JP5210598B2 - オートインデューサー−2阻害剤ならびに感染症の予防および/または治療剤 - Google Patents
オートインデューサー−2阻害剤ならびに感染症の予防および/または治療剤 Download PDFInfo
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- JP5210598B2 JP5210598B2 JP2007288556A JP2007288556A JP5210598B2 JP 5210598 B2 JP5210598 B2 JP 5210598B2 JP 2007288556 A JP2007288556 A JP 2007288556A JP 2007288556 A JP2007288556 A JP 2007288556A JP 5210598 B2 JP5210598 B2 JP 5210598B2
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Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
- Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(1)式I:
R1およびR2は、それぞれ独立して、水素、ヒドロキシ基、アリール基もしくはアルコキシ基であるか、または、R1およびR2は一緒になってオキソ基を形成し、
R3は、ハロゲンであり、
R4は、水素、アミノ基またはハロゲンである)
で表される化合物またはその塩を有効成分とするオートインデューサー−2阻害剤。
(2)式I:
R1およびR2は、それぞれ独立して、水素、ヒドロキシ基、アリール基もしくはアルコキシ基であるか、または、R1およびR2は一緒になってオキソ基を形成し、
R3は、ハロゲンであり、
R4は、水素、アミノ基またはハロゲンである)
で表される化合物またはその塩を有効成分とする感染症の予防および/または治療剤。
(3)感染症が歯周病である、(2)記載の感染症の予防および/または治療剤。
(4)齲蝕を予防するための、(2)記載の感染症の予防および/または治療剤。
(5)式Iの化合物が4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノンである(1)〜(4)のいずれかに記載の、オートインデューサー−2阻害剤、または感染症の予防および/または治療剤。
(6)式Iの化合物が3,4−ジブロモ−5−ヒドロキシ−2(5H)−フラノンである(1)〜(4)のいずれかに記載の、オートインデューサー−2阻害剤、または感染症の予防および/または治療剤。
(7)式Iの化合物が4−ブロモ−5−メトキシ−5−(4−メトキシフェニル)−2(5H)−フラノンである(1)〜(4)のいずれかに記載の、オートインデューサー−2阻害剤、または感染症の予防および/または治療剤。
(8)式Iの化合物が4−{[3−ブロモ−2−(4−メトキシフェニル)−5−オキソ−2,5−ジヒドロ−2−フラニル]オキシ}安息香酸である(1)〜(4)のいずれかに記載の、オートインデューサー−2阻害剤、または感染症の予防および/または治療剤。
R1およびR2は、それぞれ独立して、水素、ヒドロキシ基、アリール基もしくはアルコキシ基(好ましくはC1−6アルコキシ基)であるか、または、R1およびR2は一緒になってオキソ基を形成し、
R3は、ハロゲンであり、
R4は、水素、アミノ基またはハロゲンである)
で表される化合物またはその塩を有効成分とするオートインデューサー−2阻害剤に関する。
ビブリオ・ハーベイ(Vibrio harveyi)BB170株をオートインデューサー−2(AI−2)レポーター細菌として使用し、AI−2活性の指標であるレポーター細菌の発光強度をDe Keersmaecker S.C.J. et al., J. Biol. Chem., 280(20), 19563-19568, 2005と同様に測定した。すなわち、ビブリオ・ハーベイBB170株を培地にて4500倍希釈になるように調製し、各被検化合物溶液と室温で10分プレインキュベートした後、4,5−ジヒドロキシ−2,3−ペンタンジオン(DPD)を添加し、30℃にて好気振盪培養し、4時間後の発光強度をケミルミネッセンス計で測定した。レポーター菌液終濃度は5000倍希釈、各被検化合物溶液とDPDの終濃度は共に10μMとした。DPDのみ添加したものをコントロールとし、それに対する相対値として表した(図1)。また同時に被検化合物のAI−2活性も検討した。
午前に試料を採取する被験者は、試験前日就寝前の歯磨き以降、午後の被験者は試験日朝の歯磨き以降、歯磨きを停止させた。さらに試料採取30分前から飲食・喫煙を禁止させた。
1:歯肉に炎症。プロービングで出血なし
2:歯肉に炎症。プロービングで出血あり
3:自然出血・潰瘍形成
図2の結果から、歯垢中AI−2量と歯肉炎症度が相関関係を有すること(p<0.1)、従って、歯垢中のAI−2が歯肉炎に関与していることが示された。
シリアンハムスター(7W、♂)の下顎左右第一臼歯頚部に絹糸を結紮し、4日、1週間、2週間後の歯垢および下顎骨を麻酔下にて摘出した。歯垢は上記に準じ、AI−2活性測定のために処理を行い、ビブリオ・ハーベイのバイオアッセイにて、歯垢中AI−2量を測定した。また下顎骨は周辺組織を完全にトリミングした後、歯槽骨吸収深度を測定した。評価部位は摘出下顎骨の舌側面とし、摘出した下顎骨を実体顕微鏡下にて撮影し、得られた写真を画像解析に供した。歯槽骨吸収深度は第一臼歯近心咬頭頂から歯槽骨頂上までの垂直距離とした(森ら,岐阜大医紀,43, 758-767, 1995)。
シリアンハムスター(7W、♂)の下顎左右第一臼歯頚部に絹糸を結紮し、翌日より同結紮部位に被検試料を2回/日、2週間滴下した。被検試料は溶媒中10μMに調製した4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノン(実施例1の化合物1)および3,4−ジブロモ−5−ヒドロキシ−2(5H)−フラノン(実施例1の化合物2)の各溶液とし、コントロールは溶媒のみとした。溶媒として、1%DMSO含有PBSを用いた。
Claims (14)
- 式I:
R1およびR2は、それぞれ独立して、水素、ヒドロキシ基、置換基を有していてもよいフェニル基もしくはフェニルオキシ基、またはC 1−6 アルコキシ基であり、
フェニル基およびフェニルオキシ基の環上の置換基は、ハロゲン、ヒドロキシ基、ニトロ基、アミノ基、メルカプト基、シアノ基、イソシアナート基、カルボキシ基、C 1−6 アルキル基、C 2−6 アルケニル基およびC 1−6 アルコキシ基からなる群から選択され、
R 1 およびR 2 の一方が置換基を有していてもよいフェニル基もしくはフェニルオキシ基である場合、他方は水素、ヒドロキシ基またはアルコキシ基であり、R 1 およびR 2 の一方が水素である場合、他方は水素ではなく、
R3は、ハロゲンであり、
R4は、水素、アミノ基またはハロゲンである)
で表される化合物またはその塩を有効成分とするオートインデューサー−2阻害剤。 - 式I:
R1およびR2は、それぞれ独立して、水素、ヒドロキシ基、置換基を有していてもよいフェニル基もしくはフェニルオキシ基、またはC 1−6 アルコキシ基であり、
フェニル基およびフェニルオキシ基の環上の置換基は、ハロゲン、ヒドロキシ基、ニトロ基、アミノ基、メルカプト基、シアノ基、イソシアナート基、カルボキシ基、C 1−6 アルキル基、C 2−6 アルケニル基およびC 1−6 アルコキシ基からなる群から選択され、
R 1 およびR 2 の一方が置換基を有していてもよいフェニル基もしくはフェニルオキシ基である場合、他方は水素、ヒドロキシ基またはアルコキシ基であり、R 1 およびR 2 の一方が水素である場合、他方は水素ではなく、
R3は、ハロゲンであり、
R4は、水素、アミノ基またはハロゲンである)
で表される化合物またはその塩を有効成分とする感染症の予防および/または治療剤。 - 感染症が歯周病である、請求項2記載の感染症の予防および/または治療剤。
- 齲蝕を予防するための、請求項2記載の感染症の予防および/または治療剤。
- 式Iの化合物が4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノンである請求項1記載の、オートインデューサー−2阻害剤。
- 式Iの化合物が3,4−ジブロモ−5−ヒドロキシ−2(5H)−フラノンである請求項1記載の、オートインデューサー−2阻害剤。
- 式Iの化合物が4−ブロモ−5−メトキシ−5−(4−メトキシフェニル)−2(5H)−フラノンである請求項1記載の、オートインデューサー−2阻害剤。
- 式Iの化合物が4−{[3−ブロモ−2−(4−メトキシフェニル)−5−オキソ−2,5−ジヒドロ−2−フラニル]オキシ}安息香酸である請求項1記載の、オートインデューサー−2阻害剤。
- 式Iの化合物が4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノンである請求項2〜4のいずれか1項記載の、感染症の予防および/または治療剤。
- 式Iの化合物が3,4−ジブロモ−5−ヒドロキシ−2(5H)−フラノンである請求項2〜4のいずれか1項記載の、感染症の予防および/または治療剤。
- 式Iの化合物が4−ブロモ−5−メトキシ−5−(4−メトキシフェニル)−2(5H)−フラノンである請求項2〜4のいずれか1項記載の、感染症の予防および/または治療剤。
- 式Iの化合物が4−{[3−ブロモ−2−(4−メトキシフェニル)−5−オキソ−2,5−ジヒドロ−2−フラニル]オキシ}安息香酸である請求項2〜4のいずれか1項記載の、感染症の予防および/または治療剤。
- 4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノンまたはその塩を有効成分とする歯周病の予防および/または治療剤。
- 3,4−ジブロモ−5−ヒドロキシ−2(5H)−フラノンまたはその塩を有効成分とする歯周病の予防および/または治療剤。
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