Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.

abstract：:The acyloxyalkyl derivatives of a model anti-HBV dinucleotide were synthesized and evaluated as orally bioavailable prodrugs. Our studies have led to the identification of the first orally bioavailable dinucleotide prodrugs for further therapeutic development against the hepatitis B virus (HBV). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Coughlin JE,Padmanabhan S,Zhang G,Kirk CJ,Govardhan CP,Korba BE,O'Loughlin K,Green CE,Mirsalis J,Morrey JD,Iyer RP

更新日期：2010-03-01 00:00:00

abstract：:Polyoxometalates (POMs) are interesting biomedical agents due to their versatile anticancer and antiviral properties, such as remarkable anti-HIV activity. Although POMs are tunable and easily accessible inorganic drug prototypes in principle, their full potential can only be tapped by enhancing their biocompatibility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Flütsch A,Schroeder T,Grütter MG,Patzke GR

更新日期：2011-02-15 00:00:00

abstract：:The in vitro activity of novel 4-substituted imidazole antifungals was optimized by solid-phase chemistry and parallel synthesis. Potent yeast-selective as well as broad-spectrum antifungal compounds (32 and 20) were discovered. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saha AK,Liu L,Marichal P,Odds F

更新日期：2000-12-18 00:00:00

abstract：:A new synthesis of (R,S)-PPG (4-phosphonophenylglycine) and the separation of the protected enantiomers leading after deprotection to (+)- and (-)-PPG are described. Pharmacological characterization at the group III metabotropic glutamate receptors hmGluR4a and hmGluR7b revealed (+)-PPG as the active enantiomer. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gasparini F,Inderbitzin W,Francotte E,Lecis G,Richert P,Dragic Z,Kuhn R,Flor PJ

更新日期：2000-06-05 00:00:00

abstract：:A novel type of caspase inhibitor prodrug that improves systemic exposure after oral administration in rats has been designed. Such a prodrug, based on a 6,6a-dihydrofuro[3,2-d]oxazol-5(3aH)-one motif, has the advantage of rapidly liberating the active inhibitor without producing any cleavage by-product. Prodrugs 6-8,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier JD,Durrant SJ,Studley J,Lawes L,Weber P

更新日期：2012-01-01 00:00:00

abstract：:A series of new peptoids as endothelin receptor antagonists has been synthesized. Screening them for their ability to bind with endothelin receptors (ET(A) and ET(B)) competitively in the presence of (125I) endothelin led to the discovery of compounds as possible leads with IC50s in the low micromolar concentrations. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dasgupta F,Gangadhar N,Bruhaspathy M,Verma AK,Sarin S,Mukherjee AK

更新日期：2001-02-26 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：:Bioisosteric substitution of the thiourea (3, 5, 7, 9) and urea (10) moiety of PETT compounds with sulfamide (1), cyanoguanidine (2, 4) and guanidine (6, 8) functionalities, and replacement of the phenethyl group with benzoylethyl group (compounds 11-20) have been studied. Synthesis and antiviral activities are descri...

journal_title：Bioorganic & medicinal chemistry letters

authors： Högberg M,Engelhardt P,Vrang L,Zhang H

更新日期：2000-02-07 00:00:00

abstract：:We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matsumoto K,Choshi T,Hourai M,Zamami Y,Sasaki K,Abe T,Ishikura M,Hatae N,Iwamura T,Tohyama S,Nobuhiro J,Hibino S

更新日期：2012-07-15 00:00:00

abstract：:In silico modelling was used to guide the positioning of the fluorescent dye NBD-F on the cannabinoid CB2 receptor agonist JWH-015. While the ultimate fluorescent conjugate lost extensive binding affinity to the cannabinoid CB2 receptor, affinity and efficacy studies on the naphthoyl 3-position modified precursor mole...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yates AS,Doughty SW,Kendall DA,Kellam B

更新日期：2005-08-15 00:00:00

abstract：:Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of thi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith G,Ruhland T,Mikkelsen G,Andersen K,Christoffersen CT,Alifrangis LH,Mørk A,Wren SP,Harris N,Wyman BM,Brandt G

更新日期：2004-08-02 00:00:00

abstract：:Systematic SAR studies of the different regioisomers and homologues of the spiro(indane-1,4-piperidine) moiety in the growth hormone secretagogue L-162,752 are presented. Among them, spiro(3H-1-benzopyran-2,3-piperidine) was found to afford secretagogues with low nanomolar in vitro activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang L,Morriello G,Prendergast K,Cheng K,Jacks T,Chan WW,Schleim KD,Smith RG,Patchett AA

更新日期：1998-01-06 00:00:00

abstract：:Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Bagnard D,Luu B

更新日期：2006-08-01 00:00:00

abstract：:Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hudkins RL,Iqbal M,Park CH,Goldstein J,Herman JL,Shek E,Murakata C,Mallamo JP

更新日期：1998-07-21 00:00:00

abstract：:Three C(60) derivatives [C(60) (NHCH(2)CH(2)COONa)(n)(H)(n)], n=1, 5, 9] (A, B, C) with different additional number of beta-alanine were synthesized by the control of relative amount of C(60) and beta-alanine added. Hydroxyl radical scavenging activity of the adducts was evaluated in a copper-catalyzed Haber-Weiss rea...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun T,Jia Z,Xu Z

更新日期：2004-04-05 00:00:00

abstract：:To obtain modulators for reducing mitochondrial damage by the inhibition of Aβ oligomer formation, 2-phenylbenzofuran derivatives were designed and prepared. Their inhibitory activity against Aβ fibril formation was screened using ThT fluorescence assay, and the effect of derivatives on mitochondrial function was eval...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee YS,Kim HY,Youn HM,Seo JH,Kim Y,Shin KJ

更新日期：2013-11-01 00:00:00

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：:(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors and enhances performance in animal models of cognition. The routes of metabolis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jones P,Atack JR,Braun MP,Cato BP,Chambers MS,O'Connor D,Cook SM,Hobbs SC,Maxey R,Szekeres HJ,Szeto N,Wafford KA,MacLeod AM

更新日期：2006-02-15 00:00:00

abstract：:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rusnak DW,Lai Z,Lansing TJ,Rhodes N,Gilmer TM,Copeland RA

更新日期：2004-05-03 00:00:00

abstract：:The electrochemical properties of a series of N-substituted-N'-hydroxyguanidines were studied. Two oxidation potentials of each compound were obtained by cyclic voltammetry. The E(ox1) values were from 0.51 to 0.62V, while the E(ox2) values were from 1.14 to 1.81V in acetonitrile solution. Next, their enzymatic contro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cai T,Xian M,Wang PG

更新日期：2002-06-03 00:00:00

abstract：:Tricyclic sulfones were designed as gamma-secretase inhibitors and found to have excellent potency. Extensive SAR shows that a large number of sulfonamides at position 7 of the tricycle are very well tolerated. Compounds such as 15a and 15c showed remarkable in vivo potency. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasikumar TK,Qiang L,Burnett DA,Cole D,Xu R,Li H,Greenlee WJ,Clader J,Zhang L,Hyde L

更新日期：2010-06-15 00:00:00

abstract：:The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C-N bond formation/reduction/diazotizat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marepu N,Yeturu S,Pal M

更新日期：2018-11-01 00:00:00

abstract：:A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu M,Mierzwa R,He L,King A,Patel M,Pichardo J,Hart A,Butkiewicz N,Puar MS

更新日期：1999-07-19 00:00:00

abstract：:The convergent synthesis of C35-fluorinated analogues of solamin, a mono-THF Annonaceous acetogenin, has been achieved by the Sonogashira coupling of the THF ring fragment and the fluorinated γ-lactone fragment. It was revealed that the number of fluorine atoms on the γ-lactone moiety affects the growth inhibitory act...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kojima N,Suga Y,Hayashi H,Yamori T,Yoshimitsu T,Tanaka T

更新日期：2011-10-01 00:00:00

abstract：:Hippuristanol is a natural product that has recently been shown to inhibit eukaryotic translation initiation and tumor cell proliferation. To investigate the structure and activity relationship of hippuristanol, we synthesized a series of analogs by expanding the size of its F ring and determined their effects on the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li W,Dang Y,Liu JO,Yu B

更新日期：2010-05-15 00:00:00

abstract：:The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huczyński A

更新日期：2012-12-01 00:00:00

abstract：:This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chrom...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian Y,Jin J,Wang C,Lv W,Li X,Che X,Gong Y,Li Y,Li Q,Hou J,Wang PG,Shen J

更新日期：2016-05-15 00:00:00

abstract：:A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

更新日期：2009-07-01 00:00:00

abstract：:MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Noguchi T,Oishi S,Honda K,Kondoh Y,Saito T,Kubo T,Kaneda M,Ohno H,Osada H,Fujii N

更新日期：2013-07-01 00:00:00

abstract：:Ubiquitin-dependent proteolysis of cellular proteins is one of the major pathways to regulate protein function posttranslationally. Here we demonstrate a potentially general method of degrading any targeted proteins by the ubiquitin-dependent proteolysis in living cells, using small-molecule proteolysis inducer (SMPI)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang D,Baek SH,Ho A,Kim K

更新日期：2004-02-09 00:00:00