Conformational restriction of methionyl tRNA synthetase inhibitors leading to analogues with potent inhibition and excellent gram-positive antibacterial activity.

abstract：:A group of fluorophore-labeled peptide substrates of Src kinases have been synthesized with the aid of click chemistry. Some of the generated peptides exhibit an increase in fluorescence upon phosphorylation and are capable of detecting Src kinases with high sensitivity and specificity. Their availability permits real...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamaruddin MA,Ung P,Hossain MI,Jarasrassamee B,O'Malley W,Thompson P,Scanlon D,Cheng HC,Graham B

更新日期：2011-01-01 00:00:00

abstract：:In a previous study, we found that the 3,4-dihydroquinazoline derivative, 4-(Benzylcarbamoylmethyl)-2-(biphenyl-4-ylamino)-3-(5-tert-butyloxycarbamoyl-1-pentyl)-3,4-dihydroquinazoline (KYS05047), was a selective T-type Ca(2+) channel blocker with anti-proliferative effects against various cancer cells. However, the me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rim HK,Lee HW,Choi IS,Park JY,Choi HW,Choi JH,Cho YW,Lee JY,Lee KT

更新日期：2012-12-01 00:00:00

abstract：:A series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives of biological interest have been prepared by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reacti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keche AP,Hatnapure GD,Tale RH,Rodge AH,Kamble VM

更新日期：2012-11-01 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：:Two series of triamino pyrimidines and a series of triamino pyridines have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. Small structural changes in these three hetereoaromatic cores influenced the functional activi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meduna SP,Savall BM,Cai H,Edwards JP,Thurmond RL,McGovern PM

更新日期：2011-05-15 00:00:00

abstract：:Non peptide products have been found to show nanomolar binding and functional affinities at the human tachykinin NK-2 receptor. The new antagonists do not possess stereogenic centers and their thermal behaviour in solution is featured by a peculiar set of conformational stereoisomers. A macroscopic viewpoint is prefer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Altamura M,Canfarini F,Catalioto RM,Guidi A,Pasqui F,Renzetti AR,Triolo A,Maggi CA

更新日期：2002-10-21 00:00:00

abstract：:PC-1 (NPP-1) inhibitors may be useful as therapeutics for the treatment of CDDP (calcium pyrophosphate dehydrate) deposition disease and osteoarthritis. We have identified a series of potent quinazolin-4-piperidin-4-ethyl sulfamide PC-1 inhibitors. The series, however, suffers from high affinity binding to hERG potass...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel SD,Habeski WM,Cheng AC,de la Cruz E,Loh C,Kablaoui NM

更新日期：2009-06-15 00:00:00

abstract：:A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher S

更新日期：2009-08-15 00:00:00

abstract：:We have identified a novel series of alpha-methylene carbonyl compounds through structure-activity relationship (SAR) studies with high levels of anti-proliferative activities. The lead molecule, 3-methylene-2-norbornanone (3) showed potent activity (LC(50)=3-8 microM) against mutant p53 cell types and many fold selec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Reddy NL,Hill J,Ye L,Fernandes PB,Stout DM

更新日期：2004-11-15 00:00:00

abstract：:A series of benzimidazole-based inhibitors of respiratory syncytial virus (RSV) fusion were optimized for antiviral potency, membrane permeability and metabolic stability in human liver microsomes. 1-Cyclopropyl-1,3-dihydro-3-[[1-(4-hydroxybutyl)-1H-benzimidazol-2-yl]methyl]-2H-imidazo[4,5-c]pyridin-2-one (6m, BMS-433...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu KL,Sin N,Civiello RL,Wang XA,Combrink KD,Gulgeze HB,Venables BL,Wright JJ,Dalterio RA,Zadjura L,Marino A,Dando S,D'Arienzo C,Kadow KF,Cianci CW,Li Z,Clarke J,Genovesi EV,Medina I,Lamb L,Colonno RJ,Yang Z,Kr

更新日期：2007-02-15 00:00:00

abstract：:Five-coordinated oxovanadium(IV) complexes with ciprofloxacin and various uninegative bidentate amino acids have been prepared. The structure of complexes has been investigated using spectral, physicochemical, mass spectroscopy, and elemental analyses. The antimicrobial activities (MIC) of the complexes, ligands, meta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel MN,Patel SH,Chhasatia MR,Parmar PA

更新日期：2008-12-15 00:00:00

abstract：:Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16μg/mL. Notably, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang YY,Zhou CH

更新日期：2011-07-15 00:00:00

abstract：:New inhibitors of histone deacetylase (HDAC) have been synthesized and evaluated for their activity toward non small lung cancer cell line H661. Their design is based on indanone (or tetralone) systems leading to trichostatin A (TSA) analogs with limited conformational mobility. Molecular modelization at the AM1 level...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier C,Bertrand P,Gesson JP,Roche J

更新日期：2006-10-15 00:00:00

abstract：:Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gwaltney SL 2nd,Imade HM,Barr KJ,Li Q,Gehrke L,Credo RB,Warner RB,Lee JY,Kovar P,Wang J,Nukkala MA,Zielinski NA,Frost D,Ng SC,Sham HL

更新日期：2001-04-09 00:00:00

abstract：:A new class of kappa-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a (K(...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tuthill PA,Seida PR,Barker W,Cassel JA,Belanger S,DeHaven RN,Koblish M,Gottshall SL,Little PJ,DeHaven-Hudkins DL,Dolle RE

更新日期：2004-11-15 00:00:00

abstract：:New Lp-PLA(2) inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole. Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib. But interestingly, a series of quaternary ammonium salts that were isolated as by...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang K,Xu W,Liu Y,Zhang W,Wang W,Shen J,Wang Y

更新日期：2013-03-01 00:00:00

abstract：:(Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC₅₀ value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[(11)C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao M,Wang M,Miller KD,Zheng QH

更新日期：2013-08-01 00:00:00

abstract：:Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

更新日期：2020-04-15 00:00:00

abstract：:Triple-negative breast cancer (TNBC) has been reported to be correlated with high expression of proliferation markers as well as constitutive activation of metastasis-relevant signaling pathways. For many years, breast cancer researchers have been investigating specific and effective methods to treat or to control the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen L,Long C,Nguyen J,Kumar D,Lee J

更新日期：2018-02-01 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：:A new family of photonuclease, thiadiazole-naphthalimide were synthesized and evaluated. Thiadiazole group was incorporated for the first time. These compounds intercalated into DNA efficiently and damaged DNA as low as 10 microM photochemically. Mechanism experiment showed that electron transfer and radicals were inv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Y,Xu Y,Qian X,Qu B

更新日期：2003-10-20 00:00:00

abstract：:The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeut...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiang J,Ipek M,Suri V,Massefski W,Pan N,Ge Y,Tam M,Xing Y,Tobin JF,Xu X,Tam S

更新日期：2005-06-02 00:00:00

abstract：:The peptide ligase subtiligase, derived from subtilisin, has been employed in the identification of protein N-termini in complex mixtures. Here, the peptide ester substrates for the ligation reaction were optimized with respect to solubility, resulting in greater incorporation of the N-terminal tags. Additionally, the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshihara HA,Mahrus S,Wells JA

更新日期：2008-11-15 00:00:00

abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang ZQ,Liao J,Diwu Z

更新日期：2005-05-02 00:00:00

abstract：:Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiomi S,Wada K,Umeda Y,Kato H,Tsukamoto S,Ishikawa H

更新日期：2018-09-01 00:00:00

abstract：:Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller LM,Mayer SC,Berger DM,Boschelli DH,Boschelli F,Di L,Du X,Dutia M,Floyd MB,Johnson M,Kenny CH,Krishnamurthy G,Moy F,Petusky S,Tkach D,Torres N,Wu B,Xu W

更新日期：2009-01-01 00:00:00

abstract：:The Hotoda's sequence substituted with TBDPS via 5'-end nucleobase existed as parallel quadruplex structure and exhibited inhibitory activities in an HIV-1 envelop proteins mediated cell-cell fusion assay. This result demonstrated that the 5'-aromatic groups of the Hotoda's sequence are allowed to have a large spatial...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen W,Xu L,Cai L,Zheng B,Wang K,He J,Liu K

更新日期：2011-10-01 00:00:00

abstract：:Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50=8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor eff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoki T,Hyohdoh I,Furuichi N,Ozawa S,Watanabe F,Matsushita M,Sakaitani M,Ori K,Takanashi K,Harada N,Tomii Y,Tabo M,Yoshinari K,Aoki Y,Shimma N,Iikura H

更新日期：2013-12-01 00:00:00

abstract：:An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mihalic JT,Fan P,Chen X,Chen X,Fu Y,Motani A,Liang L,Lindstrom M,Tang L,Chen JL,Jaen J,Dai K,Li L

更新日期：2012-06-01 00:00:00

abstract：:Seventy-two novel 1,3,4-oxadiazole thioether derivatives containing different flexible-chain moieties were designed and synthesized. The nematicidal activities of all the title compounds were evaluated, and some compounds showed excellent nematicidal activities against citrus nematodes. The compounds 15, 16, 18, 27, 4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Wei C,Wu S,Luo Y,Wu R,Hu D,Song B

更新日期：2020-04-15 00:00:00