Syntheses and antifungal activity of pseudomycin side-chain analogues. Part 1.

abstract：:2-aminoethylbenzofurans constitute a new class of H(3) antagonists that are more rotationally constrained than most previously reported H(3) antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cowart M,Pratt JK,Stewart AO,Bennani YL,Esbenshade TA,Hancock AA

更新日期：2004-02-09 00:00:00

abstract：:The selectivity and the binding affinity of previously reported carborane-containing ligands 2 and 3 toward ERβ remains to be optimized. To improve their biological profiles, a series of iodinated carboranyl phenol derivatives (4-6) were designed and synthesized as prospective ERβ-selective ligands with high affinity....

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2017-09-01 00:00:00

abstract：:The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cowart M,Lee CH,Gfesser GA,Bayburt EK,Bhagwat SS,Stewart AO,Yu H,Kohlhaas KL,McGaraughty S,Wismer CT,Mikusa J,Zhu C,Alexander KM,Jarvis MF,Kowaluk EA

更新日期：2001-01-08 00:00:00

abstract：:We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Haffner CD,McDougald DL,Reister SM,Thompson BD,Conlee C,Fang J,Bass J,Lenhard JM,Croom D,Secosky-Chang MB,Tomaszek T,McConn D,Wells-Knecht K,Johnson PR

更新日期：2005-12-01 00:00:00

abstract：:A series of glycosyl-thioureido sulfonamides incorporating glucosamine, galactosamine, and mannosamine tails, and sulfanilamide, halogenosulfanilamide, and metanilamide heads was synthesized. Many of the new compounds showed micromolar-submicromolar affinity for the inhibition of the cytosolic isoforms I and II of the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smaine FZ,Winum JY,Montero JL,Regainia Z,Vullo D,Scozzafava A,Supuran CT

更新日期：2007-09-15 00:00:00

abstract：:A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mareddy J,Nallapati SB,Anireddy J,Devi YP,Mangamoori LN,Kapavarapu R,Pal S

更新日期：2013-12-15 00:00:00

abstract：:A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Z,Pan Y,Huang W,Yang Y,Wang Z,Li Q,Zhao Y,Zhang X,Shen Z

更新日期：2014-01-01 00:00:00

abstract：:Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu C,Yin Y,Meng F,Dun Y,Pei K,Wang C,Xu X,Wu F

更新日期：2018-06-15 00:00:00

abstract：:Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perkins JJ,Duong LT,Fernandez-Metzler C,Hartman GD,Kimmel DB,Leu CT,Lynch JJ,Prueksaritanont T,Rodan GA,Rodan SB,Duggan ME,Meissner RS

更新日期：2003-12-15 00:00:00

abstract：:Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA.2polydT and duplex polydA.polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T.A.T triplets and triple/duplex selectivity were de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Strekowski L,Hojjat M,Wolinska E,Parker AN,Paliakov E,Gorecki T,Tanious FA,Wilson WD

更新日期：2005-02-15 00:00:00

abstract：:A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase is described. This report discusses the SAR of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R potency. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wittman MD,Balasubramanian B,Stoffan K,Velaparthi U,Liu P,Krishnanathan S,Carboni J,Li A,Greer A,Attar R,Gottardis M,Chang C,Jacobson B,Sun Y,Hansel S,Zoeckler M,Vyas DM

更新日期：2007-02-15 00:00:00

abstract：:Through synthesis and assays of peptidyl substrates, we could select substrates having peptidyl complementary against lipases. The best substrate showed 20-fold improved K(m) relative to non-peptidyl substrate. Using this information, we generated selective inhibitors. Lipase activities with peptidyl substrates were r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park S,Yu J

更新日期：2012-05-01 00:00:00

abstract：:Novel derivatives of the highly potent and selective histamine H3-receptor antagonist ciproxifan (3) with different chain lengths as well as with structural variants of the cyclopropyl ketone moiety have been prepared and screened for their antagonist H3-receptor potencies in vitro and in vivo. Some derivatives (2, 6-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stark H,Ligneau X,Sadek B,Ganellin CR,Arrang JM,Schwartz JC,Schunack W

更新日期：2000-10-16 00:00:00

abstract：:Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patouret R,Doebelin C,Garcia-Ordonez RD,Chang MR,Ruiz C,Cameron MD,Griffin PR,Kamenecka TM

更新日期：2018-04-15 00:00:00

abstract：:We previously showed that fluorination of the carborane-containing selective estrogen receptor modulator (SERM) BE360 altered the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity. Here, we designed and synthesized a series of fluorinated carboranyl phenols as candidate ERβ-sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Kaise A,Endo Y

更新日期：2013-12-15 00:00:00

abstract：:Over the past 15years there have been extensive efforts to understand and reduce the high attrition rates of drug candidates with an increased focus on physicochemical properties. The fruits of this labor have been the generation of numerous efficiency indices, metric-based rules and visualization tools to help guide ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shultz MD

更新日期：2013-11-01 00:00:00

abstract：:We report a dimerization strategy to enhance the antibacterial potency of an otherwise weak cationic amphiphilic polyproline helical (CAPH) peptide. Overall, the dimeric CAPHs were more active against Escherichia coli and Staphylococcus aureus than the monomeric counterpart, reaching up to a 60-fold increase in potenc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hernandez-Gordillo V,Geisler I,Chmielewski J

更新日期：2014-01-15 00:00:00

abstract：:A series of new 9-O-substituted berberine derivatives (4a-j) as telomeric quadruplex ligands was synthesized and evaluated. The results from biophysical and biochemical assay indicated that introducing of positive charged aza-aromatic terminal group into the side chain of 9-position of berberine significantly improved...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Y,Ou TM,Tan JH,Hou JQ,Huang SL,Gu LQ,Huang ZS

更新日期：2009-07-01 00:00:00

abstract：:Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Finn J,Mattia K,Morytko M,Ram S,Yang Y,Wu X,Mak E,Gallant P,Keith D

更新日期：2003-07-07 00:00:00

abstract：:The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tandon VK,Kumar M,Awasthi AK,Saxena HO,Goswamy GK

更新日期：2004-06-21 00:00:00

abstract：:In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato F,Inoue Y,Omodani T,Imano K,Okazaki H,Takemura T,Komiya M

更新日期：2002-02-25 00:00:00

abstract：:Thirteen new 2-pyrazoline derivatives bearing benzenesulfonamide moiety (2a-m) were synthesized by condensing appropriate chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anticancer and anti-inflammatory actions. According to the protocol of the National Cancer Institute (NCI) in vitro diseas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bashir R,Ovais S,Yaseen S,Hamid H,Alam MS,Samim M,Singh S,Javed K

更新日期：2011-07-15 00:00:00

abstract：:A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Londregan AT,Aspnes G,Limberakis C,Loria PM,McClure KF,Petersen DN,Raymer B,Ruggeri RB,Wei L,Xiao J,Piotrowski DW

更新日期：2018-12-15 00:00:00

abstract：:Two (99m)Tc/Re complexes based on flavone and aurone were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography. Both (99m)Tc-labeled derivatives showed higher affinity for Aβ(1-42) aggregates than did (99m)Tc-BAT. In sections of brain tissue from an animal model of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ono M,Ikeoka R,Watanabe H,Kimura H,Fuchigami T,Haratake M,Saji H,Nakayama M

更新日期：2010-10-01 00:00:00

abstract：:Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar level...

journal_title：Bioorganic & medicinal chemistry letters

authors： Idippily ND,Gan C,Orefice P,Peterson J,Su B

更新日期：2017-02-15 00:00:00

abstract：:The stereoselective synthesis and biological activity of NPS 1407 (4a), (S)-(-)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate (4) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moe ST,Smith DL,DelMar EG,Shimizu SM,Van Wagenen BC,Balandrin MF,Chien YE,Raszkiewicz JL,Artman LD,White HS,Mueller AL

更新日期：2000-11-06 00:00:00

abstract：:Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assaye...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewellyn K,Bialonska D,Chaurasiya ND,Tekwani BL,Zjawiony JK

更新日期：2012-08-01 00:00:00

abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, has been investigated in the past decade for its promising anticancer activity due to its ability to selectively induce apoptosis in tumoral cells by binding to TRAIL receptors (TRAIL-R). Macromolecules such as agonistic monoclonal a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ion GND,Nitulescu GM,Popescu CI

更新日期：2019-09-15 00:00:00

abstract：:In order to improve the analgesic activity of lead compound 7a, two series of dispirocyclopiperazinium (DSPZ) salts 9a-h, 10a-e and compounds 14, 15 were synthesized and evaluated for their in vivo analgesic activity both by acetic acid induced writhing test and hot plate test. Compounds 9h, 14, and 15 exhibited bette...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li A,Wang X,Yue CQ,Ye J,Li CL,Li RT

更新日期：2007-09-15 00:00:00

abstract：:The discovery of the CNS-penetrant and selective alpha(2C) adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure-activity studies demonstrate the structural requirements for binding affinity, functional activity, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel SD,Habeski WM,Min H,Zhang J,Roof R,Snyder B,Bora G,Campbell B,Li C,Hidayetoglu D,Johnson DS,Chaudhry A,Charlton ME,Kablaoui NM

更新日期：2008-10-15 00:00:00