当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors.

Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors.

Abstract：

:Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Hu CH,Wang TC,Qiao JX,Haque L,Chen AYA,Taylor DS,Ying X,Onorato JM,Galella M,Shen H,Huang CS,Toussaint N,Li YX,Abell L,Adam LP,Gordon D,Wexler RR,Finlay HJ

doi

10.1016/j.bmcl.2018.10.022

subject

Has Abstract

pub_date

2018-12-15 00:00:00

pages

3721-3725

issue

23-24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30824-2

journal_volume

28

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Triterpene derivatives that inhibit human immunodeficiency virus type 1 replication.

    abstract：:Triterpene derivatives were analyzed for anti-HIV-1 activity and for cellular toxicity. Betulinic aldehyde, betulinic nitrile, and morolic acid derivatives were identified to have anti-HIV-1 activity. These derivatives inhibit a late step in virus replication, likely virus maturation. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.078

    authors： Dorr CR,Yemets S,Kolomitsyna O,Krasutsky P,Mansky LM

    更新日期：2011-01-01 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

  • Structure-related protein tyrosine phosphatase 1B inhibition by naringenin derivatives.

    abstract：:Naturally occurring flavonoids co-exist as glycoside conjugates, which dominate aglycones in their content. To unveil the structure-activity relationship of a naturally occurring flavonoid, we investigated the effects of the glycosylation of naringenin on the inhibition of enzyme systems related to diabetes (protein t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.04.054

    authors： Jung HA,Paudel P,Seong SH,Min BS,Choi JS

    更新日期：2017-06-01 00:00:00

  • Synthesis and evaluation of new iRGD peptide analogs for tumor optical imaging.

    abstract：:Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conj...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.12.112

    authors： Ye Y,Zhu L,Ma Y,Niu G,Chen X

    更新日期：2011-02-15 00:00:00

  • Potential CRF1R PET imaging agents: 1-fluoroalkylsubstituted 5-halo-3-(arylamino)pyrazin-2(1H)-ones.

    abstract：:A series of pyrazinones were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients are discussed herein. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.009

    authors： Denhart DJ,Zuev D,Ditta JL,Hartz RA,Ahuja VT,Mattson RJ,Huang H,Mattson GK,Zueva L,Nielsen JM,Kozlowski ES,Lodge NJ,Bronson JJ,Macor JE

    更新日期：2013-04-01 00:00:00

  • Bis-pyridiumaldoxime reactivators connected with CH2O(CH2)n OCH2 linkers between pyridinium rings and their reactivity against VX.

    abstract：:New bis-pyridinium oxime reactivators connected with CH2O(CH2)n OCH2 linkers between two pyridinium rings were designed and synthesized, and their reactivation potency was evaluated for AChE inhibited by organophosphorus VX agent. Among the prepared compounds, 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichlor...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.06.063

    authors： Oh KA,Yang GY,Jun D,Kuca K,Jung YS

    更新日期：2006-09-15 00:00:00

  • Use of comparative triazolinium triflate fragmentation rates as a tool to assay relative competency of Brønsted bases in N-->N proton transfer.

    abstract：:Brønsted acid-induced fragmentation of a triazoline is used as a tool to identify Brønsted base additives capable of playing the role of a proton shuttle. Relative to water, dimethyl formamide accelerates proton transfer substantially under these conditions. A series of alcohols and ethers were also used to demonstrat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.07.067

    authors： Donahue MG,Hong KB,Johnston JN

    更新日期：2009-09-01 00:00:00

  • Use of parallel-synthesis combinatorial libraries for rapid identification of potent FKBP12 inhibitors.

    abstract：:Using simple, inexpensive equipment, we have used solution-phase parallel synthesis to rapidly prepare hundreds of sulfonamide- and urea-containing FKBP inhibitors, resulting in rapid identification of extremely potent compounds in these series. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00147-6

    authors： Choi C,Li JH,Vaal M,Thomas C,Limburg D,Wu YQ,Chen Y,Soni R,Scott C,Ross DT,Guo H,Howorth P,Valentine H,Liang S,Spicer D,Fuller M,Steiner J,Hamilton GS

    更新日期：2002-05-20 00:00:00

  • Functionalized 1,3-teraryls as a new class of hepatoprotectants. Part V.

    abstract：:Functionalized 1,3-teraryls, synthesized through ring transformation of 6-aryl-3-carbomethoxy-4-methylthio-2H-pyran-2-one from arylketone have been screened for their hepatoprotective activity and of them have demonstrated significant protection in animal model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00061-4

    authors： Ram VJ,Goel A,Patnaik GK

    更新日期：1998-03-03 00:00:00

  • Dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I(Kur)).

    abstract：:A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I(Kur)) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.099

    authors： Vaccaro W,Huynh T,Lloyd J,Atwal K,Finlay HJ,Levesque P,Conder ML,Jenkins-West T,Shi H,Sun L

    更新日期：2008-12-15 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

    doi：10.1016/j.bmcl.2012.10.012

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

    更新日期：2012-12-15 00:00:00

  • Design, synthesis and bioactivity of catechin/epicatechin and 2-azetidinone derived chimeric molecules.

    abstract：:A new class of chimeric molecules have been developed. These are based on polyphenols like catechin and epicatechin and monocyclic beta-lactams. The two units are joined via a triazole linker using the 'Click Chemistry' conditions. The compounds showed good to weak antibacterial activity against Escherichia coli as we...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.084

    authors： Roy B,Chakraborty A,Ghosh SK,Basak A

    更新日期：2009-12-15 00:00:00

  • Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives.

    abstract：:A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.01.039

    authors： Bahekar SS,Shinde DB

    更新日期：2004-04-05 00:00:00

  • Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells.

    abstract：:P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127355

    authors： Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

    更新日期：2020-09-01 00:00:00

  • Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein.

    abstract：:Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, whic...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.064

    authors： Ohgane K,Karaki F,Noguchi-Yachide T,Dodo K,Hashimoto Y

    更新日期：2014-08-01 00:00:00

  • Amplification of the inhibitory activity of miglitol by monofluorination.

    abstract：:Selective monofluorination of the alpha-glycosidase inhibitor and antidiabetic agent Miglitol at position C2 creates an competitive inhibitor of five times higher activity than the parent compound. Its screening against a panel of human cell lines showed a low cytotoxicity therefore making this compound an interesting...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.08.012

    authors： Prell E,Csuk R

    更新日期：2009-10-01 00:00:00

  • Quantitating the concentration of Py-Im polyamide-fluorescein conjugates in live cells.

    abstract：:Quantitative fluorescence-based methods have been developed to determine the nuclear concentration of polyamide-fluorescein conjugates in cell culture. Confocal laser scanning microscopy and flow cytometry techniques are utilized to plot calibration curves, from which the nuclear concentration can be interpolated. Upo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.05.063

    authors： Hsu CF,Dervan PB

    更新日期：2008-11-15 00:00:00

  • Sensitive and selective viral DNA detection assay via microbead-based rolling circle amplification.

    abstract：:We report a sensitive and efficient magnetic bead-based assay for viral DNA identification using isothermal amplification of a reporting probe. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.07.064

    authors： Schopf E,Fischer NO,Chen Y,Tok JB

    更新日期：2008-11-15 00:00:00

  • Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015-2019).

    abstract：:Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints and key transcriptional events in response to extracellular and intracellular signals leading to proliferation. Significant clinical activity for ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2019.126637

    authors： Sánchez-Martínez C,Lallena MJ,Sanfeliciano SG,de Dios A

    更新日期：2019-10-15 00:00:00

  • 4-Aryl-2-anilinopyrimidines as corticotropin-releasing hormone (CRH) antagonists.

    abstract：:A series of 4-aryl-2-(N-ethylanilino)pyrimidines has been synthesized as corticotropin-releasing hormone (CRH) inhibitors. The effect of substitution on each aromatic ring on receptor binding was investigated. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00132-8

    authors： Cocuzza AJ,Hobbs FW,Arnold CR,Chidester DR,Yarem JA,Culp S,Fitzgerald L,Gilligan PJ

    更新日期：1999-04-05 00:00:00

  • Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists.

    abstract：:The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.116

    authors： Kobayashi K,Uchiyama M,Ito H,Takahashi H,Yoshizumi T,Sakoh H,Nagatomi Y,Asai M,Miyazoe H,Tsujita T,Hirayama M,Ozaki S,Tani T,Ishii Y,Ohta H,Okamoto O

    更新日期：2009-07-01 00:00:00

  • Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers.

    abstract：:The transcription factor ΔFosB accumulates in response to chronic insults such as drugs of abuse, L-3,4-dihydroxyphenylalanine (l-DOPA) or stress in specific regions of the brain, triggering long lasting neural and behavioral changes that underlie aspects of drug addiction, dyskinesia, and depression. Thus, small mole...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127300

    authors： Li Y,Liu Z,Aglyamova G,Chen J,Chen H,Bhandari M,White MA,Rudenko G,Zhou J

    更新日期：2020-08-15 00:00:00

  • Enantioselective biocatalytic synthesis of (S)-monastrol.

    abstract：:The first enantioselective biocatalytic synthesis of (S)-monastrol has been developed via an unexpected and unusual enzymatic pathway as suitable route. Whereas attempts for a direct hydrolysis of racemic monastrol were not successful, formation of racemic O-butanoyl monastrol and subsequent enantioselective hydrolysi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.05.063

    authors： Blasco MA,Thumann S,Wittmann J,Giannis A,Gröger H

    更新日期：2010-08-01 00:00:00

  • 5-oxo-15-HETE: total synthesis and bioactivity.

    abstract：:The first total synthesis of 6(E),8(Z),11(Z),13(E) 5-oxo-15-HETE 4 was accomplished. The synthetic material was evaluated with calcium mobilization assay and compared with 5-oxo-ETE the natural ligand for the OXE receptor. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.032

    authors： Patel P,Anumolu JR,Powell WS,Rokach J

    更新日期：2011-03-15 00:00:00

  • Synthesis and biological activity of retinoic acid receptor-alpha specific amides.

    abstract：:Retinoids are analogues of all-trans-retinoic acid, a powerful hormone that mediates many fundamental biological processes. Cancer and other serious hyperproliferative diseases are attractive therapeutic targets for retinoids, but the therapeutic use of retinoids is limited due to severe toxicity. We report here the d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00647-9

    authors： Beard RL,Duong TT,Teng M,Klein ES,Standevan AM,Chandraratna RA

    更新日期：2002-11-04 00:00:00

  • Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists.

    abstract：:Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biologic...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00406-1

    authors： Sielecki TM,Liu J,Mousa SA,Racanelli AL,Hausner EA,Wexler RR,Olson RE

    更新日期：2001-08-20 00:00:00

  • Solvent free, catalyst free, microwave or grinding assisted synthesis of bis-cyclic imide derivatives and their evaluation for anticancer activity.

    abstract：:Cyclic imides are well known to be very important antitumor agents such as mitonafide and amonafide etc. Based on this fact, we have synthesized two series of cyclic imide derivatives containing two cyclic imide moiety in their structures (bis-cyclic imides) and screened them for in vitro anticancer activity against f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.12.031

    authors： Kumar A,Banerjee S,Roy P,Sondhi SM,Sharma A

    更新日期：2017-02-01 00:00:00

  • Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin.

    abstract：:Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocya...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.10.007

    authors： Mizuno M,Nakanishi I,Matsumoto KI,Fukuhara K

    更新日期：2017-11-15 00:00:00

  • Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.

    abstract：:The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a di...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.12.018

    authors： Hu X,Vujanac M,Southall N,Stebbins CE

    更新日期：2013-02-15 00:00:00

  • Discovery and optimization of 2-aminopyridine derivatives as novel and selective JAK2 inhibitors.

    abstract：:Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127048

    authors： Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

    更新日期：2020-04-15 00:00:00