Himbacine derived thrombin receptor (PAR-1) antagonists: SAR of the pyridine ring.

abstract：:The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacok...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lynch CL,Willoughby CA,Hale JJ,Holson EJ,Budhu RJ,Gentry AL,Rosauer KG,Caldwell CG,Chen P,Mills SG,MacCoss M,Berk S,Chen L,Chapman KT,Malkowitz L,Springer MS,Gould SL,DeMartino JA,Siciliano SJ,Cascieri MA,Carella

更新日期：2003-01-06 00:00:00

abstract：:In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0μM and no sign...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu HW,Zhao LJ,Liu HF,Zhao D,Luo J,Xie XP,Liu WS,Zheng JX,Dai GF,Liu HM,Liu LH,Liang YB

更新日期：2014-05-15 00:00:00

abstract：:Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

更新日期：2013-05-01 00:00:00

abstract：:A convenient and efficient palladium-catalysed retro-ene-assisted method has been developed to prepare a series of 5-substituted-6-phenyl-3(2H)-pyridazinones as potential antiplatelet drugs. The most active compounds were those that contain a 3-phenyl-3-oxo-propenyl fragment or a phenylthio group at position 5 of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Coelho A,Sotelo E,Fraiz N,Yáñez M,Laguna R,Cano E,Raviña E

更新日期：2004-01-19 00:00:00

abstract：:Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The cu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ellsworth BA,Meng W,Patel M,Girotra RN,Wu G,Sher PM,Hagan DL,Obermeier MT,Humphreys WG,Robertson JG,Wang A,Han S,Waldron TL,Morgan NN,Whaley JM,Washburn WN

更新日期：2008-09-01 00:00:00

abstract：:We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldarelli SA,Boisbrun M,Alarcon K,Hamzé A,Ouattara M,Salom-Roig X,Maynadier M,Wein S,Peyrottes S,Pellet A,Calas M,Vial H

更新日期：2010-07-01 00:00:00

abstract：:In our search for potent inhibitors of the enzyme estrone sulfatase (ES), we have undertaken the synthesis and biochemical evaluation of a range of straight chain alkyl esters of 4-[(aminosulfonyl)oxy] benzoic acid. The results of the study show that the synthesised compounds possess greater inhibitory activity when c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahmed S,James K,Owen CP

更新日期：2002-09-02 00:00:00

abstract：:Cell penetrating peptide TAT was introduced into doxorubicin structure. Synthesized doxorubicin-TAT conjugate showed different intracellular distribution pattern and cell killing activity from those of free doxorubicin. Unlike free doxorubicin, doxorubicin-TAT conjugate was highly permeable to drug-resistant cells and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang JF,Yang VC

更新日期：2005-11-15 00:00:00

abstract：:Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obsc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mittal M,Kumar RB,Balagunaseelan N,Hamberg M,Jegerschöld C,Rådmark O,Haeggström JZ,Rinaldo-Matthis A

更新日期：2016-08-01 00:00:00

abstract：:Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mata-Santos T,D'Oca CDRM,Mata-Santos HA,Fenalti J,Pinto N,Coelho T,Berne ME,da Silva PEA,D'Oca MGM,Scaini CJ

更新日期：2016-02-01 00:00:00

abstract：:AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rouse MB,Seefeld MA,Leber JD,McNulty KC,Sun L,Miller WH,Zhang S,Minthorn EA,Concha NO,Choudhry AE,Schaber MD,Heerding DA

更新日期：2009-03-01 00:00:00

abstract：:A new 'naked-eye' quinoline-based 'reactive' ratiometric fluorescent probe was prepared. The reactive stoichiometry of the probe with Hg²⁺ ion was 2:1. The probe exhibited high selectivity towards Hg²⁺ ion to other metal ions with a 410-fold increase in absorbance intensity ratio (A₄₀₂/A₃₄₀) in aqueous solution over a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Yan Y,Chen S,Gao Z,Xu H

更新日期：2014-12-01 00:00:00

abstract：:We report here the development of a novel fluorescein-based probe which shows selective fluorescence enhancement on binding to a hexahistidine-tagged protein. No fluorescence change was observed with untagged protein. This probe is excitable with visible light and is considered to be suitable for use in biological app...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamoto M,Umezawa N,Kato N,Higuchi T

更新日期：2009-04-15 00:00:00

abstract：:Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conj...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Y,Zhu L,Ma Y,Niu G,Chen X

更新日期：2011-02-15 00:00:00

abstract：:Substituted dihydroquinozalin-2-ones (1-16) have been synthesized easily by the use of copper-catalyzed coupling method. The reactions of 2-haloanilines with a variety of alpha-amino acids in the presence of copper (I) iodide gave corresponding 3-substituted dihydroquinozalin-2-ones in up to 86% yield. Some new quinox...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tanimori S,Nishimura T,Kirihata M

更新日期：2009-08-01 00:00:00

abstract：:A novel series of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists are described. The series was designed to address the suboptimal PK (pharmacokinetic) and off-target profile of a class of N-aryl-benzo-[1,4]-oxazepine-4-carboxamides, represented by 1, that were identified from a high-throughput screen of the Me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilson JE,Kurukulasuriya R,Sinz C,Lombardo M,Bender K,Parker D,Sherer EC,Costa M,Dingley K,Li X,Mitelman S,Tong S,Bugianesi R,Ehrhardt A,Priest B,Ratliff K,Ujjainwalla F,Nargund R,Hagmann WK,Edmondson S

更新日期：2016-06-15 00:00:00

abstract：:We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zou Y,Albohy A,Sandbhor M,Cairo CW

更新日期：2010-12-15 00:00:00

abstract：:In this work, we have designed cyclic peptides (cIBL, cIBR, cIBC, CH4 and CH7) derived from the parent IB peptide (ICAM-1(1-21)) that are inhibitors of ICAM-1/LFA-1-mediated T-cell adhesion to Caco-2 cell monolayers. Cyclic peptide cIBR has the best activity of any of the peptides evaluated. The active ICAM-1 peptides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anderson ME,Yakovleva T,Hu Y,Siahaan TJ

更新日期：2004-03-22 00:00:00

abstract：:A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma VM,Adi Seshu KV,Vamsee Krishna C,Prasanna P,Chandra Sekhar V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Deevi DS,Rao Mamidi NV,Rajagopalan R

更新日期：2003-05-19 00:00:00

abstract：:Ceramides are the major lipid components of the stratum corneum, the major permeability barrier of the skin. Here we report a chemical synthesis of ceramide analogs covalently bonded on the silica particles, that can be used to predict the skin permeability of chemicals via HPLC methods. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yin J,Liu H,Pidgeon C

更新日期：1998-01-20 00:00:00

abstract：:Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage dis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu Y,Marshall J,Li Q,Edwards N,Chen G

更新日期：2013-04-15 00:00:00

abstract：:A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sutton JC,Bolton SA,Hartl KS,Huang MH,Jacobs G,Meng W,Ogletree ML,Pi Z,Schumacher WA,Seiler SM,Slusarchyk WA,Treuner U,Zahler R,Zhao G,Bisacchi GS

更新日期：2002-11-04 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：:Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofil...

journal_title：Bioorganic & medicinal chemistry letters

authors： Melander RJ,Liu HB,Stephens MD,Bewley CA,Melander C

更新日期：2016-12-15 00:00:00

abstract：:The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotria...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weinberg LR,Albom MS,Angeles TS,Breslin HJ,Gingrich DE,Huang Z,Lisko JG,Mason JL,Milkiewicz KL,Thieu TV,Underiner TL,Wells GJ,Wells-Knecht KJ,Dorsey BD

更新日期：2011-12-15 00:00:00

abstract：:A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a CO (14a-b) or CH(2) (19a-b) linker to the indole N(1)-position. In this regard, replacement of the 4-chlorobenzoyl group present in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chowdhury MA,Huang Z,Abdellatif KR,Dong Y,Yu G,Velázquez CA,Knaus EE

更新日期：2010-10-01 00:00:00

abstract：:A series of cis-2,6-dialkyl-4-chloro-tetrahydropyrans were prepared by means of an iron(III)-catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, SW1573, and WiDr. The results show that the presence of bulky substituents favors the Prins cyclization lead...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miranda PO,León LG,Martín VS,Padrón JI,Padrón JM

更新日期：2006-06-15 00:00:00

abstract：:Poor prognosis coupled with significant economic burden makes heart failure (HF) one of the largest issues currently facing the world population. Although a significant number of new therapies have emerged over the past 20 years to treat the underlying physiological risk factors, only two new medications specifically ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Malinowski JT,St Jean DJ Jr

更新日期：2018-05-15 00:00:00

abstract：:RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good pharmacokinetic properties in rodents. In a mouse corneal neovascularization assay, this compound inhibited VEGF-induced angiogenesis. Tested in a H460a xenograft tumor model this agent effected significant tumor growth inhibition at doses as low a...

journal_title：Bioorganic & medicinal chemistry letters

authors： McDermott LA,Higgins B,Simcox M,Luk KC,Nevins T,Kolinsky K,Smith M,Yang H,Li JK,Chen Y,Ke J,Mallalieu N,Egan T,Kolis S,Railkar A,Gerber L,Liu JJ,Konzelmann F,Zhang Z,Flynn T,Morales O,Chen Y

更新日期：2006-04-01 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