JPH10513160A - 細胞接着インヒビター - Google Patents
細胞接着インヒビターInfo
- Publication number
- JPH10513160A JPH10513160A JP8523071A JP52307196A JPH10513160A JP H10513160 A JPH10513160 A JP H10513160A JP 8523071 A JP8523071 A JP 8523071A JP 52307196 A JP52307196 A JP 52307196A JP H10513160 A JPH10513160 A JP H10513160A
- Authority
- JP
- Japan
- Prior art keywords
- phenylmethyl
- bio
- substituted
- aryl
- urea
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 5
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- DMSHKWHLXNDUST-UHFFFAOYSA-N (4-methylphenyl)urea Chemical compound CC1=CC=C(NC(N)=O)C=C1 DMSHKWHLXNDUST-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/60—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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.以下の式(I)の化合物および式(I)の薬学的に受容可能な誘導体より選択 される、細胞接着阻害化合物: ここで: Xは、-CO2H、-PO- 3H、-SO2R5、-SO3H、-OPO- 3H、-CO2R4 、および-C(O)N(R4)2からなる群より選択され; ここでR5は、アルキル、アルケニル、アルキニル、シクロアルキル、シクロ アルケニル、アリール、アリール置換アルキル、およびアリール置換アルケニル またはアリール置換アルキニルからなる群より選択される; Yは、-CO-、-SO2-、および-PO2-からなる群より選択される; R1は、アルキル、アルケニル、アルキニル、シクロアルキニル、アリール縮 合シクロアルキル、シクロアルケニル、アリール、アラルキル、アリール置換ア ルケニルまたはアリール置換アルキニル、シクロアルキル置換アルキル、シクロ アルケニル置換シクロアルキル、ビアリール、アルコキシ、アルケノキシ、アル キノキシ、アラルコキシ、アリール置換アルケノキシまたはアリール置換アルキ ノキシ、アルキルアミノ、アルケニルアミノまたはアルキニルアミノ、アリール 置換アルキルアミノ、アリール置換アルケニルアミノまたはアリール置換アルキ ニルアミノ、アリールオキシ、アリールアミノ、N-アルキルウレア置換アルキル 、N-アリールウレア置換アルキル、アルキルカルボニルアミノ置換アルキル、ア ミノカルボニル置換アルキル、ヘテロシクリル、ヘテロシクリル置換アルキル、 ヘ テロシクリル置換アミノ、カルボキシアルキル置換アラルキル、オキソカルボシ クリル縮合アリール、およびヘテロシクリルアルキルからなる群より選択される ; R2は、水素、アリール、アルキル、アルケニルまたはアルキニル、シクロア ルキル、シクロアルケニル、アリール置換アルキルからなる群より選択され、こ こでR2およびR3は、それらが結合する原子と一緒になって、複素環を形成し得 る; R3は、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケ ニル、アラルキル、アリール置換アルケニルまたはアリール置換アルキニル、ヒ ドロキシ置換アルキル、アルコキシ置換アルキル、アラルコキシ置換アルキル、 アミノ置換アルキル、(アリール置換アルキルオキシカルボニルアミノ)置換ア ルキル、チオール置換アルキル、アルキルスルホニル置換アルキル、(ヒドロキ シ置換アルキルチオ)置換アルキル、チオアルコキシ置換アルキル、アシルアミ ノ置換アルキル、アルキルスルホニルアミノ置換アルキル、アリールスルホニル アミノ置換アルキル、モルホリノアルキル、チオモルホリノアルキル、モルホリ ノカルボニル置換アルキル、チオモルホリノカルボニル置換アルキル、[N-(アル キル、アルケニルまたはアルキニル)-またはN,N-[ジアルキル、ジアルケニル、 ジアルキニルまたは(アルキル、アルケニル)-アミノ]カルボニル置換アルキル 、カルボキシル置換アルキル、ジアルキルアミノ置換アシルアミノアルキルおよ びアルギニン、アスパラギン、グルタミン、S-メチルシステイン、メチオニンお よびその対応するスルホキシドならびにスルホン誘導体、グリシン、ロイシン、 イソロイシン、アロイソロイシン、tert-ロイシン、ノルロイシン、フェニルア ラニン、チロシン、トリプトファン、プロリン、アラニン、オルニチン、ヒスチ ジン、グルタミン、バリン、トレオニン、セリン、アスパラギン酸、β-シアノ アラニン、およびアロトレオニンから選択されたアミノ酸側鎖からなる群より選 択され、ここでR2およびR3は、それらが結合する原子と一緒になって、複素環 を形成し得る; R4は、アリール、アルキル、シクロアルキル、アルケニル、シクロアルケニ ル、アルキニル置換アルキルおよびアリール置換アルキル、水素、ヘテロシクリ ル、ヘテロシクリルカルボニル、アミノカルボニル、アミド、モノアルキルアミ ノカルボニルまたはジアルキルアミノカルボニル、モノアリールアミノカルボニ ルまたはジアリールアミノカルボニル、アルキルアリールアミノカルボニル、ジ アリールアミノカルボニル、モノアシルアミノカルボニルまたはジアシルアミノ カルボニル、芳香族アシルまたは脂肪族アシル、必要に応じてアミノ、カルボキ シ、ヒドロキシ、メルカプト、モノアルキルアミノまたはジアルキルアミノ、モ ノアリールアミノまたはジアリールアミノ、アルキルアリールアミノ、ジアリー ルアミノ、モノアシルアミノまたはジアシルアミノ、アルコキシ、アルケノキシ 、アリールオキシ、チオアルコキシ、チオアルケノキシ、チオアルキノキシ、チ オアリールオキシ、およびヘテロシクリルからなる群より選択される置換基によ り置換されるアルキル、からなる群より選択され;そして nは0、1、または2である。 2.以下の式(I)の化合物および(I)の薬学的に受容可能な誘導体より選択さ れる、請求項1に記載の化合物: ここで: Xは、-CO2H、-PO- 3H、-SO2R5、-SO3H、および-OPO- 3Hからな る群より選択され; ここでR5は、アルキル、アルケニル、アルキニル、シクロアルキル、シクロ アルケニル、アリール、アリール置換アルキル、およびアリール置換アルケニル またはアリール置換アルキニルからなる群より選択される; Yは、-CO-、-SO2-、および-PO2-からなる群より選択される; R1は、アルキル、アルケニル、アルキニル、シクロアルキル、アリール縮合 シクロアルキル、シクロアルケニル、アリール、アリール置換アルキル(「アラ ルキル」)、アリール置換アルケニルまたはアリール置換アルキニル、シクロア ルキル置換アルキル、シクロアルケニル置換シクロアルキル、ビアリール、アル コキシ、アルケノキシ、アルキノキシ、アリール置換アルコキシ、(「アラルコ キシ」)、アリール置換アルケノキシまたはアリール置換アルキノキシ、アルキ ルアミノ、アルケニルアミノまたはアルキニルアミノ、アリール置換アルキルア ミノ、アリール置換アルケニルアミノまたはアリール置換アルキニルアミノ、ア リールオキシ、アリールアミノ、N-アルキルウレア置換アルキル、N-アリールウ レア置換アルキル、アルキルカルボニルアミノ置換アルキル、およびアミノカル ボニル置換アルキルからなる群より選択される; R2は、水素、アリール、アルキル、アルケニルまたはアルキニル、シクロア ルキル、シクロアルケニル、およびアリール置換アルキルからなる群より選択さ れる; R3は、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケ ニル、アラルキル、アリール置換アルケニルまたはアリール置換アルキニル、ヒ ドロキシ置換アルキル、アルコキシ置換アルキル、アラルコキシ置換アルキル、 アミノ置換アルキル、(アリール置換アルキルオキシカルボニルアミノ)置換ア ルキル、チオール置換アルキル、アルキルスルホニル置換アルキル、(ヒドロキ シ置換アルキルチオ)置換アルキル、チオアルコキシ置換アルキル、アシルアミ ノ置換アルキル、アルキルスルホニルアミノ置換アルキル、アリールスルホニル アミノ置換アルキル、モルホリノアルキル、チオモルホリノアルキル、モルホリ ノカルボニル置換アルキル、チオモルホリノカルボニル置換アルキル、[N-(アル キル、アルケニルまたはアルキニル)-またはN,N-[ジアルキル、ジアルケニル、 ジアルキニルまたは(アルキル、アルケニル)-アミノ]カルボニル置換アルキル 、カルボキシル置換アルキル、およびアルギニン、アスパラギン、グルタミン、 S-メチルシステイン、メチオニンおよびその対応するスルホキシドならびにスル ホン誘導体、グリシン、ロイシン、イソロイシン、アロイソロイシン、tert-ロ イ シン、ノルロイシン、フェニルアラニン、チロシン、トリプトファン、プロリン 、アラニン、オルニチン、ヒスチジン、グルタミン、バリン、トレオニン、セリ ン、アスパラギン酸、β-シアノアラニン、およびアロトレオニンから選択され たアミノ酸側鎖からなる群より選択される; R4は、アリール、アルキル、シクロアルキル、アルケニル、シクロアルケニ ル、アルキニル置換アルキルおよびアリール置換アルキルからなる群より選択さ れ;そして nは0、1、または2である。 3.Xが-CO2Hである、請求項1または2に記載の細胞接着阻害化合物。 4.R1が、アリール置換C1-C4アルキル基である、請求項1または2に記載の 細胞接着阻害化合物。 5.R1が(N-Ar'ウレア)-パラ-置換アリールアルキル基である、請求項4に 記載の細胞接着阻害化合物。 6.R1が(N-Ar'ウレア)-パラ-置換フェニルメチル基である、請求項5に記 載の細胞接着阻害化合物。 7.R1が以下からなる群より選択される、請求項1または2に記載の細胞接着 阻害化合物:ベンジルオキシ、シアノメチル、シクロヘキシルメチル、メチル、 n-ヘキシル、N-フェニルアミノ、フェニル、フェニルカルボニル、フェニルメチ ル、t-ブトキシ、t−ブチルアミノ、1-インダニル、1-ナフチルメチル、1-フェ ニルシクロプロピル、2-(4-ヒドロキシル-フェニル)エチル、2-(ベンジルオ キシカルボニルアミノ)フェニルメチル、2-(ビス(フェニルスルホニル)アミノ) フェニルメチル、2-(N'-フェニルウレア)フェニルメチル、2-アミノフェニル メチル、2-ベンズアミドフェニルメチル、2-ブロモ-4-ヒドロキシ-5-メトキ シフェニルメチル、2-ヒドロキシフェニルメチル、2-ナフチルメチル、2-フ ェニルエチル、2-ピリジルメチル、2-キノリニル、2-[4-(N'-フェニルウレ ア)フェニル]エチル、3-(ベンジルオキシカルボニルアミノ)フェニルメチル、 3-(N'-フェニルウレア)フェニルメチル、3-(N'-フェニルウレア)プロピル、3 -(フェニルスルホンアミド)フェニルメチル、3-アセトアミドフェニルメチル、 3-アミノフェニルメチル、3-ベンズアミドフェニルメチル、3-ヒドロキシ-4 -(N'-フェニルウレア)フェニルメチル、3-ヒドロキシフェニルメチル、3-イン ドリル、3-メトキシ-4-(N'-フェニルウレア)フェニルメチル、3-メトキシ-4 -(N'-(2-メチルフェニル)ウレア)フェニルメチル、3-メチル-4-(N'-フェニル ウレア)-フェニルメチル、3-ニトロフェニルメチル、3-フェニルプロピル、3 -ピリジルメチル、4-(2-アミノベンズアミド)フェニルメチル、4-(ベンズア ミド)フェニルメチル、4-(ベンジルオキシカルボニルアミノ)フェニルメチル、 4-(モルホリノカルボニルアミノ)フェニルメチル、4-(N'-(2-クロロフェニル )ウレア)フェニルメチル、4-(N'-(2-クロロフェニル)ウレア)-3-メトキシフ ェニルメチル、4-(N'-(2-エチルフェニル)ウレア)フェニルメチル、4-(N'-( 2-イソプロピルフェニル)ウレア)フェニルメチル、4-(N'-(2-メトキシフェニ ル)ウレア)フェニルメチル、4-(N'-(2-メチル−3−ピリジル)ウレア)フェニ ルメチル、4-(N'-(2-ニトロフェニル)ウレア)フェニルメチル、4-(N'-(2-ピ リジル)ウレア)フェニルメチル、4-(N'-(2-t-ブチルフェニル)ウレア)フェニ ルメチル、4-(N'-(2-チアゾリル)ウレア)フェニルメチル、4-(N'-(3-クロロ フェニル)ウレア)フェニルメチル、4-(N'-(3-メトキシフェニル)ウレア)フェ ニルメチル、4-(N'-(3-ピリジル)ウレア)フェニルメチル、4-(N'-(4-ピリジ ル)ウレア)フェニルメチル、4-(N'-(3-メチルフェニル)ウレア)フェニルメチ ル、4-(N'-(2-メチルフェニル)ウレア)フェニルメチル、4-(N'-ベンジルウレ ア)フェニルメチル、4-(N'-シクロヘキシルウレア)フェニルメチル、4-(N'-エ チルウレア)フェニルメチル、4-(N'-イソプロピルウレア)フェニルメチル、4- (N'-メチルウレア)フェニルメチル、4-(N'-p-トルイルウレア)フェニルメチル 、4-(N'-フェニルウレア)フェニル、4-(N'-フェニルウレア)フェニルアミノ、 4-(N'-フェニルウレア)フェニルメチル、4-(N'-t-ブチルウレア)フェニルメチ ル、4-(フェニルアミノカルボニ ルアミノメチル)フェニル、4-(フェニルスルホンアミド)フェニルメチル、4-( t-ブトキシカルボニルアミノ)フェニルメチル、4-アセトアミドフェニルメチル 、4-アミノフェニルアミノ、4-アミノフェニルメチル、4-ベンズアミドフェ ニルメチル、4-クロロフェニルメチル、4-ヒドロキシ-3-ニトロフェニルメチ ル、4-ヒドロキシフェニルメチル、4-メトキシフェニルメチル、4-ニトロフ ェニルアミノ、4-ニトロフェニルメチル、4−フェナセトアミドフェニルメチ ル、4-フェニルフェニルメチル、4−ピリジルメチル、4-トリフルオロメチル フェニルメチル、4-[2-(N'-メチルウレア)ベンズアミド]フェニルメチル、4- (N'-(2-メチルフェニル)ウレア)フェニルメチル、4-(N'-フェニル-N''-メチル グアニジノ)フェニルメチル、5-(N'-フェニルウレア)ペンチル、5-(N'-t-ブチ ルウレア)ペンチル、2,2-ジメチルプロピル、2,2-ジフェニルメチル、2,3-ベン ゾシクロブチル、3,4-ジヒドロキシフェニルメチル、3,5-ジメトキシ-4-ヒドロ キシ-フェニルメチル、4-(1-インドールカルボキシルアミノ)フェニルメチル 、6-メトキシ-5-(N'-(2-メチルフェニル)ウレア)-2-ピリジルメチル、4-(1 ,3-ベンゾオキサゾール-2-イルアミノ)-フェニルメチル、4-(1,3-イミダゾー ル-2-イルアミノ)-フェニルメチル、3-カルボキシ-1-フェニルプロピル;3- ヒドロキシ-4-(2-メチルフェニル)ウレアフェニルメチル;3-ヒドロキシ-4- (2-クロロフェニル)ウレアフェニルメチル;6-(フェニルウレア)ヘプチル、4 -フェニルウレア)ブチル;2-チエニルメチル;4-(2,6-ジメチルフェニルウレ ア)フェニルメチル;4-(2-ヒドロキシフェニルウレア)フェニルメチル;3-ブ トキシ-4-(2-メチノレフェニル)ウレアフェニルメチル;3-ブトキシ-4-(フ ェニルウレア)フェニルメチル、4-(N-2-ピラジニルウレア)フェニルメチル; 2-フェニルエチニル;5-フェニルウレア-2-ピリジルメチル;5-(2-メチル フェニルウレア)-2-ピリジルメチル;4-(3-メチル-2-ピリジルウレア)フェ ニルメチル;3-ニトロ-4-(フェニルウレア)フェニルメチル;3-アシルアミノ -4-(フェニルウレア)フェニルメチル;4-(N,N-フェニルメチルウレア)フェニ ルメチル;4-(3-ヒドロキシフェニルウレア)フェニルメチル;4-(2-アセチ ルアミノフェニルウレア)フェニルメチル;4-(2-プロピオニルアミノフェニル ウレア)フェニルメチル;4-(3-ベン ジルオキシ-2-ピリジルウレア)フェニルメチル;4-(3-メチル-2-ピリジルウ レア)フェニルメチル;4-(インドリルカルボニルアミノ)フェニルメチル;2-( 4-(フェニルウレア)フェニル)オキシラニル;4-(N,N'-フェニルメチルウレア) フェニルメチル;4-(2-ジメチルアミノフェニルウレア)フェニルメチル;4-( 2-ベンズイミダゾリルアミノ)フェニルメチル;4-(2-ベンズオキサゾリルア ミノ)フェニルメチル;4-(2-ベンズチアゾリルアミノ)フェニルメチル;4-( テトラヒドロキノリニルカルボニルアミノ)フェニルメチル;1,3-ジメチル-3-( フェニルウレア)ブチル;ヒドロキシエチルチオメチル;4-(フェニルウレア)フ ェニルエテニル;3-アミノ-4-(フェニルウレア)フェニルメチル;4-(4-ヒド ロキシフェニルウレア)フェニルメチル;4-(2-アミノフェニルウレア)フェニ ルメチル;4-((2-メチルウレア)フェニルウレア)フェニル;4-(2-ヒドロキ シフェニルウレア)-3-メトキシフェニルメチル;4-(2-メチルスルホニルメチ ルフェニルウレア)フェニルメチル;4-(2-メチルフェニルウレア)テトラヒド ロ−2−ピリミドニルメチル;3-メトキシ-4-(フェニルウレア)-2-ピリジル メチル;4-(2-トリフルオロメチルフェニルウレア)フェニルメチル;4-(3- メチル-2-ピリジルウレア)フェニルメチル;4-(2,4,(1H,3H)-キナゾリンジオ ニル)フェニルメチル;4-チオウレアフェニルメチル;4-(フェニルチオウレア )フェニルメチル;4-(ピロリジニルカルボニルアミノ)フェニルメチル;4-(2 -ベンズオキサゾリノニルカルボニルアミノ)フェニルメチル;4-(ベンジルオキ シウレア)フェニルメチル;4-(チアゾリジニルカルボニルアミノ)フェニルメチ ル;4-ベンゾイルウレアフェニルメチル;ヒドロキシルウレアフェニルメチル ;N',N'-メチルヒドロキシルウレアフェニルメチル;4-(N'-アリルウレア)フェ ニルメチル;4-(3-ピロリジニルカルボニルアミノ)フェニルメチル;4-(1- ピロリルカルボニルアミノ)フェニルメチル;4-(2-ピロリルカルボニルアミノ )フェニルメチル;4-(プロピルウレア)フェニルメチル;4-(メトキシウレア) フェニルメチル;4-(ジメチルウレア)フェニルメチル;4-(2-キナゾリニルア ミノ)フェニルメチル;4-(2-フラノイルアミノ)フェニルメチル;4-(2-ヒド ロキシ-6-メチルフェニルウレア)フェニルメチル;4-(2-ピリジルカルボニル アミノ)フェニルメチル;4- (3-ヒドロキシ-2-メチルフェニルウレア)フェニルメチル;4-(2-フルオロフ ェニルウレア)フェニルメチル;4-(3-フルオロフェニルウレア)フェニルメチ ル;4-(4-フルオロフェニルウレア)フェニルメチル;4-(2-キノリニルカル ボニルアミノ)フェニルメチル;4-(イソキノリニルカルボニルアミノ)フェニル メチル;4-(2,3-ジメチルフェニルウレア)フェニルメチル;4-(2,5-ジメチル フェニルウレア)フェニルメチル;4-(2-メチル-4-フルオロフェニルウレア) フェニルメチル;4-(2-メチル-3-フルオロフェニルウレア)フェニルメチル; 3-カルボキシ-3-フェニルプロピル;4-(5-ヒドロキシ-2-メチルフェニルウ レア)フェニルメチル;4-(4-ヒドロキシ-2-メチルフェニルウレア)フェニル メチル;4-(2,4-ジフルオロフェニルウレア)フェニルメチル;3-ジベンソフラ ニルカルボニル;4-(フェノキシカルボニルアミノ)フェニルメチル;3-フェニ ルウレアプロピル;4-(フェニルアミノカルボニルオキシ)フェニルメチル;4- シンナモイルフェニルメチル;ジベンゾフラニルメチル;4-(2-メチルフェニ ルアミノカルボニルオキシ)フェニルメチル;(メチルフェニルウレア)フェニ ルアミノ;4-(3-インドリルカルボニルアミノ)フェニルメチル;4-(フェニル アミノカルボニル)フェニルメチル;4-フェニルアルキニルフェニルメチル;4 -(3-ピロリルカルボニルアミノ)フェニルメチル;5-ニトロベンゾフラン-2- イル;5-(2-メチルフェニルウレア)ベンゾフラン-2-イル;3-カルボキシ-3 -フェニルプロピル;2-(3-ピリジル)-チアゾール-4-イル;2-(4-ピリジル) -チアゾール−4−イル;2-オキソ-4,5,6,7-テトラヒドロベンゾ[b]フラン-3- イルおよび4-オキソ-4,5,6,7-テトラヒドロベンゾ[b]フラン-3-イル;3-メト キシ-4-(フェニルカルバモイルオキシ)フェニルメチル;5-アミノ-ベンゾフラ ン-2-イル;ベンジリルアミノフェニルメチルおよび4-[N-2-カルボキシエチ ル-1-(1,3-ベンゾジオキソリル-5-イル)アミノ-N-ロイシニルアセトアミジル フェニルウレア]フェニルメチル。 8.R1が以下からなる群から選択される、請求項1または2に記載の細胞接着 阻害化合物:ベンジルオキシ、シアノメチル、シクロヘキシルメチル、メチル、 n-ヘキシル、N-フェニルアミノ、フェニル、フェニルカルボニル、フェニルメチ ル、t-ブトキシ、t−ブチルアミノ、1-インダニル、1-ナフチルメチル、1-フェ ニルシクロプロピル、2-(4-ヒドロキシ-フェニル)エチル、2-(ベンジルオキ シカルボニルアミノ)フェニルメチル、2-(ビス(フェニルスルホニル)アミノ)フ ェニルメチル、2-(N'-フェニルウレア)フェニルメチル、2-アミノフェニルメ チル、2-ベンズアミドフェニルメチル、2-ブロモ-4-ヒドロキシ-5-メトキシ フェニルメチル、2-ヒドロキシフェニルメチル、2-ナフチルメチル、2-フェ ニルエチル、2-ピリジルメチル、2-キノリニル、2-[4-(N'-フェニルウレア) フェニル]エチル、3-(ベンジルオキシカルボニルアミノ)フェニルメチル、3-( N'-フェニルウレア)フェニルメチル、3-(N'-フェニルウレア)プロピル、3-(フ ェニルスルホンアミド)フェニルメチル、3-アセトアミドフェニルメチル、3- アミノフェニルメチル、3-ベンゾアミドフェニルメチル、3-ヒドロキシ-4-(N 'フェニルウレア)フェニルメチル、3-ヒドロキシフェニルメチル、3-インドリ ル、3-メトキシ-4-(N'-フェニルウレア)フェニルメチル、3-メトキシ-4-(N' -(2-メチルフェニル)ウレア)フェニルメチル、3-メチル-4-(N'-フェニルウレ ア)-フェニルメチル、3-ニトロフェニルメチル、3-フェニルプロピル、3-ピ リジルメチル、4-(2-アミノベンゾアミド)フェニルメチル、4-(ベンゾアミド )フェニルメチル、4-(ベンジルオキシカルボニルアミノ)フェニルメチル、4-( モルホリノカルボニルアミノ)フェニルメチル、4-(N'-(2-クロロフェニル)ウ レア)フェニルメチル、4-(N'-(2-クロロフェニル)ウレア)-3-メトキシフェニ ルメチル、4-(N'-(2-エチルフェニル)ウレア)フェニルメチル、4-(N'-(2-イ ソプロピルフェニル)ウレア)フェニルメチル、4-(N'-(2-メトキシフェニル)ウ レア)フェニルメチル、4-(N'-(2-メチル−3−ピリジル)ウレア)フェニルメチ ル、4-(N'-(2-ニトロフェニル)ウレア)フェニルメチル、4-(N'-(2-ピリジル )ウレア)フェニルメチル、4-(N'-(2-t-ブチルフェニル)ウレア)フェニルメチ ル、4-(N'-(2-チアゾリル)ウレア)フェニルメチル、4-(N'-(3-クロロフェニ ル)ウレア)フェニルメチル、4-(N'-(3-メトキシフェニル)ウレア)フェニルメ チル、4-(N'-(3-ピリジル)ウレア)フェニルメチル、4-(N'-(4-ピリジル)ウ レア)フェニルメチル、4-(N'-(3-メチルフェニル)ウレア)フェニルメチル、4 -(N'-(2-メチルフェニル)ウレア) フェニルメチル、4-(N'-ベンジルウレア)フェニルメチル、4-(N'-シクロヘキ シルウレア)フェニルメチル、4-(N'-エチルウレア)フェニルメチル、4-(N'-イ ソプロピルウレア)フェニルメチル、4-(N'-メチルウレア)フェニルメチル、4- (N'-p-トルイルウレア)フェニルメチル、4-(N'-フェニルウレア)フェニル、4- (N'-フェニルウレア)フェニルアミノ、4-(N'-フェニルウレア)フェニルメチル 、4-(N'-t-ブチルウレア)フェニルメチル、4-(フェニルアミノカルボニルアミ ノメチル)フェニル、4-(フェニルスルホンアミド)フェニルメチル、4-(t-ブト キシカルボニルアミノ)フェニルメチル、4-アセトアミドフェニルメチル、4- アミノフェニルアミノ、4-アミノフェニルメチル、4-ベンズアミドフェニルメ チル、4-クロロフェニルメチル、4-ヒドロキシ-3-ニトロフェニルメチル、4 -ヒドロキシフェニルメチル、4-メトキシフェニルメチル、4-ニトロフェニル アミノ、4-ニトロフェニルメチル、4−フェナセトアミドフェニルメチル、4- フェニルフェニルメチル、4−ピリジルメチル、4-トリフルオロメチルフェニ ルメチル、4-[2-(N'-メチルウレア)ベンズアミド]フェニルメチル、4-(N'-( 2-メチルフェニル)ウレア)フェニルメチル、4-(N'-フェニル-N''-メチルグア ニジノ)フェニルメチル、5-(N'-フェニルウレア)ペンチル、5-(N'-t-ブチルウ レア)ペンチル、2,2-ジメチルプロピル、2,2-ジフェニルメチル、2,3-ベンゾシ クロブチル、3,4-ジヒドロキシフェニルメチル、3,5-ジメトキシ-4-ヒドロキシ -フェニルメチル、4-(1-インドールカルボキシルアミノ)フェニルメチル、6- メトキシ-5-(N'-(2-メチルフェニル)ウレア)-2-ピリジルメチル、4-(1,3-ベ ンズオキサゾール-2-イルアミノ)-フェニルメチルおよび4-(1,3-イミダゾー ル-2-イルアミノ)-フェニルメチル。 9.R1が、4-ヒドロキシフェニルメチル、3-メトキシ-4-(N'-フェニルウレア )-フェニルメチル、4-(N'-フェニルウレア)-フェニルメチル、4-(N'-(2- メチルフェニル)ウレア)フェニルメチル、4-(N'-(2-ピリジル)ウレア)-フ ェニルメチル、3-メトキシ-4-(N'-(2-メチルフェニル)ウレア)フェニル メチル、6-メトキシ−5-(N'-(2-メチルフェニル)ウレア)-2-ピリジルメ チル、4-(N'-3-メチル-2-ピリジルウレア)フェニルメチル、3-メト キシ-4-(N'-3-メチル-2-ピリジルウレア)フェニルメチル、および3-メトキ シ-4-(N'-2-ピリジルウレア)フェニルメチルからなる群より選択される、請 求項7に記載の細胞接着阻害化合物。 10.R1が、4-ヒドロキシフェニルメチル、3-メトキシ-4-(N'-フェニルウ レア)-フェニルメチル、4-(N'-フェニルウレア)-フェニルメチル、4-(N'- (2-メチルフェニル)ウレア)フェニルメチル、4-(N'-2-ピリジル)ウレア )-フェニルメチル、3-メトキシ-4-(N'-(2-メチルフェニル)ウレア)フェ ニルメチル、6-メトキシ−5-(N'-(2-メチルフェニル)ウレア)-2-ピリジ ルメチルからなる群より選択される、請求項9に記載の細胞接着阻害化合物。 11.Yがカルボニル基である、請求項1または2に記載の細胞接着阻害化合物 。 12.R2が水素、メチル、またはフェナシルである、請求項1または2に記載 の細胞接着阻害化合物。 13.R2が水素である、請求項12に記載の細胞接着阻害化合物。 14.R3が以下からなる群より選択されるか、あるいはR2と一緒になってプロ リン、アゼチジン、またはピペコリン環を形成する、請求項1または2に記載の 細胞接着阻害化合物:2-(メチルスルホニル)-エチル、3-(ヒドロキシプロ ピルチオ)-メチル、4-(メチルスルホニルアミノ)-ブチル、4-アセチルアミ ノブチル、アミノメチル、ベンジル、ブチル、ヒドロキシメチル、イソブチル、 メチル、メチルチオメチル、フェニルメチル、プロピル、4-(ベンジルオキシ カルボニルアミノ)-ブチル、N,N-(メチルプロパルギル)アミノ、2-(メチル チオ)エチル、2-(モルホリノ-N-カルボニル)エチル、2-(N-モルホリノ)エ チル、2-(N,N-ジメチルアミノ)エチル、4-アミノブチル、4−ベンジルオキ シフェニルメチル、2-ベンジルチオメチル、t-ブトキシカルボニルアミノメチ ル、sec-ブチル、t-ブチル、N,N-ジメチルアミノカルボニルメチル、1,1-エタノ 4-ヒドロキシフェニルメチル、1-ヒドロキシエチル、1-メトキシエチル、4-メ トキシフェニルメチル、ベンジルオキシメチル、ベンジルチオメチル、カルボニ ルメチル、2-メチルスルフィニルエチル、モルホリノ-N-カルボニルメチル、チ オモルホリノ-N-カルボニルメチル、2-フェニルエチル、アスパラギン側鎖、プ ロリン側鎖および2-チアゾリルメチル、4-(フェニルウレア)ブチル;4-( メチルウレア)ブチル;モルホリノカルボニルメチルチオメチル;モルホリノエ チルチオメチル;3-ピリジルメチル;4-メチルスルホニルアミノブチル;ヒド ロキシメチルチオメチル;2-メチルスルホニルエチル、4-プロピオニルアミノ ブチル;4-エトキシカルボニルアミノブチル;メトキシカルボニルアミノブチ ル;カルボメトキシメチルチオメチル;4-t-ブチルウレアブチル;カルボキシ メチルチオメチル;ジメチルアミドメチルチオメチル;アセチルアミノプロピル ;3-メチルウレアプロピル;4-ビオチノイルアミノブチル;2-チエニルメチ ル;3-ピリジルメチル;4-トリフルオロアセチルアミノブチル;ジメチルアミ ノメチルチオメチル;ジメチルアミノエチルチオメチル;4-(ジメチルアミノ アセチルアミノ)ブチル。 15.R3が、2-(メチルスルホニル)-エチル、3-(ヒドロキシプロピルチオ )-メチル、4-(メチルスルホニルアミノ)-ブチル、4-アセチルアミノブチル 、アミノメチル、ベンジル、ブチル、ヒドロキシメチル、イソブチル、メチル、 メチルチオメチル、フェニルメチル、プロピル、4-(ベンジルオキシカルボニ ルアミノ)-ブチル、N,N-(メチルプロパルギル)アミノ、2-(メチルチオ)エ チル、2-(モルホリノ-N-カルボニル)エチル、2-(N-モルホリノ)エチル、2- (N,N-ジメチルアミノ)エチル、4-アミノブチル、4−ベンジルオキシフェニ ルメチル、2-ベンジルチオメチル、t-ブトキシカルボニルアミノメチル、sec- ブチル、t-ブチル、N,N-ジメチルアミノカルボニルメチル、1,1-エタノ、4-ヒ ドロキシフェニルメチル、1-ヒドロキシエチル、1-メトキシエチル、4-メトキ シフェニルメチル、ベンジルオキシメチル、ベンジルチオメチル、カルボニルメ チル、2-メチルスルフィニルエチル、モルホリノ-N-カルボニルメチル、チオモ ルホリノ-N-カルボニルメチル、2-フェニルエチル、アスパラギン側鎖、プロリ ン側鎖および2-チアゾリルメチルからなる群より選択される、請求項14に記 載の細胞接着阻害化合物。 16.R3が、イソブチル、2-(メチルチオ)エチル、3-(ヒドロキシプロピ ルチオ)メチル、2-(メチルスルホニル)エチル、4-アセチルアミノブチル、 4-(メチルスルホニルアミノ)ブチル、および4-(エトキシカルボニルアミノ )ブチルからなる群より選択される、請求項14に記載の細胞接着阻害化合物。 17.R3が、イソブチル、2-(メチルチオ)エチル、3-(ヒドロキシプロピ ルチオ)メチル、2-(メチルスルホニル)エチル、4-アセチルアミノブチル、 および4-(メチルスルホニルアミノ)ブチルからなる群より選択される、請求 項16に記載の細胞接着阻害化合物。 18.R4が以下からなる群より選択される、請求項1または2に記載の細胞接 着阻害化合物:4-カルボメトキシフェニル、4-カルボキシフェニル、4-フル オロフェニル、4-メトキシフェニル、ベンジル、メチル、フェニル、フェニル メチル、フェニルエチル、4-クロロフェニル、3,4-ジフルオロフェニル、3,4- ジメトキシフェニル、2-メトキシフェニル、3-メトキシフェニル、4-メトキ シフェニル、2−ニトロフェニル、3-ピリジル、4-フェノキシフェニル;4- エトキシフェニル;4-ニトロフェニル;4-アセチルアミノフェニル;4-メチ ルウレアフェニル;2-フルオロフェニル;ナフチル;3-フルオロフェニル;3 −ニトロフェニル;水素;2-ニトロフェニル;4-シアノフェニル;3-メトキ シフェニル;4-メチルスルホニルアミノ;3-シアノフェニル;4-プロピオニ ルアミノ;4-アミノフェニル;3-アミノフェニル;4-トリフルオロメトキシ フェニル;4-メチルフェニル;4-アミノ-3-ニトロフェニル;4-ヒドロキシ −3−メトキシフェニル;4-ヘキシルオキシフェニル;4-メチルチオフェニル 、3-フラニル;4−ジメチルアミノフェニル;3-ヒドロキシ−4−ニトロフェ ニル;n-ペンチル;カルボキシメチル;2-カルボキシエチル;エチニル;2-チ エニル;2-プロペニル;2-プロピニル;メチル;およびプロピル。 19.R4が、4-カルボメトキシフェニル、4-カルボキシフェニル、4-フルオ ロフェニル、4-メトキシフェニル、ベンジル、メチル、フェニル、フェニルメ チル、フェニルエチル、4-クロロフェニル、3,4-ジフルオロフェニル、3,4-ジ メトキシフェニル、2-メトキシフェニル、3-メトキシフェニル、4-メトキシ フェニル、2−ニトロフェニル、および3-ピリジルからなる群より選択される 、請求項18に記載の細胞接着阻害化合物。 20.R4が、4-メトキシフェニル、3,4-ジメトキシフェニル、4-フルオロフ ェニル、4-カルボキシフェニル、4-カルボメトキシフェニル、フェニルエチル 、フェニルメチル、アリル、エチニル、および3,4-メチレンジオキシフェニルか らなる群より選択される、請求項18に記載の細胞接着阻害化合物。 21.R4が、4-メトキシフェニル、3,4-ジメトキシフェニル、4-フルオロフ ェニル、4-カルボキシフェニル、4-カルボメトキシフェニル、フェニルエチル 、およびフェニルメチルからなる群より選択される、請求項20に記載の細胞接 着阻害化合物。 22.YがCO、CH2、またはSO2である、請求項1または2に記載の細胞接 着阻害化合物。 23.YがCOである、請求項22に記載の細胞接着阻害化合物。 24.nが1である、請求項1または2に記載の細胞接着阻害化合物。 25.BIO-1006、BIO-1056、BIO-1089、BIO-1179、BIO-119 4、BIO-1221、BIO-1224、BIO-1238、BIO-1245、BIO-1246 、BIO-1248、BIO-1270、BIO-1282、BIO-1294、BIO-1321、 BIO-1336、BIO-1382、およびBIO-1400からなる群から選択される、 請求項2に記載の細胞接着阻害化合物。 26.BIO-1218、BIO-1272、BIO-1311、BIO-1319、BIO-134 5、BIO-1347、BIO-1358、BIO-1361、BIO-1388、BIO-1390 、BIO-1393、BIO-1396、BIO-1429、BIO-1444、BIO-1474、 BIO-1475、BIO-1490、BIO-1515、BIO-1525、BIO-1526、BI O-1536、BIO-1594、BIO-1648、BIO-1655、BIO-1721、BIO- 1725、BIO-1726、BIO-1727、BIO-1728、BIO-1729、BIO-1 730、BIO-1731、およびBIO-1732からなる群から選択される、請求項 1に記載の細胞接着阻害化合物。 27.BIO-1218、BIO-1272、BIO-1311、BIO-1347、BIO-139 3、BIO-1429、BIO-1515、BIO-1725、BIO-1726、BIO-1727 、BIO-1728、BIO-1729、BIO-1730、BIO-1731、およびBIO-17 32からなる群より選択される、請求項1に記載の細胞接着阻害化合物。 28.細胞接着の予防、阻害、または抑制に有効な量の請求項1〜27のいずれ か1つに記載の化合物、および薬学的に受容可能なキャリアを含む薬学的組成物 。 29.コルチコステロイド、気管支拡張剤、抗喘息剤、抗炎症剤、抗リウマチ剤 、免疫抑制剤、低代謝剤、免疫調節剤、抗乾癬剤、および抗糖尿病剤からなる群 より選択される薬剤をさらに含む、請求項28に記載の薬学的組成物。 30.哺乳動物における細胞接着を予防、阻害、または抑制する方法であって、 請求項28または29に記載の薬学的組成物を該哺乳動物に投与する工程を包含 する、方法。 31.請求項30に記載の方法であって、細胞接着関連炎症を予防、阻害、また は抑制するために使用される、方法。 32.請求項31に記載の方法であって、細胞接着関連免疫応答または自己免疫 応答を予防、阻害、または抑制するために使用される、方法。 33.請求項30に記載の方法であって、喘息、関節炎、乾癬、移植拒絶反応、 多発性硬化症、糖尿病、および炎症性腸疾患からなる群より選択される疾患を処 置または予防するために使用される、方法。
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2001527061A (ja) * | 1997-12-23 | 2001-12-25 | アベンテイス・フアルマ・リミテツド | 置換されたβ−アラニン |
JP2002501039A (ja) * | 1998-01-23 | 2002-01-15 | ノバルティス ファーマ アクチエンゲゼルシャフト | Vla−4アンタゴニスト |
JP2002539206A (ja) * | 1999-03-12 | 2002-11-19 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 抗炎症剤としての芳香族複素環化合物 |
JP2005519929A (ja) * | 2002-02-06 | 2005-07-07 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | インテグリンαvβ6の阻害剤 |
JP2015520130A (ja) * | 2012-04-16 | 2015-07-16 | アラーガン、インコーポレイテッドAllergan,Incorporated | ホルミルペプチド受容体2調節物質としての(2−ウレイドアセトアミド)アルキル誘導体 |
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