Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors.


:A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).


Bioorg Med Chem Lett


Zhang P,Terefenko EA,McComas CC,Mahaney PE,Vu A,Trybulski E,Koury E,Johnston G,Bray J,Deecher D




Has Abstract


2008-12-01 00:00:00














  • Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors.

    abstract::Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crys...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Huang X,Cheng CC,Fischmann TO,Duca JS,Richards M,Tadikonda PK,Reddy PA,Zhao L,Siddiqui MA,Parry D,Davis N,Seghezzi W,Wiswell D,Shipps GW Jr

    更新日期:2013-05-01 00:00:00

  • Evaluation of steroidal amines as lipid raft modulators and potential anti-influenza agents.

    abstract::The influenza A virus (IFV) possesses a highly ordered cholesterol-rich lipid envelope. A specific composition and structure of this membrane raft envelope are essential for viral entry into cells and virus budding. Several steroidal amines were investigated for antiviral activity against IFV. Both, a positively charg...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Agarwal S,Schroeder C,Schlechtingen G,Braxmeier T,Jennings G,Knölker HJ

    更新日期:2013-09-15 00:00:00

  • A comparison of the alpha-helix forming propensities and hydrogen bonding properties of serine phosphate and alpha-amino-gamma-phosphonobutyric acid.

    abstract::The ability of serine phosphate (SerP) or alpha-amino-gamma-phosphonobutyric acid (AbuP) and arginine to form a salt bridge between their side chains appears to be much greater when they are spaced i/i+4 than when they are spaced i/i+3. The side chain-side chain interaction between SerP/Arg and AbuP/Arg, positioned i/...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liehr S,Chenault HK

    更新日期:1999-09-20 00:00:00

  • Discovery of anabaenopeptin 679 from freshwater algal bloom material: Insights into the structure-activity relationship of anabaenopeptin protease inhibitors.

    abstract::Cyanobacteria possess a unique capacity for the production of structurally novel secondary metabolites compared to the biosynthetic abilities of other environmental prokaryotes such as bacteria of the genus Streptomyces. Two different strategies to explore cyanobacteria-derived natural products have been explored prev...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Harms H,Kurita KL,Pan L,Wahome PG,He H,Kinghorn AD,Carter GT,Linington RG

    更新日期:2016-10-15 00:00:00

  • The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein-associated phospholipase A(2) for evaluation in man.

    abstract::The introduction of a functionalised amido substituent into a series of 1-(biphenylmethylacetamido)-pyrimidones has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency and very encouraging developability properties. Diethylaminoethyl derivative 32, SB-435495...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Blackie JA,Bloomer JC,Brown MJ,Cheng HY,Elliott RL,Hammond B,Hickey DM,Ife RJ,Leach CA,Lewis VA,Macphee CH,Milliner KJ,Moores KE,Pinto IL,Smith SA,Stansfield IG,Stanway SJ,Taylor MA,Theobald CJ,Whittaker CM

    更新日期:2002-09-16 00:00:00

  • Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors.

    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

    pub_type: 杂志文章


    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

  • Sugar Chips immobilized with synthetic sulfated disaccharides of heparin/heparan sulfate partial structure.

    abstract::Carbohydrate chip technology has a great potential for the high-throughput evaluation of carbohydrate-protein interactions. Herein, we report syntheses of novel sulfated oligosaccharides possessing heparin and heparan sulfate partial disaccharide structures, their immobilization on gold-coated chips to prepare array-t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wakao M,Saito A,Ohishi K,Kishimoto Y,Nishimura T,Sobel M,Suda Y

    更新日期:2008-04-01 00:00:00

  • Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD.

    abstract::A multivalent approach focused on amine-based secondary binding groups was applied to the discovery of long-acting inhaled β2-agonists. Addition of amine moieties to the neutral secondary binding group of an existing β2-agonist series was found to provide improved in vivo efficacy, but also led to the formation of bio...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: McKinnell RM,Klein U,Linsell MS,Moran EJ,Nodwell MB,Pfeiffer JW,Thomas GR,Yu C,Jacobsen JR

    更新日期:2014-07-01 00:00:00

  • Efficient one-pot cyclization/folding of Rhesus θ-defensin-1 (RTD-1).

    abstract::We report an efficient approach for the chemical synthesis of Rhesus θ-defensin-1 (RTD-1) using Fmoc-based solid-phase peptide synthesis in combination with an intramolecular version of native chemical ligation. The corresponding linear thioester precursor was cyclized and folded in a one-pot reaction using reduced gl...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Aboye TL,Li Y,Majumder S,Hao J,Shekhtman A,Camarero JA

    更新日期:2012-04-15 00:00:00

  • Natural cholinesterase inhibitors from Myristica cinnamomea King.

    abstract::A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Co...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Abdul Wahab SM,Sivasothy Y,Liew SY,Litaudon M,Mohamad J,Awang K

    更新日期:2016-08-01 00:00:00

  • Rhodanine-3-acetic acid derivatives as inhibitors of fungal protein mannosyl transferase 1 (PMT1).

    abstract::The first inhibitors of fungal protein: mannosyl transferase 1 (PMT1) are described. They are based upon rhodanine-3-acetic acid and several compounds have been identified, for example, 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid (5a), which inhibit Candida albic...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Orchard MG,Neuss JC,Galley CM,Carr A,Porter DW,Smith P,Scopes DI,Haydon D,Vousden K,Stubberfield CR,Young K,Page M

    更新日期:2004-08-02 00:00:00

  • Synthesis and evaluation of 3-¹²³I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent.

    abstract::Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, (123)I-5-IA-85380 is used in human studies and requires over 6h of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethox...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Pandey SK,Pan S,Kant R,Kuruvilla SA,Pan ML,Mukherjee J

    更新日期:2012-12-15 00:00:00

  • Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.

    abstract::The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Qiao JX,Cheng X,Smallheer JM,Galemmo RA,Drummond S,Pinto DJ,Cheney DL,He K,Wong PC,Luettgen JM,Knabb RM,Wexler RR,Lam PY

    更新日期:2007-03-01 00:00:00

  • Discovery of a potent and selective small molecule hGPR91 antagonist.

    abstract::GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput sc...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bhuniya D,Umrani D,Dave B,Salunke D,Kukreja G,Gundu J,Naykodi M,Shaikh NS,Shitole P,Kurhade S,De S,Majumdar S,Reddy SB,Tambe S,Shejul Y,Chugh A,Palle VP,Mookhtiar KA,Cully D,Vacca J,Chakravarty PK,Nargund RP,W

    更新日期:2011-06-15 00:00:00

  • Synthesis and characterisation of a new amphotericin B-methoxypoly(ethylene glycol) conjugate.

    abstract::The reaction of methoxypoly(ethylene glycol)-4-nitrophenyl carbonate with amphotericin B has been used to prepare a new conjugate of amphotericin B (mPEG-AmB). A preliminary screening of in vitro antifungal activity has suggested that mPEG-AmB possesses a similar effect and a similar spectrum of activity as the conven...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sedlák M,Buchta V,Kubicová L,Simůnek P,Holcapek M,Kasparová P

    更新日期:2001-11-05 00:00:00

  • New fused benzazepine as selective D3 receptor antagonists. Synthesis and biological evaluation. Part 2: [g]-fused and hetero-fused systems.

    abstract::The synthesis and the SAR of a new series of potent and selective dopamine D(3) receptor antagonists is reported. The new scaffolds of the [g]-fused and the hetero-fused tricyclic benzazepine are here reported together with their pharmacokinetic profile. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Micheli F,Bonanomi G,Braggio S,Capelli AM,Damiani F,Di Fabio R,Donati D,Gentile G,Hamprecht D,Perini O,Petrone M,Tedesco G,Terreni S,Worby A,Heidbreder C

    更新日期:2008-02-01 00:00:00

  • PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

    abstract::Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Marwaha A,Goel RK,Mahajan MP

    更新日期:2007-09-15 00:00:00

  • Azepinone as a conformational constraint in the design of kappa-opioid receptor agonists.

    abstract::A new class of kappa-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a (K(...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tuthill PA,Seida PR,Barker W,Cassel JA,Belanger S,DeHaven RN,Koblish M,Gottshall SL,Little PJ,DeHaven-Hudkins DL,Dolle RE

    更新日期:2004-11-15 00:00:00

  • Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure.

    abstract::New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

    更新日期:1998-05-05 00:00:00

  • Synthesis of the reported structure of homocereulide and its vacuolation assay.

    abstract::Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Naka T,Hattori Y,Takenaka H,Ohta Y,Kirihata M,Tanimori S

    更新日期:2019-03-01 00:00:00

  • Cytotoxicity and DNA binding property of the dimers of triphenylethylene-coumarin hybrid with one amino side chain.

    abstract::Novel dimers of triphenylethylene-coumarin hybrid containing one amino side chain were designed and synthesized by the condensation of four dicarboxylic acids with the amino monomeric hybrids catalyzed by HATU and DIPEA at room temperature. The adding order of the reactants had a significant effect on the condensation...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tan G,Yao Y,Gu Y,Li S,Lv M,Wang K,Chen H,Li X

    更新日期:2014-07-01 00:00:00

  • Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.

    abstract::The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly sel...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liddle J,Atkinson FL,Barker MD,Carter PS,Curtis NR,Davis RP,Douault C,Dickson MC,Elwes D,Garton NS,Gray M,Hayhow TG,Hobbs CI,Jones E,Leach S,Leavens K,Lewis HD,McCleary S,Neu M,Patel VK,Preston AG,Ramirez-Molina

    更新日期:2011-10-15 00:00:00

  • Development of methyl isoxazoleazepines as inhibitors of BET.

    abstract::In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

    更新日期:2015-05-01 00:00:00

  • Imidazopyridine CB2 agonists: optimization of CB2/CB1 selectivity and implications for in vivo analgesic efficacy.

    abstract::A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was inef...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Trotter BW,Nanda KK,Burgey CS,Potteiger CM,Deng JZ,Green AI,Hartnett JC,Kett NR,Wu Z,Henze DA,Della Penna K,Desai R,Leitl MD,Lemaire W,White RB,Yeh S,Urban MO,Kane SA,Hartman GD,Bilodeau MT

    更新日期:2011-04-15 00:00:00

  • Design and synthesis of dual inhibitors for matrix metalloproteinase and cathepsin.

    abstract::The first example of dual inhibitors for matrix metalloproteinase (MMP) and cathepsin is described. An appropriate alignment of peptide-parts and two different specific functional groups in one molecule led to the discovery of a potent dual inhibitor (3a). ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yamamoto M,Ikeda S,Kondo H,Inoue S

    更新日期:2002-02-11 00:00:00

  • Solid-phase synthesis of quinol fatty alcohols, design of N/O-substituted quinol fatty alcohols and comparative activities on axonal growth.

    abstract::Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hanbali M,Bagnard D,Luu B

    更新日期:2006-08-01 00:00:00

  • The development of benzo- and naphtho-fused quinoline-2,4-dicarboxylic acids as vesicular glutamate transporter (VGLUT) inhibitors reveals a possible role for neuroactive steroids.

    abstract::Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic aci...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Carrigan CN,Patel SA,Cox HD,Bolstad ES,Gerdes JM,Smith WE,Bridges RJ,Thompson CM

    更新日期:2014-02-01 00:00:00

  • 6-arylamino-5,8-quinolinediones and 7-arylamino-5,8-isoquinolinediones as inhibitors of endothelium-dependent vasorelaxation.

    abstract::6-Arylamino-5,8-quinolinediones 3 and 7-arylamino-5,8-isoquinolinediones 4 were synthesized as inhibitors of endothelium-dependent vasorelaxation. The quinones inhibited the vasorelaxation of rat aorta with the endothelium. Among them, the quinones 3a, 3b, 3f, 4b, 4d and 4g strongly inhibited the vasorelaxation. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ryu CK,Jung SH,Lee JA,Kim HJ,Lee SH,Chung JH

    更新日期:1999-09-06 00:00:00

  • Discovery of 3-aminopicolinamides as metabotropic glutamate receptor subtype 4 (mGlu4) positive allosteric modulator warheads engendering CNS exposure and in vivo efficacy.

    abstract::This letter describes the further chemical optimization of the picolinamide-derived family of mGlu4 PAMs wherein we identified a 3-amino substituent to the picolinamide warhead that engendered potency, CNS penetration and in vivo efficacy. From this optimization campaign, VU0477886 emerged as a potent (EC50=95nM, 89% ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Gogliotti RD,Engers DW,Garcia-Barrantes PM,Panarese JD,Gentry PR,Blobaum AL,Morrison RD,Daniels JS,Thompson AD,Jones CK,Conn PJ,Niswender CM,Lindsley CW,Hopkins CR

    更新日期:2016-06-15 00:00:00

  • A simple synthesis of APM ([p-(N-acrylamino)-phenyl]mercuric chloride), a useful tool for the analysis of thiolated biomolecules.

    abstract::This study describes two novel synthetic procedures to prepare APM, a useful tool for the analysis and the purification of thiolated biomolecules. The methods developed are technically simple and robust and allowed the first full characterization of pure APM. Moreover, the efficacy of APM, as a biochemical tool, was d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lemau de Talancé V,Bauer F,Hermand D,Vincent SP

    更新日期:2011-12-15 00:00:00