Substituted benzimidazoles: A novel chemotype for small molecule hKSP inhibitors.

abstract：:A novel series of aminopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bingham AH,Davenport RJ,Gowers L,Knight RL,Lowe C,Owen DA,Parry DM,Pitt WR

更新日期：2004-01-19 00:00:00

abstract：:Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

更新日期：2017-10-15 00:00:00

abstract：:Polysulfides typically react readily with thiols, thus, reactions of endogenous cellular thiols with the polysulfide linkage in naturally-occuring pentathiepin cytotoxins are likely to be an important aspect of their biological chemistry. Here, it is reported that the reaction of thiols with the pentathiepin ring syst...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chatterji T,Gates KS

更新日期：2003-04-07 00:00:00

abstract：:In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Evindar G,Deng H,Bernier SG,Doyle E,Lorusso J,Morgan BA,Westlin WF

更新日期：2013-01-15 00:00:00

abstract：:Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier N,Clarke B,Cutler L,Demont E,Dingwall C,Dunsdon R,Hawkins J,Howes C,Hubbard J,Hussain I,Maile G,Matico R,Mosley J,Naylor A,O'Brien A,Redshaw S,Rowland P,Soleil V,Smith KJ,Sweitzer S,Theobald P,Vesey D,

更新日期：2009-07-01 00:00:00

abstract：:Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qiang X,Li Y,Yang X,Luo L,Xu R,Zheng Y,Cao Z,Tan Z,Deng Y

更新日期：2017-02-15 00:00:00

abstract：:The new binuclear platinum(II) complexes, (1,3-benzenedimethanethiolate-S)di(2,2',2"-terpyridine)diplatinum(II) chloride tetrahydrate, 5, and (1,4-benzenedimethanethiolate-S)di(2,2',2"-terpyridine)diplatinum(II) chloride tetrahydrate, 6, were synthesized in order to investigate the binding of platinum(II) complex with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurosaki H,Yamakawa N,Sumimoto M,Kimura K,Goto M

更新日期：2003-03-10 00:00:00

abstract：:The radical-scavenging capacities of ferrocenyl group and phenolic hydroxyl group in ferrocenyl chalcone were identified in this work. 1,1'-Diacetylferrocene was applied to condense with benzaldehyde, vanillin, and protocatechualdehyde to produce ferrocenyl chalcones, which were employed to interact with 2,2'-azinobis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nabi G,Liu ZQ

更新日期：2011-02-01 00:00:00

abstract：:A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Akama T,Baker SJ,Zhang YK,Hernandez V,Zhou H,Sanders V,Freund Y,Kimura R,Maples KR,Plattner JJ

更新日期：2009-04-15 00:00:00

abstract：:Gram positive (Bacillus cereus, B. subtilis), Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and Candida albicans as a representative of fungi were used for screening the in vitro antimicrobial activity of diarylamines in the 2,3,5-trimethylbenzo[b]thiophene series bearing different substituents, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ferreira IC,Calhelha RC,Estevinho LM,Queiroz MJ

更新日期：2004-12-06 00:00:00

abstract：:The synthesis and structure-activity relationship studies of 1,4,5,6-tetrahydropyridazines are described. The target compounds 3-5 represent a novel class of potent and selective CB1 receptor antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lange JH,den Hartog AP,van der Neut MA,van Vliet BJ,Kruse CG

更新日期：2009-10-01 00:00:00

abstract：:Several newer isosteric analogues of glycosyl phosphates, namely of glycosyl phosphoramidates, were synthesized in good yields using Staudinger reaction of their corresponding azides with trimethyl phosphite followed by de-O-acetylation. The structure and conformation of the fully protected analogue synthesized, namel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kannan T,Vinodhkumar S,Varghese B,Loganathan D

更新日期：2001-09-17 00:00:00

abstract：:In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu P,Liu L,Chen XZ,Li Y,Liu J,Jin ZP,Wang GQ,Lei PS

更新日期：2009-08-01 00:00:00

abstract：:Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Knust H,Achermann G,Ballard T,Buettelmann B,Gasser R,Fischer H,Hernandez MC,Knoflach F,Koblet A,Stadler H,Thomas AW,Trube G,Waldmeier P

更新日期：2009-10-15 00:00:00

abstract：:A new family of poly-guanidinium species with a benzene core as the organising agent has been developed. Their antibacterial properties have been evaluated against reference Gram positive and Gram negative bacteria, and their cytotoxicity against eukaryotic cells. Most of these compounds exhibited Minimum Inhibitory C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Massimba Dibama H,Mourer M,Duval RE,Regnouf-de-Vains JB

更新日期：2014-10-15 00:00:00

abstract：:We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production. Overall γ-secretase is not ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lübbers T,Flohr A,Jolidon S,David-Pierson P,Jacobsen H,Ozmen L,Baumann K

更新日期：2011-11-01 00:00:00

abstract：:The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubsti...

journal_title：Bioorganic & medicinal chemistry letters

authors： McClure KJ,Maher M,Wu N,Chaplan SR,Eckert WA 3rd,Lee DH,Wickenden AD,Hermann M,Allison B,Hawryluk N,Breitenbucher JG,Grice CA

更新日期：2011-09-15 00:00:00

abstract：:Guided by co-crystal structural information obtained from a different series we were exploring, a scaffold morphing and SBDD approach led to the discovery of the 1,4-disubstituted indazole series as a novel class of GKAs that potently activate GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheruvallath ZS,Gwaltney SL 2nd,Sabat M,Tang M,Wang H,Jennings A,Hosfield D,Lee B,Wu Y,Halkowycz P,Grimshaw CE

更新日期：2017-06-15 00:00:00

abstract：:A series of 4,4-disubstituted cyclohexylamine based CCR5 antagonists has been designed and synthesized. Their antiviral structure-activity relationship has been extensively explored. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan M,Aquino C,Dorsey GF Jr,Ferris R,Kazmierski WM

更新日期：2009-09-01 00:00:00

abstract：:Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood-brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zur AA,Chien HC,Augustyn E,Flint A,Heeren N,Finke K,Hernandez C,Hansen L,Miller S,Lin L,Giacomini KM,Colas C,Schlessinger A,Thomas AA

更新日期：2016-10-15 00:00:00

abstract：:The addition of exogenous ent-cholesterol suppressed the antifungal activity of the amphotericin B when added to cultures of Candida albicans, but to a lesser extent than natural cholesterol. There were no detectable differences between added 2a or 2b on the antifungal activities of jaspamide or bengazole A, two unrel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richter RK,Mickus DE,Rychnovsky SD,Molinski TF

更新日期：2004-01-05 00:00:00

abstract：:We report herein a one-pot four-enzyme approach for the synthesis of the rare sugars d-psicose, d-sorbose, l-tagatose, and l-fructose with aldolase FucA from a thermophilic source (Thermus thermophilus HB8). Importantly, the cheap starting material DL-GP (DL-glycerol 3-phosphate), was used to significantly reduce the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Cai L,Qi Q,Styslinger TJ,Zhao G,Wang PG

更新日期：2011-09-01 00:00:00

abstract：:We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents ba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shimizu H,Yasumatsu I,Hamada T,Yoneda Y,Yamasaki T,Tanaka S,Toki T,Yokoyama M,Morishita K,Iimura S

更新日期：2011-02-01 00:00:00

abstract：:A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boot JR,Boulet SL,Clark BP,Cases-Thomas MJ,Delhaye L,Diker K,Fairhurst J,Findlay J,Gallagher PT,Gilmore J,Harris JR,Masters JJ,Mitchell SN,Naik M,Simmonds RG,Smith SM,Richards SJ,Timms GH,Whatton MA,Wolfe CN,Wood

更新日期：2006-05-15 00:00:00

abstract：:The development of novel non-phosphopeptide inhibitors for the Src family SH2 domain is described. Several commercially available hydroxyl aromatic acids have been appended off the N-terminus of pYEEIE and the potent phosphopeptide inhibitors of GST-Lck-SH2 were identified via ELISA. The most potent inhibitor, caffeic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SH,Won J,Lee KH

更新日期：2002-10-07 00:00:00

abstract：:The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dou D,He G,Alliston KR,Groutas WC

更新日期：2011-05-15 00:00:00

abstract：:Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Loh VM Jr,Cockcroft XL,Dillon KJ,Dixon L,Drzewiecki J,Eversley PJ,Gomez S,Hoare J,Kerrigan F,Matthews IT,Menear KA,Martin NM,Newton RF,Paul J,Smith GC,Vile J,Whittle AJ

更新日期：2005-05-02 00:00:00

abstract：:Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cumming JN,Le TX,Babu S,Carroll C,Chen X,Favreau L,Gaspari P,Guo T,Hobbs DW,Huang Y,Iserloh U,Kennedy ME,Kuvelkar R,Li G,Lowrie J,McHugh NA,Ozgur L,Pan J,Parker EM,Saionz K,Stamford AW,Strickland C,Tadesse D,

更新日期：2008-06-01 00:00:00

abstract：:The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boto A,Gallardo JA,Hernández R,Ledo F,Muñoz A,Murguía JR,Menacho-Márquez M,Orjales A,Saavedra CJ

更新日期：2006-12-01 00:00:00

abstract：:The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gilbert EJ,Zhou G,Wong MK,Tong L,Shankar BB,Huang C,Kelly J,Lavey BJ,McCombie SW,Chen L,Rizvi R,Dong Y,Shu Y,Kozlowski JA,Shih NY,Hipkin RW,Gonsiorek W,Malikzay A,Lunn CA,Favreau L,Lundell DJ

更新日期：2010-01-15 00:00:00