In vitro efficacy of 7-benzylamino-1-isoquinolinamines against Plasmodium falciparum related to the efficacy of chalcones.

abstract：:N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barberis C,Erdman P,Czekaj M,Fire L,Pribish J,Tserlin E,Maniar S,Batchelor JD,Liu J,Patel VF,Hebert A,Levit M,Wang A,Sun F,Huang SA

更新日期：2020-12-01 00:00:00

abstract：:We have previously reported the essential structure of the opioid κ receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the κ receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the κ receptor. The exchange of the 17-N su...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nemoto T,Yamamoto N,Wada N,Harada Y,Tomatsu M,Ishihara M,Hirayama S,Iwai T,Fujii H,Nagase H

更新日期：2013-01-01 00:00:00

abstract：:In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

更新日期：2015-05-01 00:00:00

abstract：:Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting ana...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park CH,Lee C,Yang JS,Joe BY,Chun K,Kim H,Kim HY,Kang JS,Lee JI,Kim MH,Han G

更新日期：2014-06-15 00:00:00

abstract：:Structures containing the (R)-3-amino-3-methyl piperidine unit as a new pharmacophore moiety have been shown to possess moderate inhibitory activity for DPP-4 with good pharmacokinetics profile. One of these compounds was found to have good oral bioavailability and PK/PD profile in ZF-rat. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishio Y,Kimura H,Tosaki S,Sugaru E,Sakai M,Horiguchi M,Masui Y,Ono M,Nakagawa T,Nakahira H

更新日期：2010-12-15 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：:Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edgington-Mitchell LE,Barlow N,Aurelio L,Samha A,Szabo M,Graham B,Bunnett N

更新日期：2017-01-15 00:00:00

abstract：:A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjuga...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang YQ,Yuan JD,Ding HF,Song YS,Qian G,Wang JL,Ji M,Zhang Y

更新日期：2020-01-15 00:00:00

abstract：:This report details a search for alternative strains that produce the diterpenoid sphaeropsidin A (SphA) among A. candidus strains from the USDA Northern Regional Research Laboratories Culture Collection. We identified two strains that produced SphA using a limited set of test media. An initial scaled-up fermentation ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Y,Scott R,Hooper AR,Bartholomeusz GA,Kornienko A,Bills GF

更新日期：2017-12-15 00:00:00

abstract：:A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jia ZJ,Wu Y,Huang W,Zhang P,Clizbe LA,Goldman EA,Sinha U,Arfsten AE,Edwards ST,Alphonso M,Hutchaleelaha A,Scarborough RM,Zhu BY

更新日期：2004-03-08 00:00:00

abstract：:Two new γ-lactones, aspergilactones A (1) and B (2), were discovered along with two known compounds, annularin A (3) and pericoterpenoid A (4), from a culture of the sponge-associated fungus Aspergillus sp. LS45. The planar structures of 1-4 were characterized using comprehensive spectroscopic methods and comparison w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang L,Ding L,Li X,Wang N,Yan Y,Yang M,Cui W,Benjamin Naman C,Cheng K,Zhang W,Zhang B,Jin H,He S

更新日期：2019-07-01 00:00:00

abstract：:The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang L,Zhang W,Zhang X,Yin L,Chen B,Song J

更新日期：2015-11-15 00:00:00

abstract：:P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

更新日期：2020-09-01 00:00:00

abstract：:The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ambrus JI,Kelso MJ,Bremner JB,Ball AR,Casadei G,Lewis K

更新日期：2008-08-01 00:00:00

abstract：:The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, 111In-SPECT, and 64Cu- and 68Ga-PET im...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walker D,Li Y,Roxin Á,Schaffer P,Adam MJ,Perrin DM

更新日期：2016-10-15 00:00:00

abstract：:Novel, metabolically stable and centrally acting TRH analogues with substituted pyridinium moieties replacing the [His(2)] residue of the endogenous peptide were prepared by solid-phase Zincke reaction. The 1,4-dihydropyridine prodrugs of these analogues obtained after reducing the pyridinium moiety were able to reach...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prokai-Tatrai K,Perjési P,Zharikova AD,Li X,Prokai L

更新日期：2002-08-19 00:00:00

abstract：:A series of 3-aryl-2-propenoates including cinnamates, (E)-methyl/ethyl 3-[2-(1,4-dimethoxy-5,8-dione)naphthalenyl]-2-propenoates (8ba, 8bb) and (E)-methyl/ethyl 3-[2-(1,4-dihydroxy-9,10-dione)anthracenyl]-2-propenoates (9aa,9ab) was synthesized and evaluated for antitumor cytotoxicity. It was found that the ortho- or...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nam NH,You YJ,Kim Y,Hong DH,Kim HM,Ahn BZ

更新日期：2001-05-07 00:00:00

abstract：:ExoU is a potent virulence factor of Pseudomonas aeruginosa and is considered a potential therapeutic target. In order to discover novel ExoU inhibitors, we screened an in-house chemical library utilizing a yeast-based screening system. Some sulfonamides displayed significant activity without nonspecific cytotoxicity....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim D,Baek J,Song J,Byeon H,Min H,Min KH

更新日期：2014-08-15 00:00:00

abstract：:The 5,5-bicycles cis-6-oxo-hexahydro-2-oxa-1,4-diazapentalene 3 and cis-6-oxo-hexahydropyrrolo[3,2-c]pyrazole 4 were designed as rotationally restricted templates towards the preparation of inhibitors of CAC1 cysteinyl proteinases. The design strategy was exemplified through the solution and solid phase preparation of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Benn A,Flinn N,Monk T,Ramjee M,Watts J,Quibell M

更新日期：2005-03-01 00:00:00

abstract：:Positioning of reactive functional groups within a DNA duplex can enable chemical reactions that otherwise would not occur to an appreciable extent. However, few studies have quantitatively defined the extent to which the enforced proximity of reaction partners in duplex DNA can favor chemical processes. Here, we meas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Catalano MJ,Price NE,Gates KS

更新日期：2016-06-01 00:00:00

abstract：:A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT1A receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective and high affinities at the 5-HT1A receptor and serotonin reuptake site in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takeuchi K,Kohn TJ,Honigschmidt NA,Rocco VP,Spinazze PG,Hemrick-Luecke SK,Thompson LK,Evans DC,Rasmussen K,Koger D,Lodge D,Martin LJ,Shaw J,Threlkeld PG,Wong DT

更新日期：2006-05-01 00:00:00

abstract：:Novel 5-HT(7) receptor antagonists containing the benzocycloheptanone core were identified from high throughput screening. Molecular modelling and SAR studies have converted these intractable hits into a more potent, selective and tractable series, exemplified by compound (25), SB-691673. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forbes IT,Cooper DG,Dodds EK,Douglas SE,Gribble AD,Ife RJ,Lightfoot AP,Meeson M,Campbell LP,Coleman T,Riley GJ,Thomas DR

更新日期：2003-03-24 00:00:00

abstract：:A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sekhar KV,Rao VS,Devambatla RKV,Kumar MM

更新日期：2008-12-01 00:00:00

abstract：:Nine new monoterpene glycosides (1-9), together with 18 known compounds were obtained from the n-butanol soluble fraction of ethanol extract from Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectroscopic data. The inhibitory effects of these compounds (except com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Zhao F,Chen L,Jiang Z,Liu Y,Li Z,Qiu F,Yao X

更新日期：2012-12-01 00:00:00

abstract：:Ring-C modified alkaloids were synthesized from colchicine using iminonitroso Diels-Alder reactions in a highly regio- and stereoselective fashion. Several analogs exhibited cytotoxic activity similar to that of colchicine itself against PC-3 and MCF-7 cancer cell lines, by serving as prodrugs of colchicine through re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang B,Zhu ZC,Goodson HV,Miller MJ

更新日期：2010-06-15 00:00:00

abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schmitt J,Bernd M,Kutscher B,Kessler H

更新日期：1998-02-17 00:00:00

abstract：:The protein-tyrosine phosphatase (PTP) 'YopH' is a virulence factor of Yersinia pestis, the causative agent of plague. Potential use of Yersinia as a bioterrorism agent renders YopH inhibitors of therapeutic importance. Previously, we had examined the inhibitory potencies of a variety of phosphotyrosyl (pTyr) mimetics...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee K,Gao Y,Yao ZJ,Phan J,Wu L,Liang J,Waugh DS,Zhang ZY,Burke TR Jr

更新日期：2003-08-04 00:00:00

abstract：:Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu CH,Wang TC,Qiao JX,Haque L,Chen AYA,Taylor DS,Ying X,Onorato JM,Galella M,Shen H,Huang CS,Toussaint N,Li YX,Abell L,Adam LP,Gordon D,Wexler RR,Finlay HJ

更新日期：2018-12-15 00:00:00

abstract：:Enhancer of zeste homolog 2 (EZH2) serves as the catalytic subunit of the polycomb repression complex 2 (PRC2), which is implicated in cancer progression metastasis and poor prognosis. Based on our EZH2 inhibitor SKLB1049 with low nanomolar activity, we extended the "tail" region to get a series of (E)-1,2-diphenyleth...

journal_title：Bioorganic & medicinal chemistry letters

authors： He H,Hu X,Teng F,Liu Z,Zhang Q,Feng Z,Feng Q,Yu L

更新日期：2020-03-01 00:00:00

abstract：:Exogenous short-chain nucleic acids undergo rapid import into the nucleus. Fluorescence-labeled dT1-13 DNA microinjected into the cytoplasm domain of a HeLa cell was rapidly imported into the nucleus domain within 1min. This is much more rapid than what has been observed for intracellular diffusion of small molecules....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kitagawa M,Okamoto A

更新日期：2016-10-01 00:00:00