Delphine Le Broc-Ryckewaert, Nicole Pommery, Jean Pommery, Alina Ghinet, Amaury Farce, Jean-François Wiart, Philippe Gautret, Benoît Rigo, Jean-Pierre Hénichart
Drug metabolism letters
August 2011
Vol. 5(3)Pages: 209-15
Phenstatin and its derivatives are potential anticancer drug candidates according to their inhibitory properties on tubulin polymerization, cell growth and antivascular activity. However, at the present time, neither pharmacological nor metabolic studies have been conducted in order to strengthen the relevance of phenstatine as a drug discovery candidate. In the …
Virginie Andrzejak, Giulio G Muccioli, Mathilde Body-Malapel, Jamal El Bakali, Madjid Djouina, Nicolas Renault, Philippe Chavatte, Pierre Desreumaux, Didier M Lambert, Régis Millet
Bioorganic & medicinal chemistry
June 2011
Vol. 19(12)Pages: 3777-86
Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we report the first series of carboxamides derivatives possessing FAAH inhibitory activities. Among them, compound 39 displayed …
Véronique Leclerc, Mohamed Ettaoussi, Marouan Rami, Amaury Farce, Jean Albert Boutin, Philippe Delagrange, Daniel-Henri Caignard, Pierre Renard, Pascal Berthelot, Saïd Yous
European journal of medicinal chemistry
May 2011
Vol. 46(5)Pages: 1622-9
Naphthalenic analogs of MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 …
Antonio Garofalo, Laurence Goossens, Perrine Six, Amélie Lemoine, Séverine Ravez, Amaury Farce, Patrick Depreux
Bioorganic & medicinal chemistry letters
April 2011
Vol. 21(7)Pages: 2106-12
Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds have been evaluated for their enzymatic inhibition of VEGFR-2 and EGFR and for their antiproliferative activities on various cancer cell …
Nicolas Wlodarczyk, Delphine Le Broc-Ryckewaert, Pauline Gilleron, Amélie Lemoine, Amaury Farce, Philippe Chavatte, Joëlle Dubois, Nicole Pommery, Jean-Pierre Hénichart, Christophe Furman, Régis Millet
Journal of medicinal chemistry
March 2011
Vol. 54(5)Pages: 1178-90
A new class of potent farnesyltransferase inhibitors based on a 1,4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was …
Valerie Verones, Nathalie Flouquet, Amaury Farce, Pascal Carato, Stephane Leonce, Bruno Pfeiffer, Pascal Berthelot, Nicolas Lebegue
European journal of medicinal chemistry
December 2010
Vol. 45(12)Pages: 5678-84
The synthesis of new 4-amino-tetrahydroquinazolino[3,2-e]purine derivatives along with their activity in cell-free enzymatic assays on Src is reported. Some compounds emerged as moderately active inhibitors of the enzyme and showed antiproliferative effects on the murine leukemia L1210 cell line. Docking studies have been also performed to analyze the binding mode …
Jamal El Bakali, Giulio G Muccioli, Nicolas Renault, Delphine Pradal, Mathilde Body-Malapel, Madjid Djouina, Laurie Hamtiaux, Virginie Andrzejak, Pierre Desreumaux, Philippe Chavatte, Didier M Lambert, Régis Millet
Journal of medicinal chemistry
November 2010
Vol. 53(22)Pages: 7918-31
Growing evidence shows that CB(2) receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective CB(2) agonists, we describe here the medicinal chemistry approach leading to the development of CB(2) receptor inverse agonists with a 4-oxo-1,4-dihydropyridine scaffold. The compounds reported here show high affinity and potency …
Nicolas Renault, Arnaud Gohier, Philippe Chavatte, Amaury Farce
European journal of medicinal chemistry
November 2010
Vol. 45(11)Pages: 5086-99
Structure-based design of compounds targeting monoamine receptors, within the class-A G-protein coupled receptors, has been enriched by the recent crystallization of the β1 and β2 adrenoceptors. On the basis of ligand-biased homology modeling and docking-scoring calculations, a ritanserin-biased 5-HT(2C) receptor model has been built and used in a highly efficient …
Antonio Garofalo, Laurence Goossens, Amelie Lemoine, Amaury Farce, Yannick Arlot, Patrick Depreux
Journal of enzyme inhibition and medicinal chemistry
April 2010
Vol. 25(2)Pages: 158-71
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2), two protein tyrosine kinases, are involved in pathological disorders and the progression of different types of carcinomas. Concomitant inhibition of both tyrosine kinase activities appears to be an attractive target for cancer chemotherapy. A series of new quinazoline …
Frank Bienaime, Marie-Agnes Dragon-Durey, Catherine H Regnier, Sara C Nilsson, Wing H Kwan, Jacques Blouin, Mathieu Jablonski, Nicolas Renault, Marie-Anne Rameix-Welti, Chantal Loirat, Catherine Sautés-Fridman, Bruno O Villoutreix, Anna M Blom, Veronique Fremeaux-Bacchi
Kidney international
February 2010
Vol. 77(4)Pages: 339-49
Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations …
Jamal El Bakali, Frédérique Klupsch, Aurore Guédin, Bertrand Brassart, Gaëlle Fontaine, Amaury Farce, Pascal Roussel, Raymond Houssin, Jean-Luc Bernier, Philippe Chavatte, Jean-Louis Mergny, Jean-François Riou, Jean-Pierre Hénichart
Bioorganic & medicinal chemistry letters
July 2009
Vol. 19(13)Pages: 3434-8
The design and synthesis of 2,6-diphenylthiazolo[3,2-b][1,2,4]triazoles characterized by a large aromatic building block bearing cationic side chains are reported. These molecules are evaluated as telomeric G-quadruplex stabilizers and for their selectivity towards duplex DNA by competition experiments. Two compounds (14a, 19) were found active with high selectivity for telomeric G-quadruplex …
Sara C Nilsson, Leendert A Trouw, Nicolas Renault, Maria A Miteva, Ferah Genel, Marta Zelazko, Hanne Marquart, Klaus Muller, Anders G Sjöholm, Lennart Truedsson, Bruno O Villoutreix, Anna M Blom
European journal of immunology
January 2009
Vol. 39(1)Pages: 310-23
Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patients with no detectable serum FI and also close family members revealed …
Nicolas Kambia, Nicolas Renault, Sebastien Dilly, Amaury Farce, Thierry Dine, Bernard Gressier, Michel Luyckx, Claude Brunet, Philippe Chavatte
Journal of enzyme inhibition and medicinal chemistry
October 2008
Vol. 23(5)Pages: 611-6
Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl chloride (PVC) that is used in plastic tubes, in medical and paramedical devices as well as in food storage packaging. The toxicological profile of DEHP has been evaluated in a number of experimental animal models and has been extensively documented. …
Amaury Farce, Anton O Chugunov, Cédric Logé, Ahmed Sabaouni, Saïd Yous, Sébastien Dilly, Nicolas Renault, Gérard Vergoten, Roman G Efremov, Daniel Lesieur, Philippe Chavatte
European journal of medicinal chemistry
September 2008
Vol. 43(9)Pages: 1926-44
Melatonin is a neurohormone synthesized and secreted mainly during the dark period of the circadian cycle by the pineal gland. It has already been proved to be involved in a number of chronobiological processes, most of them being mediated by its membranar receptors MT1 and MT2. Both are members of …
Amaury Graulich, Sébastien Dilly, Amaury Farce, Jacqueline Scuvée-Moreau, Olivier Waroux, Cédric Lamy, Philippe Chavatte, Vincent Seutin, Jean-François Liégeois
Journal of medicinal chemistry
October 2007
Vol. 50(21)Pages: 5070-5
Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis-isoquinolinium derivatives were synthezised and evaluated using binding studies, electrophysiology, and molecular modeling. These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for the channels …
Pauline Gilleron, Nicolas Wlodarczyk, Raymond Houssin, Amaury Farce, Guillaume Laconde, Jean-François Goossens, Amélie Lemoine, Nicole Pommery, Jean-Pierre Hénichart, Régis Millet
Bioorganic & medicinal chemistry letters
October 2007
Vol. 17(19)Pages: 5465-71
A new series of FTase inhibitors containing a tricyclic moiety--dioxodibenzothiazepine or dibenzocycloheptane--has been designed and synthesized. Among them, dioxodibenzothiazepine 18d displayed significant inhibitory FTase activity (IC(50)=17.3 nM) and antiproliferative properties.
Anne-Catherine Durand, Amaury Farce, Pascal Carato, Sebastien Dilly, Said Yous, Pascal Berthelot, Philippe Chavatte
Journal of enzyme inhibition and medicinal chemistry
October 2007
Vol. 22(5)Pages: 556-62
In order to predict the antioxidant activity of 22 pinoline derivatives (1,2,3,4-tetrahydro-beta-carbolines), two dimensional quantitative-structure activity relationships (2D-QSAR) analysis of 19 hexahydropiridoindoles and 12 flavonoids was realized. Five statistically significant models were obtained from randomly constituted training sets (21 compounds) and subsquently validated with the corresponding test sets (10 compounds). …
Bruno O Villoutreix, Nicolas Renault, David Lagorce, Olivier Sperandio, Matthieu Montes, Maria A Miteva
Current protein & peptide science
August 2007
Vol. 8(4)Pages: 381-411
In today's research environment, a wealth of experimental/theoretical structural data is available and the number of therapeutically relevant macromolecular structures is growing rapidly. This, coupled with the huge number of small non-peptide potential drug candidates easily available (over 7 million compounds), highlight the need of using computer-aided techniques for the …
The tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is widely involved in signaling pathways and often deregulated in cancer. Its role in the development of prostate cancer is well established, and therapeutic strategies such as blockade of the intracellular tyrosine kinase domain with small-molecule tyrosine kinase inhibitors …
Elodie Blanc-Delmas, Nicolas Lebegue, Valérie Wallez, Véronique Leclerc, Saïd Yous, Pascal Carato, Amaury Farce, Caroline Bennejean, Pierre Renard, Daniel-Henri Caignard, Valérie Audinot-Bouchez, Pascale Chomarat, Jean Boutin, Nathalie Hennuyer, Katie Louche, Maria Carmen Carmona, Bart Staels, Luc Pénicaud, Louis Casteilla, Michel Lonchampt, Catherine Dacquet, Philippe Chavatte, Pascal Berthelot, Daniel Lesieur
Bioorganic & medicinal chemistry
November 2006
Vol. 14(22)Pages: 7377-91
A series of 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles has been synthesized and tested for PPARgamma agonist activity. SAR were developed and revealed that 6-acyl-2(3H)-benzothiazolone derivatives with 1,3-dicarbonyl group were the most potent. IP administration of compound 22 exhibited comparable levels of glucose and triglyceride correction to PO administration of rosiglitazone …