Synthesis and SAR of sulfonyl- and phosphoryl amidine compounds as anti-resorptive agents.

abstract：:A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu H,Su X,Liu XQ,Zhang KP,Hou Z,Guo C

更新日期：2019-12-01 00:00:00

abstract：:A series of gibberellin based molecules were designed and synthesized. Gibberellin derivatives bearing two alpha,beta-unsaturated ketone units showed strong anticancer activities in MTT assay towards a number of human cancer cell lines including HT29, A549, HepG2 and MKN28. The most potent gibberellin derivative (comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Sun Z,Zhang Y,Zeng X,Qing C,Liu J,Li L,Zhang H

更新日期：2009-09-15 00:00:00

abstract：:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key anal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

更新日期：2012-01-01 00:00:00

abstract：:A series of sesquiterpene compounds possessing both eudesmane and eremophilane skeletons were tested as gastric cytoprotective agents on male Wistar rats. The presence of an alpha,beta-unsaturated aldehyde on the C-7 side chain together with a hydroxyl group at C-4 is the requirement for the observed antiulcerogenic a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donadel OJ,Guerreiro E,María AO,Wendel G,Enriz RD,Giordano OS,Tonn CE

更新日期：2005-08-01 00:00:00

abstract：:The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-facto...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeong JY,Jo YH,Lee KY,Do SG,Hwang BY,Lee MK

更新日期：2014-05-15 00:00:00

abstract：:Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang H,Lu W,Li X,Cong X,Ma H,Liu X,Zhang Y,Che P,Ma R,Li H,Shen X,Jiang H,Huang J,Zhu J

更新日期：2012-01-15 00:00:00

abstract：:The ability of serine phosphate (SerP) or alpha-amino-gamma-phosphonobutyric acid (AbuP) and arginine to form a salt bridge between their side chains appears to be much greater when they are spaced i/i+4 than when they are spaced i/i+3. The side chain-side chain interaction between SerP/Arg and AbuP/Arg, positioned i/...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liehr S,Chenault HK

更新日期：1999-09-20 00:00:00

abstract：:Imidazoline-based small molecule inhibitors of p53-MDM2 interaction intended for the treatment of p53 wild-type tumors are the promising structures for design of anticancer drugs. Based on fragment approach we have investigated a key role of substituents in cis-imidazoline core for biological activity of nutlin family...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bazanov DR,Pervushin NV,Savitskaya VY,Anikina LV,Proskurnina MV,Lozinskaya NA,Kopeina GS

更新日期：2019-08-15 00:00:00

abstract：:In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato F,Inoue Y,Omodani T,Imano K,Okazaki H,Takemura T,Komiya M

更新日期：2002-02-25 00:00:00

abstract：:Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suh H,Choi KW,Lee J,Ryou C,Rhee H,Lee CH

更新日期：2016-02-15 00:00:00

abstract：:Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao D,Zhu X,Yu Y,Shao N,Wu J,McCormick KD,Dhondi P,Qin J,Mazzola R,Tang H,Rao A,Siliphaivanh P,Qiu H,Yang X,Rivelli M,Garlisi CG,Eckel S,Mukhopadhyay G,Correll C,Rindgen D,Aslanian R,Palani A

更新日期：2014-03-15 00:00:00

abstract：:A scaffold hopping strategy was successfully applied in discovering 2-aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia. Further optimization in potency and PK properties resulted in a lead series with oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HM,Smith MD,Kim JH,Caplen MA,Chan TY,McKittrick BA,Cook JA,van Heek M,Lachowicz J

更新日期：2013-12-01 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipide...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu P,Liu W,Ren J,Wang Y,Ning Y,Huang M,Hu X,Wei L,Ji M,Cai J

更新日期：2019-08-15 00:00:00

abstract：:The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar subs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ng RA,Sun M,Bowers S,Hom RK,Probst GD,John V,Fang LY,Maillard M,Gailunas A,Brogley L,Neitz RJ,Tung JS,Pleiss MA,Konradi AW,Sham HL,Dappen MS,Adler M,Yao N,Zmolek W,Nakamura D,Quinn KP,Sauer JM,Bova MP,Ruslim

更新日期：2013-08-15 00:00:00

abstract：:A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening reve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng P,Huang N,Jiang ZY,Zhang Q,Zheng YT,Chen JJ,Zhang XM,Ma YB

更新日期：2008-04-01 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：:A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mareddy J,Nallapati SB,Anireddy J,Devi YP,Mangamoori LN,Kapavarapu R,Pal S

更新日期：2013-12-15 00:00:00

abstract：:Telomeric G-rich single-stranded DNA can adopt a G-tetraplex structure which has been shown to inhibit telomerase activity. We have examined benzoindoloquinolines derivatives for their ability to stabilize an intramolecular G-quadruplex. The increase in T(m) value of the G-quadruplex was associated with telomerase inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alberti P,Schmitt P,Nguyen CH,Rivalle C,Hoarau M,Grierson DS,Mergny JL

更新日期：2002-04-08 00:00:00

abstract：:A tetrahydropyran-based inhibitor (2) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized based on the heptapeptide, N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed that 2 is indeed a competent inhibitor, albeit less potent than 1. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith AB 3rd,Sasho S,Barwis BA,Sprengeler P,Barbosa J,Hirschmann R,Cooperman BS

更新日期：1998-11-17 00:00:00

abstract：:We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stachel SJ,Coburn CA,Rush D,Jones KL,Zhu H,Rajapakse H,Graham SL,Simon A,Katharine Holloway M,Allison TJ,Munshi SK,Espeseth AS,Zuck P,Colussi D,Wolfe A,Pietrak BL,Lai MT,Vacca JP

更新日期：2009-06-01 00:00:00

abstract：:The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niu C,Ho DM,Williamson RT,Zask A,Ayral-Kaloustian S

更新日期：2010-03-01 00:00:00

abstract：:In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 sh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Flores-Ramos M,Ibarra-Velarde F,Jung-Cook H,Hernández-Campos A,Vera-Montenegro Y,Castillo R

更新日期：2017-02-01 00:00:00

abstract：:Fifteen new endoperoxides have been synthesised and tested for activity against pathogenic Candida species. These endoperoxides can be prepared in high yields, in one to three steps, from inexpensive starting materials. Despite chemical and structural similarities, their inhibitory activity against Candida growth vari...

journal_title：Bioorganic & medicinal chemistry letters

authors： Macreadie P,Avery T,Greatrex B,Taylor D,Macreadie I

更新日期：2006-02-15 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：:Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thompson SK,Washburn DG,Frazee JS,Madauss KP,Hoang TH,Lapinski L,Grygielko ET,Glace LE,Trizna W,Williams SP,Duraiswami C,Bray JD,Laping NJ

更新日期：2009-08-15 00:00:00

abstract：:Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dakin LA,Block MH,Chen H,Code E,Dowling JE,Feng X,Ferguson AD,Green I,Hird AW,Howard T,Keeton EK,Lamb ML,Lyne PD,Pollard H,Read J,Wu AJ,Zhang T,Zheng X

更新日期：2012-07-15 00:00:00

abstract：:The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uko NE,Güner OF,Barnett LMA,Matesic DF,Bowen JP

更新日期：2018-10-15 00:00:00

abstract：:An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song J,Kitamatsu M,Imamura K,Ohmori H,Watanabe K,Nakanishi K

更新日期：2013-02-01 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：:The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qiao L,Baumann CA,Crysler CS,Ninan NS,Abad MC,Spurlino JC,Desjarlais RL,Kervinen J,Neeper MP,Bayoumy SS,Williams R,Deckman IC,Dasgupta M,Reed RL,Huebert ND,Tomczuk BE,Moriarty KJ

更新日期：2006-01-01 00:00:00