当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Discovery and biological evaluation of novel 4-amino-2-phenylpyrimidine derivatives as potent and orally active GPR119 agonists.

Discovery and biological evaluation of novel 4-amino-2-phenylpyrimidine derivatives as potent and orally active GPR119 agonists.

Abstract：

:Novel 4-amino-2-phenylpyrimidine derivatives were synthesized and evaluated as GPR119 agonists. Optimization of the substituents on the phenyl ring at the 2-position and the amino group at the 4-position led to the identification of 3,4-dihalogenated and 2,4,5-trihalogenated phenyl derivatives showing potent GPR119 agonistic activity. The advanced analog (2R)-3-{[2-(4-chloro-2,5-difluorophenyl)-6-ethylpyrimidin-4-yl]amino}propane-1,2-diol (24g) was found to improve glucose tolerance at 1mg/kg po in mice and to show excellent pharmacokinetic profiles in mice and monkeys. Compound 24g also showed an excellent antidiabetic effect in diabetic kk/Ay mice after one week of single daily treatment. These results demonstrate that novel GPR119 agonist 24g improves glucose tolerance not only by enhancing glucose-dependent insulin secretion but also by preserving pancreatic β-cell function.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Negoro K,Yonetoku Y,Misawa-Mukai H,Hamaguchi W,Maruyama T,Yoshida S,Takeuchi M,Ohta M

doi

10.1016/j.bmc.2012.06.049

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

5235-46

issue

17

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00536-6

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • STD-NMR studies of two acceptor substrates of GlfT2, a galactofuranosyltransferase from Mycobacterium tuberculosis: epitope mapping studies.

    abstract：:The major structural component of the mycobacterial cell wall, the mycolyl-arabinogalactan-peptidoglycan complex, possesses a galactan core composed of approximately 30 galactofuranosyl (Galf) resides attached via alternating beta-(1-->6) and beta-(1-->5) linkages. Recent studies have shown that the entire galactan is...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.069

    authors： Szczepina MG,Zheng RB,Completo GC,Lowary TL,Pinto BM

    更新日期：2010-07-15 00:00:00

  • Synthesis of amino acid derived seven-membered lactams by RCM and their evaluation against HIV protease.

    abstract：:A versatile synthesis of hydroxylated and epoxy 1-azepin 2-ones substituted at N1, C-3 and C-4 or C-7 has been developed. The sequence involves ring-closing metathesis of an amino acid derived diene amide, followed by either epoxidation or dihydroxylation, of the resulting alkene. Assay of the product epoxides (10, 18...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.09.009

    authors： Zaman S,Campaner P,Abell AD

    更新日期：2006-12-15 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

    doi：10.1016/j.bmc.2004.01.021

    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

  • Synthesis of novel 7-oxo and 7-hydroxy trifluoroallocolchicinoids with cytotoxic effect.

    abstract：:The synthesis of 7-oxo and 7-hydroxy trifluoroallocolchicinoids was achieved through the intramolecular cyclization of o-phenyl-β-phenylalanines. The resulting compounds were evaluated for their cytotoxic activity against KB cells and their inhibitory effect towards the polymerization of tubulin. The results yielded s...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.02.043

    authors： Chosson E,Santoro F,Rochais C,Santos JS,Legay R,Thoret S,Cresteil T,Sinicropi MS,Besson T,Dallemagne P

    更新日期：2012-04-15 00:00:00

  • New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

    abstract：:The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.10.037

    authors： Fortuna CG,Berardozzi R,Bonaccorso C,Caltabiano G,Di Bari L,Goracci L,Guarcello A,Pace A,Palumbo Piccionello A,Pescitelli G,Pierro P,Lonati E,Bulbarelli A,Cocuzza CE,Musumarra G,Musumeci R

    更新日期：2014-12-15 00:00:00

  • Synthesis and chain length-anti-HIV activity relationship of fully N- and O-sulfated homooligomers of tyrosine.

    abstract：:Fully N- and O-sulfated homooligomers from octamer to nonadecamer of tyrosine were obtained as their sodium salts, aO3S-[Tyr(SO3Na)]n-ONa (n = 8-19), from reaction mixtures of tyrosine with sulfur trioxide trimethylamine and pyridine comlexes, respectively, in pyridine. Their anti-HIV activity increased along with the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00268-6

    authors： Ueki M,Watanabe S,Saitoh T,Nakashima H,Yamamoto N,Ogawara H

    更新日期：2001-02-01 00:00:00

  • Design, synthesis and biological evaluation of succinimide derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.

    abstract：:Structure-activity relationship study and in vitro biochemical studies with human leukocyte elastase, cathepsin G and proteinase 3 were conducted using a series of succinimide derivatives. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(95)00024-b

    authors： Groutas WC,Brubaker MJ,Chong LS,Venkataraman R,Huang H,Epp JB,Kuang R,Hoidal JR

    更新日期：1995-04-01 00:00:00

  • Natural products in crop protection.

    abstract：:The tremendous increase in crop yields associated with the 'green' revolution has been possible in part by the discovery and utilization of chemicals for pest control. However, concerns over the potential impact of pesticides on human health and the environment has led to the introduction of new pesticide registration...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmc.2009.01.046

    authors： Dayan FE,Cantrell CL,Duke SO

    更新日期：2009-06-15 00:00:00

  • Bromo-deaza-SAH: a potent and selective DOT1L inhibitor.

    abstract：:Chemical inhibition of proteins involved in chromatin-mediated signaling is an emerging strategy to control chromatin compaction with the aim to reprogram expression networks to alter disease states. Protein methyltransferases constitute one of the protein families that participate in epigenetic control of gene expres...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.01.049

    authors： Yu W,Smil D,Li F,Tempel W,Fedorov O,Nguyen KT,Bolshan Y,Al-Awar R,Knapp S,Arrowsmith CH,Vedadi M,Brown PJ,Schapira M

    更新日期：2013-04-01 00:00:00

  • Modeling and synthesis of novel tight-binding inhibitors of cytochrome P450 2C9.

    abstract：:Cytochrome P450 2C9 (2C9) is one of the three major drug metabolizing cytochrome P450 enzymes in human liver. Although the crystal structure of 2C9 has been solved, the important physicochemical properties of substrate-enzyme interactions remain difficult to be determined. This is due in part to the conformational fle...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.021

    authors： Peng CC,Rushmore T,Crouch GJ,Jones JP

    更新日期：2008-04-01 00:00:00

  • Synthesis and antitrichinellosis activity of some 2-substituted-[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-ones.

    abstract：:Some new thiazolo[3,2-a]benzimidazolone derivatives were synthesized using two methods. The structures of the synthesized compounds were proved by means of IR, (1)H NMR and mass spectral data. Ab initio computations were performed in order to determine the electronic structure and geometry of the investigated molecule...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.06.046

    authors： Mavrova ATs,Anichina KK,Vuchev DI,Tsenov JA,Kondeva MS,Micheva MK

    更新日期：2005-10-01 00:00:00

  • Rapid isolation of novel FK506 binding proteins from multiple organisms using gDNA and cDNA T7 phage display.

    abstract：:Reverse chemical proteomics using T7 phage display is a powerful technique for identifying cellular receptors of biologically active small molecules. However, to date this method has generally been limited to cDNA libraries constructed from mRNA isolated from eukaryotes. In this paper, we describe the construction of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.08.039

    authors： Piggott AM,Kriegel AM,Willows RD,Karuso P

    更新日期：2009-10-01 00:00:00

  • Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: novel iron chelators with enhanced pFe3+ values.

    abstract：:The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pKa values of the ligands together with the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of an amido sub...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00273-x

    authors： Liu ZD,Piyamongkol S,Liu DY,Khodr HH,Lu SL,Hider RC

    更新日期：2001-03-01 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

    doi：10.1016/j.bmc.2019.07.002

    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

  • RNA-RNA interactions between oligonucleotide substrates for aminoacylation.

    abstract：:RNA stem-loop microhelices with helix sequences based on tRNA acceptor stems can be charged with specific amino acids. Experiments were designed to test the possibility that microhelices could laterally associate through complementary loop sequences and thereby bring their attached aminoacyl groups close enough togeth...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(97)00043-6

    authors： Henderson BS,Schimmel P

    更新日期：1997-06-01 00:00:00

  • Antioxidant activity of benzoxazolinonic and benzothiazolinonic derivatives in the LDL oxidation model.

    abstract：:A series of benzazolone compounds were synthesized utilizing benzoxazolinonic and benzothiazolinonic heterocycles as the building unit. The antioxidant activity of these compounds was determined by inhibition of lipid peroxidation. The oxidation of LDL was induced in the presence of CuSO(4) or 2,2'-azobis(2-amidinopro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.09.016

    authors： Yekini I,Hammoudi F,Martin-Nizard F,Yous S,Lebegue N,Berthelot P,Carato P

    更新日期：2009-11-15 00:00:00

  • Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.

    abstract：:Protein phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neurob...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.08.042

    authors： Ogasawara S,Kiyota Y,Chuman Y,Kowata A,Yoshimura F,Tanino K,Kamada R,Sakaguchi K

    更新日期：2015-10-01 00:00:00

  • Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1).

    abstract：:NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.10.006

    authors： Mayhoub AS,Marler L,Kondratyuk TP,Park EJ,Pezzuto JM,Cushman M

    更新日期：2012-12-15 00:00:00

  • Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3).

    abstract：:High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cel...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.12.041

    authors： Brooke DG,van Dam EM,Watts CK,Khoury A,Dziadek MA,Brooks H,Graham LJ,Flanagan JU,Denny WA

    更新日期：2014-02-01 00:00:00

  • Geranylated flavonoids displaying SARS-CoV papain-like protease inhibition from the fruits of Paulownia tomentosa.

    abstract：:SARS-CoV papain-like protease (PLpro) is an important antiviral target due to its key roles in SARS virus replication. The MeOH extracts of the fruits of the Paulownia tree yielded many small molecules capable of targeting PLpro. Five of these compounds were new geranylated flavonoids, tomentin A, tomentin B, tomentin...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.03.027

    authors： Cho JK,Curtis-Long MJ,Lee KH,Kim DW,Ryu HW,Yuk HJ,Park KH

    更新日期：2013-06-01 00:00:00

  • Abenzyl 10-formyl-trideazafolic acid (abenzyl 10-formyl-TDAF): an effective inhibitor of glycinamide ribonucleotide transformylase.

    abstract：:The synthesis of N-[7-(2-amino-3,4-dihydro-4-oxo-quinazolin-6-yl) -6-formyl-1-oxo-heptyl]-L-glutamic acid (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enzyme-assembled tight binding inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide transf...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(97)00123-5

    authors： Boger DL,Haynes NE,Warren MS,Ramcharan J,Marolewski AE,Kitos PA,Benkovic SJ

    更新日期：1997-09-01 00:00:00

  • 4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.

    abstract：:A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.07.040

    authors： Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期：2018-08-15 00:00:00

  • Indole and benzimidazole derivatives as steroid 5alpha-reductase inhibitors in the rat prostate.

    abstract：:A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among these compounds, 4-¿2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy¿buty ric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)80018-7

    authors： Takami H,Kishibayashi N,Ishii A,Kumazawa T

    更新日期：1998-12-01 00:00:00

  • Dimeric cinnamoylamide analogues for regulation of tyrosinase activity in melanoma cells: A role of diamide-link chain length.

    abstract：:Dimeric cynnamoyl analogues (DCAs) with depigmenting activity have been developed. In this study, a role of diamide linkage chain length of DCAs as a tyrosinase inhibitor was investigated on tyrosinase inhibitory activity, antioxidative activity, hydrophobicity and anti-melanogenesis as well as structural characterist...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.10.036

    authors： Ha JH,Park SN

    更新日期：2018-12-15 00:00:00

  • Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3.

    abstract：:The scorpion toxin AmmTx3 is a specific blocker of Kv4 channels. It was shown to have interesting potential for neurological disorders. In this study, we report the first chemical synthesis of AmmTx3 by using the native chemical ligation strategy and validate its biological activity. We determined its 3D structure by ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.12.009

    authors： Zoukimian C,Meudal H,De Waard S,Ouares KA,Nicolas S,Canepari M,Béroud R,Landon C,De Waard M,Boturyn D

    更新日期：2019-01-01 00:00:00

  • Cytotoxicity mechanisms of pyrazino[1,2-b]isoquinoline-4-ones and SAR studies.

    abstract：:The cytotoxicity showed by 1b, an interesting representant of the title compounds, for HT-29 human colon cancer cells (CI(50) value of 1.95 x 10(-7)M) has been related to the induced cell death at the G2 phase and not to DNA damage. This compound promotes the degradation of components of the G2/M checkpoint machinery,...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.10.007

    authors： Ortín I,González JF,Cuesta Ede L,Manguan-García C,Perona R,Avendaño C

    更新日期：2009-12-01 00:00:00

  • Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

    abstract：:Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.03.001

    authors： Amano Y,Yamaguchi T,Tanabe E

    更新日期：2014-04-15 00:00:00

  • QSAR for non-nucleoside inhibitors of HIV-1 reverse transcriptase.

    abstract：:By means of QSAR algorithms we model the potency pIC(90) [mM] of 154 non-nucleoside reverse transcriptase inhibitors (NNRTI) of the wild-type HIV-1 virus, considered as the second generation analogues of Efavirenz. In addition, 56 inhibitors of the K-103N viral mutant form are also investigated. A pool of 1494 theoret...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.05.027

    authors： Duchowicz PR,Fernández M,Caballero J,Castro EA,Fernández FM

    更新日期：2006-09-01 00:00:00

  • DNA-binding peptides searched from the solid-phase combinatorial library with the use of the magnetic beads attaching the target duplex DNA.

    abstract：:We have exhibited successful and rapid screening of DNA-binding peptide ligands from solid-phase library beads with the use of the target DNA-conjugated magnetic beads. The target duplex DNA (3) has a polyether linker between two complementary sequences (T4A3G-ether linker-CT3A4) and is stable in the duplex form durin...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00298-9

    authors： Alam MR,Maeda M,Sasaki S

    更新日期：2000-02-01 00:00:00

  • A novel thrombin binding aptamer containing a G-LNA residue.

    abstract：:In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.06.008

    authors： Virno A,Randazzo A,Giancola C,Bucci M,Cirino G,Mayol L

    更新日期：2007-09-01 00:00:00