Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists.

abstract：:The bacterial repair enzyme MutT hydrolyzes the damaged nucleotide OdGTP (the 5'-triphosphate derivative of 8-oxo-2'-deoxyguanosine; OdG), which is a known mutagen and has been linked to antibacterial action. Previous work has indicated important roles for the C8-oxygen, N7-hydrogen, and C2-exocyclic amine during OdGT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hamm ML,McFadden EJ,Ghio M,Lindell MA,Gerien KS,O'Handley SF

更新日期：2016-04-15 00:00:00

abstract：:Structure-activity studies on the oxytocin antagonist 1 (L-371,257) have identified a new series of high affinity, receptor-selective OT antagonists in which the N-acetyl-4-piperidinyl ether terminus in 1 has been replaced with a 1-(aryl)ethoxy group. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuo MS,Bock MG,Freidinger RM,Guidotti MT,Lis EV,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Williams PD,Woyden CJ

更新日期：1998-11-03 00:00:00

abstract：:We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes SJ,Millan DS,Kilty IC,Lewthwaite RA,Mathias JP,O'Reilly MA,Pannifer A,Phelan A,Stühmeier F,Baldock DA,Brown DG

更新日期：2011-11-01 00:00:00

abstract：:Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity agains...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee AC,Ramanujulu PM,Poulsen A,Williams M,Blanchard S,Ma DM,Bonday Z,Goh KL,Goh KC,Goh MK,Wood J,Dymock BW

更新日期：2012-06-15 00:00:00

abstract：:Group A streptococcus is a Gram-positive bacteria that causes a range of infectious diseases. Targeting the bacteria, a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, was synthesised utilising carbohydrate chemistry and solid-phase peptide synthesis proce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Simerska P,Lu H,Toth I

更新日期：2009-02-01 00:00:00

abstract：:A phytochemical study on the roots of Pongamia pinnata afforded five new isoflavone and isoflavanone derivatives (1-5), including two previously undescribed phenylisoflavones possessing an 1,2-oxetane ring, along with 21 known compounds (6-26) among which compound 18 is the first time to be isolated from nature. The s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wen R,Lv H,Jiang Y,Tu P

更新日期：2018-04-01 00:00:00

abstract：:Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen P,Horton LB,Mikulski RL,Deng L,Sundriyal S,Palzkill T,Song Y

更新日期：2012-10-01 00:00:00

abstract：:A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over bindi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Kato T,Yamamoto I,Shimizu A,Mizutani S,Asai M,Kawamoto H,Ito S,Yoshizumi T,Hirayama M,Ozaki S,Ohta H,Okamoto O

更新日期：2009-06-01 00:00:00

abstract：:A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antoszczak M,Maj E,Stefańska J,Wietrzyk J,Janczak J,Brzezinski B,Huczyński A

更新日期：2014-04-01 00:00:00

abstract：:Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide ...

journal_title：Bioorganic & medicinal chemistry letters

authors： El-Ayache NC,Li SH,Warnock M,Lawrence DA,Emal CD

更新日期：2010-02-01 00:00:00

abstract：:A methyl group at the 2-position of methyl mesopyropheophorbide-a was transformed to the 2-formyl group to give methyl mesopyropheophorbide-f, one of the chlorophyll-f analogs. The 2-formylation moved the redmost electronic absorption band in a solution to a longer wavelength and the bathochromic shift was comparable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu M,Kinoshita Y,Tamiaki H

更新日期：2014-08-15 00:00:00

abstract：:The design and syntheses of new fluoroquinolone antibacterial agents having pyrrolidine ring at C-7 position are described. The pyrrolidine ring is optically active and possesses methyloxime functional group. Two of them have excellent in vitro antibacterial activities and pharmacokinetic profiles. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi DR,Shin JH,Yang J,Yoon SH,Jung YH

更新日期：2004-03-08 00:00:00

abstract：:A series of glutathione derivatives 1-4, modified at the N,S and/or COOH sites, with in vitro antitrypanosomal activity were tested against bloodstream form Trypanosoma brucei 247 wild type and a T. b. brucei 247 strain over-expressing the multiple drug resistance protein (MRPA) by 50-100x to assess the susceptibility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alibu VP,Daunes S,D'Silva C

更新日期：2013-08-01 00:00:00

abstract：:8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a potential D(4)-receptor ligand was synthesized using oxidative iodo-destannylation reaction. The preliminary biodistribution studies of radioiodinated iozapine have shown that the compound is taken up in the brains of mice and rabbits. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joshua AV,Sharma SK,Strelkov A,Scott JR,Martin-Iverson MT,Abrams DN,Silverstone PH,McEwan AJ

更新日期：2007-07-15 00:00:00

abstract：:The multiple-step, one-pot procedure for a series of 2-substituted-3-phosphono-1-thia-4-aza-2-cyclohexene-5-carboxylates, analogues of the natural, sulfur amino acid metabolite lanthionine ketimine (LK), its 5-ethyl ester (LKE) and 2-substituted LKEs is described. Initiating the synthesis with the Michaelis-Arbuzov pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen D,Hensley K,Denton TT

更新日期：2018-02-15 00:00:00

abstract：:IRAK4 plays a critical role in the IL-1R and TLR signalling, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of permeable N-(1H-pyrazol-4-yl)carboxamides was developed by introducing lipophilic bicyclic cores in place o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim J,Altman MD,Baker J,Brubaker JD,Chen H,Chen Y,Kleinschek MA,Li C,Liu D,Maclean JK,Mulrooney EF,Presland J,Rakhilina L,Smith GF,Yang R

更新日期：2015-11-15 00:00:00

abstract：:The catalytic subunit of the Ser/Thr protein phosphatase 1 (PP1cat) hydrolyses N-acetyl Arg-Arg-Ala-phosphoThr-Val-Ala (K(M) = 3.7 mM) in a reaction that is inhibited competitively by inorganic phosphate (Pi, Ki = 1.6 mM) but unaffected by the product peptide alcohol at concentrations up to 3 mM. The enzyme does not c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanvoisin J,Gani D

更新日期：2001-02-26 00:00:00

abstract：:3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng H,Dirlam JP,Ziegler CB,Lundy KM,Hayashi SF,Kamicker BJ,Dutra JK,Daniel KL,Santoro SL,George DM,Bertsche CD,Sakya SM,Suarez-Contreras M

更新日期：2002-09-02 00:00:00

abstract：:Caffeoylglucosides, which have a glucose ring as a central linker, were synthesized from methyl D-glucosides, and their anti-HIV-1 activities were tested. Among them, four dicaffeoylglucosides (IC50 = 29.1+/-35.1 microM), 6a, 6b, 9b and 10b, showed HIV-1 integrase inhibitory activity as potent as L-chicoric acid. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim SN,Lee JY,Kim HJ,Shin CG,Park H,Lee YS

更新日期：2000-08-21 00:00:00

abstract：:To discover new natural-product-based insecticidal agents, a series of novel oxime derivatives of podophyllotoxin-based phenazines modified in the C, D and E rings of podophyllotoxin were prepared and tested as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhi X,Yang C,Yu X,Xu H

更新日期：2014-12-15 00:00:00

abstract：:A series of alpha(v)beta(3) antagonists based on a thiophene scaffold were synthesized via two routes and evaluated for in vitro biological activity. We have identified several structurally similar antagonists with different selectivities towards alpha(IIb)beta(3), alpha(v)beta(5) and alpha(5)beta(1) at the cellular l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bubenik M,Meerovitch K,Bergeron F,Attardo G,Chan L

更新日期：2003-02-10 00:00:00

abstract：:Beta-hemoglobinopathies such as sickle cell disease represent a major global unmet medical need. De-repression of fetal hemoglobin in erythrocytes is a clinically validated approach for the management of sickle cell disease, but the only FDA-approved medicine for this purpose has limitations to its use. We conducted a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Benowitz AB,Eberl HC,Erickson-Miller CL,Gilmartin AG,Gore ER,Montoute MN,Wu Z

更新日期：2018-12-15 00:00:00

abstract：:Coxsackievirus and related enteroviruses are important human pathogens that cause various diseases with clinical manifestations ranging from trivial flu-like syndromes to dangerous or even fatal diseases such as myocarditis, meningitis and encephalitis. Here, we report on our continuous SAR study focused on 9-(bicyclo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sála M,De Palma AM,Hřebabecký H,Dejmek M,Dračínský M,Leyssen P,Neyts J,Mertlíková-Kaiserová H,Nencka R

更新日期：2011-07-15 00:00:00

abstract：:A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using iso...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewawasam P,Erway M,Thalody G,Weiner H,Boissard CG,Gribkoff VK,Meanwell NA,Lodge N,Starrett JE Jr

更新日期：2002-04-08 00:00:00

abstract：:A convenient solid phase peptide synthetic (SPPS) route is reported for the preparation of antimycobacterial wollamides. The method is based on on-resin head-to-tail cyclization and is fast, efficient and amenable to automation. The in vitro antimycobacterial activities of the newly synthesized wollamides were evaluat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asfaw H,Wetzlar T,Martinez-Martinez MS,Imming P

更新日期：2018-09-15 00:00:00

abstract：:In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1,ω-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roman BI,De Ryck T,Verhasselt S,Bracke ME,Stevens CV

更新日期：2015-03-01 00:00:00

abstract：:A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Khadikar PV,Singh S,Jaiswal M,Mandloi D

更新日期：2004-09-20 00:00:00

abstract：:Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique str...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hirai G,Oguri H,Hayashi M,Koyama K,Koizumi Y,Moharram SM,Hirama M

更新日期：2004-05-17 00:00:00

abstract：:Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamazaki H,Nakayama W,Takahashi O,Kirikoshi R,Izumikawa Y,Iwasaki K,Toraiwa K,Ukai K,Rotinsulu H,Wewengkang DS,Sumilat DA,Mangindaan RE,Namikoshi M

更新日期：2015-08-15 00:00:00

abstract：:Novel phenol bis-Mannich adducts were identified as IL-2 expression inhibitors in a T cell proliferation screening assay. Analogues of the lead compound were prepared through parallel synthesis and a highly selective IL-2 inhibitor was discovered that provided a suitable compound for further optimization. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Geng B,Fleming PR,Umlauf S,Lin A,Pallai PV

更新日期：2002-03-11 00:00:00