alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1.

abstract：:Potent cyclin dependent kinase inhibitors were prepared using parallel synthesis methodology. Treating advanced intermediate 2 with a variety of hydrazides in DMSO at 80 degrees C for 30 min gave the desired acylsemicarbazides in good to excellent yield. Several compounds were active against cdk4/D1 and cdk2/E in the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nugiel DA,Vidwans A,Dzierba CD

更新日期：2004-11-15 00:00:00

abstract：:A significant increase in plasma glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase was observed 6 h after intraperitoneal administration of D-galactosamine (D-Galn). Three hours after administration of D-Galn, the vitamin C concentration in the liver decreased significantly compared to that in a ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishioka H,Kishioka T,Iida C,Fujii K,Ichi I,Kojo S

更新日期：2006-06-01 00:00:00

abstract：:Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Don MJ,Lewis DF,Wang SY,Tsai MW,Ueng YF

更新日期：2003-08-04 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

abstract：:Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ~19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key role...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peel M,Scribner A

更新日期：2013-08-15 00:00:00

abstract：:Exogenous short-chain nucleic acids undergo rapid import into the nucleus. Fluorescence-labeled dT1-13 DNA microinjected into the cytoplasm domain of a HeLa cell was rapidly imported into the nucleus domain within 1min. This is much more rapid than what has been observed for intracellular diffusion of small molecules....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kitagawa M,Okamoto A

更新日期：2016-10-01 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：:The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tremblay MR,Simard J,Poirier D

更新日期：1999-10-04 00:00:00

abstract：:(Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bohn P,Mouchard F,Rouvet J,de Boisgrollier AC,Vera P

更新日期：2013-03-01 00:00:00

abstract：:We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abbott L,Betschmann P,Burchat A,Calderwood DJ,Davis H,Hrnciar P,Hirst GC,Li B,Morytko M,Mullen K,Yang B

更新日期：2007-03-01 00:00:00

abstract：:Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution ...

journal_title：Bioorganic & medicinal chemistry letters

authors： da S Souza LG,Almeida MCS,Lemos TLG,Ribeiro PRV,de Brito ES,Silva VLM,Silva AMS,Braz-Filho R,Costa JGM,Rodrigues FFG,Barreto FS,de Moraes MO

更新日期：2016-01-15 00:00:00

abstract：:Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao J,Midde N,Zhu J,Terry AV,McInnes C,Chapman JM

更新日期：2016-11-15 00:00:00

abstract：:Forty caffeate analogues were synthesized via a convenient method starting from vanillin with moderate to good yields. The testing of biological activity of these compounds against HIV-1 integrase indicates that four compounds: bornyl caffeate, bornyl 2-nitrocaffeate, 5-nitrocaffeic acid and 5-nitrocaffeic acid phenet...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia CN,Li HB,Liu F,Hu WX

更新日期：2008-12-15 00:00:00

abstract：:We report a sensitive and efficient magnetic bead-based assay for viral DNA identification using isothermal amplification of a reporting probe. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schopf E,Fischer NO,Chen Y,Tok JB

更新日期：2008-11-15 00:00:00

abstract：:Acetyl CoA carboxylase (ACC) catalyzes the carboxylation of acetyl CoA to form malonyl CoA. In skeletal muscle and heart, malonyl CoA functions to regulate lipid oxidation by inhibition of carnitine palmitoyltransferase-1, an enzyme which controls the entry of long chain fatty acids into mitochondria. We have found th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seng TW,Skillman TR,Yang N,Hammond C

更新日期：2003-10-06 00:00:00

abstract：:In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 μM. Mecha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang H,Zhang WJ,Li PH,Wang J,Dong CZ,Zhang K,Chen HX,Du ZY

更新日期：2018-05-01 00:00:00

abstract：:We previously identified o-carborane bisphenol BE360 (4) as a selective estrogen receptor modulator (SERM), which ameliorated bone loss without inducing estrogenic action in uterus of OVX and ORX mice. Here, we synthesized a fluorinated derivative, B-fluorinated o-carborane bisphenol BE310 (5) by means of S(N)Ar react...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2012-07-15 00:00:00

abstract：:An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclospori...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scribner A,Houck D,Huang Z,Mosier S,Peel M,Scorneaux B

更新日期：2010-11-15 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 new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC(50)=2microM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC(50)<20nM). Additionally, physicochemical and pharmacokinetic properties ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Steinhagen H,Gerisch M,Mittendorf J,Schlemmer KH,Albrecht B

更新日期：2002-11-04 00:00:00

abstract：:Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fish PV,Deur C,Gan X,Greene K,Hoople D,Mackenny M,Para KS,Reeves K,Ryckmans T,Stiff C,Stobie A,Wakenhut F,Whitlock GA

更新日期：2008-04-15 00:00:00

abstract：:We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qin J,Dhondi P,Huang X,Mandal M,Zhao Z,Pissarnitski D,Zhou W,Aslanian R,Zhu Z,Greenlee W,Clader J,Zhang L,Cohen-Williams M,Jones N,Hyde L,Palani A

更新日期：2011-01-15 00:00:00

abstract：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00

abstract：:Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against gram-pos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kutterer KM,Davis JM,Singh G,Yang Y,Hu W,Severin A,Rasmussen BA,Krishnamurthy G,Failli A,Katz AH

更新日期：2005-05-16 00:00:00

abstract：:The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-facto...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeong JY,Jo YH,Lee KY,Do SG,Hwang BY,Lee MK

更新日期：2014-05-15 00:00:00

abstract：:A range of amphiphilic sorbitan ethers has been synthesized in two steps from sorbitan following an acetalization/hydrogenolysis sequence. These sorbitan ethers and the acetal intermediates have been evaluated as antimicrobials against Gram-negative and Gram-positive bacteria. No antimicrobial activity was observed fo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Belmessieri D,Gozlan C,Duclos MC,Dumitrescu O,Lina G,Redl A,Duguet N,Lemaire M

更新日期：2017-10-15 00:00:00

abstract：:The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SK,Vobbalareddy S,Shivaramakrishna S,Krishnamraju A,Rajjak SA,Casturi SR,Akhila V,Rao YK

更新日期：2004-04-05 00:00:00

abstract：:A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun LQ,Chen J,Mattson RJ,Epperson JR,Deskus JA,Li WS,Takaki K,Hodges DB,Iben L,Mahle CD,Ortiz A,Molstad D,Ryan E,Yeleswaram K,Xu C,Luo G

更新日期：2003-12-15 00:00:00

abstract：:A three-step protocol for SAR development was introduced and applied to the SAR studies of the MK2 inhibitor program. Following this protocol, key conformational features and functional groups for improving MK2 inhibitor activity were quickly identified. Through this effort, the initial gap observed between in vitro b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang X,Zhu X,Chen X,Zhou W,Xiao D,Degrado S,Aslanian R,Fossetta J,Lundell D,Tian F,Trivedi P,Palani A

更新日期：2012-01-01 00:00:00

abstract：:The design, synthesis, and IMPDH inhibitory activity of a series of phosphonic acid-containing analogues of mycophenolic acid are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watkins WJ,Chen JM,Cho A,Chong L,Collins N,Fardis M,Huang W,Hung M,Kirschberg T,Lee WA,Liu X,Thomas W,Xu J,Zeynalzadegan A,Zhang J

更新日期：2006-07-01 00:00:00