Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy.

abstract：:The synthesis, structure-activity relationship and modeling of a series of 5-substituted-N-aryl pyridazinone based p38alpha inhibitors are described. In comparing the series to the similar N-aryl pyridinone series, it was found that the pyridazinones maintained a weaker interaction to the p38 enzyme, and therefore sho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jerome KD,Hepperle ME,Walker JK,Xing L,Devraj RV,Benson AG,Baldus JE,Selness SR

更新日期：2010-05-15 00:00:00

abstract：:Pathological calcifications induced by deposition of basic phosphate crystals or hydroxyapatite (HA) on soft tissues are a large family of diseases comprising of ankylosing spondylitis (AS), end-stage osteoarthritis (OA) and vascular calcification. High activity of tissue non-specific alkaline phosphatase (TNAP) is a ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chang L,Duy do L,Mébarek S,Popowycz F,Pellet-Rostaing S,Lemaire M,Buchet R

更新日期：2011-04-15 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：: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：:Benzalacetone synthase (BAS) and chalcone synthase (CHS) are plant-specific type III polyketide synthases (PKSs), sharing 70% amino acid sequence identity and highly homologous overall protein structures. BAS catalyzes the decarboxylative coupling of 4-coumaroyl-CoA with malonyl-CoA to produce the diketide benzalaceto...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shimokawa Y,Morita H,Abe I

更新日期：2010-09-01 00:00:00

abstract：:Pulvinone and several 3-fluoro-4-morpholino substituted pulvinone derivatives were synthesized in five steps from a common precursor, phenyl acetic acid. Most of synthetic morpholine substituted pulvinones showed inhibitory activity against Esherichia coli. For the first time, the inhibition of pulvinone and its deriv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu HW,Xu C,Fan ZQ,Zhao LJ,Liu HM

更新日期：2013-02-01 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：:Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patterson JT,Isaacson J,Kerwin L,Atassi G,Duggal R,Bresson D,Zhu T,Zhou H,Fu Y,Kaufmann GF

更新日期：2017-12-15 00:00:00

abstract：:A novel series of quinolizidine salicylamides was synthesized as specific inhibitors of the H1 subtype of influenza A viruses. These inhibitors inhibit the pH-induced fusion process, thereby blocking viral entry into host cells. Compound 16 was the most active inhibitor in this series with an EC50 of 0.25 microg/mL in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu KL,Ruediger E,Luo G,Cianci C,Danetz S,Tiley L,Trehan AK,Monkovic I,Pearce B,Martel A,Krystal M,Meanwell NA

更新日期：1999-08-02 00:00:00

abstract：:Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the aff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enzensperger C,Kilian S,Ackermann M,Koch A,Kelch K,Lehmann J

更新日期：2007-03-01 00:00:00

abstract：:Although Au(I) complexes have been used to treat rheumatoid arthritis for over 75 years, their mechanism of action is still poorly understood. A family of enzymes responsible for joint destruction in rheumatoid arthritis, the cathepsins, has been discussed as a possible biological target of Au(I). In this study, inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chircorian A,Barrios AM

更新日期：2004-10-18 00:00:00

abstract：:'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gibbons S,Zloh M

更新日期：2010-07-15 00:00:00

abstract：:A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Webster SP,Ward P,Binnie M,Craigie E,McConnell KM,Sooy K,Vinter A,Seckl JR,Walker BR

更新日期：2007-05-15 00:00:00

abstract：:A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang C,Corte JR,Rossi KA,Bozarth JM,Wu Y,Sheriff S,Myers JE Jr,Luettgen JM,Seiffert DA,Wexler RR,Quan ML

更新日期：2017-09-01 00:00:00

abstract：:Fifteen new alpha-acylaminoketones were prepared by four different routes in an initial effort to optimize the potency of these compounds as ecdysone agonists. The compounds were assayed in mammalian cells expressing the ecdysone receptors from Bombyx mori (BmEcR) and Choristoneura fumiferana (CfEcR) for their ability...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tice CM,Hormann RE,Thompson CS,Friz JL,Cavanaugh CK,Saggers JA

更新日期：2003-06-02 00:00:00

abstract：:We have synthesized and evaluated a series of 1,4-disubstituted-triazole derivatives for inhibition of the rat Na(V)1.6 sodium channel isoform, an isoform thought to play an important role in controlling neuronal firing. Starting from a series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rivara M,Patel MK,Amori L,Zuliani V

更新日期：2012-10-15 00:00:00

abstract：:The introduction of a functionalised amido substituent into a series of 1-(biphenylmethylacetamido)-pyrimidones has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency and very encouraging developability properties. Diethylaminoethyl derivative 32, SB-435495...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blackie JA,Bloomer JC,Brown MJ,Cheng HY,Elliott RL,Hammond B,Hickey DM,Ife RJ,Leach CA,Lewis VA,Macphee CH,Milliner KJ,Moores KE,Pinto IL,Smith SA,Stansfield IG,Stanway SJ,Taylor MA,Theobald CJ,Whittaker CM

更新日期：2002-09-16 00:00:00

abstract：:Certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl- gamma-butyrolactones were synthesized and evaluated for their anticancer activity. These compounds demonstrated a strong growth inhibitory activity against leukemia cell lines but are relatively inactive against non-small cell lung cancers and CNS cancers. The ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang TC,Lee KH,Chen YL,Liou SS,Tzeng CC

更新日期：1998-10-06 00:00:00

abstract：:The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously desc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin H,Yamashita DS,Xie R,Zeng J,Wang W,Leber J,Safonov IG,Verma S,Li M,Lafrance L,Venslavsky J,Takata D,Luengo JI,Kahana JA,Zhang S,Robell KA,Levy D,Kumar R,Choudhry AE,Schaber M,Lai Z,Brown BS,Donovan BT,Mi

更新日期：2010-01-15 00:00:00

abstract：:Incubation of epicubenol synthase with farnesyl pyrophosphate in the presence of 11.1 atom% H2(18)O gave epicubenol (2) in which the hydroxyl oxygen atom was shown to be derived exclusively from water, as established by GC-selected ion monitoring MS of the derived TMS-epicubenol derivative (15). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cane DE,Ke N

更新日期：2000-01-17 00:00:00

abstract：:Mismatch binding protein MutS binding to bulge structure in DNA duplexes was controlled by UV irradiation. 4-O-(2-Nitrobenzyl)thymidine or 4-O-[2-(2-nitrophenyl)propyl]thymidine was incorporated into DNA duplexes a bulged position. The MutS did not bind to the caged DNA duplexes but bound after removing the 2-nitroben...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Ohno Y,Ohno K,Takeshita L,Kanamori T,Masaki Y,Sekine M

更新日期：2016-10-01 00:00:00

abstract：:Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen P,Horton LB,Mikulski RL,Deng L,Sundriyal S,Palzkill T,Song Y

更新日期：2012-10-01 00:00:00

abstract：:In order to investigate the relationship between tyrosine phosphorylation of β-catenin and transcriptional activity of β-catenin in Hela and Bcap-37 cells, genistein (a tyrosine kinase inhibitor) was used to inhibit tyrosine phosphorylation in cells. Our results showed the total β-catenin protein levels were mainly eq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qian HY,Zhang DG,Wang HW,Pei DS,Zheng JN

更新日期：2014-06-01 00:00:00

abstract：:The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5-C6 bond length as well as the H5-H6 coupling constants were probed. It was found that the bond length and coupling constants corre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang S,Gronert S,Wu W

更新日期：2011-11-01 00:00:00

abstract：:Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1) enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li G,Hasvold LA,Tao ZF,Wang GT,Gwaltney SL 2nd,Patel J,Kovar P,Credo RB,Chen Z,Zhang H,Park C,Sham HL,Sowin T,Rosenberg SH,Lin NH

更新日期：2006-04-15 00:00:00

abstract：:In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ranjith PK,Rajeesh P,Haridas KR,Susanta NK,Row TN,Rishikesan R,Kumari NS

更新日期：2013-09-15 00:00:00

abstract：:A novel synthetic method was developed for the synthesis of venlafaxine using inexpensive reagents. An improvement in the method, in the yield was achieved for the conversion of the venlafaxine. This is an improved version, simple and efficient method for the large-scale synthesis of venlafaxine. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basappa,Kavitha CV,Rangappa KS

更新日期：2004-06-21 00:00:00

abstract：:Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC(50) approximately 5.5...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mahale S,Aubry C,James Wilson A,Jenkins PR,Maréchal JD,Sutcliffe MJ,Chaudhuri B

更新日期：2006-08-15 00:00:00

abstract：:Two new technetium complexes containing a piperidine template have been synthesized and evaluated as possible leads for the development of dopamine transporter (DAT) imaging agents. Binding data for the corresponding rhenium complexes containing either a monoaminomonoamide (MAMA') or a diaminodithiol (DADT) chelating ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hoepping A,Babich J,Zubieta JA,Johnson KM,Machill S,Kozikowski AP

更新日期：1999-11-15 00:00:00

abstract：:Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

更新日期：2008-01-01 00:00:00