A three-step protocol for lead optimization: quick identification of key conformational features and functional groups in the SAR studies of non-ATP competitive MK2 (MAPKAPK2) inhibitors.

abstract：:The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatme...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aman W,Lee J,Kim M,Yang S,Jung H,Hah JM

更新日期：2016-02-15 00:00:00

abstract：:Ceramides are the major lipid components of the stratum corneum, the major permeability barrier of the skin. Here we report a chemical synthesis of ceramide analogs covalently bonded on the silica particles, that can be used to predict the skin permeability of chemicals via HPLC methods. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yin J,Liu H,Pidgeon C

更新日期：1998-01-20 00:00:00

abstract：:The synthesis and structure-activity relationships of zygosporamide, a known potent and selective cytotoxic natural product against SF-268 and RXF 393 cell lines, are described. The potencies of the synthetic zygosporamide are similar to those reported for the natural product toward all cancer cell lines examined with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Zhang F,Zhang Y,Liu JO,Ma D

更新日期：2008-08-01 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：:In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thorarensen A,Li J,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Sarver RW

更新日期：2007-06-01 00:00:00

abstract：:A library of acylhydrazone iron chelators was synthesized and tested for its ability to inhibit the growth of a chloroquine-resistant strain of Plasmodium falciparum. Some of these new compounds are significantly more active than desferrioxamine DFO, the iron chelator in widespread clinical use and also than the most ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Melnyk P,Leroux V,Sergheraert C,Grellier P

更新日期：2006-01-01 00:00:00

abstract：:Herein, we reported the synthesis of 16 novel steroidal thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides under solvent-free conditions using microwave irradiation. The yields obtained are in the range of 84-96% using microwave method and 46-62% using convention...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Shi Z,Liu M,Liu X

更新日期：2012-12-15 00:00:00

abstract：:Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZD,Jensen PR,Fenical W

更新日期：1999-07-19 00:00:00

abstract：:Mass-directed isolation of the CH(2)Cl(2)/MeOH extract from the leaves of Cryptocarya obovata resulted in the purification of a new trypanocidal alpha-pyrone, 7',8'-dihydroobolactone (1). The chemical structure of 1 was determined by 1D/2D NMR, MS and CD data analysis. 7',8'-Dihydroobolactone was shown to inhibit Tryp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davis RA,Demirkiran O,Sykes ML,Avery VM,Suraweera L,Fechner GA,Quinn RJ

更新日期：2010-07-15 00:00:00

abstract：:A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewis TA,Young MA,Arrington MP,Bayless L,Cai X,Collart P,Eckman JB,Ellis JL,Ene DG,Libertine L,Nicolas JM,Scannell RT,Wels BF,Wenberg K,Wypij DM

更新日期：2004-11-15 00:00:00

abstract：:A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fensome A,Bender R,Cohen J,Collins MA,Mackner VA,Miller LL,Ullrich JW,Winneker R,Wrobel J,Zhang P,Zhang Z,Zhu Y

更新日期：2002-12-02 00:00:00

abstract：:A series of leinamycin derivatives were synthesized and evaluated for antitumor activity. Modifications at C-8 and C-9 positions revealed a broad structure-activity relationship in vitro and some derivatives showed potent antiproliferative activity against HeLa S3 cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kanda Y,Ashizawa T,Saitoh Y,Saito H,Gomi K,Okabe M

更新日期：1998-04-21 00:00:00

abstract：:We constructed a label-free and detector-free aptazyme-based riboswitch sensor for detecting the cofactor of the aptazyme. This riboswitch, which usually suppresses the gene expression with its anti-RBS sequence bound to the RBS of its own mRNA (OFF), activates the translation only when a cofactor is added to release ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogawa A,Maeda M

更新日期：2007-06-01 00:00:00

abstract：:Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP(1) receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP(1) receptor that displayed good ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hall A,Brown SH,Chessell IP,Chowdhury A,Clayton NM,Coleman T,Giblin GM,Hammond B,Healy MP,Johnson MR,Metcalf A,Michel AD,Naylor A,Novelli R,Spalding DJ,Sweeting J,Winyard L

更新日期：2007-02-15 00:00:00

abstract：:Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two i...

journal_title：Bioorganic & medicinal chemistry letters

authors： An XD,Liu H,Xu ZL,Jin Y,Peng X,Yao YM,Geng M,Long YQ

更新日期：2015-02-01 00:00:00

abstract：:Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antiba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vatmurge NS,Hazra BG,Pore VS,Shirazi F,Chavan PS,Deshpande MV

更新日期：2008-03-15 00:00:00

abstract：:The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and evaluated in vitro. In general, the compounds were much less potent in inducing platelet aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： McComsey DF,Hecker LR,Andrade-Gordon P,Addo MF,Maryanoff BE

更新日期：1999-01-18 00:00:00

abstract：:The ability of serine phosphate (SerP) or alpha-amino-gamma-phosphonobutyric acid (AbuP) and arginine to form a salt bridge between their side chains appears to be much greater when they are spaced i/i+4 than when they are spaced i/i+3. The side chain-side chain interaction between SerP/Arg and AbuP/Arg, positioned i/...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liehr S,Chenault HK

更新日期：1999-09-20 00:00:00

abstract：:Derivatives of phaeosphaeride A (PPA) were synthesised and characterised; then anti-cancer studies were carried out on the A549 cancer cell line. It was found that the acetyl derivative (compound 3) displayed comparable in vitro cytotoxicity to that of PPA (EC50=49±7 μM and EC50=46±5 μM, respectively), while chloroace...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abzianidze VV,Prokofieva DS,Chisty LA,Bolshakova KP,Berestetskiy AO,Panikorovskii TL,Bogachenkov AS,Holder AA

更新日期：2015-12-01 00:00:00

abstract：:Practical, asymmetric total syntheses of the title phospholipids from a readily available myo-inositol derivative as well as short chain and cross-linkable aminoether analogues are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Falck JR,Krishna UM,Capdevila JH

更新日期：2000-08-07 00:00:00

abstract：:The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), r...

journal_title：Bioorganic & medicinal chemistry letters

authors： DeChristopher B,Park SH,Vong L,Bamford D,Cho HH,Duvadie R,Fedolak A,Hogan C,Honda T,Pandey P,Rozhitskaya O,Su L,Tomlinson E,Wallace I

更新日期：2019-04-15 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

authors： Tamamura H,Sugioka M,Odagaki Y,Omagari A,Kan Y,Oishi S,Nakashima H,Yamamoto N,Peiper SC,Hamanaka N,Otaka A,Fujii N

更新日期：2001-02-12 00:00:00

abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

更新日期：1998-05-05 00:00:00

abstract：:A series of oligo-peptide based catalysts were prepared using Fmoc solid-phase peptide synthesis. It was found that peptides with N-terminal proline residues catalyzed an aldol reaction yielding enantiomeric enriched product. Peptide H-Pro-Glu-Leu-Phe-OH catalyzed the reaction with good activity and moderate enantiose...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kofoed J,Nielsen J,Reymond JL

更新日期：2003-08-04 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

authors： Stachel SJ,Coburn CA,Rush D,Jones KL,Zhu H,Rajapakse H,Graham SL,Simon A,Katharine Holloway M,Allison TJ,Munshi SK,Espeseth AS,Zuck P,Colussi D,Wolfe A,Pietrak BL,Lai MT,Vacca JP

更新日期：2009-06-01 00:00:00

abstract：:A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Byun D,Chen X,Doerffler E,Leavitt SA,Sheng XC,Yang CY,Kim CU

更新日期：2012-01-15 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 series of derivatives of the new ring system pyrrolo[2,3-h]quinoline-2-one was synthesized and evaluated as photoreagents toward cultured human tumor cells. Remarkable phototoxycity resulted for some derivatives, especially those bearing the phenyl group at the 7-position. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barraja P,Diana P,Lauria A,Montalbano A,Almerico AM,Dattolo G,Cirrincione G,Viola G,Dall'Acqua F

更新日期：2003-08-18 00:00:00

abstract：:A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartz RA,Vrudhula VM,Ahuja VT,Grace JE,Lodge NJ,Bronson JJ,Macor JE

更新日期：2017-03-15 00:00:00

abstract：:Mismatch binding protein MutS binding to bulge structure in DNA duplexes was controlled by UV irradiation. 4-O-(2-Nitrobenzyl)thymidine or 4-O-[2-(2-nitrophenyl)propyl]thymidine was incorporated into DNA duplexes a bulged position. The MutS did not bind to the caged DNA duplexes but bound after removing the 2-nitroben...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Ohno Y,Ohno K,Takeshita L,Kanamori T,Masaki Y,Sekine M

更新日期：2016-10-01 00:00:00