当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent.

Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent.

Abstract：

:We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation. Nevertheless, we succeeded a gram scale synthesis, according to an expeditious three steps route, without intermediate purification. This latter point is of utmost interest in reducing the ecologic impact and production costs in the perspective of further scale-up processes. The purity of NRPa-308 has been attested by means of conventional structural analyses and its crystallisation allowed a structural assessment by X-Ray diffraction. We also reported the remarkable chemical stability of this molecule in acidic, neutral and basic aqueous media. Eventually, we observed for the first time the accumulation of NRPa-308 in two types of human breast cancer cells MDA-MB231 and BT549.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Brachet E,Dumond A,Liu WQ,Fabre M,Selkti M,Raynaud F,Hermine O,Benhida R,Belmont P,Garbay C,Lepelletier Y,Ronco C,Pagès G,Demange L

doi

10.1016/j.bmcl.2019.126710

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

126710

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30668-7

journal_volume

29

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • 3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor.

    abstract：:Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous stud...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.078

    authors： Moreno L,Cabedo N,Ivorra MD,Sanz MJ,Castel AL,Carmen Álvarez M,Cortes D

    更新日期：2013-09-01 00:00:00

  • Synthesis of a bis-azido analogue of acromelic acid for radioisotope-free photoaffinity labeling and biochemical studies.

    abstract：:A novel acromelic acid analogue containing a phenyl group possessing two different types of azido functional groups, of which one is the aromatic N3 acting as a photoaffinity group to bind to a target protein by photoirradiation and the other is alkyl N3 group which survives photolysis acting as a detecting group thro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.01.083

    authors： Sun P,Wang GX,Furuta K,Suzuki M

    更新日期：2006-05-01 00:00:00

  • Chemical constituents of Miliusa balansae leaves and inhibition of nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells.

    abstract：:Methanolic extract of Miliusa balansae Finet et Gagnep exerts an anti-inflammatory effect via inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Three new megastigmane glycosides, milbasides A-C (1-3), together with fifteen known compounds (4-18), were ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.07.056

    authors： Thao NP,Luyen BT,Tai BH,Cuong NM,Kim YC,Minh CV,Kim YH

    更新日期：2015-09-15 00:00:00

  • Conjugation of spermine enhances cellular uptake of the stapled peptide-based inhibitors of p53-Mdm2 interaction.

    abstract：:We report the first synthesis of the C-terminally spermine-conjugated stapled peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological, biophysical and cellular uptake assays with the spermine-conjugated stapled peptides revealed that spermine conjugation minimally affects biological activity while ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.10.009

    authors： Muppidi A,Li X,Chen J,Lin Q

    更新日期：2011-12-15 00:00:00

  • Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity.

    abstract：:Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the trea...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.03.032

    authors： May-Dracka TL,Arduini R,Bertolotti-Ciarlet A,Bhisetti G,Brickelmaier M,Cahir-McFarland E,Enyedy I,Fontenot JD,Hesson T,Little K,Lyssikatos J,Marcotte D,McKee T,Murugan P,Patterson T,Peng H,Rushe M,Silvian L,Spilker K

    更新日期：2018-06-01 00:00:00

  • Structural basis of the dynamic mechanism of ligand binding to cyclooxygenase.

    abstract：:Molecular modeling studies performed on the two cyclooxygenase (COX) isozymes suggest that the cavity at the mouth of the active site on the membrane domain that may act as an actual binding site of COX ligands. Actual docking of different inhibitors at this site provides a structural basis to explain the dynamics of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00481-3

    authors： Llorens O,Perez JJ,Palomer A,Mauleon D

    更新日期：1999-10-04 00:00:00

  • The discovery of potent cRaf1 kinase inhibitors.

    abstract：:A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00668-x

    authors： Lackey K,Cory M,Davis R,Frye SV,Harris PA,Hunter RN,Jung DK,McDonald OB,McNutt RW,Peel MR,Rutkowske RD,Veal JM,Wood ER

    更新日期：2000-02-07 00:00:00

  • Optimization of halopemide for phospholipase D2 inhibition.

    abstract：:Halopemide, which was identified by HTS to inhibit phospholipase D2 (PLD2), provided the basis for an exploratory effort to identify potent inhibitors of PLD2 for use as inflammatory mediators. Parallel synthesis and purification were utilized to rapidly identify orally available amide analogs derived from indole 2-ca...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.01.059

    authors： Monovich L,Mugrage B,Quadros E,Toscano K,Tommasi R,LaVoie S,Liu E,Du Z,LaSala D,Boyar W,Steed P

    更新日期：2007-04-15 00:00:00

  • Indole-based heterocyclic inhibitors of p38alpha MAP kinase: designing a conformationally restricted analogue.

    abstract：:p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00653-x

    authors： Mavunkel BJ,Chakravarty S,Perumattam JJ,Luedtke GR,Liang X,Lim D,Xu YJ,Laney M,Liu DY,Schreiner GF,Lewicki JA,Dugar S

    更新日期：2003-09-15 00:00:00

  • New CD1d agonists: synthesis and biological activity of 6″-triazole-substituted α-galactosyl ceramides.

    abstract：:Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.05.009

    authors： Jervis PJ,Graham LM,Foster EL,Cox LR,Porcelli SA,Besra GS

    更新日期：2012-07-01 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

  • A divergent chemoenzymatic route to an intermediate for nucleoside analogues.

    abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.033

    authors： Basak A,Bisai S

    更新日期：2005-05-16 00:00:00

  • Design and synthesis of beta-carboxamido phosphonates as potent inhibitors of imidazole glycerol phosphate dehydratase.

    abstract：:We describe the synthesis and enzymatic activity of a library of beta-carboxamido phosphonates as inhibitors of imidazole glycerol phosphate dehydratase (IGPD). Biological results suggest the presence of an enzymatic interaction site not previously observed for other inhibitors of IGPD. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00338-8

    authors： Schweitzer BA,Loida PJ,Thompson-Mize RL,CaJacob CA,Hegde SG

    更新日期：1999-07-19 00:00:00

  • Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.

    abstract：:The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.06.072

    authors： Levin JI,Chen JM,Laakso LM,Du M,Du X,Venkatesan AM,Sandanayaka V,Zask A,Xu J,Xu W,Zhang Y,Skotnicki JS

    更新日期：2005-10-01 00:00:00

  • New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center.

    abstract：:Introducing a second chiral center on our previously described 1,2,4-triazole, allowed us to increase diversity and elongate the 'C-terminal part' of the molecule. Therefore, we were able to explore mimics of the substance P analogs described as inverse agonists. Some compounds presented affinities in the nanomolar ra...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.04.003

    authors： Maingot M,Blayo AL,Denoyelle S,M'Kadmi C,Damian M,Mary S,Gagne D,Sanchez P,Aicher B,Schmidt P,Müller G,Teifel M,Günther E,Marie J,Banères JL,Martinez J,Fehrentz JA

    更新日期：2016-05-15 00:00:00

  • Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.

    abstract：:This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.081

    authors： Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

    更新日期：2007-03-01 00:00:00

  • Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.

    abstract：:Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.05.090

    authors： Petrov KG,Zhang YM,Carter M,Cockerill GS,Dickerson S,Gauthier CA,Guo Y,Mook RA Jr,Rusnak DW,Walker AL,Wood ER,Lackey KE

    更新日期：2006-09-01 00:00:00

  • Synthesis and evaluation of 2-phenyl-1,4-butanediamine-based CCR5 antagonists for the treatment of HIV-1.

    abstract：:We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.030

    authors： Tallant MD,Duan M,Freeman GA,Ferris RG,Edelstein MP,Kazmierski WM,Wheelan PJ

    更新日期：2011-03-01 00:00:00

  • Dopamine/serotonin receptor ligands. Part 15: Oxygenation of the benz-indolo-azecine LE 300 leads to novel subnanomolar dopamine D1/D5 antagonists.

    abstract：:Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the aff...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.093

    authors： Enzensperger C,Kilian S,Ackermann M,Koch A,Kelch K,Lehmann J

    更新日期：2007-03-01 00:00:00

  • Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB.

    abstract：:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.09.072

    authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

    更新日期：2015-11-15 00:00:00

  • Novel lead for potent inhibitors of breast cancer resistance protein (BCRP).

    abstract：:From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibito...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.11.004

    authors： Pick A,Müller H,Wiese M

    更新日期：2010-01-01 00:00:00

  • Synthesis and PGE₂ production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells.

    abstract：:We present the synthesis and biological evaluation of a collection of s-triazine derivatives as a novel scaffold of compounds with the capability to inhibit the PGE₂ production in LPS-induced RAW 264.7 macrophage cells. A total of 12 derivatives were synthesized and assayed for PGE₂ reduction at 10 μM concentration. T...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.10.031

    authors： Kang SM,Lee J,Jin JH,Kim M,Lee S,Lee HH,Shin JS,Lee KT,Lee JY

    更新日期：2014-12-01 00:00:00

  • Discovery of 'molecular switches' within a GIRK activator scaffold that afford selective GIRK inhibitors.

    abstract：:This letter describes a multi-dimensional SAR campaign based on a potent, efficacious and selective GIRK1/2 activator (~10-fold versus GIRK1/4 and inactive on nonGIRK 1-containing GIRKs, GIRK 2 or GIRK2/3). Further chemical optimization through an iterative parallel synthesis effort identified multiple 'molecular swit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.023

    authors： Wen W,Wu W,Romaine IM,Kaufmann K,Du Y,Sulikowski GA,Weaver CD,Lindsley CW

    更新日期：2013-08-15 00:00:00

  • Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino[2,3-d]pyrimidine core.

    abstract：:A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synt...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.028

    authors： Dow RL,Andrews M,Aspnes GE,Balan G,Michael Gibbs E,Guzman-Perez A,Karki K,Laperle JL,Li JC,Litchfield J,Munchhof MJ,Perreault C,Patel L

    更新日期：2011-10-15 00:00:00

  • The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimethoxychalcone induces unfolded protein response-mediated apoptosis in A549 lung cancer cells.

    abstract：:The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimenthoxyochalcone (named DK-139) exhibits anti-inflammatory and anti-tumor invasion properties. However, effects of DK-139 on tumor cell growth remain unknown. In the present study, we evaluated the inhibitory activity of DK-139 against human lung cancer cells. Tr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.07.003

    authors： Gil HN,Koh D,Lim Y,Lee YH,Shin SY

    更新日期：2018-09-15 00:00:00

  • Rapid solid-phase synthesis of DNA-binding pyrrole-imidazole polyamides.

    abstract：:Pyrrole-imidazole polyamides can be synthesized to target predetermined sequences of DNA with nanomolar affinity and high specificity, and have been shown to modulate gene transcription both in vitro and in vivo. To make polyamides more readily available to biological laboratories, we have developed a rapid solid-phas...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00359-1

    authors： Krutzik PO,Chamberlin AR

    更新日期：2002-08-19 00:00:00

  • Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles.

    abstract：:A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.12.087

    authors： Kreusch A,Han S,Brinker A,Zhou V,Choi HS,He Y,Lesley SA,Caldwell J,Gu XJ

    更新日期：2005-03-01 00:00:00

  • Carboxy derivatized glucosamine is a potent inhibitor of matrix metalloproteinase-9 in HT1080 cells.

    abstract：:Experimental evidences have confirmed that matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions and recent advances in medicinal chemistry approach to the design of MMP inhibitors with desired structural and functional properties. Among MMPs, MMP-9 has demonstrated to pla...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.03.077

    authors： Mendis E,Kim MM,Rajapakse N,Kim SK

    更新日期：2006-06-15 00:00:00

  • Orally bioavailable factor Xa inhibitors containing alpha-substituted gem-dimethyl P4 moieties.

    abstract：:In an effort to identify a potential back-up to apixaban (Eliquis®), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent FXa binding affinity (FXa Ki), good human plasma anticoagulant...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.101

    authors： Orwat MJ,Qiao JX,He K,Rendina AR,Luettgen JM,Rossi KA,Xin B,Knabb RM,Wexler RR,Lam PY,Pinto DJ

    更新日期：2014-08-01 00:00:00

  • Design and synthesis of novel delta opioid receptor agonists and their pharmacologies.

    abstract：:We re-examined the accessory site of the 4,5-epoxymorphinan skeleton by camdas conformational analysis in an effort to deign novel delta opioid receptor antagonists. We synthesized three novel compounds (SN-11, 23 and 28) with a 10-methylene bridge and without a 4,5-epoxy ring. Among them, compounds SN-23 (17-isobutyl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.03.099

    authors： Nagase H,Osa Y,Nemoto T,Fujii H,Imai M,Nakamura T,Kanemasa T,Kato A,Gouda H,Hirono S

    更新日期：2009-05-15 00:00:00