N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF.

abstract：:A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)-antagonists. The most potent compounds were found in the class of (piperazine-1-yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau JF,Jeppesen CB,Rimvall K,Hohlweg R

更新日期：2006-10-15 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

authors： Wang Y,Wright SC,Larrick JW

更新日期：2003-02-10 00:00:00

abstract：:The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim YJ,Jeon Y,Kim T,Lim WC,Ham J,Park YN,Kim TJ,Ko H

更新日期：2017-02-15 00:00:00

abstract：:A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keith JM,Jones W,Pierce JM,Seierstad M,Palmer JA,Webb M,Karbarz M,Scott BP,Wilson SJ,Luo L,Wennerholm M,Chang L,Rizzolio M,Rynberg R,Chaplan S,Guy Breitenbucher J

更新日期：2020-10-15 00:00:00

abstract：:To design artificial restriction enzymes, synthetic catalytic centers that effectively hydrolyze linear double-stranded polydeoxyribonucleotides are needed. The Co(III) complex of cyclen (CoCyc) attached to polystyrene derivatives hydrolyzes linearized pUC18 DNA with half-lives as short as 30 min at 25 degrees C. The ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeung CS,Song JB,Kim YH,Suh J

更新日期：2001-12-03 00:00:00

abstract：:The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modification into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [d-2-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fichna J,do-Rego JC,Janecki T,Staniszewska R,Poels J,Broeck JV,Costentin J,Schiller PW,Janecka A

更新日期：2008-02-15 00:00:00

abstract：:The purpose of the present study was the synthesis and the biological screening of new analogues of N/OFQ(1-13)NH2, the minimal sequence maintaining the same activity as the natural peptide nociceptin. In order to investigate the role of Lys, we substituted Lys at positions 9 and/or 13 by Orn, Dab (diaminobutanoic aci...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naydenova ED,Zhivkova VI,Zamfirova RN,Vezenkov LT,Dobrinova YG,Mateeva PI

更新日期：2006-08-01 00:00:00

abstract：:A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elliott JM,Carling RW,Chambers M,Chicchi GG,Hutson PH,Jones AB,MacLeod A,Marwood R,Meneses-Lorente G,Mezzogori E,Murray F,Rigby M,Royo I,Russell MG,Sohal B,Tsao KL,Williams B

更新日期：2006-11-15 00:00:00

abstract：:A novel class of 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine derivatives was designed, synthesized and evaluated as human nitric oxide synthase (NOS) inhibitors. Structure-activity relationship studies based on various basic amine side chains attached at the 1-position of the 2,3,4,5-tetrahydro-1H-benzo[b]...

journal_title：Bioorganic & medicinal chemistry letters

authors： Annedi SC,Ramnauth J,Cossette M,Maddaford SP,Dove P,Rakhit S,Andrews JS,Porreca F

更新日期：2012-04-01 00:00:00

abstract：:We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brachet E,Dumond A,Liu WQ,Fabre M,Selkti M,Raynaud F,Hermine O,Benhida R,Belmont P,Garbay C,Lepelletier Y,Ronco C,Pagès G,Demange L

更新日期：2019-12-15 00:00:00

abstract：:DNA G-quadruplex is an attractive drug target for anticancer therapy. Most G-quadruplex ligands have little selectivity, due to π-stacking interaction with common G-tetrads surface. Thanks to the varieties of G-quadruplex grooves, the groove-binding ligand is expected to create high selectivity. Therefore, developing ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li J,Jin X,Hu L,Wang J,Su Z

更新日期：2011-12-01 00:00:00

abstract：:2-O-carboxymethylpyrogallol derivatives (4-17) were synthesized, with their in vitro inhibitory activities against PTP1B and in vivo antihyperglycemic effects examined. Compound 14, the most potent among the series, showed a K(i) value of 1.1 microM against PTP1B, 7-fold lower than that against TC-PTP. When compound 1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bhattarai BR,Shrestha S,Ham SW,Kim KR,Cheon HG,Lee KH,Cho H

更新日期：2007-10-01 00:00:00

abstract：:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rusnak DW,Lai Z,Lansing TJ,Rhodes N,Gilmer TM,Copeland RA

更新日期：2004-05-03 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

authors： Patel HK,Grotzfeld RM,Lai AG,Mehta SA,Milanov ZV,Chao Q,Sprankle KG,Carter TA,Velasco AM,Fabian MA,James J,Treiber DK,Lockhart DJ,Zarrinkar PP,Bhagwat SS

更新日期：2009-09-01 00:00:00

abstract：:GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2012-02-15 00:00:00

abstract：:Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transpor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Omran Z,Kay G,Hector EE,Knott RM,Cairns D

更新日期：2011-04-15 00:00:00

abstract：:The synthesis and receptor binding of novel adenosine receptor antagonists is described. We found that non-xanthine 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives may have high affinity and substantial selectivity for the adenosine A(1) receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： van Tilburg EW,van der Klein PA,de Groote M,Beukers MW,IJzerman AP

更新日期：2001-08-06 00:00:00

abstract：:We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martín-Gago P,Ramón R,Aragón E,Fernández-Carneado J,Martin-Malpartida P,Verdaguer X,López-Ruiz P,Colás B,Cortes MA,Ponsati B,Macias MJ,Riera A

更新日期：2014-01-01 00:00:00

abstract：:Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang X,Krasnova L,Wu KB,Wu WS,Cheng TJ,Wong CH

更新日期：2018-09-01 00:00:00

abstract：:N6-Substituted adenosine analogues containing cyclic hydrazines or chiral hydroxy (ar)alkyl groups, designed to interact with the S2 and S3 receptor subregions, have been synthesized and their binding to the adenosine A1 and A2A receptors have been investigated. Examples of both types of compounds were found to exhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ha SB,Melman N,Jacobson KA,Nair V

更新日期：1997-12-16 00:00:00

abstract：:A new class of (E)-2-alkyl-2-(4-methanesulfonylphenyl)-1-phenylethenes were designed for evaluation as selective cyclooxygense-2 (COX-2) inhibitors. The target olefins were synthesized, via a Takeda olefination reaction, followed by oxidation of the respective thiomethyl olefinic intermediate. In vitro COX-1/COX-2 inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uddin MJ,Rao PN,Rahim MA,McDonald R,Knaus EE

更新日期：2004-10-04 00:00:00

abstract：:Esculentoside A (EsA) has been reported to possess anti-inflammatory activity and selective inhibitory activity towards cyclooxygenase-2. A series of derivatives of EsA were synthesized by converting the C-28 carboxylic acid group into amides. The haemolytic activity and inhibitory activity towards cyclooxygenase-2 we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu F,Yi Y,Sun P,Zhang D

更新日期：2007-12-01 00:00:00

abstract：:We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, whic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LX,Zhou XB,Xiao ML,Jiang N,Liu F,Zhou WX,Wang XK,Zheng ZB,Li S

更新日期：2014-08-15 00:00:00

abstract：:A novel indole series of PGD2 receptor (DP receptor) antagonists is presented. Optimization of this series led to the identification of potent and selective DP receptor antagonists. In particular, antagonists 35 and 36 were identified with Ki values of 2.6 and 1.8 nM, respectively. These two antagonists are also poten...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sturino CF,Lachance N,Boyd M,Berthelette C,Labelle M,Li L,Roy B,Scheigetz J,Tsou N,Brideau C,Cauchon E,Carriere MC,Denis D,Greig G,Kargman S,Lamontagne S,Mathieu MC,Sawyer N,Slipetz D,O'Neill G,Wang Z,Zamboni R

更新日期：2006-06-01 00:00:00

abstract：:A series of cysteine diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low mi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perrey DA,Narla RK,Uckun FM

更新日期：2000-03-20 00:00:00

abstract：:A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu S,Sanchez TW,Liu Y,Yin Y,Neamati N,Zhao G

更新日期：2013-11-15 00:00:00

abstract：:The continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with HIV co-infection mean the search for new antileishmanial agents has never been more urgent. We have identified the benzodiazepines as a structural class for antileishman...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clark RL,Carter KC,Mullen AB,Coxon GD,Owusu-Dapaah G,McFarlane E,Duong Thi MD,Grant MH,Tettey JN,Mackay SP

更新日期：2007-02-01 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Congdon MD,Childress ES,Patwardhan NN,Gumkowski J,Morris EA,Kharel Y,Lynch KR,Santos WL

更新日期：2015-11-01 00:00:00

abstract：:A series of anthranilodinitrile-based biaryls were synthesized and evaluated in vitro against extracellular promastigotes and intracellular amastigotes of Leishmania donovani. Among various screened compounds, a biaryl with trifluoromethyl group 5f showed 83% inhibition against promastigotes and 70% inhibition against...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh FV,Vatsyayan R,Roy U,Goel A

更新日期：2006-05-15 00:00:00

abstract：:The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar rang...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao Z,Waters NC,Woodard CL,Li Z,Li PK

更新日期：2001-11-05 00:00:00