当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

Abstract：

:The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Young RJ,Adams C,Blows M,Brown D,Burns-Kurtis CL,Chan C,Chaudry L,Convery MA,Davies DE,Exall AM,Foster G,Harling JD,Hortense E,Irvine S,Irving WR,Jackson S,Kleanthous S,Pateman AJ,Patikis AN,Roethka TJ,Senger S,

doi

10.1016/j.bmcl.2011.01.131

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

1582-7

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00165-X

journal_volume

21

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Compound instability in dimethyl sulphoxide, case studies with 5-aminopyrimidines and the implications for compound storage and screening.

    abstract：:The oxidation reactions of 5-aminopyrimidine derivatives in dimethyl sulphoxide (DMSO) were studied. The DMSO solutions of the studied compounds became deeply coloured within a few hours or days. The oxidation products can undergo further condensation reactions with the starting pyrimidines to yield bipyrimidines and/...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.08.065

    authors： Procházková E,Jansa P,Březinová A,Cechová L,Mertlíková-Kaiserová H,Holý A,Dračínský M

    更新日期：2012-10-15 00:00:00

  • Thieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDK1 inhibitors discovered by fragment-based screening.

    abstract：:Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity agains...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.080

    authors： Lee AC,Ramanujulu PM,Poulsen A,Williams M,Blanchard S,Ma DM,Bonday Z,Goh KL,Goh KC,Goh MK,Wood J,Dymock BW

    更新日期：2012-06-15 00:00:00

  • Fipronil-based photoaffinity probe for Drosophila and human beta 3 GABA receptors.

    abstract：:Modification of the major insecticide fipronil (1) by replacing three pyrazole substituents (hydrogen for both cyano and amino and trifluoromethyldiazirinyl for trifluoromethylsulfinyl) gives a candidate photoaffinity probe (3) of high potency (IC(50) 2-28 nM) in blocking the chloride channel of Drosophila and human b...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00604-7

    authors： Sirisoma NS,Ratra GS,Tomizawa M,Casida JE

    更新日期：2001-11-19 00:00:00

  • New antiprotozoal agents: their synthesis and biological evaluations.

    abstract：:Here we report identification of new lead compounds based on quinoline and indenoquinolines with variable side chains as antiprotozoal agents. Quinolines 32, 36 and 37 (Table 1) and indenoquinoline derivatives 14 and 23 (Table 2) inhibit the in vitro growth of the Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma bru...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.054

    authors： Upadhayaya RS,Dixit SS,Földesi A,Chattopadhyaya J

    更新日期：2013-05-01 00:00:00

  • Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.

    abstract：:A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we ident...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.045

    authors： Ruebsam F,Murphy DE,Tran CV,Li LS,Zhao J,Dragovich PS,McGuire HM,Xiang AX,Sun Z,Ayida BK,Blazel JK,Kim SH,Zhou Y,Han Q,Kissinger CR,Webber SE,Showalter RE,Shah AM,Tsan M,Patel RA,Thompson PA,Lebrun LA,Hou HJ,

    更新日期：2009-11-15 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

  • Design and synthesis of a beta-amino phosphotyrosyl mimetic suitably protected for peptide synthesis.

    abstract：:Mimetics of phosphotyrosine (pTyr) such as phosphonomethylphenylalanine (Pmp) have traditionally retained alpha-amino functionality. However, beta-amino acids represent isomeric variants, which may exhibit properties that are distinct from the parent. Reported herein is the first beta-amino pTyr mimetic (Pmp(beta)) be...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00783-7

    authors： Lee K,Zhang M,Yang D,Burke TR Jr

    更新日期：2002-12-02 00:00:00

  • Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp.

    abstract：:A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.062

    authors： Faria JV,dos Santos MS,Bernardino AM,Becker KM,Machado GM,Rodrigues RF,Canto-Cavalheiro MM,Leon LL

    更新日期：2013-12-01 00:00:00

  • Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).

    abstract：:A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.05.003

    authors： Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

    更新日期：2004-07-16 00:00:00

  • The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds.

    abstract：:We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were foun...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00137-3

    authors： Ahmed S,James K,Owen CP,Patel CK,Sampson L

    更新日期：2002-05-06 00:00:00

  • Neomycin-phenolic conjugates: polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding.

    abstract：:Here we present a proof-of-concept study, combining two known antimicrobial agents into a hybrid structure in order to develop an emergent cationic detergent-like interaction with the bacterial membrane. Six amphiphilic conjugates were prepared by copper (I)-catalyzed 1,3-dipolar cycloaddition between a neomycin B-der...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.01.025

    authors： Findlay B,Zhanel GG,Schweizer F

    更新日期：2012-02-15 00:00:00

  • InCl3 mediated one-pot multicomponent synthesis, anti-microbial, antioxidant and anticancer evaluation of 3-pyranyl indole derivatives.

    abstract：:A simple and convenient method for the one-pot three-component synthesis of 3-pyranyl indoles has been accomplished by tandem Knoevenagel-Michael reaction of 3-cyanoacetyl indole, various aromatic aldehydes and malononitrile catalyzed by InCl(3) in ethanol under reflux conditions. The newly synthesized 3-pyranyl indol...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.07.039

    authors： Lakshmi NV,Thirumurugan P,Noorulla KM,Perumal PT

    更新日期：2010-09-01 00:00:00

  • Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors.

    abstract：:A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity ag...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.06.060

    authors： Narva S,Chitti S,Amaroju S,Bhattacharjee D,Rao BB,Jain N,Alvala M,Sekhar KVGC

    更新日期：2017-08-15 00:00:00

  • Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties.

    abstract：:We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.006

    authors： Li X,Zhang S,Zhang YK,Liu Y,Ding CZ,Zhou Y,Plattner JJ,Baker SJ,Bu W,Liu L,Kazmierski WM,Duan M,Grimes RM,Wright LL,Smith GK,Jarvest RL,Ji JJ,Cooper JP,Tallant MD,Crosby RM,Creech K,Ni ZJ,Zou W,Wright J

    更新日期：2011-04-01 00:00:00

  • Discovery of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides as small molecule inhibitors of PCSK9.

    abstract：:A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier l...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.10.029

    authors： Londregan AT,Aspnes G,Limberakis C,Loria PM,McClure KF,Petersen DN,Raymer B,Ruggeri RB,Wei L,Xiao J,Piotrowski DW

    更新日期：2018-12-15 00:00:00

  • Efficient construction of 6-azasteroids: dual inhibitors of steroidal 5 alpha-reductase.

    abstract：:A new route to 17 beta-substituted-6-azaandrost-4-en-3-ones, potent dual inhibitors of type 1 and 2 steroidal 5 alpha-reductase, is described. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00611-8

    authors： Sharp MJ,Fang FG

    更新日期：1998-12-01 00:00:00

  • Development of an automated assay for accelerated in vitro detection of DNA adduct-inducing and crosslinking agents.

    abstract：:Current techniques for the identification of DNA adduct-inducing and DNA interstrand crosslinking agents include electrophoretic crosslinking assays, electrophoretic gel shift assays, DNA and RNA stop assays, mass spectrometry-based methods and 32P-post-labelling. While these assays provide considerable insight into t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2021.127813

    authors： Medan J,Sleebs BE,Lackovic K,Watson KG,Evison BJ,Phillips DR,Cutts SM

    更新日期：2021-01-21 00:00:00

  • Identification and characterization of β-sitosterol target proteins.

    abstract：:β-Sitosterol is the most abundant plant sterol in the human diet. It is also the major component of several traditional medicines, including saw palmetto and devil's claw. Although β-sitosterol is effective against enlarged prostate in human clinical trials and has anti-cancer and anti-inflammatory activities, the mec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.03.007

    authors： Lomenick B,Shi H,Huang J,Chen C

    更新日期：2015-11-01 00:00:00

  • On-resin cyclization of peptide ligands of the Vascular Endothelial Growth Factor Receptor 1 by copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition.

    abstract：:Cyclic peptides were obtained, on-resin, by the copper (I) catalysed 1,3-dipolar cycloaddition of azides and alkynes. The reaction led exclusively to the formation of the expected cyclomonomeric products which acted as ligands of the Vascular Endothelial Growth Factor receptor 1. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.07.087

    authors： Goncalves V,Gautier B,Regazzetti A,Coric P,Bouaziz S,Garbay C,Vidal M,Inguimbert N

    更新日期：2007-10-15 00:00:00

  • Alpha-ketoamides, alpha-ketoesters and alpha-diketones as HCV NS3 protease inhibitors.

    abstract：:Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00074-3

    authors： Han W,Hu Z,Jiang X,Decicco CP

    更新日期：2000-04-17 00:00:00

  • Lp-PLA2 inhibitory activities of fatty acid glycerols isolated from Saururus chinensis roots.

    abstract：:(R)-Glycerol-monolinoleate 4 and (R)-glycerol-monostearate 5 were isolated from the ethyl acetate extracts of Saururus chinensis roots and (R)- or (S)-fatty acid glycerols 4 and 5 were synthesized for confirming their structures and evaluating their inhibitory activities against Lp-PLA(2). The (R)-4 and (S)-4 exhibite...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.05.056

    authors： Lee WS,Kim MJ,Beck YI,Park YD,Jeong TS

    更新日期：2005-08-01 00:00:00

  • Selective oxidation of 5-hydroxymethylcytosine with micelle incarcerated oxidants to determine it at single base resolution.

    abstract：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.017

    authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

    更新日期：2015-12-15 00:00:00

  • Design of benzoic acid inhibitors of influenza neuraminidase containing a cyclic substitution for the N-acetyl grouping.

    abstract：:A 2-pyrrolidinone ring containing a single hydroxymethyl side chain effectively replaces the N-acetylamino group of 4-(N-acetylamino)-3-guanidinobenzoic acid, a low micromolar inhibitor of influenza neuraminidase. This novel structural template affords new opportunities to evolve more potent benzoic acid inhibitors. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00318-2

    authors： Brouillette WJ,Atigadda VR,Luo M,Air GM,Babu YS,Bantia S

    更新日期：1999-07-19 00:00:00

  • Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives.

    abstract：:2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoid of alkylating property towards the synthetic model of heme Mn(II)-TPP. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00837-5

    authors： Cointeaux L,Berrien JF,Peyrou V,Provot O,Ciceron L,Danis M,Robert A,Meunier B,Mayrargue J

    更新日期：2003-01-06 00:00:00

  • Anticonvulsant and analgesic in neuropathic pain activity in a group of new aminoalkanol derivatives.

    abstract：:As part of the presented research, thirteen new aminoalkanol derivatives were designed and obtained by chemical synthesis. In vivo studies (mice, i.p.) showed anticonvulsant activity (MES) of nine compounds, and in the case of one compound (R,S-trans-2-((2-(2,3,5-trimethylphenoxy)ethyl)amino)cyclohexan-1-ol, 4) both a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127325

    authors： Pańczyk K,Rapacz A,Furgała-Wojas A,Sałat K,Koczurkiewicz-Adamczyk P,Łucjanek M,Skiba-Kurek I,Karczewska E,Sowa A,Żelaszczyk D,Siwek A,Popiół J,Pękala E,Marona H,Waszkielewicz A

    更新日期：2020-08-15 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 and structure evaluation of a novel cantharimide and its cytotoxicity on SK-Hep-1 hepatoma cells.

    abstract：:A remarkable control of the potency of cantharimide is described based on the electronic properties of functional group and it exhibits a relatively less toxic effect to the non-malignant hematological disorder bone marrow cells. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.12.039

    authors： Kok SH,Chui CH,Lam WS,Chen J,Lau FY,Wong RS,Cheng GY,Lai PB,Leung TW,Yu MW,Tang JC,Chan AS

    更新日期：2007-03-01 00:00:00

  • Synthesis and biological evaluation of the pirfenidone derivatives as antifibrotic agents.

    abstract：:A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this ki...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.11.038

    authors： Ma Z,Pan Y,Huang W,Yang Y,Wang Z,Li Q,Zhao Y,Zhang X,Shen Z

    更新日期：2014-01-01 00:00:00

  • Synthesis and biological evaluation of two novel DAT-binding technetium complexes containing a piperidine based analogue of cocaine.

    abstract：:Two new technetium complexes containing a piperidine template have been synthesized and evaluated as possible leads for the development of dopamine transporter (DAT) imaging agents. Binding data for the corresponding rhenium complexes containing either a monoaminomonoamide (MAMA') or a diaminodithiol (DADT) chelating ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00562-4

    authors： Hoepping A,Babich J,Zubieta JA,Johnson KM,Machill S,Kozikowski AP

    更新日期：1999-11-15 00:00:00

  • Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes.

    abstract：:The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure as central template for nonpeptide RGD mim...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00216-5

    authors： Pandey A,Seroogy J,Volkots D,Smyth MS,Rose J,Mehrotra MM,Heath J,Ruhter G,Schotten T,Scarborough RM

    更新日期：2001-05-21 00:00:00