当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity.

Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity.

Abstract：

:Metastin has been identified as a metastasis suppressor gene product that mediates its function through a G protein coupled receptor, GPR54. To refine insight into the critical pharmacophore for the activation of GPR54, we have conducted alanine and d-amino acid scanning on a biologically active metastin fragment (45-54). Based on these data and structures of peptides previously reported to activate GPR54, a series of shortened metastin (45-54) derivatives were synthesized and tested for the ability to induce GPR54 signaling. These biological experiments were performed in yeast containing human GPR54 that was coupled to the pheromone response pathway and a pheromone responsive lacZ reporter gene. Compounds 32, 33, and 39, which possess an N-terminal basic group and a C-terminal RW-amide motif, were strong agonists, similar to the level of metastin. This may provide an approach to reverse the pro-metastatic effect of metastin deletion in multiple malignant tumors.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Niida A,Wang Z,Tomita K,Oishi S,Tamamura H,Otaka A,Navenot JM,Broach JR,Peiper SC,Fujii N

doi

10.1016/j.bmcl.2005.09.054

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

134-7

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(05)01190-X

journal_volume

16

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites.

    abstract：:Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.013

    authors： Snead AN,Miyakawa M,Tan ES,Scanlan TS

    更新日期：2008-11-15 00:00:00

  • Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

    abstract：:The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.041

    authors： Liu L,Ma H,Tang Y,Chen W,Lu Y,Guo J,Duan JA

    更新日期：2012-01-01 00:00:00

  • Decreasing the CYP2D6 contribution to metabolism of a CK1ε inhibitor.

    abstract：:Our internal casein kinase 1ε lead inhibitor, compound 1 was partially cleared by the polymorphic cytochrome P450 2D6. CYP2D6 involvement in metabolism implies more extensive clinical trials. We therefore wanted to reduce the contribution to clearance by this enzyme. We utilized metabolism reports for compound 1 perfo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.10.031

    authors： Vaz RJ,Li Y,Metz M,Yang D,Shen H,Munson M

    更新日期：2018-12-15 00:00:00

  • Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 2: (3-Substituted-5-halo-2-pyridinyl)guanidines.

    abstract：:Based on previous modeling predictions, a series of (3-substituted-5-chloro-2-pyridinyl)guanidines have been designed with good potency and selectivity for urokinase-type plasminogen activator (uPA). Compound 36 has a K(i) of 0.17 microM and greater than 300-fold selectivity with respect to tPA and plasmin. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00702-8

    authors： Barber CG,Dickinson RP

    更新日期：2002-01-21 00:00:00

  • Design and synthesis of novel RXR-selective modulators with improved pharmacological profile.

    abstract：:New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.08.048

    authors： Michellys PY,Boehm MF,Chen JH,Grese TA,Karanewsky DS,Leibowitz MD,Liu S,Mais DA,Mapes CM,Reifel-Miller A,Ogilvie KM,Rungta D,Thompson AW,Tyhonas JS,Yumibe N,Ardecky RJ

    更新日期：2003-11-17 00:00:00

  • Novel benzothiazinones (BTOs) as allosteric modulator or substrate competitive inhibitor of glycogen synthase kinase 3β (GSK-3β) with cellular activity of promoting glucose uptake.

    abstract：:Glycogen synthase kinase 3β (GSK-3β) plays a key role in insulin metabolizing pathway and therefore inhibition of the enzyme might provide an important therapeutic approach for treatment of insulin resistance and type 2 diabetes. Recently, discovery of ATP noncompetitive inhibitors is gaining importance not only due t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.10.078

    authors： Zhang P,Li S,Gao Y,Lu W,Huang K,Ye D,Li X,Chu Y

    更新日期：2014-12-15 00:00:00

  • Inhibitors of anthrax lethal factor based upon N-oleoyldopamine.

    abstract：:The structural features of an anthrax lethal factor inhibitor, N-oleoyldopamine (OLDA, 1) have been probed. The oleic acid moiety is critical, but, more interestingly, the presence of the double bond and its geometry were found to play an essential role. One compound, 5, was found to be an uncompetitive inhibitor of l...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.02.044

    authors： Gaddis BD,Rubert Pérez CM,Chmielewski J

    更新日期：2008-04-01 00:00:00

  • Synthesis of enamino-2-oxindoles via conjugate addition between α-azido ketones and 3-alkenyl oxindoles: Cytotoxicity evaluation and apoptosis inducing studies.

    abstract：:A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.07.038

    authors： Kumar NP,Vanjari Y,Thatikonda S,Pooladanda V,Sharma P,Sridhar B,Godugu C,Kamal A,Shankaraiah N

    更新日期：2018-12-01 00:00:00

  • Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors.

    abstract：:Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00893-4

    authors： Lim HS,Oh YS,Suh PG,Chung SK

    更新日期：2003-01-20 00:00:00

  • Novel steroidal saponins, Sch 725737 and Sch 725739, from a marine starfish, Novodinia antillensis.

    abstract：:Bioassay-guided fractionation of an active fraction from an extract of a marine starfish, Novodinia antillensis, led to the isolation and identification of two new saponins, Sch 725737 (1) and Sch 725739 (2). Compound 1 was identified as the NaV1.8 inhibitor with IC(50) of approximately 9 microM. The purification and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.08.025

    authors： Yang SW,Chan TM,Buevich A,Priestley T,Crona J,Reed J,Wright AE,Patel M,Gullo V,Chen G,Pramanik B,Chu M

    更新日期：2007-10-15 00:00:00

  • Synthesis and immunological activity of an oligosaccharide-conjugate as a vaccine candidate against Group A Streptococcus.

    abstract：:The synthesis and immunogenicity of a tetanus toxoid (TT)-conjugate of the hexasaccharide portion of the cell-wall polysaccharide (CWPS) of the Group A Streptococcus (GAS) is described. The synthesis relies on the reaction of an allyl glycoside of the hexasaccharide with cysteamine, followed by the reaction of the res...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.042

    authors： Auzanneau FI,Borrelli S,Pinto BM

    更新日期：2013-11-15 00:00:00

  • Combinatorial synthesis of SSAO inhibitors using sonogashira coupling: SAR of aryl propargylic amines.

    abstract：:The structure-activity relationships for semicarbazide-sensitive amine oxidase (SSAO) inhibitors based on arylpropynylamines was investigated using solution-phase combinatorial Sonogashira coupling. The results suggest that binding to the active site occurs by coordination of the amine to the proximal copper(II) and f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00506-6

    authors： Conn C,Shimmon R,Cordaro F,Hargraves TL,Ibrahim P

    更新日期：2001-10-08 00:00:00

  • Triterpene and diterpene inhibitors of pyruvate dehydrogenase kinase (PDK).

    abstract：:Several oximes of triterpenes with a 17-beta hydroxyl and abietane derivatives are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 micromol/kg. However, the mechanism ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00380-7

    authors： Aicher TD,Damon RE,Koletar J,Vinluan CC,Brand LJ,Gao J,Shetty SS,Kaplan EL,Mann WR

    更新日期：1999-08-02 00:00:00

  • Synthesis and quantitative structure-activity relationship (QSAR) analysis of some novel oxadiazolo[3,4-d]pyrimidine nucleosides derivatives as antiviral agents.

    abstract：:We have synthesized a series of 4H,6H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleoside and their anti-vesicular stomatitis virus (VSV) activities in Wish cell were also investigated in vitro. It was found that most compounds showed obvious anti-VSV activities and compound 9 with ribofuranoside improved ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.11.065

    authors： Xu X,Wang J,Yao Q

    更新日期：2015-01-15 00:00:00

  • New class of 8-aryl-7-deazaguanine cell permeable fluorescent probes.

    abstract：:A one step synthesis of fluorescent 8-aryl-(7-deazaguanines) has been accomplished. Probes exhibit blue to green high quantum yield fluorescence in a variety of organic and aqueous solutions, high extinction coefficients, and large Stokes shifts often above 100 nm. The probes are highly cell permeable, and exhibit sta...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.08.054

    authors： Dhimitruka I,Eubank TD,Gross AC,Khramtsov VV

    更新日期：2015-10-15 00:00:00

  • 2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.

    abstract：:Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.024

    authors： Golebiowski A,Paul Beckett R,Van Zandt M,Ji MK,Whitehouse D,Ryder TR,Jagdmann E,Andreoli M,Mazur A,Padmanilayam M,Cousido-Siah A,Mitschler A,Ruiz FX,Podjarny A,Schroeter H

    更新日期：2013-04-01 00:00:00

  • Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis.

    abstract：:During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have s...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00526-5

    authors： Di Santo R,Costi R,Artico M,Massa S,Lampis G,Deidda D,Pompei R

    更新日期：1998-10-20 00:00:00

  • Synthesis of [¹⁸F]-labeled (2-(2-fluoroethoxy)ethyl)triphenylphosphonium cation as a potential agent for myocardial imaging using positron emission tomography.

    abstract：:[(18)F]-labeled molecular probe for the detection of myocardial perfusion deficit is driving particular interest due to its high clinical applicability. Thus, we synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)triphenylphosphonium salt ([(18)F]3) that specifically accumulates in myocardium according to mitochondrial membr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.005

    authors： Kim DY,Kim HJ,Yu KH,Min JJ

    更新日期：2012-01-01 00:00:00

  • The 'Ethereal' nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics.

    abstract：:To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonis...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.09.060

    authors： Bazin HG,Murray TJ,Bowen WS,Mozaffarian A,Fling SP,Bess LS,Livesay MT,Arnold JS,Johnson CL,Ryter KT,Cluff CW,Evans JT,Johnson DA

    更新日期：2008-10-15 00:00:00

  • 2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket.

    abstract：:Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel IT...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.09.098

    authors： Lo HY,Bentzien J,Fleck RW,Pullen SS,Khine HH,Woska JR Jr,Kugler SZ,Kashem MA,Takahashi H

    更新日期：2008-12-01 00:00:00

  • Identification of potent and selective MMP-13 inhibitors.

    abstract：:A potent, selective series of MMP-13 inhibitors has been derived from a weak (3.2 microM) inhibitor that did not bear a zinc chelator. Structure-based drug design strategies were employed to append a Zn-chelating group to one end of the molecule and functionality to enhance selectivity to the other. A compound from th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.06.019

    authors： Wu J,Rush TS 3rd,Hotchandani R,Du X,Geck M,Collins E,Xu ZB,Skotnicki J,Levin JI,Lovering FE

    更新日期：2005-09-15 00:00:00

  • Arylcarboxyamino-substituted diaryl ureas as potent and selective FLT3 inhibitors.

    abstract：:A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.07.024

    authors： Patel HK,Grotzfeld RM,Lai AG,Mehta SA,Milanov ZV,Chao Q,Sprankle KG,Carter TA,Velasco AM,Fabian MA,James J,Treiber DK,Lockhart DJ,Zarrinkar PP,Bhagwat SS

    更新日期：2009-09-01 00:00:00

  • Developing potential Helicobacter pylori urease inhibitors from novel oxoindoline derivatives: Synthesis, biological evaluation and in silico study.

    abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.08.025

    authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

    更新日期：2018-10-15 00:00:00

  • PSMA-targeted bispecific Fab conjugates that engage T cells.

    abstract：:Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.09.065

    authors： Patterson JT,Isaacson J,Kerwin L,Atassi G,Duggal R,Bresson D,Zhu T,Zhou H,Fu Y,Kaufmann GF

    更新日期：2017-12-15 00:00:00

  • New peptide deformylase inhibitors design, synthesis and pharmacokinetic assessment.

    abstract：:The docking approach for the screening of designed small molecule ligands, led to the identification of a critical arginine residue in peptide deformylase for spiro cyclopropyl PDF inhibitor's extra hydrophobic binding, providing us a useful tool for searching more efficient PDF inhibitors to fight for horrifying anti...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.05.077

    authors： Lv F,Chen C,Tang Y,Wei J,Zhu T,Hu W

    更新日期：2016-08-01 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

  • 4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors.

    abstract：:A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficac...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.04.046

    authors： Lee S,Lee H,Yi KY,Lee BH,Yoo SE,Lee K,Cho NS

    更新日期：2005-06-15 00:00:00

  • 1,3-Di(quinolin-2-yl)guanidine binds to GGCCCC hexanucleotide repeat DNA in C9ORF72.

    abstract：:Aberrant expansion of GGGGCC (G4C2) hexanucleotide repeat (HNR) in the first intron of C9ORF72 has been found in frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALD). The non-canonical DNA structures of the expanded repeats are causative to repeat instability leading to contraction and expansion. We dem...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.06.032

    authors： Shibata T,Murakami E,Nakatani K

    更新日期：2018-08-01 00:00:00

  • Aminoalkyl phenyl sulfones--a novel series of 5-HT7 receptor ligands.

    abstract：:A novel series of 5-HT(7) receptor ligands has been identified and evaluated, providing compounds showing a broad spectrum of functional activities and good selectivity over selected receptors and ion channels. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.11.067

    authors： Raubo P,Beer MS,Hunt PA,Huscroft IT,London C,Stanton JA,Kulagowski JJ

    更新日期：2006-03-01 00:00:00

  • Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.

    abstract：:Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorop...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.01.028

    authors： Pinto DJ,Smallheer JM,Corte JR,Austin EJ,Wang C,Fang T,Smith LM 2nd,Rossi KA,Rendina AR,Bozarth JM,Zhang G,Wei A,Ramamurthy V,Sheriff S,Myers JE Jr,Morin PE,Luettgen JM,Seiffert DA,Quan ML,Wexler RR

    更新日期：2015-04-01 00:00:00