Abstract:
:Modulation of DNA repair pathways in oncology has been an area of intense interest in the last decade, not least as a consequence of the promising clinical activity of poly(ADP-ribose) polymerase (PARP) inhibitors. In this review article, we highlight inhibitors of the phosphatidylinositol 3-kinase related kinase (PIKK) family as of potential interest in the treatment of cancer, both in combination with DNA-damaging therapies and as stand-alone agents.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Finlay MR,Griffin RJdoi
10.1016/j.bmcl.2012.06.053subject
Has Abstractpub_date
2012-09-01 00:00:00pages
5352-9issue
17eissn
0960-894Xissn
1464-3405pii
S0960-894X(12)00804-9journal_volume
22pub_type
杂志文章,评审abstract::1,2,4-Oxadiazoles have been prepared in parallel using 1,1'-carbonyldiimidazole (CDI) as a reagent for both formation and cyclodehydration of O-acyl benzamidoximes. The use of CDI facilitates parallel purification of the oxadiazole products by simple liquid-liquid extraction and filtration. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00712-4
更新日期:1999-01-18 00:00:00
abstract::The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeut...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.03.093
更新日期:2005-06-02 00:00:00
abstract::During the course of our investigations in the field of azole antimicrobial agents, we have identified BM212 a pyrrole derivative with good in vitro activity against mycobacteria and candidae. These findings prompted us to prepare new pyrrole derivatives 2-6 in the hope of increasing the activity. The microbiological ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00510-7
更新日期:1999-10-18 00:00:00
abstract::We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00158-0
更新日期:2002-05-20 00:00:00
abstract::Mycobacterium tuberculosis pantothenate synthetase is a potential anti-tuberculosis target, and a high-throughput screening system was previously developed to identify its inhibitors. Using a similar system, we screened a small library of compounds and identified actinomycin D (ActD) as a weak inhibitor of pantothenat...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.05.021
更新日期:2011-07-01 00:00:00
abstract::The synthesis and antihypertensive activity of racemates and enantiomers of substituted 2,3,8,8a-tetrahydro-7H-oxazolo[3,2-a]pyridinedicarboxylates have been reported. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00691-5
更新日期:2000-02-21 00:00:00
abstract::Four N-Fmoc protected polyoxyethylene-based amino acid type linkers were designed and synthesized for peptide derivatization in solid phase. Three of them were obtained in a crystalline form. The crystallized linkers can be stored at 4 degrees C for 2 years without significant decomposition. Protocols for biotinylatio...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.09.067
更新日期:2004-01-05 00:00:00
abstract::The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have exc...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.08.028
更新日期:2007-10-01 00:00:00
abstract::We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug wit...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.05.001
更新日期:2010-07-01 00:00:00
abstract::Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. To examine the distance between the two ligand binding sites (C1A and C1B) of PKC, we designed and synthesized two series of isobenzofuranone dimers. Peak binding activities were observed for the C3-acyl cha...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.02.098
更新日期:2004-06-07 00:00:00
abstract::Two novel α-linked sialyltrisaccharide imidazolium-type probes (ITags) based on the structures of biologically relevant 6'-sialyllactosamine and 3'-sialyllactosamine were efficiently and stereoselectively prepared using a chemo-enzymatic approach. The apparent kinetic parameters for the enzyme catalyzed transformation...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.07.049
更新日期:2015-10-01 00:00:00
abstract::A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used a...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.10.011
更新日期:2013-12-15 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::The inhibitive activities of the human immunodeficiency virus protease inhibitors ritonavir (RTV) boosted indinavir (IDV) and RTV boosted lopinavir (LPV) for erythrocytic stage malaria were evaluated in rhesus macaques. The IDV/RTV regimen effectively inhibits the replication of Plasmodium knowlesi with clinically rel...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2015.02.014
更新日期:2015-04-01 00:00:00
abstract::A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compo...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00668-x
更新日期:2000-02-07 00:00:00
abstract::The synthesis of a series of new antitumour agents, the benzothiazole substituted quinol ethers and esters, is reported via the hypervalent iodine mediated oxidation of hydroxylated 2-phenylbenzothiazoles. The products were found to be active in vitro against human colon and breast cancer cell lines with IC50 values i...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00027-5
更新日期:2000-03-06 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::Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid in...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.10.027
更新日期:2011-12-15 00:00:00
abstract::Penicillium digitatum, as well as five other citrus pathogenic species, (Penicillium ulaiense Link, Geotrichum citri Link, Botrytis cinerea P. Micheli ex Pers., Lasiodiplodia theobromae (Pat.) Griffon & Maubl., and Phomopsis citri (teleomorph Diaporthe citri)) were observed to convert 6',7'-epoxybergamottin (1) into 6...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.01.081
更新日期:2012-03-15 00:00:00
abstract::After the widespread use of the acyclic purine nucleoside analogues for therapy of herpes simplex virus (HSV) infection since the 1980s, new antiviral strategies are urgently needed to counter the emergence of drug-resistant clinical isolates. In this report, we define the anti-HSV efficacies of three optimized 2-amin...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.05.079
更新日期:2012-07-15 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::Pradimicins are a group of antiviral and antifungal natural products from Actinomadura hibisca. Two putative O-methyltransferase genes, pdmF and pdmT, are present in the pradimicin biosynthetic gene cluster. However, there is only one methoxy group (11-OCH3) in pradimicins. Through heterologous expression and in vitro...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.05.068
更新日期:2017-08-01 00:00:00
abstract::The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly sel...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.07.082
更新日期:2011-10-15 00:00:00
abstract::A facile 1,3-dipolar cycloaddition of azomethine ylide generated in situ from the reaction of 1,3-thiazolane-4-carboxylic acid and isatin to 2-arylidene-1,3-indanediones furnished novel dispiro-oxindolylpyrrolothiazoles regio- and stereo-selectively in moderate to good yields (60-92%). In vitro antitubercular screenin...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2010.10.080
更新日期:2010-12-15 00:00:00
abstract::A methyl group at the 2-position of methyl mesopyropheophorbide-a was transformed to the 2-formyl group to give methyl mesopyropheophorbide-f, one of the chlorophyll-f analogs. The 2-formylation moved the redmost electronic absorption band in a solution to a longer wavelength and the bathochromic shift was comparable ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.06.022
更新日期:2014-08-15 00:00:00
abstract::Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was hi...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)00986-1
更新日期:2003-02-10 00:00:00
abstract::A new cytotoxic oxysterol, 16beta-hydroxy-5alpha-cholestane-3,6-dione was isolated from the red alga Jania rubens. Its structure was established by spectroscopic method. The ID50 value was 0.5 microg/mL. ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00504-7
更新日期:2000-11-20 00:00:00
abstract::The (S,S,S,R,S,R)-configurated cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activity against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the major conformation the asymmetric conformer, containing a cis-amide bond ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00688-7
更新日期:2003-10-06 00:00:00
abstract::Alzheimer's disease is characterized by the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [(18)F]fluoropropylcurcumin ([(18)F]FP-curcumin), which demonstrated excellent binding affinity (K(i)=0.07 nM) for Aβ(1-40) aggregates and good pharmacokinetics in...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.08.003
更新日期:2011-10-01 00:00:00
abstract::In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 res...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(99)00595-8
更新日期:1999-12-06 00:00:00