Exogenous fluorescent tracer agents based on pegylated pyrazine dyes for real-time point-of-care measurement of glomerular filtration rate.


:Novel pyrazine carboxamides bearing hydrophilic poly(ethylene glycol) (PEG) moieties were designed, synthesized, and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, compounds 4d and 5c that contain about 48 ethylene oxide units in the PEG chain exhibited the most favorable physicochemical and renal clearance properties. In vitro studies show that these two compounds have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that 4d and 5c have a higher urine recovery of the injected dose than iothalamate (a commonly considered gold standard GFR agent). Pharmacokinetic studies show that these two compounds exhibit a plasma clearance equivalent to iothalamate, but with a faster (i.e. lower) terminal half-life than iothalamate (possibly from restricted distribution into the extracellular space due to large molecular size and hydrodynamic volume). Furthermore, the plasma clearance of 4d and 5c remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration exclusively. Finally, noninvasive real-time monitoring of this class of compounds was demonstrated by pharmacokinetic clearance of 5c by optical measurements in rat model, which correlates strongly with plasma concentration of the tracer. Hence, 4d and 5c are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.


Bioorg Med Chem


Poreddy AR,Neumann WL,Freskos JN,Rajagopalan R,Asmelash B,Gaston KR,Fitch RM,Galen KP,Shieh JJ,Dorshow RB




Has Abstract


2012-04-15 00:00:00














  • Medicinal attributes of pyrazolo[3,4-d]pyrimidines: a review.

    abstract::Pyrazolopyrimidines are the fused heterocyclic ring systems which structurally resemble purines which prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The advent of their first bioactivity as adenosine antagonis...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Chauhan M,Kumar R

    更新日期:2013-09-15 00:00:00

  • Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents.

    abstract::Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amid...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ling Y,Wang Z,Zhu H,Wang X,Zhang W,Wang X,Chen L,Huang Z,Zhang Y

    更新日期:2014-01-01 00:00:00

  • Synthesis and in vitro evaluation of aspartate transcarbamoylase inhibitors.

    abstract::The design, synthesis, and evaluation of a series of novel inhibitors of aspartate transcarbamoylase (ATCase) are reported. Several submicromolar phosphorus-containing inhibitors are described, but all-carboxylate compounds are inactive. Compounds were synthesized to probe the postulated cyclic transition-state of the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Coudray L,Pennebaker AF,Montchamp JL

    更新日期:2009-11-15 00:00:00

  • Synthesis of substituted diphenyl sulfones and their structure-activity relationship with the antagonism of 5-НТ6 receptors.

    abstract::Substituted diphenyl sulfones (10a-n) were synthesised, and the structures were confirmed by NMR, LC-MS and X-ray crystallography. Their antagonistic activities towards 5-HT₆ receptor were assessed in a cell-based functional assay. Diphenyl sulfone 10a, in spite of being the smallest and simplest known sulfonyl-contai...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ivachtchenko A,Golovina E,Kadieva M,Mitkin O,Tkachenko S,Okun I

    更新日期:2013-08-01 00:00:00

  • Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain.

    abstract::Two new alpha-pyridone metabolites, iromycins E and F, were isolated from cultures of strain Streptomyces sp. Dra 17, thus expanding the recently discovered iromycin family. The inhibitory potential on the mitochondrial respiratory chain was examined and revealed that iromycin metabolites block NADH oxidation in beef ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Surup F,Shojaei H,von Zezschwitz P,Kunze B,Grond S

    更新日期:2008-02-15 00:00:00

  • Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1).

    abstract::A series of quinolinequinones bearing various substituents has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (hNQO1) was studied. A range of quinolinequinones were selected for study, and were specifically designed to probe the e...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fryatt T,Pettersson HI,Gardipee WT,Bray KC,Green SJ,Slawin AM,Beall HD,Moody CJ

    更新日期:2004-04-01 00:00:00

  • Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

    abstract::We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinan...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ishida J,Yamamoto H,Kido Y,Kamijo K,Murano K,Miyake H,Ohkubo M,Kinoshita T,Warizaya M,Iwashita A,Mihara K,Matsuoka N,Hattori K

    更新日期:2006-03-01 00:00:00

  • Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy.

    abstract::Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an impo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: He J,Li D,Xiong K,Ge Y,Jin H,Zhang G,Hong M,Tian Y,Yin J,Zeng H

    更新日期:2012-06-15 00:00:00

  • Melanogenesis inhibitors from the rhizomes of Alpinia officinarum in B16 melanoma cells.

    abstract::The 80% aqueous acetone extract from the rhizomes of Alpinia officinarum, a Chinese medicinal herb, were found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, four diarylheptanoids [5-hydroxy-1,7-diphenyl-3-heptanone, 7-(4('')-hydroxy-3('')-methoxyphe...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Matsuda H,Nakashima S,Oda Y,Nakamura S,Yoshikawa M

    更新日期:2009-08-15 00:00:00

  • Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C.

    abstract::Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoshimitsu Y,Oishi S,Miyagaki J,Inuki S,Ohno H,Fujii N

    更新日期:2011-09-15 00:00:00

  • Actin-binding doliculide causes premature senescence in p53 wild type cells.

    abstract::Addressing the actin cytoskeleton as future anticancer target can be an innovative chemotherapeutic approach to combat malignancies. Doliculide is a potent stabilizer of actin filaments and can be used as tool and therapeutic lead in cancer research. Though a variety of molecules are known to bind to actin and lead to...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Foerster F,Chen T,Altmann KH,Vollmar AM

    更新日期:2016-01-15 00:00:00

  • Synthesis, anticancer activity, and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system.

    abstract::Described herein are our limited structure-activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focus...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Xie M,Lapidus RG,Sadowska M,Edelman MJ,Hosmane RS

    更新日期:2016-06-15 00:00:00

  • Synthesis of chlorogenic acid derivatives with promising antifungal activity.

    abstract::Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma CM,Kully M,Khan JK,Hattori M,Daneshtalab M

    更新日期:2007-11-01 00:00:00

  • Synthesis and receptor binding affinity of new selective GluR5 ligands.

    abstract::Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid recept...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bunch L,Johansen TH,Bräuner-Osborne H,Stensbøl TB,Johansen TN,Krogsgaard-Larsen P,Madsen U

    更新日期:2001-04-01 00:00:00

  • Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.

    abstract::A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brullo C,Massa M,Villa C,Ricciarelli R,Rivera D,Pronzato MA,Fedele E,Barocelli E,Bertoni S,Flammini L,Bruno O

    更新日期:2015-07-01 00:00:00

  • Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones.

    abstract::Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. Pseudohypericin turned out to be a quite strong inhibitor of TrxR1 (IC(50)=4.40μM) being far more effective...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sorrentino F,Karioti A,Gratteri P,Rigobello MP,Scutari G,Messori L,Bindoli A,Chioccioli M,Gabbiani C,Bergonzi MC,Bilia AR

    更新日期:2011-01-01 00:00:00

  • Synthesis and biochemical activity of novel amidine derivatives as m1 muscarinic receptor agonists.

    abstract::As part of a continuing effort aimed at the development of selective, efficacious, and centrally active m1 muscarinic agonists for the treatment of Alzheimer's disease, a series of amide and hydrazide amidine derivatives (2a-e and 3b-d) was synthesized and examined for muscarinic agonist activity. Preliminary biochemi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ojo B,Dunbar PG,Durant GJ,Nagy PI,Huzl JJ 3rd,Periyasamy S,Ngur DO,el-Assadi AA,Hoss WP,Messer WS Jr

    更新日期:1996-10-01 00:00:00

  • A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies.

    abstract::A series of new Luotonin A derivatives with substituents at rings A and E was synthesized, together with some E-ring-unsubstituted derivatives. Subsequently, the compound library was examined in silico for their binding into a previously proposed site in the DNA/topoisomerase I binary complex. Whereas no convincing co...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ibric A,Battisti V,Deckardt S,Haller AV,Lee C,Prötsch C,Langer T,Heffeter P,Schueffl HH,Marian B,Haider N

    更新日期:2020-05-01 00:00:00

  • Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives.

    abstract::A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wolin RL,Santillán A Jr,Tang L,Huang C,Jiang X,Lovenberg TW

    更新日期:2004-08-15 00:00:00

  • Covalent inhibition of SUMO and ubiquitin-specific cysteine proteases by an in situ thiol-alkyne addition.

    abstract::Posttranslational modification of proteins with ubiquitin and ubiquitin-like modifiers such as SUMO can be reverted by specific proteases, also referred to as deubiquitinases and isopeptidases, most of which are cysteine-dependent. We have found that the replacement of the conserved C-terminal glycine with propargylam...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sommer S,Weikart ND,Linne U,Mootz HD

    更新日期:2013-05-01 00:00:00

  • Synthesis of 1-D- and 1-L-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside establishes substrate specificity of the Mycobacterium tuberculosis enzyme AcGI deacetylase.

    abstract::Mycothiol (MSH, 1-D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside) is the principal low molecular weight thiol in actinomycetes. The enzyme 1-D-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (AcGI deacetylase) is involved in the biosynthesis of MSH and forms the fre...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Nicholas GM,Eckman LL,Kovác P,Otero-Quintero S,Bewley CA

    更新日期:2003-06-12 00:00:00

  • 2,3-Disubstituted quinuclidines as a novel class of dopamine transporter inhibitors.

    abstract::There is considerable interest in developing dopamine transporter (DAT) inhibitors as potential therapies for the treatment of cocaine abuse. We report herein our pharmacophore-based discovery and molecular modeling-assisted rational design of 2,3-disubstituted quinuclidines as potent DAT inhibitors with a novel chemi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sakamuri S,Enyedy IJ,Zaman WA,Tella SR,Kozikowski AP,Flippen-Anderson JL,Farkas T,Johnson KM,Wang S

    更新日期:2003-03-20 00:00:00

  • N-Aroyl-3,5-bis(benzylidene)-4-piperidones: a novel class of antimycobacterial agents.

    abstract::A number of 3,5-bis(benzylidene)-4-piperidones 1 and some N-4-(2-aminoethoxy)phenylcarbonyl analogs 3-6 display excellent in vitro antimycobacterial properties. In particular, 1c and 6d are potent antimycobacterials which are well tolerated in mice and are identified as important lead molecules. The nature of both the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Das U,Das S,Bandy B,Stables JP,Dimmock JR

    更新日期:2008-04-01 00:00:00

  • Karavilagenin C derivatives as antimalarials.

    abstract::Karavilagenin C (1), a cucurbitane-type triterpenoid, previously isolated from the aerial parts of Momordica balsamina, was acylated with different alkanoyl, aroyl and cinnamoyl chlorides/anydrides, yielding ten new mono or diesters, karavoates F (7) and H-P (8-16). Furthermore, the new compound cucurbalsaminol C (17)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ramalhete C,Lopes D,Molnár J,Mulhovo S,Rosário VE,Ferreira MJ

    更新日期:2011-01-01 00:00:00

  • Discovery of pyridine-based agrochemicals by using Intermediate Derivatization Methods.

    abstract::Pyridine-based compounds have been playing a crucial role as agrochemicals or pesticides including fungicides, insecticides/acaricides and herbicides, etc. Since most of the agrochemicals listed in the Pesticide Manual were discovered through screening programs that relied on trial-and-error testing and new agrochemic...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Guan AY,Liu CL,Sun XF,Xie Y,Wang MA

    更新日期:2016-02-01 00:00:00

  • Functionalized 6-(piperidin-1-yl)-8,9-diphenyl purines as inverse agonists of the CB1 receptor - SAR efforts towards selectivity and peripheralization.

    abstract::Antagonists of type 1 cannabinoid receptors (CB1) may be useful in treating diabetes, hepatic disorders, and fibrosis. Otenabant (1) is a potent and selective CB1 inverse agonist that was under investigation as an anti-obesity agent, but its development was halted once adverse effects associated with another marketed ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Amato G,Wiethe R,Manke A,Vasukuttan V,Snyder R,Runyon S,Maitra R

    更新日期:2019-08-15 00:00:00

  • Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors.

    abstract::Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a l...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ross-Macdonald P,de Silva H,Patel V,Truong A,He A,Neuhaus I,Tilford C,Ji R,Siemers N,Greer A,Carboni J,Gottardis M,Menard K,Lee F,Dodier M,Frennesson D,Sampognaro A,Saulnier M,Trainor G,Vyas D,Zimmermann K,Wittm

    更新日期:2012-03-15 00:00:00

  • Selective binding and controlled release of anticancer drugs by polyanionic cyclodextrins.

    abstract::The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cheng JG,Yu HJ,Chen Y,Liu Y

    更新日期:2018-05-15 00:00:00

  • Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens.

    abstract::Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E(2)) was explored extensively using a number of diff...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kim HY,Sohn J,Wijewickrama GT,Edirisinghe P,Gherezghiher T,Hemachandra M,Lu PY,Chandrasena RE,Molloy ME,Tonetti DA,Thatcher GR

    更新日期:2010-01-15 00:00:00

  • Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold.

    abstract::A series of 3-amino-benzo[d]isoxazole-/3-aminoindazole-based compounds were designed, synthesized and pharmacologically evaluated as tyrosine kinase c-Met inhibitors. The SAR study was conducted leading to identification of nine compounds (8d, 8e, 12, 28a-d, 28h and 28i) with IC50s less than 10nM against c-Met. Compou...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jiang X,Liu H,Song Z,Peng X,Ji Y,Yao Q,Geng M,Ai J,Zhang A

    更新日期:2015-02-01 00:00:00