New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors.

abstract：:The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Monte FL,Kramer T,Boländer A,Plotkin B,Eldar-Finkelman H,Fuertes A,Dominguez J,Schmidt B

更新日期：2011-09-15 00:00:00

abstract：:A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC(50)=2microM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC(50)<20nM). Additionally, physicochemical and pharmacokinetic properties ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Steinhagen H,Gerisch M,Mittendorf J,Schlemmer KH,Albrecht B

更新日期：2002-11-04 00:00:00

abstract：:Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of them, a coumarin derivative, ranks amongst the most active compounds in the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wrodnigg TM,Withers SG,Stütz AE

更新日期：2001-04-23 00:00:00

abstract：:A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P(1) hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P(1) moiety. Replacement of the benzothiophene with different heterocyclic sy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Nemoto PA,Kim JM,Hao MH,Qian KC,Farrow NA,Albaugh DR,Fowler DM,Schneiderman RD,Michael August E,Martin L,Hill-Drzewi M,Pullen SS,Takahashi H,De Lombaert S

更新日期：2011-08-01 00:00:00

abstract：:The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitr...

journal_title：Bioorganic & medicinal chemistry letters

authors： McAtee JJ,Castle SL,Jin Q,Boger DL

更新日期：2002-05-06 00:00:00

abstract：:The transcription factor nuclear factor-κB (NF-κB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu DC,Gong GH,Wei CX,Jin XJ,Quan ZS

更新日期：2016-03-15 00:00:00

abstract：:The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nes WD,He L,Mangla AT

更新日期：1998-12-15 00:00:00

abstract：:We report examples of a series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogues 12-15 prepared from a common functionalized building block 11 that can be conveniently synthesized on a large scale and in optically pure form. Isoindoline analogue 15 is the most cytotoxic agent in this series, has the highest D...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masterson LA,Croker SJ,Jenkins TC,Howard PW,Thurston DE

更新日期：2004-02-23 00:00:00

abstract：:A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruel R,L'Heureux A,Thibeault C,Lapointe P,Martel A,Qiao JX,Hua J,Price LA,Wu Q,Chang M,Zheng J,Huang CS,Wexler RR,Rehfuss R,Lam PY

更新日期：2013-12-15 00:00:00

abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

更新日期：2004-08-02 00:00:00

abstract：:In an effort to discover potent antitumor agents, a series of novel C-7-heteroaryl-substituted camptothecin derivatives were designed and synthesized via microwave-promoted Suzuki coupling reaction. These analogs were then assessed for cytotoxicity against three human tumor cell lines, A549, HCT116, HT-29, and inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang L,Huang Y,Zhang J,Tong L,Chen Y,Lu W,Huang Q

更新日期：2014-03-15 00:00:00

abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

更新日期：2020-11-01 00:00:00

abstract：:3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hale JJ,Doherty G,Toth L,Li Z,Mills SG,Hajdu R,Ann Keohane C,Rosenbach M,Milligan J,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala S

更新日期：2004-07-05 00:00:00

abstract：:We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang S,Jia XD,Liu ML,Lu Y,Guo HY

更新日期：2012-09-15 00:00:00

abstract：:Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaiya T,Aoyama S,Kohda K

更新日期：1999-04-05 00:00:00

abstract：:A graftable LDV (Leu-Asp-Val) peptidomimetic molecule (B-c) has been prepared from 3-(5-amino-2-hydroxy)phenyl-propionic acid, as alpha(4)beta(1) (VLA-4) integrin ligand. For that purpose, the mechanism of 3-(4-azidophenyl)propionic acid rearrangement has been revisited. Activation of Durapore DVPP-hydrophilic membran...

journal_title：Bioorganic & medicinal chemistry letters

authors： Momtaz M,Rerat V,Gharbi S,Gérard E,Pourcelle V,Marchand-Brynaert J

更新日期：2008-02-01 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li T,Bunnelle WH,Ryther KB,Anderson DJ,Malysz J,Helfrich R,Grønlien JH,Håkerud M,Peters D,Schrimpf MR,Gopalakrishnan M,Ji J

更新日期：2010-06-15 00:00:00

abstract：:Modification of the major insecticide fipronil (1) by replacing three pyrazole substituents (hydrogen for both cyano and amino and trifluoromethyldiazirinyl for trifluoromethylsulfinyl) gives a candidate photoaffinity probe (3) of high potency (IC(50) 2-28 nM) in blocking the chloride channel of Drosophila and human b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sirisoma NS,Ratra GS,Tomizawa M,Casida JE

更新日期：2001-11-19 00:00:00

abstract：:We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matsumoto K,Choshi T,Hourai M,Zamami Y,Sasaki K,Abe T,Ishikura M,Hatae N,Iwamura T,Tohyama S,Nobuhiro J,Hibino S

更新日期：2012-07-15 00:00:00

abstract：:A focused set of heterocyclic quinones based on the benzothiazole, benzoxazole, benzimidazole, indazole and isoindole was prepared and screened with respect to the inhibition of the phosphatase activity of CDC25C. Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lavergne O,Fernandes AC,Bréhu L,Sidhu A,Brézak MC,Prévost G,Ducommun B,Contour-Galcera MO

更新日期：2006-01-01 00:00:00

abstract：:Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2 antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2 receptors, with high-affinity (K(i)=0.12 and 0.62nM, respectively). In functi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bernstein PR,Aharony D,Albert JS,Andisik D,Barthlow HG,Bialecki R,Davenport T,Dedinas RF,Dembofsky BT,Koether G,Kosmider BJ,Kirkland K,Ohnmacht CJ,Potts W,Rumsey WL,Shen L,Shenvi A,Sherwood S,Stollman D,Russell K

更新日期：2001-10-22 00:00:00

abstract：:A cyclic imine conjugated to a fluorescent dansyl group was synthesized and used for covalent labeling of proteins. The covalent attachment to proteins was confirmed by gel electrophoresis and mass analysis. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo HM,Minakawa M,Ueno L,Tanaka F

更新日期：2009-02-15 00:00:00

abstract：:A series of gibberellin based molecules were designed and synthesized. Gibberellin derivatives bearing two alpha,beta-unsaturated ketone units showed strong anticancer activities in MTT assay towards a number of human cancer cell lines including HT29, A549, HepG2 and MKN28. The most potent gibberellin derivative (comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Sun Z,Zhang Y,Zeng X,Qing C,Liu J,Li L,Zhang H

更新日期：2009-09-15 00:00:00

abstract：:Quantitative fluorescence-based methods have been developed to determine the nuclear concentration of polyamide-fluorescein conjugates in cell culture. Confocal laser scanning microscopy and flow cytometry techniques are utilized to plot calibration curves, from which the nuclear concentration can be interpolated. Upo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsu CF,Dervan PB

更新日期：2008-11-15 00:00:00

abstract：:1-((Substituted)methyl)quinoxaline-2,3(1H,4H)-dione (2a-e) and 1-((substituted)acryloyl)quinoxaline-2,3(1H,4H)-dione (4a-c) were synthesized from quinoxaline-2,3(1H,4H)-dione 1 and evaluated for their antimicrobial activities. Results of the antitubercular screening against Mycobacterium tuberculosis H(37)Rv showed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramalingam P,Ganapaty S,Rao ChB

更新日期：2010-01-01 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cook BN,Bentzien J,White A,Nemoto PA,Wang J,Man CC,Soleymanzadeh F,Khine HH,Kashem MA,Kugler SZ Jr,Wolak JP,Roth GP,De Lombaert S,Pullen SS,Takahashi H

更新日期：2009-02-01 00:00:00

abstract：:Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Tsujita T,Ito H,Ozaki S,Tani T,Ishii Y,Okuda S,Tadano K,Fukuroda T,Ohta H,Okamoto O

更新日期：2009-08-15 00:00:00

abstract：:A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Acker BA,Jacobsen EJ,Rogers BN,Wishka DG,Reitz SC,Piotrowski DW,Myers JK,Wolfe ML,Groppi VE,Thornburgh BA,Tinholt PM,Walters RR,Olson BA,Fitzgerald L,Staton BA,Raub TJ,Krause M,Li KS,Hoffmann WE,Hajos M,Hurst RS,

更新日期：2008-06-15 00:00:00

abstract：:To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison R,Zheng Z,Jennings IG,Thompson PE,Al-Rawi JMA

更新日期：2016-11-15 00:00:00