APOPTOSIS-INDUCING AGENTS FOR TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

• Main Authors: GEORGE DOHERTY, GERARD SULLIVAN, TAO ZHI-FU, STEVEN ELMORE, SONG XIAOHONG, LAURA HEXAMER, AARON R KUNZER, LE WANG, MICHAEL WENDT, LISA HASVOLD, XILU WANG, TODD M HANSEN, ROBERT MANTEI, ANDREW J SOUERS, DING HONG, GARY T WANG, MILAN BRUNCKO
• Format: Patent
• Language: English; Japanese
• Published: 18.06.2015
• 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 compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, and methods of treating diseases in which anti-apoptotic Bcl-2 protein is expressed.SOLUTION: There are provided compounds represented by the formula (I). An example of specific compounds is 4-{4-[(4'-chloro-1,1'-biphenyl-2-yl)methyl]piperazin-1-yl}-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide. [Ais N or C; and B, Dare Eare each independently H, R, OR, SR, S(O)R, SORor the like, or Eand Ytogether with the atoms to which they are attached represent benzene, naphthylene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene. 【課題】抗アポトーシスＢｃｌ−２タンパク質の活性を阻害する化合物、ならびに抗アポトーシスＢｃｌ−２タンパク質が発現されている疾患の治療方法の提供。【解決手段】式（Ｉ）で示される化合物。具体的化合物として、４−｛４−［（４′−クロロ−１，１′−ビフェニル−２−イル）メチル］ピペラジン−１−イル｝−Ｎ−（｛３−ニトロ−４−［（テトラヒドロ−２Ｈ−ピラン−４−イルメチル）アミノ］フェニル｝スルホニル）−２−（１Ｈ−ピロロ［２，３−ｂ］ピリジン−５−イルオキシ）ベンズアミドが例示される。［Ａ１はＮ又はＣ；Ｂ１、Ｄ１又はＥ１は各々独立にＨ、Ｒ１、ＯＲ１、ＳＲ１、Ｓ（Ｏ）Ｒ１、ＳＯ２Ｒ１等；又はＥ１及びＹ１がそれらが結合している原子と一体となって、ベンゼン、ナフチレン、ヘテロアレーン、シクロアルカン、シクロアルケン、複素環アルカン又は複素環アルケン］【選択図】なし