当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Design and synthesis of novel CCR2 antagonists: investigation of non-aryl/heteroaryl binding motifs.

Design and synthesis of novel CCR2 antagonists: investigation of non-aryl/heteroaryl binding motifs.

Abstract：

:This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with regards to potency (binding to hCCR2), dofetilide activity and metabolic stability (in vitro HLM) for this series. The resulting outcome was the identification of compounds with excellent properties for the investigation of the role of CCR2 in disease.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Trujillo JI,Huang W,Hughes RO,Rogier DJ,Turner SR,Devraj R,Morton PA,Xue CB,Chao G,Covington MB,Newton RC,Metcalf B

doi

10.1016/j.bmcl.2011.01.052

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

1827-31

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00075-8

journal_volume

21

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.

    abstract：:Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.08.063

    authors： Zhao H,Liu G,Xin Z,Serby MD,Pei Z,Szczepankiewicz BG,Hajduk PJ,Abad-Zapatero C,Hutchins CW,Lubben TH,Ballaron SJ,Haasch DL,Kaszubska W,Rondinone CM,Trevillyan JM,Jirousek MR

    更新日期：2004-11-15 00:00:00

  • Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition.

    abstract：:We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.046

    authors： Fox BM,Natero R,Richard K,Connors R,Roveto PM,Beckmann H,Haller K,Golde J,Xiao SH,Kayser F

    更新日期：2011-04-15 00:00:00

  • Optimization of pancreatic lipase inhibition by Cudrania tricuspidata fruits using response surface methodology.

    abstract：:The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-facto...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.03.067

    authors： Jeong JY,Jo YH,Lee KY,Do SG,Hwang BY,Lee MK

    更新日期：2014-05-15 00:00:00

  • Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.11.070

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

    更新日期：2011-01-01 00:00:00

  • Discovery of dual ZAP70 and Syk kinases inhibitors by docking into a rare C-helix-out conformation of Syk.

    abstract：:The non-receptor tyrosine kinase Syk (spleen tyrosine kinase) is a pharmaceutical relevant target because its over-activation is observed in several autoimmune diseases, allergy, and asthma. Here we report the identification of two novel inhibitors of Syk by high-throughput docking into a rare C-helix-out conformation...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.083

    authors： Zhao H,Caflisch A

    更新日期：2014-03-15 00:00:00

  • Synthesis and structure-activity relationships of bengazole A analogs.

    abstract：:Analogs of the potent antifungal agent, bengazole A, were prepared and evaluated against Candida spp. in both microbroth dilution and disk diffusion assays. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.069

    authors： Mulder RJ,Shafer CM,Dalisay DS,Molinski TF

    更新日期：2009-06-01 00:00:00

  • Synthesis of novel orthoalkylaminophenol derivatives as potent neuroprotective agents in vitro.

    abstract：:A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00504-1

    authors： Larget R,Lockhart B,Pfeiffer B,Neudorffer A,Fleury MB,Largeron M

    更新日期：1999-10-18 00:00:00

  • Design, synthesis, and structure-activity relationship studies of novel tetrazole antifungal agents with potent activity, broad antifungal spectrum and high selectivity.

    abstract：:In this letter, we report our efforts to design, synthesize and evaluate biological activities of a series of novel hybridized compounds containing 1-tetrazole and 4-pyridinyl-1,2,4-triazole-3-one. An analysis of structure-activity data indicates that the target compounds with bulky and hydrophobic side chains exhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.12.040

    authors： Qian A,Zheng Y,Wang R,Wei J,Cui Y,Cao X,Yang Y

    更新日期：2018-02-01 00:00:00

  • Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.

    abstract：:Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was selected for in vivo evaluation of lipolysis induction, metabolic rate increase, and ca...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.08.056

    authors： Edmondson SD,Mastracchio A,He J,Chung CC,Forrest MJ,Hofsess S,MacIntyre E,Metzger J,O'Connor N,Patel K,Tong X,Tota MR,Van der Ploeg LH,Varnerin JP,Fisher MH,Wyvratt MJ,Weber AE,Parmee ER

    更新日期：2003-11-17 00:00:00

  • Lobophorins A and B, new antiinflammatory macrolides produced by a tropical marine bacterium.

    abstract：:Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00337-6

    authors： Jiang ZD,Jensen PR,Fenical W

    更新日期：1999-07-19 00:00:00

  • Lead detoxification activities and ADMET hepatotoxicities of a class of novel 5-(1-carbonyl-L-amino-acid)-2,2-dimethyl-[1,3]dithiolane-4-carboxylic acids.

    abstract：:By linking the mercapto groups with isopropyl and introducing L-amino acid into the 5-carboxyl of DMSA a class of novel 5-(1-carbonyl-L-amino-acid)-2,2- dimethyl-[1,3]dithiolane-4-carboxylic acids were prepared. Their in vivo activities were evaluated on lead loaded mice at the dose of 0.4 mmol/kg. The results showed ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.070

    authors： Xu Y,Wang Y,Zhao M,Hou B,Peng L,Zheng M,Wu J,Peng S

    更新日期：2011-03-15 00:00:00

  • Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity.

    abstract：:A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.03.051

    authors： Artyushin OI,Sharova EV,Vinogradova NM,Genkina GK,Moiseeva AA,Klemenkova ZS,Orshanskaya IR,Shtro AA,Kadyrova RA,Zarubaev VV,Yarovaya OI,Salakhutdinov NF,Brel VK

    更新日期：2017-05-15 00:00:00

  • Isolation and characterization of an active-site peptide from a sterol methyl transferase with a mechanism-based inhibitor.

    abstract：:Chemical affinity labeling of pure sterol methyl transferase (SMT) from Saccharomyces cerevisiae using the mechanism-based irreversible inhibitor, [3-3H]26,27-dehydrozymosterol, inhibited the SMT with an apparent Ki of 1.1 microM and k(inact) of 1.52 min(-1). The protein-inhibitor adduct was subjected to cleavage with...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00242-5

    authors： Marshall JA,Nes WD

    更新日期：1999-06-07 00:00:00

  • Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors.

    abstract：:Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.03.104

    authors： Agai-Csongor E,Domány G,Nógrádi K,Galambos J,Vágó I,Keserű GM,Greiner I,Laszlovszky I,Gere A,Schmidt E,Kiss B,Vastag M,Tihanyi K,Sághy K,Laszy J,Gyertyán I,Zájer-Balázs M,Gémesi L,Kapás M,Szombathelyi Z

    更新日期：2012-05-15 00:00:00

  • Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis.

    abstract：:Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eos...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.024

    authors： Scott JM,Baccei C,Bain G,Broadhead A,Evans JF,Fagan P,Hutchinson JH,King C,Lorrain DS,Lee C,Prasit P,Prodanovich P,Santini A,Stearns BA

    更新日期：2011-11-01 00:00:00

  • Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions.

    abstract：:The inhibition of the newly discovered cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozyme XIII of murine origin (mCA XIII) has been investigated with a series of anions, such as the physiological ones (bicarbonate, chloride), or the metal complexing anions (cyanate, cyanide, azide, hydrogen sulfide, etc), nitrate, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.086

    authors： Innocenti A,Lehtonen JM,Parkkila S,Scozzafava A,Supuran CT

    更新日期：2004-11-01 00:00:00

  • Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist.

    abstract：:The synthesis and SAR of benzylamine side chain analogs of the NK-1 receptor antagonist CP-99,994 are described. The 5-trifluoromethoxy analog, CP-122,721, shows superior in vivo blockade of NK-1 receptor mediated responses. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00012-2

    authors： Rosen TJ,Coffman KJ,McLean S,Crawford RT,Bryce DK,Gohda Y,Tsuchiya M,Nagahisa A,Nakane M,Lowe JA 3rd

    更新日期：1998-02-03 00:00:00

  • Discovery of phenyl acetamides as potent and selective GPR119 agonists.

    abstract：:The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.01.091

    authors： Zhu C,Wang L,Zhu Y,Guo ZZ,Liu P,Hu Z,Szewczyk JW,Kang L,Chicchi G,Ehrhardt A,Woods A,Seo T,Woods M,van Heek M,Dingley KH,Pang J,Salituro GM,Powell J,Terebetski JL,Hornak V,Campeau LC,Orr RK,Ujjainwalla F,Mil

    更新日期：2017-03-01 00:00:00

  • Suzuki coupling based synthesis and in vitro cytotoxic evaluation of 7-heteroaryl-substituted camptothecin analogs.

    abstract：:In an effort to discover potent antitumor agents, a series of novel C-7-heteroaryl-substituted camptothecin derivatives were designed and synthesized via microwave-promoted Suzuki coupling reaction. These analogs were then assessed for cytotoxicity against three human tumor cell lines, A549, HCT116, HT-29, and inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.049

    authors： Wang L,Huang Y,Zhang J,Tong L,Chen Y,Lu W,Huang Q

    更新日期：2014-03-15 00:00:00

  • Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.

    abstract：:The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00130-0

    authors： McAtee JJ,Castle SL,Jin Q,Boger DL

    更新日期：2002-05-06 00:00:00

  • X-ray crystal structure of JNK2 complexed with the p38alpha inhibitor BIRB796: insights into the rational design of DFG-out binding MAP kinase inhibitors.

    abstract：:JNK2 and p38alpha are closely related mitogen-activated protein kinases that regulate various cellular activities and are considered drug targets for inflammatory diseases. We have determined the X-ray crystal structure of the clinical phase II p38alpha inhibitor BIRB796 bound to its off-target JNK2. This shows for th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.157

    authors： Kuglstatter A,Ghate M,Tsing S,Villaseñor AG,Shaw D,Barnett JW,Browner MF

    更新日期：2010-09-01 00:00:00

  • Comparison of 2-phenylspiroindenes and 2-phenylspiroindenediones as estrogen receptor ligands--modeling and binding data don't agree!

    abstract：:A series of 2-phenylspiroindenediones was prepared. The spiroindenediones were found to be less active than the corresponding spiroindenes as estrogen receptor ligands and failed to demonstrate the receptor subtype selectivity that had been anticipated from molecular modeling. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.058

    authors： Blizzard TA,Mosley RT,Birzin ET,Chan W,Hammond ML

    更新日期：2004-03-08 00:00:00

  • Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells.

    abstract：:A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Prelimina...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.09.032

    authors： Liu YR,Luo JZ,Duan PP,Shao J,Zhao BX,Miao JY

    更新日期：2012-11-15 00:00:00

  • Multi-step parallel synthesis enabled optimization of benzofuran derivatives as pan-genotypic non-nucleoside inhibitors of HCV NS5B.

    abstract：:In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with <10 nM potency. In addition, th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127004

    authors： Xiao D,Dai X,Liu H,He S,Shi ZC,Ludmerer SW,Li F,Nargund R,Palani A

    更新日期：2020-04-01 00:00:00

  • Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.

    abstract：:Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions we...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.027

    authors： Glunz PW,Zhang X,Zou Y,Delucca I,Nirschl AH,Cheng X,Weigelt CA,Cheney DL,Wei A,Anumula R,Luettgen JM,Rendina AR,Harpel M,Luo G,Knabb R,Wong PC,Wexler RR,Priestley ES

    更新日期：2013-09-15 00:00:00

  • Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system xc- transporter: Initial homology model.

    abstract：:Microwave accelerated reaction system (MARS) technology provided a good method to obtain selective and open isoxazole ligands that bind to and inhibit the Sxc- antiporter. The MARS provided numerous advantages, including: shorter time, better yield and higher purity of the product. Of the newly synthesized series of i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.08.080

    authors： Matti AA,Mirzaei J,Rudolph J,Smith SA,Newell JL,Patel SA,Braden MR,Bridges RJ,Natale NR

    更新日期：2013-11-01 00:00:00

  • Biotinylated-spiperone ligands for quantum dot labeling of the dopamine D2 receptor in live cell cultures.

    abstract：:We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.02.024

    authors： Tomlinson ID,Kovtun O,Crescentini TM,Rosenthal SJ

    更新日期：2019-04-15 00:00:00

  • Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity.

    abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.083

    authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

    更新日期：2016-12-15 00:00:00

  • An efficient synthetic route for preparation of antimycobacterial wollamides and evaluation of their in vitro and in vivo efficacy.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.07.021

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

    更新日期：2018-09-15 00:00:00

  • Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

    abstract：:A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.06.043

    authors： Wang SG,Kong LY,Li YH,Cheng XY,Su F,Tang S,Bi CW,Jiang JD,Li YH,Song DQ

    更新日期：2015-09-01 00:00:00