Papers by Isabelle McCort
ChemInform, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of Medicinal Chemistry, Nov 1, 1997
ChemInform, Aug 4, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, Jun 23, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, May 25, 2010
ABSTRACT Four enantiopure pseudo-aza-di-(or tri-)saccharides have been synthesized by aminocycliz... more ABSTRACT Four enantiopure pseudo-aza-di-(or tri-)saccharides have been synthesized by aminocyclization of a C2-symmetrical d-manno-bis-epoxide either with a primary amine having a polyhydroxylated tetrahydrofuran skeleton or with a polyhydroxylated piperidine or azepan.
ChemInform, Jun 15, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Tetrahedron, Apr 1, 2003
Anhydro-1-(aryl or alkylamino)-1-deoxy-D-sorbitol derivatives have been prepared in four steps fr... more Anhydro-1-(aryl or alkylamino)-1-deoxy-D-sorbitol derivatives have been prepared in four steps from isosorbide, a by-product from the starch industry. The inhibitory activities of these new compounds have been evaluated towards 13 glycosidases. A first lead-compound was identified, which inhibited b-N-acetylglucosaminidase from bovine kidney (82% inhibition at 1 mM).
ChemInform, Aug 21, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, Jun 19, 2010
Synthesis of Ester-and Amide-Linked Pseudo-Azadisaccharides via Coupling of D-Glucose with 6-Amin... more Synthesis of Ester-and Amide-Linked Pseudo-Azadisaccharides via Coupling of D-Glucose with 6-Amino-6-deoxy-2,5-imino-D-glucitol.-Hydrolytically-resistant pseudodisaccharides such as (III) and (V), in which C-1 of 6-amino-2,5-D-glucitol is linked to C-6 of D-glucose through an ester or amide bond, are described.
Organic and Biomolecular Chemistry, 2009
The 1,2-O-isopropylidene and 1,2-O-dibenzyloxy-NH bis-aziridines, precursors of all the N-protect... more The 1,2-O-isopropylidene and 1,2-O-dibenzyloxy-NH bis-aziridines, precursors of all the N-protected bis-aziridines, were obtained according to our previous procedure. 1 Bis-indolylmaleimide 5d and indolocarbazole 6b were synthesized according to classical procedures. 2 General procedure for the synthesis of 9a-d and 10a-c. To a solution of crude NH bis-aziridine (1.0 eq) in DMF (0.4 M) cooled at-15 °C, were slowly added Et 3 N (15.0 eq) and a solution of either TsCl, SES-Cl, Mts-Cl, (2.5 eq) or Boc 2 O (1.0 eq) in DMF (1 M). After stirring for 4 h at this temperature, the mixture was poured in H 2 O and extracted with Et 2 O. The organic layers were then dried over MgSO 4 , filtered and concentrated. The residue was purified by column chromatography (cyclohexane/EtOAc/NH 4 OH: 85/15/1). (2S,2'S)-[(1R,2R)-1,2-O-Isopropylidene-ethan-diyl]-N,N'-[2-(trimethylsilyl)ethylsulfonyl]-bisaziridine (9b). SES N SES N O O O-Isopropylidene NH bis-aziridine, obtained from 3,4-O-isopropylidene-1,6-dideoxy-1,6-diazido-Dmannitol (460 mg, 1.69 mmol), and SES-Cl (850 mg, 4.25 mmol) yielded 9b (550 mg, 64%) as a white solid; R f 0.30 (cyclohexane/EtOAc, 7/3); mp 87-88 °C; [α] D 20-37 (c 1.0 in CH 2 Cl 2); IR (ATR) 2954,
Nature Communications, Dec 5, 2019
Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors that operate at... more Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity~4000-fold lower than other mGluRs and a maximal activation of onlỹ 10%, seemingly too low for activation at synapses. However, mGluR7 heterodimerizes, and we find it to associate with mGluR2 in the hippocampus. Strikingly, the mGluR2/7 heterodimer has high affinity and efficacy. mGluR2/7 shows cooperativity in which an unliganded subunit greatly enhances activation by agonist bound to its heteromeric partner, and a unique conformational pathway to activation, in which mGluR2/7 partially activates in the Apo state, even when its LBDs are held open by antagonist. High sensitivity and an unusually broad dynamic range should enable mGluR2/7 to respond to both glutamate transients from nearby release and spillover from distant synapses.
ChemInform, Jun 23, 2010
ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)über... more ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)übergeführt, die Wirkung gegen Leukämiezellen der Maus besitzen. Am wirksamsten ist die Verbindung (IIIa). (UV-spektroskopische Daten).
Journal of medicinal chemistry, Jan 8, 2018
A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. ... more A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an l-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties...
Nature Communications, 2017
Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response ... more Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential ‘on-off’ switch of pDC activity with therapeutic potential.
International Journal of Peptide and Protein Research, 2009
The sulfated tyrosine present in the sequence of CCK8 Asp26-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2,... more The sulfated tyrosine present in the sequence of CCK8 Asp26-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2, seems to play a critical role in the recognition of CCK-A binding sites. In this work, we have investigated whether the presence of an anionic charge on the tyrosine moiety is strictly necessary and whether the sulfate moiety interacts with a divalent cation in the receptor subsite. For this purpose, the novel amino acids (L,D)Phe(p-CH2CO2H) and (L,D) Phe(p-CH2CONHOH), as well as their L-resolved forms were introduced into the sequence of Ac[X27, Nle28, Nle31]-CCK27-33 by solid phase method. The biological activities of these new derivatives were compared to two almost equiactive analogues of CCK8, Ac[Phe(p-CH2SO3H)27, Nle28, Nle31]-CCK27-33 and Boc[Nle28, Nle31]-CCK27-33 (BDNL) and to the nonsulfated analogue of the latter peptide (BDNL NS). All these new CCK-related analogues behave as agonists in stimulating pancreatic amylase release and display high affinity for brain binding sites (KI approximately 3-11 nM) but the only peptides which retain affinity for CCK-A receptors (KI approximately 20 nM) are those containing a p-carboxymethyl phenylalanine. Thus, introduction of this amino acid under an esterified form on the side chain, into specific and potent CCK-B agonists could allow compounds endowed with good bioavailabilities to be obtained.
Pharmacology Biochemistry and Behavior, 1994
effects of the selective CCK-B agonists, BC 264 and BC 197, and the nonselective CCK agonist BDNL... more effects of the selective CCK-B agonists, BC 264 and BC 197, and the nonselective CCK agonist BDNL were investigated in the elevated plus-maze in rats. BDNL and BC 197 induced anxiogeniclike effects, in contrast to BC 264, which had no effect. The behavioral responses induced by BDNL were not significantly blocked by L-365,260, but were suppressed by CI-988, another selective CCK-B antagonist, and by high doses of L-364,718, a selective CCK-A antagonist. BC 197-induced effects were also blocked by CI-988. Competition experiments performed with [3H]pBC 264 using brain membranes of guinea pig, mouse, and rat were significantly better fitted when analyzed by a two site model than by a one site model with BC 197 but not with BC 264. Moreover, BC 264 produced anxiogeniclike effects when administered with increasing doses of L-365,260 and opposing effects with increasing doses of CI-988. Together these results give pharmacological and behavioral evidence for the existence of CCK-B receptor subtypes. Cholecystokinin CCK-B agonists CCK-B receptors Subtypes Elevated plus-maze Scopolamine Chlordiazepoxide FG 7142 Rat Mouse Guinea pig Amphetamine
Journal of Medicinal Chemistry, 1992
... Agnes Dorville,t Isabelle McCort-Tranchepain,+ Dominique Vichard,t William Sather,? ... Bigge... more ... Agnes Dorville,t Isabelle McCort-Tranchepain,+ Dominique Vichard,t William Sather,? ... Bigge, CF; Drummond, J. T.; Johnson, G.; Malone, T.; Pro-bert, A. w., Jr.; Marcoux, F. w.; Coughenour, LL; Brahce, L. J. Exploration of phenyl-spaced 2-amino-(5-9)-phosphono-alkanoic acids ...
ChemInform, Jun 11, 2012
Michael addition of N-9 adenine (I) to tert-butylacrylate or acrylic acid proceeds under phase-tr... more Michael addition of N-9 adenine (I) to tert-butylacrylate or acrylic acid proceeds under phase-transfer catalysis in the presence of DABCO to give N-alkylated products (III).
Neuroscience Letters, 2021
Cocaine addiction is a serious health issue in Western countries. Despite the regular increase in... more Cocaine addiction is a serious health issue in Western countries. Despite the regular increase in cocaine consumption across the population, there is no specific treatment for cocaine addiction. Critical roles for glutamate neurotransmission in the rewarding effects of psychostimulants as well as relapse have been suggested and accumulating evidence indicates that targeting mGlu group III receptors could represent a promising strategy to develop therapeutic compounds to treat addiction. In this context, the aim of our study was to examine the effect of LSP2-9166, a mGlu4/mGlu7 receptor orthosteric agonist, on the motivation for cocaine intake. We used an intravenous self-administration paradigm in male Wistar rats as a reliable model of voluntary drug intake. We first evaluated the direct impact of cocaine on Grm4 and Grm7 gene expression. Voluntary cocaine intake under a fixed ratio schedule of injections induced an increase of both mGlu4 and mGlu7 receptor transcripts in nucleus accumbens and hippocampus. We then evaluated the ability of LSP2-9166 to affect cocaine self-administration under a progressive ratio schedule of reinforcement. We found that this compound inhibits the motivation to obtain the drug, although it induced a hypolocomotor effect which could biais motivation index. Our findings demonstrate that mGlu group III receptors represent new targets for decreasing motivation to self-administer cocaine.
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Papers by Isabelle McCort