Regiospecific one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives in the solid state under microwave irradiations.

abstract：:The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

更新日期：2010-12-15 00:00:00

abstract：:In this study, we synthesized an Azo-py phosphoramidite, featuring azobenzene and pyrene units, as a novel fluorescent and isomeric (trans- and cis-azobenzene units) material, which we incorporated in an i-motif DNA sequence. We then monitored the structural dynamics and changes in fluorescence as the modified DNA seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joo HN,Van Thi Nguyen T,Chae HK,Seo YJ

更新日期：2017-06-01 00:00:00

abstract：:Forty-seven 2-benzoylaminobenzoic esters were synthesized and evaluated in anti-platelet aggregation, inhibition of superoxide anion generation, and inhibition of neutrophil elastase release assays. Most 2-benzoylamino-4-chlorobenzoic acid derivatives showed selective inhibitory effects on arachidonic acid (AA)-induce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsieh PW,Hwang TL,Wu CC,Chiang SZ,Wu CI,Wu YC

更新日期：2007-03-15 00:00:00

abstract：:A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartz RA,Vrudhula VM,Ahuja VT,Grace JE,Lodge NJ,Bronson JJ,Macor JE

更新日期：2017-03-15 00:00:00

abstract：:p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mavunkel BJ,Chakravarty S,Perumattam JJ,Luedtke GR,Liang X,Lim D,Xu YJ,Laney M,Liu DY,Schreiner GF,Lewicki JA,Dugar S

更新日期：2003-09-15 00:00:00

abstract：:Optically active phenylpropanoic acid derivatives [(S)-5, and (R)-5] were prepared, and their affinities for peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma were evaluated. Binding assay and cell-based reporter assay indicated that the activity of these compounds is enantio-dependent, and resides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miyachi H,Nomura M,Tanase T,Suzuki M,Murakami K,Awano K

更新日期：2002-02-11 00:00:00

abstract：:A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kulkarni SS,Newman AH

更新日期：2007-04-01 00:00:00

abstract：:The B(6) vitamers have been shown to display beneficial therapeutic effects in cardiovascular related disorders. The design of novel antiplatelet agents using pyridoxine as a template has led to the discovery of a class of novel cardio- and cerebro-protective agents. The present study describes the synthesis of severa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang W,Yao J,Pham V,Whitney T,Froese D,Friesen A,Stang L,Xu C,Shuaib A,Diakur JM,Haque W

更新日期：2004-09-20 00:00:00

abstract：:Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity rel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Geldenhuys WJ,Caporoso J,Leeper TC,Lee YK,Lin L,Darvesh AS,Sadana P

更新日期：2017-01-15 00:00:00

abstract：:Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel IT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Bentzien J,Fleck RW,Pullen SS,Khine HH,Woska JR Jr,Kugler SZ,Kashem MA,Takahashi H

更新日期：2008-12-01 00:00:00

abstract：:A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hong SS,Lee SA,Kim N,Hwang JS,Han XH,Lee MK,Jung JK,Hong JT,Kim Y,Lee D,Hwang BY

更新日期：2011-02-15 00:00:00

abstract：:Cu(II) complexes of Alzheimer's disease-related β-amyloid (Aβ) peptides exhibit metal-centered oxidation chemistry. The metallo-Aβ complexes are the hallmark of the disease and have been attributed to the generation of reactive oxygen species (ROS), causing oxidative stress. In this communication, the inhibitions of t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashim A,Wang L,Juneja K,Ye Y,Zhao Y,Ming LJ

更新日期：2011-11-01 00:00:00

abstract：:This study explores the possible use of reactive oxygen-activated DNA modifying agents against acute myeloid leukemia (AML). A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds ha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bell-Horwath TR,Vadukoot AK,Thowfeik FS,Li G,Wunderlich M,Mulloy JC,Merino EJ

更新日期：2013-05-15 00:00:00

abstract：:The Golden Triangle is a visualization tool developed from in vitro permeability, in vitro clearance and computational data designed to aid medicinal chemists in achieving metabolically stable, permeable and potent drug candidates. Classifying compounds as permeable and stable and plotting molecular weight (MW) versus...

journal_title：Bioorganic & medicinal chemistry letters

authors： Johnson TW,Dress KR,Edwards M

更新日期：2009-10-01 00:00:00

abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li W,Li S,Higai K,Sasaki T,Asada Y,Ohshima S,Koike K

更新日期：2013-11-01 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：:A polyphemusin peptide analogue, T22 ([Tyr(5,12), Lys7]-polyphemusin II), and its shortened potent analogues, T134 (des-[Cys(8,13), Tyr(9,12)]-[D-Lys10, Pro11, L-citrulline16]-T22 without C-terminal amide) and T140 [[L-3-(2-naphthyl)alanine3]-T134], strongly inhibit the T-cell line-tropic (T-tropic) HIV-1 infection th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamamura H,Omagari A,Oishi S,Kanamoto T,Yamamoto N,Peiper SC,Nakashima H,Otaka A,Fujii N

更新日期：2000-12-04 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：: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：:Nine new monoterpene glycosides (1-9), together with 18 known compounds were obtained from the n-butanol soluble fraction of ethanol extract from Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectroscopic data. The inhibitory effects of these compounds (except com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Zhao F,Chen L,Jiang Z,Liu Y,Li Z,Qiu F,Yao X

更新日期：2012-12-01 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 library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 00:00:00

abstract：:Cross-linkage of the branches of poly(ethylenimine) (PEI) suppresses flexibility of the polymer as revealed by decreased affinity of the amino groups on PEI backbone towards proton or Ni(II) ion. The cross-linkage improves ability of the PEI derivative equipped with beta-cyclodextrin to deacylate an ester containing t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suh J,Noh YS

更新日期：1998-06-02 00:00:00

abstract：:To develop more valuable and effective fungicide candidates, a novel series of 3,4-dichloroisothioxazole-based cycloalkylsulfonamides were synthesized and their structures were identified by 1H NMR, 13C NMR, MS and elemental analysis. Compound 3k was further confirmed by X-ray single crystal diffraction. The in vitro ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Wang M,Ahmed M,He L,Ji M,Qi Z,Li X

更新日期：2019-06-01 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 series of novel 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives was designed, and synthesized based on our previous studies. Also their activities were evaluated as competitive inhibitors of protein tyrosine phosphatase 1B (PTP1B). Compounds 6d-6g, 7b, 7c, 7e, 7j, 7k, 7m, 14b and 14e-14f showed potent ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Z,Liu Z,Lee W,Kim SN,Yoon G,Cheon SH

更新日期：2014-08-01 00:00:00

abstract：:Our series of competitive antagonists against the G-protein coupled receptor P2Y(14) were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Robichaud J,Fournier JF,Gagné S,Gauthier JY,Hamel M,Han Y,Hénault M,Kargman S,Levesque JF,Mamane Y,Mancini J,Morin N,Mulrooney E,Wu J,Black WC

更新日期：2011-07-15 00:00:00

abstract：:Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the ami...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majmudar JD,Hahne K,Hrycyna CA,Gibbs RA

更新日期：2011-05-01 00:00:00

abstract：:We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, whic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LX,Zhou XB,Xiao ML,Jiang N,Liu F,Zhou WX,Wang XK,Zheng ZB,Li S

更新日期：2014-08-15 00:00:00

abstract：:By developing a new synthetic procedure for introduction of side chains onto the camptothecin ring system, we were able to achieve the preparation of a number of analogs bearing bulky, hydrophobic groups directly attached to the 7-position. These include 7-tert-butylcamptothecin, 7-benzylcamptothecin and the correspon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Manikumar G,Wadkins RM,Bearss D,Von Hoff DD,Wani MC,Wall ME

更新日期：2004-11-01 00:00:00