Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors.

abstract：:Phosphorothioate oligodeoxynucleotides containing CpG motifs have immunostimulatory activity. Appropriate substitution of deoxynucleosides in the flanking region of CpG-containing phosphorothioate oligodeoxynucleotides with 2'-O-methylribonucleosides results in significant decreases or increases in their immunostimula...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Q,Yu D,Agrawal S

更新日期：1999-12-20 00:00:00

abstract：:We report a rapid method for profiling of kinases using a strategy that couples the merits of combinatorics (in rapid diversity generation) with the throughput attainable using microarrays (in parallel screening). Alanine-scanning, deletion and positional-scanning peptide libraries of a kinase substrate were synthesiz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uttamchandani M,Chan EW,Chen GY,Yao SQ

更新日期：2003-09-15 00:00:00

abstract：:A developing therapy of cystic fibrosis caused by the DeltaF508 mutation in CFTR employs correction of defective CFTR chloride channel gating by a 'potentiator' and of defective CFTR protein folding by a 'corrector'. Based on SAR data for phenylglycine-type potentiators and bithiazole correctors, we designed a hybrid ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mills AD,Yoo C,Butler JD,Yang B,Verkman AS,Kurth MJ

更新日期：2010-01-01 00:00:00

abstract：:A new series of benzene and isoquinoline sulfonamide derivatives were synthesized by nucleophilic displacement reaction on benzene and isoquinoline sulfonyl chlorides by substituted amines (primary and secondary). The title compounds were evaluated for antimalarial activity against Plasmodium falciparum in vitro and s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar Parai M,Panda G,Srivastava K,Kumar Puri S

更新日期：2008-01-15 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：:VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a promising target for the development of therapeutics for the treatment of a variety of human cancers. Here, we report the first example of a successful application of the structure-based virtual screening to identify novel BRAF inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park H,Choi H,Hong S,Hong S

更新日期：2011-10-01 00:00:00

abstract：:High throughput screening for β-lactamase inhibitors afforded biphenyl hits such as 1. Hit confirmation and X-ray soaking experiments with Pseudomonas Aeruginosa AmpC enzyme led to the identification of an aryl boronic acid-serine complex 4, which was formed from phenyl boronic acid 8 (an impurity in compound 1) and e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang SW,Pan J,Root Y,Scapin G,Xiao L,Su J

更新日期：2020-01-15 00:00:00

abstract：:Six diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group were synthesized and characterized by elemental analysis, FAB-MS, FT-IR, (1)H and (13)C NMR along with a single crystal X-ray diffraction for a representative compound. All the complexes were evaluated for the cytotoxicity ag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xing Y,Lou L,Chen X,Ye Q,Xu Y,Xie C,Jiang J,Liu W

更新日期：2012-03-15 00:00:00

abstract：:Series of short amino terminal modified cationic peptides were designed and synthesized. All of the synthesized compounds were tested against gram-positive as well as gram-negative bacterial strain. Some of the compounds exhibit potent antibacterial activity and no hemolytic activity even at high dose level (1000 micr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bisht GS,Rawat DS,Kumar A,Kumar R,Pasha S

更新日期：2007-08-01 00:00:00

abstract：:The steroidogenic enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a therapeutic target in the management of androgen-sensitive diseases such as prostate cancer and benign prostate hyperplasia. In this Letter, we designed and synthesized the first fluorescent inhibitor of this enzyme by combining a fluorog...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kenmogne LC,Maltais R,Poirier D

更新日期：2016-05-01 00:00:00

abstract：:Hitherto unknown protective effect of N,α-L-rhamnopyranosyl vincosamide (VR), isolated from Moringa oleifera leaves in isoproterenol (ISO)-induced cardiac toxicity was evaluated in rats. Oral administration of VR at 40 mg/kg for 7 days markedly reduced the ISO-induced increase in the levels of serum cardiac markers su...

journal_title：Bioorganic & medicinal chemistry letters

authors： Panda S,Kar A,Sharma P,Sharma A

更新日期：2013-02-15 00:00:00

abstract：:Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park JY,Hwan Lim S,Ram Kim B,Jae Jeong H,Kwon HJ,Song GY,Bae Ryu Y,Song Lee W

更新日期：2017-07-15 00:00:00

abstract：:Through synthesis and assays of peptidyl substrates, we could select substrates having peptidyl complementary against lipases. The best substrate showed 20-fold improved K(m) relative to non-peptidyl substrate. Using this information, we generated selective inhibitors. Lipase activities with peptidyl substrates were r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park S,Yu J

更新日期：2012-05-01 00:00:00

abstract：:NCSi-gb is a neocarzinostatin chromophore (NCS-chrom) metabolite which binds strongly to certain two-base DNA bulges. Compared with previously reported NCSi-gb analogues, a new analogue with a different aminoglycoside position was synthesized, and it showed strong fluorescence and improved binding and sequence selecti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao Z,Kappen LS,Goldberg IH

更新日期：2006-06-01 00:00:00

abstract：:Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： van Veldhoven JP,Blad CC,Artsen CM,Klopman C,Wolfram DR,Abdelkadir MJ,Lane JR,Brussee J,Ijzerman AP

更新日期：2011-05-01 00:00:00

abstract：:A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Chen X,Cho A,Delaney WE 4th,Doerffler E,Fardis M,Ji M,Mertzman M,Pakdaman R,Pyun HJ,Rowe T,Yang CY,Sheng XC,Kim CU

更新日期：2011-06-15 00:00:00

abstract：:New A-ring modified betulinic acid derivatives having small steric hindrance were prepared and tested for cytotoxic activity on 3 cancer cell lines: 10 compounds showed stronger cytotoxic activity than betulinic acid. Especially, the compounds bearing 1-ene-3-oxo with electron-withdrawing groups at C2 showed strong cy...

journal_title：Bioorganic & medicinal chemistry letters

authors： You YJ,Kim Y,Nam NH,Ahn BZ

更新日期：2003-10-06 00:00:00

abstract：:Herein we outline the antibacterial activity of amino acid containing thiazolidinediones and rhodanines against Gram-positive bacteria Staphylococcus aureus ATCC 31890, Staphylococcus epidermidis and Bacillus subtilis ATCC 6633. The rhodanine derivatives were generally more active than the analogous thiazolidinediones...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zvarec O,Polyak SW,Tieu W,Kuan K,Dai H,Pedersen DS,Morona R,Zhang L,Booker GW,Abell AD

更新日期：2012-04-15 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

authors： Seio K,Tokugawa M,Kanamori T,Tsunoda H,Ohkubo A,Sekine M

更新日期：2012-04-01 00:00:00

abstract：:Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Chen Y,Pontillo J,Guo Z,Huang CQ,Wu D,Madan A,Chen T,Wen J,Xie Q,Tucci FC,Rowbottom M,Zhu YF,Wade W,Saunders J,Bozigian H,Struthers RS

更新日期：2008-06-01 00:00:00

abstract：:The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guerrini R,Rizzi D,Zucchini M,Tomatis R,Regoli D,Calo' G,Salvadori S

更新日期：2003-02-10 00:00:00

abstract：:A novel 6-aminopurine scaffold bearing an N9-cis-cyclobutyl moiety was designed using structure-based molecular design based on two known CDK inhibitors, dinaciclib and Cmpd-27. A series of novel 6-aminopurine compounds was prepared for structure-activity relationship (SAR) studies of CDK2 and CDK5 inhibitors. Among t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SJ,Kim E,Yoo M,Lee JY,Park CH,Hwang JY,Ha JD

更新日期：2017-09-15 00:00:00

abstract：:The synthesis of [1-[(5-hydroxy-4-(phenylmethyl)-3-oxazolidinyl)carbonyl]-2-ethylpropy lcarbamic acid phenylmethyl ester (2; MDL 104,903), a potent inhibitor of calpain, is described. Synthesis of related compounds, which offer insights into the mechanism of action for 2, are also described, as is an O-acetyl prodrug ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peet NP,Kim HO,Marquart AL,Angelastro MR,Nieduzak TR,White JN,Friedrich D,Flynn GA,Webster ME,Vaz RJ,Linnik MD,Koehl JR,Mehdi S,Bey P,Emary B,Hwang KK

更新日期：1999-08-16 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

authors： Martín E,Morán A,Martín ML,San Román L,Puebla P,Medarde M,Caballero E,San Feliciano A

更新日期：2000-02-21 00:00:00

abstract：:Phosphopeptide prodrugs bearing two S-acyl-2-thioethyl (SATE) biolabile phosphate protections were developed. They are capable to inhibit the Shc/Grb2 interaction and MAP kinases (ERK1 and ERK2) phosphorylation in cellular assay. The S-acetyl-2-thioethyl (MeSATE) analogue showed an IC50 of 1 microM in the inhibition o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu WQ,Vidal M,Mathé C,Périgaud C,Garbay C

更新日期：2000-04-03 00:00:00

abstract：:The objective of this Letter is to report the first (to our knowledge) in vivo proof of concept for a sulfenamide prodrug to orally deliver a poorly soluble drug containing a weakly-acidic NH-acid from a conventional solid dosage formulation. This proof of concept was established using BMS-708163 (1), a gamma secretas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guarino VR,Olson RE,Everlof JG,Wang N,McDonald I,Haskell R,Clarke W,Lentz KA

更新日期：2020-02-01 00:00:00

abstract：:Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zak M,Liederer BM,Sampath D,Yuen PW,Bair KW,Baumeister T,Buckmelter AJ,Clodfelter KH,Cheng E,Crocker L,Fu B,Han B,Li G,Ho YC,Lin J,Liu X,Ly J,O'Brien T,Reynolds DJ,Skelton N,Smith CC,Tay S,Wang W,Wang Z,Xi

更新日期：2015-02-01 00:00:00

abstract：:Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Witherington J,Bordas V,Haigh D,Hickey DM,Ife RJ,Rawlings AD,Slingsby BP,Smith DG,Ward RW

更新日期：2003-05-05 00:00:00

abstract：:The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kusumi K,Shinozaki K,Yamaura Y,Hashimoto A,Kurata H,Naganawa A,Otsuki K,Matsushita T,Sekiguchi T,Kakuuchi A,Yamamoto H,Seko T

更新日期：2016-02-15 00:00:00

abstract：:SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC(50) value of 34 nM. [(11)C]SB-216763 (3-(2,4-dichlorophenyl)-4-(1-[(11)C]methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay cor...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2011-01-01 00:00:00