Thiourea inhibitors of herpes viruses. Part 1: bis-(aryl)thiourea inhibitors of CMV.

abstract：:A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang T,Duncan L,Gu W,O'Dowd H,Wei Y,Perola E,Parsons J,Gross CH,Moody CS,Arends SJ,Charifson PS

更新日期：2012-06-01 00:00:00

abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

更新日期：2016-12-15 00:00:00

abstract：:A computer-aided drug design strategy leads to the identification of a new class of p38 inhibitors based on the 2-tolyl-(1,2,3-triazol-1-yl-4-carboxamide) scaffold. The tolyl triazole amides provided a potent platform amenable to optimization. Further exploration leads to compounds with greater than 100-fold improveme...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cogan DA,Aungst R,Breinlinger EC,Fadra T,Goldberg DR,Hao MH,Kroe R,Moss N,Pargellis C,Qian KC,Swinamer AD

更新日期：2008-06-01 00:00:00

abstract：:Protein-protein interactions (PPIs) present a formidable challenge to medicinal chemistry. The extended and open nature of many binding sites at protein interfaces has made it difficult to find useful chemical matter by traditional screening methods using standard screening libraries. This Digest focuses on the progre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Magee TV

更新日期：2015-06-15 00:00:00

abstract：:A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high bi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HS,Jin MK,Kang SU,Lim JO,Tran PT,Hoang VH,Ann J,Ha TH,Pearce LV,Pavlyukovets VA,Blumberg PM,Lee J

更新日期：2014-06-15 00:00:00

abstract：:Current antibiotics for treating Clostridium difficile infections (CDI), that is, metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Doll NK,Casadei G,Bremner JB,Lewis K,Kelso MJ

更新日期：2014-01-15 00:00:00

abstract：:Eighteen new hydrazino-1,3-thiazole derivatives were evaluated against 8 strains of multi-resistant Candida spp. Introduction of an indolyl moiety linked to the hydrazone function enhanced the in vitro anti-Candida activity, with an activity spectrum towards Candida albicans strains. Introduction of a (S)-2-aminoethyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maillard LT,Bertout S,Quinonéro O,Akalin G,Turan-Zitouni G,Fulcrand P,Demirci F,Martinez J,Masurier N

更新日期：2013-03-15 00:00:00

abstract：:We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harada K,Mizukami J,Watanabe T,Mori G,Ubukata M,Suwa K,Fukuda S,Negoro T,Sato M,Inaba T

更新日期：2019-02-01 00:00:00

abstract：:A highly practicable synthesis of both enantiomers of 3-hydroxypipecolic acid derivatives 1, 2, 3, 4 is described. Screening of these molecules for glycosidase inhibition has been examined. Compound 3 was shown to be a potent inhibitor of beta-N-acetylglucosaminidase as well as Escherichia coli beta-glucuronidase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohara C,Takahashi R,Miyagawa T,Yoshimura Y,Kato A,Adachi I,Takahata H

更新日期：2008-03-15 00:00:00

abstract：:A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of α-glycoprotein were evaluated in rat and dog pharmacokinetics. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Skerlj R,Bridger G,Zhou Y,Bourque E,McEachern E,Langille J,Harwig C,Veale D,Yang W,Li T,Zhu Y,Bey M,Baird I,Sartori M,Metz M,Mosi R,Nelson K,Bodart V,Wong R,Fricker S,Mac Farland R,Huskens D,Schols D

更新日期：2011-12-01 00:00:00

abstract：:We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Adva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forsyth T,Kearney PC,Kim BG,Johnson HW,Aay N,Arcalas A,Brown DS,Chan V,Chen J,Du H,Epshteyn S,Galan AA,Huynh TP,Ibrahim MA,Kane B,Koltun ES,Mann G,Meyr LE,Lee MS,Lewis GL,Noguchi RT,Pack M,Ridgway BH,Shi X,

更新日期：2012-12-15 00:00:00

abstract：:Beginning with carbazole 1a, the amide and alkyl substituents were optimized to maintain potency while adding solubilizing groups. Efforts to replace the 3-amino-9-ethylcarbazole core, a known carcinogen, used the SAR generated in the carbazole series for guidance and led to the synthesis of a number of core-modified ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hammond M,Elliott RL,Gillaspy ML,Hager DC,Hank RF,LaFlamme JA,Oliver RM,DaSilva-Jardine PA,Stevenson RW,Mack CM,Cassella JV

更新日期：2003-06-16 00:00:00

abstract：:The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Calugi L,Lenci E,Innocenti R,Trabocchi A

更新日期：2020-07-01 00:00:00

abstract：:To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Winneroski LL,Ardecky RJ,Babine RE,Brooks DA,Etgen GJ,Hutchison DR,Kauffman RF,Kunkel A,Mais DE,Montrose-Rafizadeh C,Ogilvie KM,Oldham BA,Peters MK,Rito CJ,Rungta DK,Tripp AE,Wilson SB,Xu Y,Zink RW,McCarthy

更新日期：2004-12-20 00:00:00

abstract：:Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The cu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ellsworth BA,Meng W,Patel M,Girotra RN,Wu G,Sher PM,Hagan DL,Obermeier MT,Humphreys WG,Robertson JG,Wang A,Han S,Waldron TL,Morgan NN,Whaley JM,Washburn WN

更新日期：2008-09-01 00:00:00

abstract：:Four stereoisomeric hybrids of the polyketide natural products callystatin A and leptomycin B have been prepared by parallel synthetic routes involving chiral allenylstannane methodology. Like their natural counterparts, these hybrids exhibit nanomolar levels of cytotoxicity toward HCT-116 human colon cancer cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marshall JA,Mikowski AM,Bourbeau MP,Schaaf GM,Valeriote F

更新日期：2006-01-15 00:00:00

abstract：:The chiral analogues of gemfibrozil 5-(2,5-dimethylphenoxy)-2-methylpentanoic acid and 5-(2,5-dimethylphenoxy)-2-ethylpentanoic acid were synthesized in optically active form using (S)-4-(1-methylethyl)-2-oxazolidinone as chiral auxiliary. All compounds inhibit human platelet aggregation. From these data, one can surm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ammazzalorso A,Amoroso R,Baraldi M,Bettoni G,Braghiroli D,De Filippis B,Duranti A,Moretti M,Tortorella P,Tricca ML,Vezzalini F

更新日期：2002-03-11 00:00:00

abstract：:Chalcone type compound 1a ((E)-6'-benzylidene-4a'-methyl-4',4a',7',8'-tetrahydro-3'H-spiro[[1,3]dithiolane-2,2'-naphthalen]-5'(6'H)-one) was discovered as an potent inhibitor in melanogenesis. To define its structure-activity relationship, a series of analogs 1b-n, dithiolane truncated 2a-b and ring A removed 3a-e wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thanigaimalai P,Lee KC,Sharma VK,Rao EV,Roh E,Kim Y,Jung SH

更新日期：2011-04-01 00:00:00

abstract：:The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujie A,Iwamoto T,Sato B,Muramatsu H,Kasahara C,Furuta T,Hori Y,Hino M,Hashimoto S

更新日期：2001-02-12 00:00:00

abstract：:A novel method to generate RNA binding D-peptide has been developed. To achieve the screening method, phage display was applied to "Mirrored" RNA (L-enantiomer of RNA). We have selected pre-miR21 as an initial screening target to demonstrate the method. The mirrored pre-miR-21 binding peptide sequences were successful...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sakamoto K,Otake K,Umemoto T

更新日期：2017-02-15 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

authors： Xiang YF,Qian CW,Xing GW,Hao J,Xia M,Wang YF

更新日期：2012-07-15 00:00:00

abstract：:Previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. These series of compounds were discovered through an HTS campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burgeson JR,Gharaibeh DN,Moore AL,Larson RA,Amberg SM,Bolken TC,Hruby DE,Dai D

更新日期：2013-11-01 00:00:00

abstract：:An artificial neural network based approach using Atomic5 fragmental descriptors has been developed to predict the octanol-water partition coefficient (logP). We used a pre-selected set of organic molecules from PHYSPROP database as training and test sets for a feedforward neural network. Results demonstrate the super...

journal_title：Bioorganic & medicinal chemistry letters

authors： Molnár L,Keseru GM,Papp A,Gulyás Z,Darvas F

更新日期：2004-02-23 00:00:00

abstract：:Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner-Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the P(2)(') position of keto-ACE resulted in a significant increase in C-domain-se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nchinda AT,Chibale K,Redelinghuys P,Sturrock ED

更新日期：2006-09-01 00:00:00

abstract：:Bacterial resistance is rapidly growing, necessitating the need to discover new agents. Novel bacterial topoisomerase inhibitors (NBTIs) are new class of broad-spectrum antibacterial agents targeting bacterial DNA gyrase and topoisomerase IV. This class of inhibitors binds to an alternative binding site relative to fl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SB,Kaelin DE,Wu J,Miesel L,Tan CM,Meinke PT,Olsen DB,Lagrutta A,Wei C,Peng X,Wang X,Fukuda H,Kishii R,Takei M,Shibata T,Ohata K,Takano H,Kurasaki H,Takeuchi T,Nishimura A,Fukuda Y

更新日期：2015-06-01 00:00:00

abstract：:The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Y,Sit SY,Chen J,Swidorski JJ,Liu Z,Sin N,Venables BL,Parker DD,Nowicka-Sans B,Lin Z,Li Z,Terry BJ,Protack T,Rahematpura S,Hanumegowda U,Jenkins S,Krystal M,Dicker ID,Meanwell NA,Regueiro-Ren A

更新日期：2018-05-15 00:00:00

abstract：:We present the synthesis and biological evaluation of a collection of s-triazine derivatives as a novel scaffold of compounds with the capability to inhibit the PGE₂ production in LPS-induced RAW 264.7 macrophage cells. A total of 12 derivatives were synthesized and assayed for PGE₂ reduction at 10 μM concentration. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang SM,Lee J,Jin JH,Kim M,Lee S,Lee HH,Shin JS,Lee KT,Lee JY

更新日期：2014-12-01 00:00:00

abstract：:We report (a) on the synthesis of a long-wavelength fluorescent coumarin containing an allyloxy acetate moiety, (b) the synthesis of two linkers containing an allyloxy acetate and an alkyne or azide function, respectively, and (c) the selective modification human serum albumin by a sequential method involving Pd(II) c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cserép GB,Herner A,Wolfbeis OS,Kele P

更新日期：2013-11-01 00:00:00

abstract：:A novel series of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists are described. The series was designed to address the suboptimal PK (pharmacokinetic) and off-target profile of a class of N-aryl-benzo-[1,4]-oxazepine-4-carboxamides, represented by 1, that were identified from a high-throughput screen of the Me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilson JE,Kurukulasuriya R,Sinz C,Lombardo M,Bender K,Parker D,Sherer EC,Costa M,Dingley K,Li X,Mitelman S,Tong S,Bugianesi R,Ehrhardt A,Priest B,Ratliff K,Ujjainwalla F,Nargund R,Hagmann WK,Edmondson S

更新日期：2016-06-15 00:00:00

abstract：:On the search for anti-cancer compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the rhizomes of Acorus gramineus resulted in the isolation and identification of thirteen phenolic derivatives (1-13) including two new 8-O-4'-neolignans, n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim KH,Moon E,Kim HK,Oh JY,Kim SY,Choi SU,Lee KR

更新日期：2012-10-01 00:00:00