JPH06507643A - Egfおよび/又はpdgf受容体チロシンキナーゼを阻害するビスモノ−および二環式アリールおよびヘテロアリール化合物 - Google Patents
Egfおよび/又はpdgf受容体チロシンキナーゼを阻害するビスモノ−および二環式アリールおよびヘテロアリール化合物Info
- Publication number
- JPH06507643A JPH06507643A JP5500068A JP50006893A JPH06507643A JP H06507643 A JPH06507643 A JP H06507643A JP 5500068 A JP5500068 A JP 5500068A JP 50006893 A JP50006893 A JP 50006893A JP H06507643 A JPH06507643 A JP H06507643A
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- dimethoxyquinoline
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.異常な細胞増殖に特徴がある疾患を患っている患者における異常な細胞増殖 を阻害する方法であって、ビス環構造であって一番目の環がアリール又はヘテロ アリールであり二番目の環がアリール、ヘテロアリール、炭素環式、又はヘテロ 炭素環式であり、該環が0から約2個のヘテロ原子を含む置換又は未置換単環式 環であるかあるいは0から約4個のヘテロ原子を含む二環式環であるものを有す る化合物あるいはその薬学的に許容できる塩を、EGFおよび/又はPDGF受 容体を阻害するのに有効な量、該患者に投与することを含む上記方法。 2.薬学的に有効な量の請求項1記載の化合物を薬学的に許容できる担体と混合 した状態で含む、異常な細胞増殖阻害のための医薬組成物。 3.下記一般式の化合物又はその薬学的に許容できる塩を、薬学的に許容できる 担体と混合した状態で含む医薬組成物の薬学的に有効量を該患者に投与すること を含む請求項1記載の方法: ▲数式、化学式、表等があります▼ 式中: ArIは約5から約12の原子をからなる置換又は未置換モノ−又は二環式アリ ール又はヘテロアリール環構造であり、各単環式環は0から約3個のヘテロ原子 を含み、名二環式環はヘテロ原子が燐位の酸素および/又は硫黄原子でない場合 にはN、OそしてSから選ばれる0から約4個のヘテロ原子を含み、そして置換 基は環構造の任意の適当な位置に存在し、Rと記載されている;ArIIはAr Iのところで記載したものであるか、又は飽和炭素環式でもよく該環は0から約 2個のヘテロ原子を含む飽和又は不飽和単環式環であるかあるいは0から約4個 のヘテロ原子を含む二環式環である;Xは(CHR1)0−4又は(CHR1) m−Z−(CHR1)nである;ZはO、NR′、S、SO又はSO2である。 mおよびnは0から3であり、m+n=0〜3である;水素以外のR置換基は、 独立であり、アルキル、アルケニル、フェニル、アラルキル、アラルケニル、ヒ ドロキシ、アルコキシ、アラルコキシ、アシルオキシ、ハロ、ハロアルキル、ア ミノ、モノ−及びジ−アルキルアミノ、アシルアミノ、カルボキシ、カルボアル コキシ、カルボアラルコキシ、カルボアルコキシアルキル、カルボアルコキシア ルケニル、アミド、モノ−およびジアルキルアミド、そしてN、N−シクロアル キルアミドを含む;RとRは互いにケトでもよい; R1およびR′は水素又はアルキルである;又はその薬学的に許容できる塩。 4.薬学的有効量の請求項3記載の化合物を薬学的に許容できる担体と混合した 状態で含む、細胞増殖阻害のための医薬組成物。 5.請求項3記載の方法であって、ArIおよびArIIがフェニル、ナフチル 、2−(1H)ピリドニル、ピリジル、キノリニル、チエニル、1(2H)−イ ンキノロニル、インドリル、ナフチリデニル、ベンゾチアゾリル、キノキサリニ ル、ベンゾチアゾリル、キノリン−N−オキシド、インキノリン−N−オキシド 、キナゾリニル、キノキサリニル−N−オキシド、キナゾリニル−N−オキシド 、ベンズオキサジニル、フタラジニル又はシンノリニルから独立に選ばれ、Rは 水素、アルキル、アルコキシ、ヒドロキシ、ハロ又はトリフルオロメチルから選 ばれる上記方法。 6.請求項5記載の方法であって該化合物が以下の一般式の1つによって記載さ れる方法; ▲数式、化学式、表等があります▼,▲数式、化学式、表等があります▼▲数式 、化学式、表等があります▼,▲数式、化学式、表等があります▼,▲数式、化 学式、表等があります▼,▲数式、化学式、表等があります▼,▲数式、化学式 、表等があります▼,▲数式、化学式、表等があります▼,▲数式、化学式、表 等があります▼,▲数式、化学式、表等があります▼,▲数式、化学式、表等が あります▼,▲数式、化学式、表等があります▼,▲数式、化学式、表等があり ます▼,▲数式、化学式、表等があります▼,7.請求項6記載の方法であって 、該化合物が以下の一般式である方法:▲数式、化学式、表等があります▼ 式中ArIIはチエニル、フェニル、ピリジル、キノリニル、インドリル、フラ ニル、イミダゾリル、2(1H)−ピリドニル、1(2H)−インキノロニル、 及びチアゾリルであり、Rは水素、低級アルキル、低級アルコキシ、ヒドロキシ 又はハロである。 8.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数式 、化学式、表等があります▼ 9.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数式 、化学式、表等があります▼ 10.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 11.請求項7記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 12.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 13.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 14.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 15.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 16.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 17.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 18.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 19.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 20.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 21.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 22.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 23.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 24.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 25.請求項6記載の方法であって、該化合物が以下の一般式である方法;▲数 式、化学式、表等があります▼ 26.請求項1記載の方法であって、投与される該化合物が;3−(4−メトキ シフェニル)−6、7−ジメトキシキノリン;3−(チエン−3−イル)−6、 7−ジメトキシキノリン;3−(チエン−3−イル)−7−メトキシキノリン; 3−(4−メトキシフェニル)−6、7−ジメトキシキノリン;3−(2−クロ ロチエン−2−イル)−6、7−ジメトキシキノリン;3−(3−フルオロ−4 −メトキシフェニル)−6、7−ジメトキシキノリン;2−(4−メトキシフェ ニル)−6、7−ジメトキシキノキサリン;3−(2−クロロチエン−2−イル )−5、7−ジメトキシキノリン;2−フェニル−6、7−ジメチルキノキサリ ン;2−(チエン−3−イル)キノキサリン;6、7−ジメチル−2−(チエン −3−イル)−キノキサリン;3−(4−メトキシフェニル)−6、7−ジメト キシキノリン;3−(チエン−3−イル)−6、7−ジメトキシキノリン;3− (チエン−3−イル)−7−メトキシキノリン;3−(4−メトキシフェニル) −6、7−ジメトキシキノリン;3−(2−クロロチエン−2−イル)−6、7 −ジメトキシキノリン;3−(3−フルオロ−4−メトキシフェニル)−6、7 −ジメトキシキノリン;2−(4−メトキシフェニル)−6、7−ジメトキシキ ノキサリン;3−(2−クロロチエン−2−イル)−5、7−ジメトキシキノリ ン;3−(チエン−3−イル)−6、7−ジメチルキノリン;3−(1−シクロ ペンタ−1−エニル)−6、7−ジメトキシキノリン;3−シクロペンチル−6 、7−ジメトキシキノリン;4−(3−フェニルプロピルオキシ)−6、7−ジ メトキシキノリン;3−(チエン−3−イル)−6、7−ジメトキシキノリン− N−オキシド;3−(2−クロロチオフェン−5−イル)−5、7−ジメトキシ キノリン;3−(3−フルオロ−4−メトキシフェニル)−6、7−ジメトキシ キノリン;3−(3−フルオロフェニル)−6、7−ジメトキシキノリン;4− (2−フェニルエトキシ)−6、7−ジメトキシキノリン;3−(4−メトキシ ベンジルオキシ)−6、7−ジメトキシキノリン;2−(4−メトキシフェニル )−6、7−ジメトキシキノキサリン;2−(チエン−3−イル)−6、7−ジ メトキシキノキサリン;2−フェニル−6、7−ジメトキシキノキサリン;6、 7−ジメチル−2−(チエン−3−イル)−キノキサリン;2−フェニル−6、 7−ジエトキシキノキサリン;2−(3−チエニル)−6、7−ジエトキシキノ キサリン;2−(5−クロロ−2−チエニル)−6、7−ジエトキシキノキサリ ン;2−(5−クロロ−2−チエニル)−6、7−ジメトキシキノキサリン;3 −(3−フルオロ−4−メトキシフェニル)−7−フルオロキノリン;3−(チ エン−3−イル)−5、7−ジメチルキノリン;3−(5−クロロチエン−2− イル)−6、7−ジメチルキノリン;3−(チエン−3−イル)−6、7−ジフ ルオロキノリン又は3−(4−メトキシフェニル)−7−メトキシ−1−ナフタ レノール;からなる群から選ばれる上記方法。 27.乾癬疾患を患っている患者における乾癬治療方法であって、請求項2記載 の抗乾癬有効組成物を該患者に投与することを含む方法。 28.アテローム性動脈硬化症疾患を患っている患者におけるアテローム性動脈 硬化症治療方法であって、請求項2記載の抗アレステローム性動脈硬化有効組成 物を該患者に投与することを含む方法。 29.血管再閉塞疾患を患っている患者における血管再閉塞治療方法であって、 請求項2記載の組成物の有効量を該患者に投与することを含む方法。 30.請求項29記載の方法であって、該疾患が血管形成過程から生ずる方法。 31.以下の: 3−(4−メトキシフェニル)−6、7−ジメトキシキノリン;3−(チエン− 3−イル)−6、7−ジメトキシキノリン;3−(チエン−3−イル)−7−メ トキシキノリン;3−(4−メトキシフェニル)−6、7−ジメトキシキノリン ;3−(2−クロロチエン−2−イル)−6、7−ジメトキシキノリン;3−( 3−フルオロ−4−メトキシフェニル)−6、7−ジメトキシキノリン;2−( 4−メトキシフェニル)−6、7−ジメトキシキノキサリン;3−(2−クロロ チエン−2−イル)−5、7−ジメトキシキノリン;3−(チエン−3−イル) −6、7−ジメチルキノリン;3−(1−シクロペンタ−1−エニル)−6、7 −ジメトキシキノリン;3−シクロペンチル−6、7−ジメトキシキノリン;4 −(3−フェニルプロピルオキシ)−6、7−ジメトキシキノリン;3−(チエ ン−3−イル)−6、7−ジメトキシキノリン−N−オキシド;3−(2−クロ ロチオフェン−5−イル)−5、7−ジメトキシキノリン;3−(3−フルオロ −4−メトキシフェニル)−6、7−ジメトキシキノリン;3−(3−フルオロ フェニル)−6、7−ジメトキシキノリン;4−(2−フェニルエトキシ)−6 、7−ジメトキシキノリン;3−(4−メトキシベンジルオキシ)−6、7−ジ メトキシキノリン;2−(4−メトキシフェニル)−6、7−ジメトキシキノキ サリン;2−(チエン−3−イル)−6、7−ジメトキシキノキサリン;2−フ ェニル−6、7−ジメトキシキノキサリン;6、7−ジメチル−2−(チエン− 3−イル)−キノキサリン;2−フェニル−6、7−ジエトキシキノキサリン; 2−(3−チエニル)−6、7−ジエトキシキノキサリン;2−(5−クロロ− 2−チエニル)−6、7−ジエトキシキノキサリン;2−(5−クロロ−2−チ エニル)−6、7−ジメトキシキノキサリン;3−(3−フルオロ−4−メトキ シフェニル)−7−フルオロキノリン;3−(チエン−3−イル)−5、7−ジ メチルキノリン;3−(5−クロロチエン−2−イル)−6、7−ジメチルキノ リン;3−(チエン−3−イル)−6、7−ジフルオロキノリン又は3−(4− メトキシフェニル)−7−メトキシ−1−ナフタレノール;からなる群から選ば れる化合物。 32.活性成分が請求項31の化合物から選ばれる医薬組成物。
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US8053445B2 (en) | 2001-09-14 | 2011-11-08 | Shionogi & Co., Ltd. | Utilities of olefin derivatives |
JP2005516927A (ja) * | 2001-12-13 | 2005-06-09 | アボット・ラボラトリーズ | 癌治療用のキナーゼ阻害剤としての3−(フェニル−アルコキシ)−5−(フェニル)−ピリジン誘導体および関連化合物 |
JP2005536486A (ja) * | 2002-07-09 | 2005-12-02 | アストラゼネカ アクチボラグ | 癌の処置に使用するためのキナゾリン誘導体 |
JP2006512315A (ja) * | 2002-11-04 | 2006-04-13 | エヌピーエス ファーマスーティカルズ インコーポレイテッド | カルシリティックとしてのキナゾリノン化合物 |
US7750001B2 (en) | 2005-03-11 | 2010-07-06 | Zenyaku Kogyo Kabushikikaisha | Immunosuppressive agent and anti-tumor agent comprising heterocyclic compound as active ingredient |
US8338414B2 (en) | 2005-03-11 | 2012-12-25 | Zenyaku Kogyo Kabushikikaisha | Immunosuppressive agent and anti-tumor agent comprising heterocyclic compound as active ingredient |
JP2012531436A (ja) * | 2009-06-25 | 2012-12-10 | アムジエン・インコーポレーテツド | 複素環式化合物およびそれらのpi3k活性阻害剤としての使用 |
JP2016539917A (ja) * | 2013-10-15 | 2016-12-22 | ヤンセン ファーマシューティカ エヌ.ベー. | Rorγtのアルキル結合キノリニルモジュレーター |
US10201546B2 (en) | 2013-10-15 | 2019-02-12 | Janssen Pharmaceutica Nv | Quinolinyl modulators of RORγt |
US10369146B2 (en) | 2013-10-15 | 2019-08-06 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
Also Published As
Publication number | Publication date |
---|---|
GR3024955T3 (en) | 1998-01-30 |
MX9202181A (es) | 1993-05-01 |
SG64322A1 (en) | 1999-04-27 |
AU1993492A (en) | 1992-12-30 |
DE69222637T2 (de) | 1998-02-26 |
CA2102780C (en) | 2007-01-09 |
DK0584222T3 (da) | 1998-02-23 |
DE69222637D1 (de) | 1997-11-13 |
EP0584222A1 (en) | 1994-03-02 |
ATE159009T1 (de) | 1997-10-15 |
ES2108120T3 (es) | 1997-12-16 |
EP0584222A4 (en) | 1994-07-06 |
US5409930A (en) | 1995-04-25 |
CA2102780A1 (en) | 1992-11-11 |
EP0584222B1 (en) | 1997-10-08 |
JP3507071B2 (ja) | 2004-03-15 |
WO1992020642A1 (en) | 1992-11-26 |
AU658646B2 (en) | 1995-04-27 |
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