- Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling
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In a flow microreactor, aryllithiums bearing a piperidylmethyl group were generated using nBuLi by precise residence time control and effective temperature control, and then selectively borylated with boronic esters such as 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (BpinOiPr) and trimethyl borate B(OMe)3 by fast mixing. Moreover, the direct integration with Suzuki–Miyaura cross coupling were successfully achieved to obtain nitrogen-containing biaryl compounds. The present method could be applied for the straightforward synthesis of the key intermediate of a bioactive component bearing a piperidylmethyl-biphenyl framework.
- Aizawa, Yoko,Ashikari, Yosuke,Colella, Marco,Fujita, Chiemi,Higuma, Ryosuke,Ishikawa, Susumu,Jiang, Yiyuan,Luisi, Renzo,Maekawa, Kei,Nagaki, Aiichiro,Sakaue, Hodaka,Shimizu, Yutaka,Shite, Ibuki,Takahashi, Yusuke,Takegawa, Toshihiro,Takumi, Masahiro,Yamashita, Hiroki,Yonekura, Yuya
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supporting information
p. 618 - 622
(2020/02/04)
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- Bis(het)aryl-1,2,3-triazole quinuclidines as α7 nicotinic acetylcholine receptor ligands: Synthesis, structure affinity relationships, agonism activity, [18F]-radiolabeling and PET study in rats
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In this paper we describe the design and synthesis of bis(Het)Aryl-1,2,3-triazole quinuclidine α7R ligands using an efficient three-step sequence including a Suzuki-Miyaura cross coupling reaction with commercially available and home-made boron derivatives. The exploration of SAR required the preparation of uncommon boron derivatives. Forty final drugs were tested for their ability to bind the target and nine of them exhibited Ki values below nanomolar concentrations. The best scores were always obtained when the 5-phenyl-2-thiophenyl core was attached to the triazole. The selectivity of these compounds towards the nicotinic α4β2 and serotoninergic 5HT3 receptors was assessed and their brain penetration was quantified by the preparation and in vivo evaluation of two [18F] radiolabelled derivatives. It can be expected from our results that some of these compounds will be suitable for further developments and will have effects on cognitive disorders.
- Ouach, Aziz,Vercouillie, Johnny,Bertrand, Emilie,Rodrigues, Nuno,Pin, Frederic,Serriere, Sophie,Boiaryna, Liliana,Chartier, Agnes,Percina, Nathalie,Tangpong, Pakorn,Gulhan, Zuhal,Mothes, Celine,Deloye, Jean-Bernard,Guilloteau, Denis,Page, Guylene,Suzenet, Franck,Buron, Frederic,Chalon, Sylvie,Routier, Sylvain
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p. 449 - 469
(2019/07/03)
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- Palladium(ii)-catalysed ortho-arylation of N-benzylpiperidines
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PdII-catalysed ortho-arylation of benzylic heterocycles with arylboronic acid pinacol esters (Ar-BPin) via directed C-H bond activation to generate the desired biaryl products is reported. This methodology is efficient and applicable to a wide range of functionalised Ar-BPin and benzylic heterocycles, allowing the direct synthesis of important biaryl motifs in modest to good yield. This journal is
- Tan, Peng Wen,Haughey, Maxwell,Dixon, Darren J.
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supporting information
p. 4406 - 4409
(2015/03/18)
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- DIARYL-SUBSTITUTED TETRAHYDROISOQUINOLINES AS HISTAMINE H3RECEPTOR AND SEROTONIN TRANSPORTER MODULATORS
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Certain diaryl-substituted tetrahydroisoquinoline compounds are histamine H3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and/or serotonin-mediated diseases.
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Page/Page column 23-24
(2009/01/20)
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- Dual serotonin transporter inhibitor/histamine H3 antagonists: Development of rigidified H3 pharmacophores
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A series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H3 antagonists is described. The introduction of polar aromatic spacers as part of the histamine H3 pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.
- Keith, John M.,Barbier, Ann J.,Wilson, Sandy J.,Miller, Kirstin,Boggs, Jamin D.,Fraser, Ian C.,Mazur, Curt,Lovenberg, Timothy W.,Carruthers, Nicholas I.
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p. 5325 - 5329
(2008/03/18)
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