2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors.

abstract：:The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Voss ME,Rainka MP,Fleming M,Peterson LH,Belanger DB,Siddiqui MA,Hruza A,Voigt J,Gray K,Basso AD

更新日期：2012-05-15 00:00:00

abstract：:The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b']difuran-1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang CB,Liu Y,Liu ZF,Duan SZ,Li MY,Chen W,Li Y,Zhang HB,Yang XD

更新日期：2017-04-15 00:00:00

abstract：:In an effort to discover oral inverse agonists of RORγt to treat inflammatory diseases, a new 2,6-difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfone tem...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Jiang B,Lu Z,Stachura S,Weigelt CA,Sack JS,Khan J,Ruzanov M,Wu DR,Yarde M,Shen DR,Zhao Q,Salter-Cid LM,Carter PH,Murali Dhar TG

更新日期：2020-10-01 00:00:00

abstract：:A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Faria JV,dos Santos MS,Bernardino AM,Becker KM,Machado GM,Rodrigues RF,Canto-Cavalheiro MM,Leon LL

更新日期：2013-12-01 00:00:00

abstract：:Pyrimidine analogs of antimycobacterial purines have been synthesized and their biological activities evaluated. Several 5-formamidopyrimidines exhibited profound activity against Mycobacterium tuberculosis in vitro (IC(90)< or =1.5 microg/mL), and they were essentially inactive against other bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Braendvang M,Charnock C,Gundersen LL

更新日期：2009-06-15 00:00:00

abstract：:The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mathew SC,Ghosh N,By Y,Berthault A,Virolleaud MA,Carrega L,Chouraqui G,Commeiras L,Condo J,Attolini M,Gaudel-Siri A,Ruf J,Parrain JL,Rodriguez J,Guieu R

更新日期：2009-12-01 00:00:00

abstract：:The SmI(2)-promoted three-component coupling reaction of thiophene-2-carboxylate, indole-2-carbaldehyde and acetophenone provides an expedient route to a series of tetracyclic carbazolothiophene compounds bearing the indole and thiophene rings. Among these samples, 9-benzyl-4-methyl-4-(4-hydroxyphenyl)-10-oxo-4,10-dih...

journal_title：Bioorganic & medicinal chemistry letters

authors： Babu G,Yu HM,Yang SM,Fang JM

更新日期：2004-03-08 00:00:00

abstract：:In the search of new antihyperglycemic agents and following rational approach of drug designing here new 2-hydrazolyl-4-thiazolidinone-5-carboxylic acids (4a-g) with pyrazolyl pharmacophore have been synthesized via thia Michael addition reaction of 1-((3-(4-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thios...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bhosle MR,Mali JR,Pal S,Srivastava AK,Mane RA

更新日期：2014-06-15 00:00:00

abstract：:A series of substituted 3,4-dihydronaphthalen-1(2H)-ones with high binding affinity for the benzodiazepine site of GABAA receptors containing the alpha5-subunit has been identified. These compounds have consistently higher binding affinity for the GABAA alpha5 receptor subtype over the other benzodiazepine-sensitive G...

journal_title：Bioorganic & medicinal chemistry letters

authors： Szekeres HJ,Atack JR,Chambers MS,Cook SM,Macaulay AJ,Pillai GV,MacLeod AM

更新日期：2004-06-07 00:00:00

abstract：:A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang P,Terefenko EA,McComas CC,Mahaney PE,Vu A,Trybulski E,Koury E,Johnston G,Bray J,Deecher D

更新日期：2008-12-01 00:00:00

abstract：:A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC(50) of 0.033microM against Kv1.5 and is selective against other ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gross MF,Beaudoin S,McNaughton-Smith G,Amato GS,Castle NA,Huang C,Zou A,Yu W

更新日期：2007-05-15 00:00:00

abstract：:Quinazolinone derivatives were synthesized and evaluated as non-peptidic growth hormone secretagogues. Modeling guided design of quinazolinone compound 21 led to a potency enhancement of greater than 200-fold compared to human growth hormone secretagogue affinity of a screening lead 4. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Z,Gao Y,Bakshi RK,Chen MH,Rohrer SP,Feighner SD,Pong SS,Howard AD,Blake A,Birzin ET,Locco L,Parmar RM,Chan WW,Schaeffer JM,Smith RG,Patchett AA,Nargund RP

更新日期：2000-01-03 00:00:00

abstract：:Modulating the structural dynamics of biomembranes by inducing bilayer curvature and lipid packing defects has been highlighted as a practical tool to modify membrane-dependent cellular processes. Previously, we have reported on an amphipathic helical peptide derived from the N-terminal segment (residues 1-18, EpN18) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsu WY,Masuda T,Afonin S,Sakai T,Arafiles JVV,Kawano K,Hirose H,Imanishi M,Ulrich AS,Futaki S

更新日期：2020-06-15 00:00:00

abstract：:We report a fluorinated and iodinated radiotracer as a probe for PET/SPECT to detect of β-amyloid (Aβ) plaques in the brain of patients with Alzheimer's disease (AD). We successfully designed and synthesized the fluorinated and iodinated aurone derivative (3) and its radiolabels ([(125)I]3 and [(18)F]3). In binding ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watanabe H,Ono M,Kimura H,Kagawa S,Nishii R,Fuchigami T,Haratake M,Nakayama M,Saji H

更新日期：2011-11-01 00:00:00

abstract：:Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pk(a) of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pk(a) 6-8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arbuckle W,Baugh M,Belshaw S,Bennett DJ,Bruin J,Cai J,Cameron KS,Claxton C,Dempster M,Everett K,Fradera X,Hamilton W,Jones PS,Kinghorn E,Long C,Martin I,Robinson J,Westwood P

更新日期：2011-02-01 00:00:00

abstract：:The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'-(N,N-d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao ZG,Joshi BV,Klutz AM,Kim SK,Lee HW,Kim HO,Jeong LS,Jacobson KA

更新日期：2006-02-01 00:00:00

abstract：:Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ghosh AK,Kumaragurubaran N,Hong L,Kulkarni S,Xu X,Miller HB,Reddy DS,Weerasena V,Turner R,Chang W,Koelsch G,Tang J

更新日期：2008-02-01 00:00:00

abstract：:A new immobilization chemistry for covalent attachment of phosphorylated oligonucleotides on epoxy-activated glass surface via opening of oxirane ring is described. The proposed strategy results in excellent immobilization efficiency, spot homogeneity, and morphology. The constructed microarray was successfully demons...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mahajan S,Kumar P,Gupta KC

更新日期：2006-11-01 00:00:00

abstract：:Antibiotic resistance has prompted efforts to discover antibiotics with novel mechanisms of action. FtsZ is an essential protein for bacterial cell division, and has been viewed as an attractive target for the development of new antibiotics. Sanguinarine is a benzophenanthridine alkaloid that prevents cytokinesis in b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Parhi A,Kelley C,Kaul M,Pilch DS,LaVoie EJ

更新日期：2012-12-01 00:00:00

abstract：:Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Quang TH,Ngan NTT,Ko W,Kim DC,Yoon CS,Sohn JH,Yim JH,Kim YC,Oh H

更新日期：2014-12-15 00:00:00

abstract：:A series of novel amino acid ester derivatives of 2,3-substituted isoindolinones was synthesized and evaluated for p53-mediated apoptotic activity. The rationale for augmentation of the target activity of 2,3-substituted isoindolinones was based on the introduction of new fragments in the structure of the inhibitor th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grigoreva TA,Novikova DS,Petukhov AV,Gureev MA,Garabadzhiu AV,Melino G,Barlev NA,Tribulovich VG

更新日期：2017-12-01 00:00:00

abstract：:We previously showed that fluorination of the carborane-containing selective estrogen receptor modulator (SERM) BE360 altered the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity. Here, we designed and synthesized a series of fluorinated carboranyl phenols as candidate ERβ-sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Kaise A,Endo Y

更新日期：2013-12-15 00:00:00

abstract：:A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bi X,Li W,Sasaki T,Li Q,Mitsuhata N,Asada Y,Zhang Q,Koike K

更新日期：2011-11-01 00:00:00

abstract：:A series of acetylenic chalcones were evaluated for antimalarial and antitubercular activity. The antimalarial data for this series suggests that growth inhibition of the W2 strain of Plasmodium falciparum can be imparted by the introduction of a methoxy group ortho to the acetylenic group. Most compounds were more ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hans RH,Guantai EM,Lategan C,Smith PJ,Wan B,Franzblau SG,Gut J,Rosenthal PJ,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:Fast atom bombardment mass spectrometry that can directly analyze lysophospholipids was used to quantitatively determine the kinetics of phospholipase A2. This method is 1250 times more sensitive than the colorimetric assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isomura S,Ito K,Haruna M

更新日期：1999-02-08 00:00:00

abstract：:Conformationally restricted analogues of the central linker unit of bacterial methionyl tRNA synthetase (MRS) inhibitors have been prepared. The (1S,2R)-cyclopentylmethyl moiety was identified as the preferred cyclic linker, with significant diastereo- and enantioselectivity of activity. Combination of this linker wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jarvest RL,Berge JM,Brown P,Houge-Frydrych CS,O'Hanlon PJ,McNair DJ,Pope AJ,Rittenhouse S

更新日期：2003-04-07 00:00:00

abstract：:A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen TK,Ankersen M,Raun K,Hansen BS

更新日期：2001-07-23 00:00:00

abstract：:Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the opti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y,Liu XH,Saunders M,Pearce S,Foulks JM,Parnell KM,Clifford A,Nix RN,Bullough J,Hendrickson TF,Wright K,McCullar MV,Kanner SB,Ho KK

更新日期：2014-01-15 00:00:00

abstract：:The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reactin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang Z,Fang Z,He W,Wang Z,Gan H,Tian Q,Guo K

更新日期：2016-04-01 00:00:00

abstract：:In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takaoka Y,Shigenaga M,Imai M,Nukadzuka Y,Ishimaru Y,Saito K,Yokoyama R,Nishitani K,Ueda M

更新日期：2016-01-01 00:00:00