Dual function inhibitors of relevance to chronic obstructive pulmonary disease.

abstract：:Glutathione reductase (GR), is responsible for the existence of GSH molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme glutathione reductase, and inhibitors are therefore expected to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sentürk M,Talaz O,Ekinci D,Cavdar H,Küfrevioğlu OI

更新日期：2009-07-01 00:00:00

abstract：:QSAR models represent the relationship of biological activity with either physicochemical parameters or structural indices. QSAR study was performed on some arylpiperazines as 5-HT(1A)/alpha(1)-adrenergic receptor antagonists using E-state indices to identify the pharmacophoric requirements. It was found that some of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Debnath B,Samanta S,Naskar SK,Roy K,Jha T

更新日期：2003-09-01 00:00:00

abstract：:The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and evaluated in vitro. In general, the compounds were much less potent in inducing platelet aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： McComsey DF,Hecker LR,Andrade-Gordon P,Addo MF,Maryanoff BE

更新日期：1999-01-18 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：:A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, repres...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Z,Zheng G,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

更新日期：2011-01-01 00:00:00

abstract：:The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (+/-)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the impor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Legendre O,Pecic S,Chaudhary S,Zimmerman SM,Fantegrossi WE,Harding WW

更新日期：2010-01-15 00:00:00

abstract：:A series of pyrrolo[2,3-d]pyrimidines was synthesized and evaluated as inhibitors of Lck. Lck accommodates a diverse set of substituents at N-7. Altering the substituent at N-7 provided compound 13, an orally available lck inhibitor which inhibited TCR mediated IL-2 production after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Calderwood DJ,Johnston DN,Munschauer R,Rafferty P

更新日期：2002-06-17 00:00:00

abstract：:We have optimized 2-aminomethylphenylamine derivative as a factor Xa inhibitor. Several polar functional groups were introduced in the central phenyl ring, and we focused on zwitter ionic compound showing continuous inhibitory activity in oral administration test. In vitro and oral activities were improved by optimiza...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mochizuki A,Nagata T,Kanno H,Takano D,Kishida M,Suzuki M,Ohta T

更新日期：2011-12-15 00:00:00

abstract：:This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

更新日期：2007-03-01 00:00:00

abstract：:Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kashyap M,Das D,Preet R,Mohapatra P,Satapathy SR,Siddharth S,Kundu CN,Guchhait SK

更新日期：2012-04-01 00:00:00

abstract：:The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the mos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choe H,Kim J,Hong S

更新日期：2013-08-01 00:00:00

abstract：:In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan YM,Dai HQ,Du Y,Schneider B,Guo H,Li DP,Zhang LX,Fu H,Dong XP,Cheng YX

更新日期：2012-06-15 00:00:00

abstract：:A series of quinazolinone derived Schiff base derivatives 7-28 were synthesized and characterized as novel antioxidants and anti-inflammatory agents. The in vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid (AA), gallic acid (GA), butylatedhydroxytol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rakesh KP,Manukumar HM,Gowda DC

更新日期：2015-03-01 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：:The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guerrini R,Rizzi D,Zucchini M,Tomatis R,Regoli D,Calo' G,Salvadori S

更新日期：2003-02-10 00:00:00

abstract：:The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Siu M,Pastor R,Liu W,Barrett K,Berry M,Blair WS,Chang C,Chen JZ,Eigenbrot C,Ghilardi N,Gibbons P,He H,Hurley CA,Kenny JR,Cyrus Khojasteh S,Le H,Lee L,Lyssikatos JP,Magnuson S,Pulk R,Tsui V,Ultsch M,Xiao Y,Zh

更新日期：2013-09-01 00:00:00

abstract：:COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. The pharmacological and pharmacokinetic SAR of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mantell SJ,Stephenson PT,Monaghan SM,Maw GN,Trevethick MA,Yeadon M,Walker DK,Selby MD,Batchelor DV,Rozze S,Chavaroche H,Lemaitre A,Wright KN,Whitlock L,Stuart EF,Wright PA,Macintyre F

更新日期：2009-08-01 00:00:00

abstract：:The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Levin JI,Chen JM,Laakso LM,Du M,Du X,Venkatesan AM,Sandanayaka V,Zask A,Xu J,Xu W,Zhang Y,Skotnicki JS

更新日期：2005-10-01 00:00:00

abstract：:To elucidate the role of the hydrophobic alkyl tail of acetogenins in the inhibitory action, we synthesized an acetogenin derivative possessing the shortest tail (i.e., methyl group) and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicated that the alkyl tail, which is o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Motoyama T,Yabunaka H,Miyoshi H

更新日期：2002-08-19 00:00:00

abstract：:A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3-triazol-4-yl-/5-yl moieties were synthesized by employing click chemistry. The new sulfocoumarins incorporated cycloalkyl, tert-butyl and substituted aryl moieties at the triazole ring, and were investigated for the inhibition of four human (h) c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grandane A,Tanc M,Zalubovskis R,Supuran CT

更新日期：2014-03-01 00:00:00

abstract：:An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mecha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng CB,Gao WC,Pang PP,Ma X,Peng LC,Yang L,Li X

更新日期：2021-01-11 00:00:00

abstract：:A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verma S,Nagarathnam D,Shao J,Zhang L,Zhao J,Wang Y,Li T,Mull E,Enyedy I,Wang C,Zhu Q,Altieri M,Jordan J,Dang TT,Reddy S

更新日期：2005-04-15 00:00:00

abstract：:Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jian XE,Yang F,Jiang CS,You WW,Zhao PL

更新日期：2020-04-15 00:00:00

abstract：:Isodesmosine and desmosine are crosslinking amino acids that are present only in elastin. They are useful biomarkers for the degradation of elastin, which occurs during the progression of chronic obstructive pulmonary disease (COPD) and related diseases. This Letter describes the synthesis of [(13)C3,(15)N1]-labeled i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tanigawa T,Komatsu A,Usuki T

更新日期：2015-01-01 00:00:00

abstract：:The peptide ligase subtiligase, derived from subtilisin, has been employed in the identification of protein N-termini in complex mixtures. Here, the peptide ester substrates for the ligation reaction were optimized with respect to solubility, resulting in greater incorporation of the N-terminal tags. Additionally, the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshihara HA,Mahrus S,Wells JA

更新日期：2008-11-15 00:00:00

abstract：:Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH(2) were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prokai-Tatrai K,Nguyen V,Zharikova AD,Braddy AC,Stevens SM,Prokai L

更新日期：2003-03-24 00:00:00

abstract：:A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, mu opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective mu opioid receptor antagonist, which interacts selectively with mu peripheral recept...

journal_title：Bioorganic & medicinal chemistry letters

authors： Le Bourdonnec B,Barker WM,Belanger S,Wiant DD,Conway-James NC,Cassel JA,O'Neill TJ,Little PJ,DeHaven RN,DeHaven-Hudkins DL,Dolle RE

更新日期：2008-03-15 00:00:00

abstract：:In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu P,Liu L,Chen XZ,Li Y,Liu J,Jin ZP,Wang GQ,Lei PS

更新日期：2009-08-01 00:00:00

abstract：:A few naturally occurring prenyl- and prenyloxycoumarins and several new related synthetic derivatives were evaluated as inhibitors of squalene-hopene cyclase (SHC), a useful model enzyme, to predict their interactions with oxidosqualene cyclase (OSC). Umbelliprenin-10',11'-monoepoxide (IC(50) 2.5 microM) and the corr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cravotto G,Balliano G,Robaldo B,Oliaro-Bosso S,Chimichi S,Boccalini M

更新日期：2004-04-19 00:00:00

abstract：:Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintilla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majumdar S,Burgman M,Haselton N,Grinnell S,Ocampo J,Pasternak AR,Pasternak GW

更新日期：2011-07-01 00:00:00