Search results for "quinolines"

Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR.

2003

Dysregulation of extracellular matrix turnover is an important feature of many inflammatory processes. Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta. We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO. Moreover, by use of an in vitro degradation assay we found that the cytoplasmic fractions of NO-treated cells contained a higher capacity to degrade MMP-9 transcripts than those obtained from contro…

Organocatalytic Enantioselective Functionalization of Hydroxyquinolines through an Aza-Friedel-Crafts Alkylation with Isatin-derived Ketimines

2018

[EN] A highly enantioselective addition of hydroxyquinolines to isatin-derived ketimines has been realized using a quinine-derived thiourea organocatalyst. The reaction affords chiral 3-amino-2-oxindoles bearing a quinoline moiety with a quaternary stereocenter in high yields (up to 98%) and excellent enantioselectivities (up to 99%). Moreover, we can extend this methodology for the enantioselective functionalization of 5-hydroxyisoquinoline. This methodology represents, to the best of our knowledge, the first enantioselective addition of hydroxyquinolines to imines.

Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization.

2015

An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz–Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.

Differential reactivity of fluorinated homopropargylic amino esters vs gold(I) salts. The role of the nitrogen protecting group

2015

The reaction of several homopropargyl amino esters 4, bearing aromatic substituents and a benzyl group as nitrogen substituents, with gold(I) salts gave rise to fluorinated quinolines 6 in a tandem hydroarylation-isomerization process. On the other hand, homopropargyl amino esters 7 containing a carbamate group underwent the carbonyl addition over the triple bond in the presence of gold(I) salts, rendering fluorinated oxazines 8. The use of chiral sulfoxides allowed us to develop the asymmetric version of this protocol. This two processes complete the differential reactivity showed by these types of susbtrates, depending on the nature of the nitrogen protecting group. (C) 2014 Elsevier B.V.…

Selective chiral inhibition of Ca2+ entry promoted by bisbenzyltetrahydroisoquinolines in rat uterus.

1992

Abstract The effects of diltiazem and six bisbenzyltetrahydroisoquinoline alkaloids (antioquine, 7-O-methylantioquine, dimethylantioquine, monterine, granjine and cordobimine) were studied in rat isolated uterus in order to clarify the mechanisms of their relaxant actions. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only alkaloids with absolute configurations (1R,1′S or 1R,1′R) acted intracellularly, promoting relaxation of contractile responses induced by oxytocin in a Ca2+-free medium, as does papaverine. Alkaloids of the antioquine series (1S,1′R) selectively inhibited Ca2+ entry. The grea…

Organocatalytic approach to benzofused nitrogen-containing heterocycles: enantioselective total synthesis of (+)-angustureine.

2008

Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives

2009

Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor. (C) 2009 Elsevier Masson SAS. All ri…

Nanolayered Cobalt-Molybdenum Sulfides as Highly Chemo- and Regioselective Catalysts for the Hydrogenation of Quinoline Derivatives

2018

[EN] Herein, a general protocol for the preparation of a broad range of valuable N-heterocyclic products by hydrogenation of quinolines and related N-heteroarenes is described. Interestingly, the catalytic hydrogenation of the N-heteroarene ring is chemoselectively performed when other facile reducible functional groups, including alkenes, ketones, cyanides, carboxylic acids, esters, and amides, are present. The key to successful catalysis relies on the use of a nanolayered cobalt-molybdenum sulfide catalyst hydrothermally synthesized from earth-abundant metal precursors. This heterogeneous system displays a tunable composition of phases that allows for catalyst regeneration. Its catalytic …

Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.

2018

Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)a and IFN? and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activit…

Quinoline anticancer agents active on DNA and DNA-interacting proteins: From classical to emerging therapeutic targets.

2021

Quinoline is one of the most important and versatile nitrogen heterocycles embodied in several biologically active molecules. Within the numerous quinolines developed as antiproliferative agents, this review is focused on compounds interfering with DNA structure or with proteins/enzymes involved in the regulation of double helix functional processes. In this light, a special focus is given to the quinoline compounds, acting with classical/well-known mechanisms of action (DNA intercalators or Topoisomerase inhibitors). In particular, the quinoline drugs amsacrine and camptothecin (CPT) have been studied as key lead compounds for the development of new agents with improved PK and tolerability…