审
doi:10.1016/j.bmcl.2012.09.046
更新日期:2012-12-01 00:00:00
abstract::We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed tha...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00664-8
更新日期:2001-02-12 00:00:00
abstract::In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6c-Cl (the 'in-chloride') position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6c-Cl group were found that ensure high conversion with mini...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.12.027
更新日期:2016-02-01 00:00:00
abstract::Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim. Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer. However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined. Thus, the cur...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 信件
doi:10.1016/j.bmcl.2013.04.007
更新日期:2013-06-15 00:00:00
abstract::Neutral fluorescent active di-pyrene modified gamma-cyclodextrin (1) was synthesized in order to discriminate with single and double strand DNA (ssDNA and dsDNA, respectively) with high selectivity. The binding and selectivity of 1 for dsDNA was indicated by increase of the fluorescent intensity in an addition of dsDN...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.04.066
更新日期:2010-06-01 00:00:00
abstract::Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiment...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.09.028
更新日期:2016-10-15 00:00:00
abstract::19-Hydroxyeicosatetraenoic acid (19-HETE, 1), a metabolically and chemically labile cytochrome P450 eicosanoid, has diverse biological activities including antagonism of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE, 2). A SAR study was conducted to develop robust analogs of 1 with improved in vitro and...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.08.020
更新日期:2019-10-01 00:00:00