Abstract:
:A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher Sdoi
10.1016/j.bmcl.2009.06.090subject
Has Abstractpub_date
2009-08-15 00:00:00pages
4622-5issue
16eissn
0960-894Xissn
1464-3405pii
S0960-894X(09)00933-0journal_volume
19pub_type
杂志文章abstract::Aromatase is a target of pharmacological interest for the treatment of estrogen-dependent cancers. Azole derivatives such as letrozole or anastrozole have been developed for aromatase inhibition and are used for the treatment of breast tumors. In this paper, four 4-triazolylflavans were synthesized and were found to e...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.07.090
更新日期:2004-10-18 00:00:00
abstract::Acyl derivatives of 4-(aminomethyl)-N-hydroxybenzamide are potent sub-type selective HDAC6 inhibitors. Constrained heterocyclic analogs based on 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine show further enhanced HDAC6 selectivity and inhibitory activity in cells. Homology models suggest that the heterocyclic spacer can mo...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.10.022
更新日期:2014-12-01 00:00:00
abstract::The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.06.008
更新日期:2013-09-01 00:00:00
abstract::A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00108-5
更新日期:1998-04-07 00:00:00
abstract::The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in v...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.05.053
更新日期:2007-08-01 00:00:00
abstract::Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45nM. The in vivo effects of these compounds in ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00303-7
更新日期:2002-08-05 00:00:00
abstract::Ortho-substituted biphenyl moieties are widely used in drug design. We herein report a successful use of the perpendicular conformation of the alpha-substituted phenylcyclopropyl groups to mimic the aplanar, biologically active conformation of the ortho-substituted biphenyl moieties to achieve structural diversity. Th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.05.095
更新日期:2008-07-15 00:00:00
abstract::The identification and optimization of a series of substituted tetrahydro-beta-carbolines with potent activity against human papillomavirus is described. Structure-activity studies focused on the substitution pattern and chirality of the beta-carboline ring system are discussed. Optimization of these parameters led to...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.10.123
更新日期:2010-01-01 00:00:00
abstract::Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.05.060
更新日期:2016-07-15 00:00:00
abstract::We report, for the first time, that certain N-acetylthiourea derivatives serve as highly potent and isozyme selective activators for the recombinant form of human histone deacetylase-8 in the assay system containing Fluor-de-Lys as a fluorescent substrate. The experimental data reveals that such activating feature is ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.07.080
更新日期:2011-10-01 00:00:00
abstract::Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising ta...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.12.051
更新日期:2017-02-01 00:00:00
abstract::Regio- and/or chemo-selective reductions of taxinine (1a), a taxane diterpenoid readily obtainable from the needles of a Japanese yew (Taxus cuspidata), at the 5-O-cinnamoyl and 4-exo-methylene moieties have been accomplished by the catalytic hydrogenation over Pd/C or Rh/C to obtain 5-O-phenylpropionylated taxinine A...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00620-4
更新日期:1999-12-20 00:00:00
abstract::The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.09.037
更新日期:2006-01-01 00:00:00
abstract::In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection meth...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.03.028
更新日期:2013-05-15 00:00:00
abstract::A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase is described. This report discusses the SAR of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R potency. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.11.041
更新日期:2007-02-15 00:00:00
abstract::Bifunctional molecules containing both a biotin and a substrate unit have been designed and synthesized for phage display screening of mutant libraries of haloalkane dehalogenase enzymes. The molecules were assembled using a convergent modular synthetic strategy. One molecule was synthesized to evaluate the concept of...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00697-0
更新日期:1999-01-18 00:00:00
abstract::A verbenachalcone derivative was synthesized and shown to protect N2a cells from caspase induction caused by serum starvation and to enhance the effect of NGF on neurite outgrowth in PC12 cells. As an initial investigation of the compound's mechanism(s) of action, we performed differential gene expression profiling in...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.12.001
更新日期:2005-02-15 00:00:00
abstract::The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.07.048
更新日期:2012-09-15 00:00:00
abstract::Analogues of BIBP 3226, (R)-N(alpha)-diphenylacetyl-N-(4-hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity. Combination with a N(G)...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00292-4
更新日期:2000-07-17 00:00:00
abstract::The radical-scavenging capacities of ferrocenyl group and phenolic hydroxyl group in ferrocenyl chalcone were identified in this work. 1,1'-Diacetylferrocene was applied to condense with benzaldehyde, vanillin, and protocatechualdehyde to produce ferrocenyl chalcones, which were employed to interact with 2,2'-azinobis...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.12.051
更新日期:2011-02-01 00:00:00
abstract::The non-receptor tyrosine kinase Syk (spleen tyrosine kinase) is a pharmaceutical relevant target because its over-activation is observed in several autoimmune diseases, allergy, and asthma. Here we report the identification of two novel inhibitors of Syk by high-throughput docking into a rare C-helix-out conformation...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.01.083
更新日期:2014-03-15 00:00:00
abstract::A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.02.077
更新日期:2005-05-02 00:00:00
abstract::The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.08.048
更新日期:2013-10-15 00:00:00
abstract::A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.06.094
更新日期:2004-09-20 00:00:00
abstract::A small library of 1-aminoalkyl 2-naphthols has been synthesized through the direct Mannich reaction of 2-naphthols with (hetero)aromatic aldehydes and secondary amines. All of the Mannich bases having a thiophen-2-yl ring in their structure had good activity against Gram-positive bacteria, irrespective of the nature ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.03.098
更新日期:2016-05-15 00:00:00
abstract::In order to elucidate the essential structural features for KDR kinase inhibitors, three-dimensional pharmacophore hypotheses were built on the basis of a set of known KDR kinase inhibitors selected from the literature with CATALYST program. Several methods tools used in validation of pharmacophore hypothsis were pres...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.01.089
更新日期:2007-04-15 00:00:00
abstract::The synthesis of 1- and 2-substituted aza-benzothiopyranoindazoles has been accomplished. The comparisons of the in vitro antitumor activities of the 2-substituted analogues with the benzothiopyranoindazole chemotypes indicate that the positioning of the nitrogen atom at C-9 (9-aza analogue 4d) leads to a substrate wi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00689-7
更新日期:2000-02-07 00:00:00
abstract::Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique str...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.02.064
更新日期:2004-05-17 00:00:00
abstract::Glycosyldisulfides can interact efficiently with carbohydrate-binding entities. This has been shown for a range of thiosaccharide dimers when tested for their effects against the lectin Concanavalin A using a modified quartz crystal microbalance-technique. Contrary to the thiosaccharide monomers, showing no significan...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.04.024
更新日期:2005-06-02 00:00:00
abstract::A new class of selective nonsteroidal glucocorticoid receptor modulators typified by N-[3-[benzyl-(4-chloro-2-fluoro-benzyl)-amino]-2-methyl-phenyl]-methanesulfonamide 19 has been discovered. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.02.013
更新日期:2004-05-03 00:00:00