AbstractAmination of the heterocyclic skeleton is first carried out under conditions A).

A wide range of 3,6-di(hetero) arylated title imidazole derivatives are obtained with good functional group tolerance by C-3 pallado-catalyzed functionalization performed with low catalyst loading.

The first efficient synthesis of various 1,4‐disubstituted pyrido[1′,2′:1,5]pyrazolo[3,4‐d]pyridazines is reported. The reactivity toward chlorine release at the C‐1 and C‐4 positions was investigated. SNAr and palladium‐catalysed cross‐coupling reactions were carried out, and conditions were optimised for each procedure. 1,4‐Bis(het)aryl derivatives were obtained under a Suzuki cross‐coupling procedure whereas SNAr substitution was achieved mainly at C‐1 in preference to C‐4. The monosubstituted C‐4 morpholino derivative was used as a starting material to provide dissymmetrical 1,4‐diaminated or 1‐(het)aryl‐4‐morpholino products.

Herein a novel access to functionalizable 6-substituted imidazo[1,2-a]imidazole scaffolds is described. The reactivity of this heterobicyclic unit toward direct C-H arylation was studied, and conditions allowing regioselective arylation at position 3 were successfully developed. The practicability of this method is manifested by the ligandless conditions and low catalyst loading. The strategy is functional group tolerant and provides rapid access to a large variety of 3,6-di(hetero)arylated imidazo[1,2-a]imidazole derivatives. A second arylation at position 2 was then carried out, and a library of diversified 2,3,6-tri(hetero)arylated imidazo[1,2-a]imidazoles was generated in good yields. A one-pot, two-step procedure was finally developed.

ChemInformVolume 46, Issue 44 Heterocyclic Compounds ChemInform Abstract: Synthesis of 1,4-Disubstituted Pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyridazines by Means of SNAr and Palladium-Catalyzed Reactions. Rabia Belaroussi, Rabia Belaroussi Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorAhmed El Hakmaoui, Ahmed El Hakmaoui Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorNathalie Percina, Nathalie Percina Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorAgnes Chartier, Agnes Chartier Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorMathieu Marchivie, Mathieu Marchivie Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorStephane Massip, Stephane Massip Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorChristian Jarry, Christian Jarry Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorMohamed Akssira, Mohamed Akssira Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorGerald Guillaumet, Gerald Guillaumet Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorSylvain Routier, Sylvain Routier Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this author Rabia Belaroussi, Rabia Belaroussi Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorAhmed El Hakmaoui, Ahmed El Hakmaoui Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorNathalie Percina, Nathalie Percina Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorAgnes Chartier, Agnes Chartier Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorMathieu Marchivie, Mathieu Marchivie Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorStephane Massip, Stephane Massip Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorChristian Jarry, Christian Jarry Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorMohamed Akssira, Mohamed Akssira Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorGerald Guillaumet, Gerald Guillaumet Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this authorSylvain Routier, Sylvain Routier Inst. Chim. Org. Anal., CNRS, Univ. Orleans, F-45067 Orleans, Fr.Search for more papers by this author First published: 15 October 2015 https://doi.org/10.1002/chin.201544186Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue44November, 2015 RelatedInformation

An original and efficient palladium-catalyzed amination of imidazo[2,1-b][1,3,4]thiadiazole is reported. The SNAr and Buchwald–Hartwig cross-coupling reactions were investigated to access C-2 aminated imidazo[1,2-b][1,3,4]thiadiazole derivatives. The reaction conditions were optimized under microwave irradiation, and a wide range of amines were used to determine the scope and limitations of the method. To complete this study, the palladium-catalyzed and SNAr amination reactions were compared to determine the best strategy. The X-ray crystallographic data of imidazo[2,1-b][1,3,4]thiadiazole derivative 20 was used to formally establish the structures of the products.

An efficient, simple, and convenient synthetic procedure for the synthesis of tetracyclic spirooxindole derivatives, starting from N-protected isatins and 2-fluoropyridine, was success-fully developed. It enables the facile formation of a new class of spirooxindoles in which the oxindole core is fused with various heterocycles at the C-3 position.

In this report, we describe the synthesis of a novel library of α7 nAChR ligands based on the modulation of the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly synthesized under stereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor with Ki measured between 14 and 133 nM. The best fluorinated candidate was selected and radiolabeled. The potent [18F]4 PET tracer was evaluated in rats and its brain accumulation quantified.

AbstractThe synthesis of the title compounds (VII) is based on the condensation of 1‐aminopyridinium salt (I) with dimethyl acetylenedicarboxylate followed by regioselective saponification to give the key intermediate (IV) which can be converted to the useful tricyclic derivatives.

(−)-R-Enantiomers of agomelatine analogues were more potent at serotonin 5-HT2C receptors than (+)-S-enantiomers, and showed antidepressant-like properties in a tail suspension test.

An efficient and convenient method was developed for the formation of S-substituted thiotriazoles through an unprecedented organometallic addition and subsequent ring-opening sequence of 3-substituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole. The method is applicable to a wide range of substrates containing different functional groups and furnishes excellent yields of the corresponding N-unsubstituted 3- or 5-alkyl, aryl, alkynyl and alkenyl sulfanyl-1,2,4-triazole products.

An efficient and convenient method was developed for the formation of polysubstituted thiazolo[3,2-b][1,2,4]triazoles through C-5 (het)arylation. The direct C–H activation protocol giving access to di- and trisubstituted derivatives in excellent yields was optimized. The method is suitable for use with a wide range of (hetero)aryl bromides, and allows access to a collection of C-5,6 bis(het)aryl derivatives with full regioselectivity. The results are supported by a full description of all final compounds, and X-ray crystallographic data confirmed that the spectroscopic analyses were interpreted correctly.

La condensation des 2-(2-aminophenyl)benzimdiadzoles 2a-d , avec le bromure de bromoacetyle ( BBA ) en utilisant deux methodes differentes, a permis de synthetiser les 5Hbenzimidazo[1,2-d][1,4]benzodiazepine-6(7H)-ones 3a-d avec des rendements satisfaisants. La structure exacte de ces composes 3a-d a ete etablie par la diffraction aux rayons X du derive 3a .

We recently synthesized from aconitine a series of drugs with in vitro and in vivo antitumor properties, among which bis[O-(14-benzoylaconine-8-yl)]suberate (BBAS) was the most active (Eur J Med Chem 2012; 54: 343). In the present work, we used the NCI panel of 60 human tumor cell lines to identify the most sensitive cell lines and drugs with comparable cytotoxicity profiles. GI50 values of BBAS ranged between 0.12 and 6.5 μM. Activity was higher than average for leukemia and melanoma cell lines, especially SK-MEL-5 and SK-MEL-28, for the COLO-205 and HT-29 (colorectal) and MDA-MB-468 (breast) cancer cell lines. We evaluated the correlation between the GI50 of BBAS and those of 125 antiproliferative compounds with various mechanisms of action, using Bonferroni correction for multiple testing, and we observed a highly significant correlation with the GI50s of nitrosoureas. Interestingly, BBAS cytotoxicity was inversely correlated with the expression levels of MGMT (p = 0.009), an enzyme involved in the repair of nitrosourea-induced DNA damage. However, no correlation was found with the expression of 102 other genes involved in DNA repair. Antitumor activity was tested on immunodeficient mice with subcutaneously xenografted COLO-205, HT-29, MDA-MB-468, SK-MEL-5 and SK-MEL-28 cell lines. At 10 mg/kg, there was a significant reduction in tumor size with T/C values of 41 % and 43 % for COLO-205 and SK-MEL-28 cell lines, respectively. The drug was less active on HT-29 and SK-MEL-5 and inactive on MDA-MB-468 xenografts. Cell cycle studies showed an accumulation of BBAS-treated cells in G2/M phase after treatment at 20 μM. Together, our results allowed the identification of a potentially new class of anticancer agent displaying a mechanism of action related to that of nitrosoureas.

AbstractA novel and efficient route for the synthesis of the rare title compounds (V) is reported by sequential coupling involving a regioselective chlorine discrimination.

Nous decrivons dans cet article, l’action du 2-aminobenzimidazole 1 sur les 4-arylidene-2-methyl(phenyl)oxozolin-5-one 2a-d dans le n-butanol. La reaction conduit aux pyrimido [1,2-a]benzimidazoles 3a-d attendus avec des rendements satisfaisants. Nous avons montre egalement que les resultats obtenus sont independants de la nature du substituant en position 2 des composes 2a-d .Le derive 3b a ete ensuite alkyle dans les conditions de la catalyse par transfert de phase. Les structures des differents composes obtenus ont ete determinees par voies spectroscopiques et rayons-X notamment dans le cas du compose 5 .

Previously unknown N-3-substituted pyrido[1′,2′:1,5]py­razo­lo[3,4-d]pyrimidine derivatives were synthesized by a straightforward four-step synthesis. Starting from a 1-aminopyridinium salt, dimethyl acetylenedicarboxylate condensation followed by a fully regioselective saponification led to a pyrazolo[1,5-a]pyridine monoester as a key intermediate. A Curtius rearrangement directly followed by amine condensation afforded a urea library. A final pyrimidine ring closure resulted in achievement of the heterocyclic construction. This straightforward strategy provides an efficient method to easily access a library of rare tricyclic scaffolds and highly valuable derivatives.