Abstract:
:A concise synthesis of three novel C2-C3 unsaturated pyrrolo[2,1-c][1,4]benzodiazepine analogues (18-20) containing conjugated acrylyl C2-substituents is reported that utilises Heck coupling to install the C2-acrylyl side chains. These analogues possess significant cytotoxicity according to the NCI 60-cell line screen with 18 surpassing anthramycin (1) in potency.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Chen Z,Gregson SJ,Howard PW,Thurston DEdoi
10.1016/j.bmcl.2003.12.094subject
Has Abstractpub_date
2004-03-22 00:00:00pages
1547-9issue
6eissn
0960-894Xissn
1464-3405pii
S0960894X04000459journal_volume
14pub_type
杂志文章abstract::Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inh...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.10.015
更新日期:2016-09-15 00:00:00
abstract::PC-1 (NPP-1) inhibitors may be useful as therapeutics for the treatment of CDDP (calcium pyrophosphate dehydrate) deposition disease and osteoarthritis. We have identified a series of potent quinazolin-4-piperidin-4-ethyl sulfamide PC-1 inhibitors. The series, however, suffers from high affinity binding to hERG potass...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.04.006
更新日期:2009-06-15 00:00:00
abstract::Retinoid X Receptor (RXR) specific ligands are currently being investigated for the treatment of metabolic diseases such as type II diabetes. We report the synthesis of conformationally locked retinoids, which are potent RXR selective ligands, and the attempted synthesis of 9-cyclopropyl locked analogs of RA and 9-cis...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00048-7
更新日期:1999-02-22 00:00:00
abstract::A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.02.081
更新日期:2005-05-02 00:00:00
abstract::The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1). ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.06.029
更新日期:2011-08-15 00:00:00
abstract::A series of Incentrom A analogs that inhibit the chromosome segregation process in yeast were synthesized and tested for their effects on chromosome stability and cell proliferation. Pharmacophore and structure-activity relationship of Incentrom A for the anti-yeast activity were established. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.07.006
更新日期:2008-08-15 00:00:00
abstract::Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.12.028
更新日期:2009-02-01 00:00:00
abstract::Wheat cell-free expression systems based on wheat germ extract (WGE) enable us to briefly synthesize various types of proteins in vitro merely by exogenously adding their mRNA templates. Moreover, it is possible to produce larger amounts of protein by thoroughly removing the endosperm, which contains many translation ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 信件
doi:10.1016/j.bmcl.2019.06.058
更新日期:2019-08-15 00:00:00
abstract::The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their antifilarial activities are delineated. Some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00255-9
更新日期:2000-07-03 00:00:00
abstract::The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.05.025
更新日期:2012-07-01 00:00:00
abstract::We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of th...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.07.011
更新日期:2008-08-15 00:00:00
abstract::Mo(VI) and Mo(V) salts both react selectively with Hantzsch esters to produce substitute pyridines in good-to-excellent yield (75-99%). The remarkable reactivity and selectivity of MoOCl(4) under reflux of acetonitrile and MoCl(5) in dichloromethane at room temperature encouraged us to propose that molybdenum-containi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.04.043
更新日期:2012-06-01 00:00:00
abstract::Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00123-7
更新日期:1999-04-05 00:00:00
abstract::2'-O-[N-(4-Aminobutylcarbamoyl)]uridine (U(abcm)) was synthesized and incorporated into oligonucleotides. The oligonucleotides incorporating U(abcm) formed more stable duplexes with their complementary and mismatched RNAs than those containing 2'-O-carbamoyluridine (U(cm)). The stability of duplex with a U(abcm)-rG ba...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.02.012
更新日期:2012-04-01 00:00:00
abstract::Beta-2'-C-methyl purines (1, 2) are known inhibitors of hepatitis C virus (HCV). We herein report the synthesis, biological and enzymatic evaluation of their 5'-phosphoramidate ProTides. Described herein are seven l-alanine phosphoramidate derivatives with variations to the amino acid ester. The 1-naphthyl phosphorami...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.05.122
更新日期:2009-08-01 00:00:00
abstract::Bromofluoroacetophenone derivatives which produce fluorine substituted phenyl radicals that cleave DNA upon excitation were investigated as a novel photonuclease. Pyrrolecarboxamide-conjugated bromofluoroacetophenones; 4'-bromo-2'-fluoroacetophenone and 2'-bromo-4'-fluoroacetophenone were synthesized and their DNA cle...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00212-9
更新日期:2003-05-19 00:00:00
abstract::Cyclic peptides were obtained, on-resin, by the copper (I) catalysed 1,3-dipolar cycloaddition of azides and alkynes. The reaction led exclusively to the formation of the expected cyclomonomeric products which acted as ligands of the Vascular Endothelial Growth Factor receptor 1. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.07.087
更新日期:2007-10-15 00:00:00
abstract::A new siderophore, N5,N6-thiodipropanoyl-bis[N1,N10-bis(2,3-dihydroxy benzoyl-spermidine)]-Fe (III) complex or H2LFe has been synthesised. The reaction of the reduced form of this complex with dioxygen has been investigated through electrochemical study and revealed the formation of a new species assumed to be H2O2. T...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00371-6
更新日期:1999-08-16 00:00:00
abstract::Indolinonic hydroxylamines (IH), representing a new type of antioxidants, are comparative to alpha-tocopherol to protect lipids from oxidation. To elucidate the structure-activity relationship for IH, B3LYP/6-31G(d, p) method was employed to calculate the O-H bond dissociation enthalpy (BDE), a theoretical parameter t...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(01)00724-7
更新日期:2002-01-21 00:00:00
abstract::Dantrolene, the only therapeutic agent for malignant hyperthermia, is known to have not only a muscle relaxant effect, but also a neuroprotective effect and Alzheimer's disease improving effect. Recently, it has been reported that dantrolene has a weak inhibitory effect on acetylcholinesterase (AChE), which is a thera...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.126888
更新日期:2020-02-15 00:00:00
abstract::An artificial neural network based approach using Atomic5 fragmental descriptors has been developed to predict the octanol-water partition coefficient (logP). We used a pre-selected set of organic molecules from PHYSPROP database as training and test sets for a feedforward neural network. Results demonstrate the super...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.12.024
更新日期:2004-02-23 00:00:00
abstract::A series of N-phenylnicotinamides (1-40) were designed and evaluated in vitro for their COX inhibitory activities. Most of the synthesized compounds were proved to be potent and selective inhibitors of COX-1. Compound 28 showed the most potent COX-1 inhibitory activity (COX-1 IC(50) = 0.68 ± 0.07 μM) and good selectiv...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.11.062
更新日期:2011-01-01 00:00:00
abstract::Atrial fibrillation (AF) is a major cause of stroke, heart failure, sudden death and cardiovascular morbidity. The Kv1.5 potassium channel conducts the IKur current and has been demonstrated to be predominantly expressed in atrial versus ventricular tissue. Blockade of Kv1.5 has been proven to be an effective approach...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2019.03.006
更新日期:2019-05-15 00:00:00
abstract::Prostate cancer is one of the leading causes of death among males in the world. Prostate cancer cells have been shown to express upregulated chemokine receptor CCR5, a G protein-coupled receptor (GPCR) that relates to the inflammation process. Anibamine, a natural product containing a pyridine ring and two aliphatic s...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.06.029
更新日期:2015-09-01 00:00:00
abstract::In the search of molecules that can serve as leads in the design of a new drug for the treatment of Chagas' disease, we found that some brevifolin carboxylate derivatives isolated from Geranium bellum Rose, inactivate triosephosphate isomerase from Trypanosoma cruzi (TcTIM) in a species-specific manner. After spectros...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.08.055
更新日期:2009-10-15 00:00:00
abstract::A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.07.024
更新日期:2009-09-01 00:00:00
abstract::The four 2,2,5-regioisomer counterparts of SCH 51048 were synthesized and evaluated. As with the parent series, only the two cis isomers possessed any in vitro activity, and only the activity of the isomer with the R-configuration at the tetrahydrofuran 2-carbon was significant. The activity data suggests that oxygen ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00282-2
更新日期:2002-07-08 00:00:00
abstract::Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.12.065
更新日期:2006-04-01 00:00:00
abstract::We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.04.033
更新日期:2009-06-01 00:00:00
abstract::A series of multisubstituted indole-acrylonitrile hybrids were designed, synthesized and evaluated for their potential cytotoxic activities. The bio-evaluation results indicated that some of the target compounds (such as 3a, 3f, 3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402, and HL-77...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.03.011
更新日期:2014-04-15 00:00:00