Discovery of novel nonsteroidal glucocorticoid receptor modulators.

abstract：:Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27...

journal_title：Bioorganic & medicinal chemistry letters

authors： Na M,Cui L,Min BS,Bae K,Yoo JK,Kim BY,Oh WK,Ahn JS

更新日期：2006-06-15 00:00:00

abstract：:A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1- ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alberati D,Hainzl D,Jolidon S,Krafft EA,Kurt A,Maier A,Pinard E,Thomas AW,Zimmerli D

更新日期：2006-08-15 00:00:00

abstract：:Aminoglycosides have been shown to target A-form nucleic acids. Our work has previously shown that neomycin (and other aminoglycosides) bind and stabilize DNA/RNA triplexes and other A-form nucleic acids. We report herein the unexpected B-form duplex stabilization shown by aminoglycoside dimers (neomycin-neomycin and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arya DP,Coffee RL Jr,Xue L

更新日期：2004-09-20 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 00:00:00

abstract：:A new class of inhibitors of HIV-1 integrase has been optimized to provide selective and highly efficient strand transfer inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donghi M,Kinzel OD,Summa V

更新日期：2009-04-01 00:00:00

abstract：:A series of 4'-hydroxyphenyl-aryl-carbaldehyde oximes (5b) was prepared and found to have high affinity (4nM) and modest selectivity (39-fold) for estrogen receptor-beta (ERbeta). Substitution of one of the core rings of the scaffold based around these novel ligands further expanded our knowledge in the quest toward a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mewshaw RE,Bowen SM,Harris HA,Xu ZB,Manas ES,Cohn ST

更新日期：2007-02-15 00:00:00

abstract：:O6-Benzylguanine (O6-BG) is a substrate of O6-methylguanine-DNA methyltransferase (MGMT), which is involved in drug resistance of chemotherapy in the majority of glioblastoma multiform. For clinical diagnosis, it is hoped that the MGMT expression level could be determined by a noninvasive method to understand the deta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koyama H,Ikenuma H,Toda H,Kondo G,Hirano M,Kato M,Abe J,Yamada T,Wakabayashi T,Ito K,Natsume A,Suzuki M

更新日期：2017-05-01 00:00:00

abstract：:Aromatase is a target of pharmacological interest for the treatment of estrogen-dependent cancers. Azole derivatives such as letrozole or anastrozole have been developed for aromatase inhibition and are used for the treatment of breast tumors. In this paper, four 4-triazolylflavans were synthesized and were found to e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yahiaoui S,Pouget C,Fagnere C,Champavier Y,Habrioux G,Chulia AJ

更新日期：2004-10-18 00:00:00

abstract：:A series of 5-[(5-aryl-1H-pyrazol-3-yl)methyl]-1H-tetrazoles 3a-h have been synthesized and evaluated for their in vivo antihyperglycemic activity. Some of the synthesized compounds have shown significant glucose lowering activity in male Sprague-Dawley rats in sucrose loaded model. These compounds were also evaluated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharon A,Pratap R,Tiwari P,Srivastava A,Maulik PR,Ram VJ

更新日期：2005-04-15 00:00:00

abstract：:Retinoids are analogues of all-trans-retinoic acid, a powerful hormone that mediates many fundamental biological processes. Cancer and other serious hyperproliferative diseases are attractive therapeutic targets for retinoids, but the therapeutic use of retinoids is limited due to severe toxicity. We report here the d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Beard RL,Duong TT,Teng M,Klein ES,Standevan AM,Chandraratna RA

更新日期：2002-11-04 00:00:00

abstract：:The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin KJ,Koo KD,Yoo KH,Kang YK,Park SW,Kim DJ

更新日期：2001-09-03 00:00:00

abstract：:A series of borinic acid picolinate esters were synthesized and screened for their minimum inhibitory concentration (MIC) against Gram-positive and -negative bacteria. Our lead compounds were then screened for anti-inflammatory activity. From these studies, we identified 3-hydroxypyridine-2-carbonyloxy-bis(3-chloro-4-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baker SJ,Akama T,Zhang YK,Sauro V,Pandit C,Singh R,Kully M,Khan J,Plattner JJ,Benkovic SJ,Lee V,Maples KR

更新日期：2006-12-01 00:00:00

abstract：:Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relations...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tchamo DN,Dijoux-Franca MG,Mariotte AM,Tsamo E,Daskiewicz JB,Bayet C,Barron D,Conseil G,Di Pietro A

更新日期：2000-06-19 00:00:00

abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

更新日期：2009-11-01 00:00:00

abstract：:To develop potent chemotherapeutic agents for treating colorectal cancers, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamide derivatives were designed. Twenty-two novel derivatives were synthesized and their cytotoxicities were measured using a clonogenic long-term survival assay. Of these derivatives, 3-(...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin SY,Ahn S,Yoon H,Jung H,Jung Y,Koh D,Lee YH,Lim Y

更新日期：2016-09-01 00:00:00

abstract：:Analysis of the enantiomers of rosiglitazone in a PPAR gamma binding assay suggests that the (S)-(-)-isomer is responsible for the antidiabetic activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Parks DJ,Tomkinson NC,Villeneuve MS,Blanchard SG,Willson TM

更新日期：1998-12-15 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：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

更新日期：2003-02-10 00:00:00

abstract：:Amide- and ester-linked kinase inhibitor-cytotoxin conjugates were rationally designed and synthesised as prototype hypoxia-activated anticancer mutual prodrugs. Chemical reduction of an aryl nitro trigger moiety was shown to initiate a spontaneous cyclisation/fragmentation reaction that simultaneously released the ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sansom GN,Kirk NS,Guise CP,Anderson RF,Smaill JB,Patterson AV,Kelso MJ

更新日期：2019-05-15 00:00:00

abstract：:Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic ro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Balti M,Plas A,Meinguet C,Haufroid M,Thémans Q,Efrit ML,Wouters J,Lanners S

更新日期：2017-08-01 00:00:00

abstract：:The efficient synthesis of an enzyme cleavable biotinylated diazirinyl photoaffinity ligand is described to allow the effective manipulation of the photolabeled biocomponents. The compound contains a glutamic acid gamma-methyl ester, which is a precursor of the substrate for V8 protease, between the diazirinyl photoph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto M,Okamoto S,Nabeta K,Hatanaka Y

更新日期：2004-05-17 00:00:00

abstract：:The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cashman DJ,Rife JP,Kellogg GE

更新日期：2001-01-22 00:00:00

abstract：:The discovery of the potency-enhancing effect of 5-substitutions on the novel 2-arylindoles as nonpeptidyl GnRH receptor antagonists led to the identification of several analogues with high affinities on the GnRH receptor. The syntheses and SARs of these 5-substituted-2-arylindole analogues are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu L,Lo JL,Yang YT,Cheng K,Smith RG,Fisher MH,Wyvratt MJ,Goulet MT

更新日期：2001-02-26 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:Two new heterocycles, pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole, were prepared in three steps from 3-aminocarbazole and 3-aminoindole, respectively. The key Friedel-Crafts intramolecular cyclization was realized under microwave irradiation using montmorillonite K-10 clay as a catalyst. The pyrimido[4,5-c]carb...

journal_title：Bioorganic & medicinal chemistry letters

authors： Debray J,Zeghida W,Baldeyrou B,Mahieu C,Lansiaux A,Demeunynck M

更新日期：2010-07-15 00:00:00

abstract：:Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Siedlecki J,Hill J,Parr I,Yu X,Morytko M,Zhang Y,Silverman J,Controneo N,Laganas V,Li T,Li J,Keith D,Shimer G,Finn J

更新日期：2003-12-01 00:00:00

abstract：:Selective inhibitors of protein tyrosine phosphatases (PTPases) are of great interest as therapeutic agents and research tools. Several phenylalanine derivatives (1, 2) designed as phosphotyrosine mimetics or irreversible active site inhibitors were successfully synthesized, then incorporated into a combinatorial libr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan Z,Kahn M,Qabar M,Urban J,Kim HO,Blaskovich MA

更新日期：2003-06-16 00:00:00

abstract：:Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi HH,Bao J,Zhang Q,Ma B,Gu GY,Zhang PL,Ou-Yang G,Wu ZM,Ying HJ,Ou-Yang PK

更新日期：2016-10-01 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：: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