Heterocyclic thrombin inhibitors. Part 1: design and synthesis of amidino-phenoxy quinoline derivatives.

abstract：:Silybin is the major flavonolignan of silymarin and it displays a plethora of biological effects, generally ascribed to its antioxidant properties. Herein we shall describe an efficient synthetic strategy to obtain a variety of new and more water-soluble silybin and 2,3-dehydrosilybin (DHS) derivatives in which the 23...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zarrelli A,Sgambato A,Petito V,De Napoli L,Previtera L,Di Fabio G

更新日期：2011-08-01 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：:A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewawasam P,Fan W,Knipe J,Moon SL,Boissard CG,Gribkoff VK,Starrett JE

更新日期：2002-07-08 00:00:00

abstract：:The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dou D,He G,Alliston KR,Groutas WC

更新日期：2011-05-15 00:00:00

abstract：:Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both ra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zartman CB,Bell IM,Gallicchio SN,Graham SL,Kane SA,Mallee JJ,Rutledge RZ,Salvatore CA,Vacca JP,Williams TM

更新日期：2011-11-15 00:00:00

abstract：:Thermal transformation of the (+)-catechin (1) with heating processing afforded a new oxidation product, gambiriin D (2), along with catechin [6'-8]-catechin (3), and (+)-epicatechin (4). The structure of a new catechin dimer with C-C linkage was determined on the basis of spectroscopic data interpretation. The catech...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim T,Choi HJ,Eom SH,Lee J,Kim TH

更新日期：2014-03-15 00:00:00

abstract：:Thirty-five novel chromone derivatives containing dithioacetal moiety were designed, synthesized, and their anti-TMV activities were evaluated through half-leaf method. The results showed compound c23 illustrates highly curative, protective and inactivating activities against TMV at 500 mg/L, with the values of 68.8%,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li M,Zan N,Huang M,Jiang D,Hu D,Song B

更新日期：2020-03-01 00:00:00

abstract：:In the present study, an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl)carbonyl]-2,4-dihydro-3H-pyrazol-3-one (4a-j) have been described by using conventional and non-conventional (microwave) techniques. Microwave assisted reactions showed that require shorter reaction time and good yi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sivakumar KK,Rajasekaran A,Senthilkumar P,Wattamwar PP

更新日期：2014-07-01 00:00:00

abstract：:Inositols play an important role in membrane lipid metabolism and mitogenic signaling of most cancer cells. There is paucity of data on the distribution of radiolabelled inositols. Based on work previously carried out on 1-deoxy-1-[(18)F]fluoro-scyllo-inositol ([(18)F]2), we began a program of work to label myo-inosit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carroll L,Perumal M,Vasdev N,Robins E,Aboagye EO

更新日期：2012-10-01 00:00:00

abstract：:Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two i...

journal_title：Bioorganic & medicinal chemistry letters

authors： An XD,Liu H,Xu ZL,Jin Y,Peng X,Yao YM,Geng M,Long YQ

更新日期：2015-02-01 00:00:00

abstract：:Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synt...

journal_title：Bioorganic & medicinal chemistry letters

authors： Addla D,Jallapally A,Gurram D,Yogeeswari P,Sriram D,Kantevari S

更新日期：2014-01-01 00:00:00

abstract：:Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-6...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiina I,Sano Y,Nakata K,Kikuchi T,Sasaki A,Ikekita M,Hasome Y

更新日期：2007-05-01 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：:Starting from a weak omeprazole screening hit, replacement of the pyridine with a 1,3-benzodioxole moiety, modification of the thioether linkage, and substitution of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3 agonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carlton DL,Collin-Smith LJ,Daniels AJ,Deaton DN,Goetz AS,Laudeman CP,Littleton TR,Musso DL,Morgan RJ,Szewczyk JR,Zhang C

更新日期：2008-10-15 00:00:00

abstract：:Benzofuran-5-ol derivatives were synthesized and tested for in vitro antifungal activity against Candida, Aspergillus species, and Cryptococcus neoformans. Among them tested, many benzofuran-5-ols showed good antifungal activity. The results suggest that benzofuran-5-ols would be promising antifungal agents. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ryu CK,Song AL,Lee JY,Hong JA,Yoon JH,Kim A

更新日期：2010-11-15 00:00:00

abstract：:A series of 2-phenylbenzofuran derivatives with a diphenylmethylcarbamoyl group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. They had inhibitory activities against both enzymes and the 6-carbamoyl derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishibashi K,Nakajima K,Sugioka Y,Sugiyama M,Hamada T,Horikoshi H,Nishi T

更新日期：1998-03-17 00:00:00

abstract：:An asymmetric synthesis of alpha-amino acids with novel beta-branched side chains has been implemented. The syntheses feature a p-toluenesulfinylimine induced chiral Strecker approach and were found to be applicable to the introduction of both aliphatic and aromatic beta-branched sidechains for preparation of previous...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang M,Porte A,Diamantidis G,Sogi K,Kubrak D,Resnick L,Mayer SC,Wang Z,Kreft AF,Harrison BL

更新日期：2007-05-01 00:00:00

abstract：:The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar ren...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lacombe P,Aspiotis R,Bayly C,Chen A,Dubé D,Fortin R,Gallant M,Juteau H,Liu S,McKay D,Roy P,Wu T

更新日期：2010-10-01 00:00:00

abstract：:p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mavunkel BJ,Chakravarty S,Perumattam JJ,Luedtke GR,Liang X,Lim D,Xu YJ,Laney M,Liu DY,Schreiner GF,Lewicki JA,Dugar S

更新日期：2003-09-15 00:00:00

abstract：:A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)-antagonists. The most potent compounds were found in the class of (piperazine-1-yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau JF,Jeppesen CB,Rimvall K,Hohlweg R

更新日期：2006-10-15 00:00:00

abstract：:Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han X,Civiello RL,Conway CM,Cook DA,Davis CD,Degnan AP,Jiang XJ,Macci R,Mathias NR,Moench P,Pin SS,Schartman R,Signor LJ,Thalody G,Tora G,Whiterock V,Xu C,Macor JE,Dubowchik GM

更新日期：2013-03-15 00:00:00

abstract：:A series of substituted 2-(aminoheteroaryl)-thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen P,Norris D,Das J,Spergel SH,Wityak J,Leith L,Zhao R,Chen BC,Pitt S,Pang S,Shen DR,Zhang R,De Fex HF,Doweyko AM,McIntyre KW,Shuster DJ,Behnia K,Schieven GL,Barrish JC

更新日期：2004-12-20 00:00:00

abstract：:Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thompson SK,Washburn DG,Frazee JS,Madauss KP,Hoang TH,Lapinski L,Grygielko ET,Glace LE,Trizna W,Williams SP,Duraiswami C,Bray JD,Laping NJ

更新日期：2009-08-15 00:00:00

abstract：:A water-soluble derivative of N-fused porphyrin (NFP) possessing a nona-arginine (R9) peptide tail was synthesized for the first time by a Cu(I)-catalyzed azide-alkyne 'click' reaction. In aqueous solution, at pH 8, the conjugated molecule (NFP-R9) exists as free base and protonated below pH<6.5 to form monoprotonated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ikawa Y,Harada H,Toganoh M,Furuta H

更新日期：2009-05-01 00:00:00

abstract：:The selective inhibition of coagulation factor Xa has emerged as an attractive strategy for the discovery of novel antithrombotic agents. Here we describe highly potent benzamidine factor Xa inhibitors based on a vicinally-substituted heterocyclic core. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fevig JM,Pinto DJ,Han Q,Quan ML,Pruitt JR,Jacobson IC,Galemmo RA Jr,Wang S,Orwat MJ,Bostrom LL,Knabb RM,Wong PC,Lam PYS,Wexler RR

更新日期：2001-03-12 00:00:00

abstract：:Novel 6,8-difluoro-1-alkyl-5-amino-1,4-dihydro-4-oxo-7-{4-substituted piperazin-1-yl}-quinoline-3-carboxylic acids, with the substituents at 4th position of piperazine being -[2(pyridine-4-carbonyl) hydrazono]propyl and -2 [(pyrazine-2-carbonyl) amino] ethyl, were synthesized and evaluated in vivo against Mycobacteriu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shindikar AV,Viswanathan CL

更新日期：2005-04-01 00:00:00

abstract：:The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Linder MR,Heckeroth AR,Najdrowski M,Daugschies A,Schollmeyer D,Miculka C

更新日期：2007-08-01 00:00:00

abstract：:3-Hydroxyethyl- and 3-hydroxypropyl-7-substituted-tetrahydroisoquinolines (9, 10, 16, and 17) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although alpha(2)-adrenoceptor affinity decreased for these compounds, sele...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grunewald GL,Romero FA,Seim MR,Criscione KR,Deupree JD,Spackman CC,Bylund DB

更新日期：2005-02-15 00:00:00

abstract：:[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglut...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kato H,Yashiro A,Mizuno A,Nishida Y,Kobayashi K,Shinohara H

更新日期：2001-11-19 00:00:00

abstract：:The synthesis and receptor binding of novel adenosine receptor antagonists is described. We found that non-xanthine 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives may have high affinity and substantial selectivity for the adenosine A(1) receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： van Tilburg EW,van der Klein PA,de Groote M,Beukers MW,IJzerman AP

更新日期：2001-08-06 00:00:00