BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS

• Main Authors: BIN MA, GNANASAMBANDAM KUMARAVEL, JERMAINE THOMAS, KEVIN M GUCKIAN, ZHENG GUO ZHU, TAVERAS ARTHUR G, LIN EDWARD YIN-SHIANG, RICHARD D CALDWELL, LIU XIAOGAO
• Format: Patent
• Language: English; Japanese
• Published: 01.09.2016
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; 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 novel, potent and selective compounds that have agonist activity at one or more sphingosine 1-phosphate (S1P) receptors, having enhanced potency, selectivity and oral bioavailability.SOLUTION: The invention provides compounds represented by formula (IIa), (IIIa) or (IIIb), or pharmaceutically acceptable salts thereof. (Xto Xare each independently H, halogen, hydroxy, nitro, cyano, alkoxy, acyl, trialkylamino, aryl, heteroaryl or the like; W is -O-; Cy is a substituted/unsubstituted cycloalkyl group; and Ris a substituent connected to a nitrogen-containing site through substituted/unsubstituted methylene and having carboxylic acid, ester, imide, sulfonamide, sulfonic acid, phosphonic acid or the like at an end.)SELECTED DRAWING: None 【課題】増強された効力、選択性および経口バイオアベイラビリティを有する、強力かつ選択的な新規の１つ以上のスフィンゴシン１−リン酸（Ｓ１Ｐ）受容体に対するアゴニスト活性を有する化合物の提供。【解決手段】式(IIa)、(IIIa)又は(IIIb)で表される化合物、又はそれらの医薬として許容し得る塩。（X1〜X6は各々独立にＨ、ハロゲン、ヒドロキシ、ニトロ、シアノ、アルコキシ、アシル、トリアルキルアミノ、アリール、ヘテロアリール等；Wは-O-；Cyは置換/無置換のシクロアルキル基；R3は置換/無置換のメチレンを介して窒素含有部位と連結し、末端部にカルボン酸、エステル、イミド、スルホンアミド、スルホン酸、ホスホン酸等を有す置換基）【選択図】なし