1-[2-(2,4-DIMETHYLPHENYLSULFANYL)-PHENYL]PIPERAZINE AS COMPOUND HAVING COMBINED SEROTONIN REUPTAKE, 5-HT3 AND 5-HT1A ACTIVITY FOR TREATING COGNITIVE IMPAIRMENT

• Main Authors: FALDT ANDRE, MOORE NICHOLAS, ROCK MICHAEL HAROLD, STENSBOEL TINE BRYAN, JOERGENSEN MORTEN, HOLM RENE, BANG-ANDERSEN BENNY, LOPEZ DE DIEGO HEIDI, BRODERSEN JOERGEN, MEALY MICHAEL J, MOERK ARNE, RINGGAARD LONE MUNCH
• Format: Patent
• Language: English; Japanese
• Published: 12.01.2017
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

PROBLEM TO BE SOLVED: To provide a chemical crystal and a pharmaceutical composition having serotonin reuptake, serotonin receptor 1A (5-HT) and serotonin receptor (5HT) activity for treating cognitive impairment in patients with depression or the like.SOLUTION: There is provided a method for synthesizing 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine represented by the following formula by reacting 2,4-dimethyl-thiophenol and 1,2-halogen phenol in presence of a palladium complex and further reacting with piperidine. There is provided a crystal having a peak of specific powder X-ray diffraction refraction and represented by the following formula and a tablet containing the crystal, calcium hydrogen phosphate anhydride, corn starch, PVP-VA copolymer, microcrystalline cellulose, sodium starch glycolate, talc and magnesium stearate and manufactured by a wet granulation method.SELECTED DRAWING: None 【課題】うつ病等の患者における認識機能障害の治療にセロトニン再取り込み、セロトニン受容体１Ａ（５−ＨＴ１Ａ）及びセロトニン受容体（５ＨＴ３）活性を有する化合物結晶と医薬組成物の提供。【解決手段】２，４−ジメチル−チオフェノールと１，２−ハロゲンフェノールをパラジウム錯体の存在下で反応させ、更にピペリジンと反応させる方法で下式で表される１−［２−（２，４−ジメチル−フェニルスルファニル）−フェニル］−ピペラジンを合成する方法。下式で表される特定の粉末Ｘ線回折反射のピークを有する結晶とその結晶を含有し無水カルシウム水素ホスファート、トウモロコシデンプン、ＰＶＰ−ＶＡコポリマー、微結晶性セルロース、ナトリウムデンプングリコラート、タルクおよびマグネシウムステアラートを含む湿式造粒法により製造される錠剤。【選択図】なし