JP4590159B2 - グルコース再吸収阻害剤およびpparモジュレーターを含んで成る併用療法 - Google Patents
グルコース再吸収阻害剤およびpparモジュレーターを含んで成る併用療法 Download PDFInfo
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- JP4590159B2 JP4590159B2 JP2002578975A JP2002578975A JP4590159B2 JP 4590159 B2 JP4590159 B2 JP 4590159B2 JP 2002578975 A JP2002578975 A JP 2002578975A JP 2002578975 A JP2002578975 A JP 2002578975A JP 4590159 B2 JP4590159 B2 JP 4590159B2
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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Description
A.用語
いくつかの用語を、下および本開示を通じてのそれらの使用により定義する。
置換メチルエーテル
置換メチルエーテルの例は、メトキシメチル、メチルチオメチル、t−ブチルチオメチル、(フェニルジメチルシリル)メトキシメチル、ベンジルオキシメチル、p−メトキシベンジルオキシメチル、(4−メトキシフェノキシ)メチル、グアヤコールメチル、t−ブトキシメチル、4−ペンテニルオキシメチル、シロキシメチル、2−メトキシエトキシメチル、2,2,2−トリクロロエトキシメチル、ビス(2−クロロエトキシ)メチル、2−(トリメチルシリル)エトキシメチル、テトラヒドロピラニル、3−ブロモテトラヒドロピラニル、テトラヒドロチオピラニル、1−メトキシシクロヘキシル、4−メトキシテトラヒドロピラニル、4−メトキシテトラヒドロチオピラニル、4−メトキシテトラヒドロチオピラニルS,S−ジオキシド、1−[(2−クロロ−4−メチル)フェニル]−4−メトキシピペリジン−4−イル、1,4−ジオキサン−2−イル、テトラヒドロフラニル、テトラヒドロチオフラニルおよび2,3,3a,4,5,6,7,7a−オクタヒドロ−7,8,8−トリメチル−4,7−メタノベンゾフラン−2−イルを包含する。
置換エチルエーテル
置換エチルエーテルの例は、1−エトキシエチル、1−(2−クロロエトキシ)エチル、1−メチル−1−メトキシエチル、1−メチル−1−ベンジルオキシエチル、1−メチル−1−ベンジルオキシ−2−フルオロエチル、2,2,2−トリクロロエチル、2−トリメチルシリルエチル、2−(フェニルセレニル)エチル、t−ブチル、アリル、p−クロロフェニル、p−メトキシフェニル、2,4−ジニトロフェニル、ベンジルおよびポリエチレングリコールエーテルを包含する。
置換ベンジルエーテル
置換ベンジルエーテルの例は、p−メトキシベンジル、3,4−ジメトキシベンジル、o−ニトロベンジル、p−ニトロベンジル、p−ハロベンジル、2,6−ジクロロベンジル、p−シアノベンジル、p−フェニルベンジル、2−および4−ピコリル、3−メチル−2−ピコリルN−オキシド、ジフェニルメチル、p,p’−ジニトロベンズヒドリル、5−ジベンゾスベリル、トリフェニルメチル、α−ナフチルジフェニルメチル、p−メトキシフェニルジフェニルメチル、ジ(p−メトキシフェニル)フェニルメチル、トリ(p−メトキシフェニル)メチル、4−(4’−ブロモフェナシルオキシ)フェニルジフェニルメチル、4,4’,4”−トリス(4,5−ジクロロフタルイミドフェニル)メチル、4,4’,4”−トリス(レブリノイルオキシフェニル)メチル、4,4’,4”−トリス(ベンゾイルオキシフェニル)メチル、3−(イミダゾル−1−イルメチル)ビス(4’,4”−ジメトキシフェニル)メチル、1,1−ビス(4−メトキシフェニル)−1’−ピレニルメチル、9−アントリル、9−(9−フェニル)キサンテニル、9−(9−フェニル−10−オキソ)アントリル、1,3−ベンゾジチオラン−2−イル、ならびにベンズイソチアゾリルS,S−ジオキシドを包含する。
シリルエーテル
シリルエーテルの例は、トリメチルシリル、トリエチルシリル、トリイソプロピルシリル、ジメチルイソプロピルシリル、ジエチルイソプロピルシリル、ジメチルトヘキシルシリル、t−ブチルジメチルシリル、t−ブチルジフェニルシリル、トリベンジルシリル、トリ−p−キシリルシリル、トリフェニルシリル、ジフェニルメチルシリルおよびt−ブチルメトキシフェニルシリルを包含する。
エステル
エーテルに加え、ヒドロキシル基はエステルとして保護してよい。エステルの例は、ギ酸エステル、ベンゾイルギ酸エステル、酢酸エステル、クロロ酢酸エステル、ジクロロ酢酸エステル、トリクロロ酢酸エステル、トリフルオロ酢酸エステル、メトキシ酢酸エステル、トリフェニルメトキシ酢酸エステル、フェノキシ酢酸エステル、p−クロロフェノキシ酢酸エステル、p−P−フェニル酢酸エステル、3−フェニルプロピオン酸エステル、4−オキソペンタン酸エステル(レブリン酸エステル)、4,4−(エチレンジチオ)ペンタン酸エステル、ピバル酸エステル、アダマントエート、クロトン酸エステル、4−メトキシクロトン酸エステル、安息香酸エステル、p−フェニル安息香酸エステル、2,4,6−トリメチル安息香酸エステル(メシトエート)およびポリエチレングリコールエステルを包含する。
炭酸エステル
単酸エステルの例は、メチル、9−フルオレニルメチル、エチル、2,2,2−トリクロロエチル、2−(トリメチルシリル)エチル、2−(フェニルスルホニル)エチル、2−(トリフェニルホスホニオ)エチル、イソブチル、ビニル、アリル、p−ニトロフェニル、ベンジル、p−メトキシベンジル、3,4−ジメトキシベンジル、o−ニトロベンジル、p−ニトロベンジル、S−ベンジルチオカルボン酸エステル、4−エトキシ−1−ナフチル、メチルジチオカルボン酸エステルおよびポリエチレングリコール炭酸エステルを包含する。
補助型開裂(assisted cleavage)
補助型開裂の例は、2−ヨード安息香酸エステル、4−アジド酪酸エステル、4−ニトロ−4−メチルペンタン酸エステル、o−(ジブロモメチル)安息香酸エステル、2−ホルミルベンゼンスルホン酸エステル、2−(メチルチオメトキシ)エチル炭酸エステル、4−(メチルチオメトキシ)酪酸エステルおよび2−(メチルチオメトキシメチル)安息香酸エステルを包含する。
雑多なエステル
雑多なエステルの例は、2,6−ジクロロ−4−メチルフェノキシ酢酸エステル、2,6−ジクロロ−4−(1,1,3,3−テトラメチルブチル)フェノキシ酢酸エステル、2,4−ビス(1,1−ジメチルプロピル)フェノキシ酢酸エステル、クロロジフェニル酢酸エステル、イソ酪酸エステル、モノコハク酸エステル、(E)−2−メチル−2−ブテン酸エステル(チグロエート)、o−(メトキシカルボニル)安息香酸エステル、p−P−安息香酸エステル、α−ナフトエ酸エステル、硝酸エステル、アルキルN,N,N’,N’−テトラメチルホスホロジアミデート、N−フェニルカルバメート、ホウ酸エステル、ジメチルホスフィノチオイルおよび2,4−ジニトロフェニルスルフェン酸エステルを包含する。
スルホン酸エステル
スルホン酸エステルの例は、硫酸エステル、メタンスルホン酸エステル(メシル酸エステル)、ベンジルスルホン酸エステルおよびトシル酸エステルを包含する。
1,2−および1,3−ジオールの保護
環状アセタールおよびケタール
環状アセタールおよびケタールの例は、メチレン、エチリデン、1−t−ブチルエチリデン、1−フェニルエチリデン、(4−メトキシフェニル)エチリデン、2,2,2−トリクロロエチリデン、アセトニド(イソプロピリデン)、シクロペンチリデン、シクロヘキシリデン、シクロへプチリデン、ベンジリデン、p−メトキシベンジリデン、2,4−ジメトキシベンジリデン、3,4−ジメトキシベンジリデンおよび2−ニトロベンジリデンを包含する。
環状オルトエステル
環状オルトエステルの例は、メトキシメチレン、エトキシメチレン、ジメトキシメチレン、1−メトキシエチリデン、1−エトキシエチリデン、1,2−ジメトキシエチリデン、α−メトキシベンジリデン、1−(N,N−ジメチルアミノ)エチリデン誘導体、α−(N,N−ジメチルアミノ)ベンジリデン誘導体および2−オキサシクロペンチリデンを包含する。
シリル誘導体
シリル誘導体の例は、ジ−t−ブチルシリレン基、および1,3−(1,1,3,3−テトライソプロピルジシロキサニリデン)誘導体を包含する。
B.グルコース再吸収阻害剤
高血糖の一治療方法は、血中グルコース濃度が正常化されるように過剰のグルコースを尿中に直接排泄することである。例えば、腸および腎の絨毛膜中で主に見出されるナトリウム依存性グルコース共輸送体(SGLT)は、グルコース吸収の正常な過程に積極的に関与するタンパク質の一ファミリーである。それらのなかで、SGLT1は腸および腎上皮細胞中に存在する(Leeら,1994)一方、SGLT2は腎の上皮中で見出される(Youら,1995,MacKenzieら,1994)。腸におけるグルコース吸収は、主として、2:1のNa+:グルコース輸送比を伴い、高親和性低容量輸送体SGLT1により媒介される。SAAT1としてもまた知られるSGLT2は、1:1の比でNa+およびグルコースを輸送し、そして低親和性高容量輸送体として機能する。これらのSGLTを表1に特徴づける:
の構造を有する、糖尿病の治療および/もしくは予防に有用な化合物もしくはその製薬学的に許容できる塩を開示する。
の1つを有する。
の構造を有する、糖尿病の治療および/もしくは予防に有用な化合物もしくはその製薬学的に許容できる塩を開示する。
の構造を有する、糖尿病の治療および/もしくは予防に有用な化合物もしくはその製薬学的に許容できる塩を開示する。
の構造を有する、糖尿病の治療および/もしくは予防に有用な化合物もしくはその製薬学的に許容できる塩を開示する。
C.PPARモジュレーター
チアゾリジンジオン(TZD)および非チアゾリジンジオンインスリン感作物質は、標的器官および組織でのインスリンの効果を高めることにより末梢インスリン抵抗性を低下させる。これらの薬物は、特異的インスリン応答性遺伝子の転写を増大させる核受容体ペルオキシソーム増殖剤応答性受容体γ(PPARγ)を結合かつ活性化することが既知である。PPAR−γアゴニストの例は:
(1)ロシグリタゾン(アバンジア(AVANDIA)として知られる、2,4−チアゾリジンジオン、5−((4−(2−(メチル−2−ピリジニルアミノ)エトキシ)フェニル)メチル)−、(Z)−2−ブテンジオエート(1:1)もしくは5−((4−(2−(メチル−2−ピリジニルアミノ)エトキシ)フェニル)メチル)−2,4−チアゾリジンジオン;BRL 49653、BRL 49653C、BRL 49653c、SB 210232もしくはロシグリタゾンマレイン酸塩としてもまた知られる);
(2)ピオグリタゾン(アクトス(ACTOS)、ザクトス(ZACTOS)もしくはグルスチン(GLUSTIN)として知られる、2,4−チアゾリジンジオン、5−((4−(2−(5−エチル−2−ピリジニル)エトキシ)フェニル)メチル)−、一塩酸塩、(+−)−、もしくは5−((4−(2−(5−エチル−2−ピリジル)エトキシ)フェニル)メチル)−2,4−チアゾリジンジオン;AD 4833、U 72107、U 72107A、U 72107E、ピオグリタゾン塩酸塩(USAN)としてもまた知られる);
(3)トログリタゾン(ノスカル(NOSCAL)、レズリン(REZULIN)、ロモジン(ROMOZIN)もしくはプリレイ(PRELAY)として知られる、5−((4−((3,4−ジヒドロ−6−ヒドロキシ−2,5,7,8−テトラメチル−2H−1−ベンゾピラン−2−イル)メトキシ)フェニル)メチル)−2,4−チアゾリジンジオン;CI 991、CS 045、GR 92132、GR 92132Xとしてもまた知られる);
(4)イサグリタゾン(MCC−555もしくはネトグリタゾンもしくはネオグリタゾンとしてもまた知られる、(+)−5−[[6−[(2−フルオロフェニル)メトキシ]−2−ナフタレニル]メチル]−2,4−チアゾリジンジオン、もしくは5−((6−((2−フルオロフェニル)メトキシ)−2−ナフタレニル)メチル)−2,4−チアゾリジンジオン、もしくは5−(6−(2−フルオロベンジルオキシ)ナフタレン−2−イルメチル)チアゾリジン−2,4−ジオン);および
(5)5−BTZD
のようなチアゾリジンジオンである。
(1)JT−501(JTT 501、PNU−1827、PNU−716−MET−0096、もしくはPNU 182716:イソキサゾリジン−3,5−ジオン、4−((4−(2−フェニル−5−メチル)−1,3−オキサゾリル)エチルフェニル−4)メチル−);
(2)KRP−297(5−(2,4−ジオキソチアゾリジン−5−イルメチル)−2−メトキシ−N−(4−(トリフルオロメチル)ベンジル)ベンズアミド、もしくは5−((2,4−ジオキソ−5−チアゾリジニル)メチル)−2−メトキシ−N−((4−(トリフルオロメチル)フェニル)メチル)ベンズアミド);および
(3)ファルグリタザール(Farglitazar)(L−チロシン、N−(2−ベンゾイルフェニル)−o−(2−(5−メチル−2−フェニル−4−オキサゾリル)エチル)−、もしくはN−(2−ベンゾイルフェニル)−O−(2−(5−メチル−2−フェニル−4−オキサゾリル)エチル)−L−チロシン、またはGW2570もしくはGI−262570)
を挙げることができる。
(1)AD 5075;
(2)R 119702((+−)−5−(4−(5−メトキシ−1H−ベンズイミダゾル−2−イルメトキシ)ベンジル)チアゾリン−2,4−ジオン塩酸塩、またはCI 1037もしくはCS 011);
(3)CLX−0940(ペルオキシソーム増殖剤応答性受容体αアゴニスト/ペルオキシソーム増殖剤応答性受容体γアゴニスト);
(4)LR−90(2,5,5−トリス(4−クロロフェニル)−1,3−ジオキサン−2−カルボン酸、PPARα/γアゴニスト);
(5)ツラリック(Tularik)(PPARγアゴニスト);
(6)CLX−0921(PPARγアゴニスト);
(7)CGP−52608(PPARアゴニスト);
(8)GW−409890(PPARアゴニスト);
(9)GW−7845(PPARアゴニスト);
(10)L−764406(PPARアゴニスト);
(11)LG−101280(PPARアゴニスト);
(12)LM−4156(PPARアゴニスト);
(13)リサレスタット(Risarestat)(CT−112);
(14)YM 440(PPARアゴニスト);
(15)AR−H049020(PPARアゴニスト);
(16)GW 0072(4−(4−((2S,5S)−5−(2−(ビス(フェニルメチル)アミノ)−2−オキソエチル)−2−ヘプチル−4−オキソ−3−チアゾリジニル)ブチル)安息香酸);
(17)GW 409544(GW−544もしくはGW−409544);
(18)NN 2344(DRF 2593);
(19)NN 622(DRF 2725);
(20)AR−H039242(AZ−242);
(21)GW 9820(フィブラート);
(22)GW 1929(GW 2331として知られる、N−(2−ベンゾイルフェニル)−O−(2−(メチル−2−ピリジニルアミノ)エチル)−L−チロシン、PPARα/γアゴニスト);
(23)SB 219994((S)−4−(2−(2−ベンゾキサゾリルメチルアミノ)エトキシ)−α−(2,2,2−トリフルオロエトキシ)ベンゼンプロパン酸、もしくは3−(4−−(2−(N−(2−ベンゾキサゾリル)−N−メチルアミノ)エトキシ)フェニル)−2(S)−(2,2,2−トリフルオロエトキシ)プロピオン酸、もしくはベンゼンプロパン酸、4−(2−(2−ベンゾキサゾリルメチルアミノ)エトキシ−α−(2,2,2−トリフルオロエトキシ)−、(αS)−、PPARα/γアゴニスト);
(24)L−796449(PPARα/γアゴニスト);
(25)フェノフィブラート(トリコール(TRICOR)、リプコール(LIPCOR)、リパンチル(LIPANTIL)、リピジルミクロ(LIPIDIL MICRO)として知られる、プロパン酸、2−[4−(4−クロロベンゾイル)フェノキシ]−2−メチル−、1−メチルエステル、PPARαアゴニスト);
(26)GW−9578(PPARαアゴニスト);
(27)GW−2433(PPARα/γアゴニスト);
(28)GW−0207(PPARγアゴニスト);
(29)LG−100641(PPARγアゴニスト);
(30)LY−300512(PPARγアゴニスト);
(31)NID525−209(NID−525);
(32)VDO−52(VDO−52);
(33)LG 100754(ペルオキシソーム増殖剤応答性受容体アゴニスト);
(34)LY−510929(ペルオキシソーム増殖剤応答性受容体アゴニスト);
(35)ベキサロテン(タルグレチン(TARGRETIN)、タルグレチン(TARGRETYN)、タルグレキシン(TARGREXIN)として知られる4−(1−(3,5,5,8,8−ペンタメチル−5,6,7,8−テトラヒドロ−2−ナフタレニル)エテニル)安息香酸;LGD 1069、LG 100069、LG 1069、LDG 1069、LG 69、RO 264455としてもまた知られる);および
(36)GW−1536(PPARα/γアゴニスト)。
D.付加的な抗糖尿病薬
本発明により第三の抗糖尿病薬として使用することができる抗糖尿病薬は、限定されるものでないが以下を挙げることができる:
(A)限定されるものでないが:
(1)ベキサロテン(タルグレチン(TARGRETIN)、タルグレチン(TARGRETYN)、タルグレキシン(TARGREXIN)として知られる、4−(1−(3,5,5,8,8−ペンタメチル−5,6,7,8−テトラヒドロ−2−ナフタレニル)エテニル安息香酸;LGD 1069、LG 100069、LG 1069、LDG 1069、LG 69、RO 264455としてもまた知られる);
(2)9−cis−レチノイン酸;
(3)AGN−4326(ALRT−4204、AGN−4204、ALRT−326、ALRT−324もしくはLGD 1324としてもまた知られる);
(4)LGD 1324(ALRT 324);
(5)LG 100754;
(6)LY−510929;
(7)LGD 1268(ALRT 268もしくはLG 100268として知られる6−(1,1,4,4,6−ペンタメチル−1,2,3,4−テトラヒドロ−ナフト−7−イルシクロプロプ−1−イル)ニコチン酸);および
(8)LG 100264
を挙げることができるレチノイド−X受容体(RXR)モジュレーター(またインスリン感作薬、)。
(B)他のインスリン感作薬は、限定されるものでないが:
(1)INS−1(D−カイロイノシトール、もしくはD−1,2,3,4,5,6−ヘキサヒドロキシシクロヘキサン);
(2)タンパク質チロシンホスファターゼ1B(PTP−1B)阻害剤;
(3)グリコーゲン合成酵素キナーゼ−3(GSK3)阻害剤;
(4)ZD2079(ICI D 2079としてもまた知られる、塩化(R)−N−(2−(4−(カルボキシメチル)フェノキシ)エチル)−N−(2−ヒドロキシ−2−フェネチル)アンモニウム)もしくはAZ 40140のようなβ3アドレナリン受容体アゴニスト;
(5)グリコーゲンホスホリラーゼ阻害剤;
(6)フルクトース−1,6−ビスホスファターゼ阻害剤;
(7)クロミックピコリネート、硫酸バナジル(オキシ硫酸バナジウム);
(8)KP 102(有機バナジウム化合物);
(9)クロミックポリニコチネート;
(10)カリウムチャンネルアゴニストNN 414;
(11)YM 268(5,5’−メチレン−ビス(1,4−フェニレン)ビスメチレンビス(チアゾリジン−2,4−ジオン);
(12)TS 971;
(13)T 174((+−)−5−(2,4−ジオキソチアゾリジン−5−イルメチル)−2−(2−ナフチルメチル)ベンズオキサゾール);
(14)SDZ PGU 693((+)−trans−2(S−((4−クロロフェノキシ)メチル)−7α−(3,4−ジクロロフェニル)テトラヒドロピロロ(2,1―b)オキサゾル−5−(6H)−オン);
(15)S 15261((−)−4−(2−((9H−フルオレン−9−イルアセチル)アミノ)エチル)安息香酸2−((2−メトキシ−2−(3−(トリフルオロメチル)フェニル)エチル)アミノ)エチルエステル);
(16)AZM 134(アリザイム(Alizyme));
(17)アリアッド(ARIAD);
(18)R 102380;
(19)PNU 140975(1−(ヒドラジノイミノメチル)ヒドラジノ)酢酸;
(20)PNU 106817(2−(ヒドラジノイミノメチル)ヒドラジノ)酢酸;
(21)NC 2100(5−((7−(フェニルメトキシ)−3−キノリニル)メチル)−2,4−チアゾリジンジオン;
(22)MXC 3255;
(23)MBX 102;
(24)ALT 4037;
(25)AM 454;
(26)JTP 20993(2−(4−(2−(5−メチル−2−フェニル−4−オキサゾリル)エトキシ)ベンジル)−マロン酸ジメチルジエステル);
(27)デクスリポタム(Dexlipotam)(5(R)−(1,2−ジチオラン−3−イル)ペンタン酸、(R)−αリポ酸もしくは(R)−チオクト酸としてもまた知られる);
(28)BM 170744(2,2−ジクロロ−12−(p−クロロフェニル)ドデカン酸);
(29)BM 152054(5−(4−(2−(5−メチル−2−(2−チエニル)オキサゾル−4−イル)エトキシ)ベンゾチエン−7−イルメチル)チアゾリジン−2,4−ジオン);
(30)BM 131258(5−(4−(2−(5−メチル−2−フェニルオキサゾル−4−イル)エトキシ)ベンゾチエン−7−イルメチル)チアゾリジン−2,4−ジオン);
(31)CRE 16336(EML 16336);
(32)HQL 975(3−(4−(2−(5−メチル−2−フェニルオキサゾル−4−イル)エトキシ)フェニル)−2(S)−(プロピルアミノ)プロピオン酸);
(33)DRF 2189(5−((4−(2−(1−インドリル)エトキシ)フェニル)メチル)チアゾリジン−2,4−ジオン);
(34)DRF 554158;
(35)DRF−NPCC;
(36)CLX 0100、CLX 0101、CLX 0900もしくはCLX 0901;
(37)IκBキナーゼ(IκKB)阻害剤
(38)マイトジェン活性化プロテインキナーゼ(MAPK)阻害剤
p38 MAPK刺激物質
(39)ホスファチジルイノシチド三リン酸
(40)インスリン再循環受容体阻害剤
(41)グルコース輸送体4モジュレーター
(42)TNF−αアンタゴニスト
(43)プラズマ細胞分化抗原−1(PC−1)アンタゴニスト
(44)脂肪細胞脂質結合タンパク質(ALBP/aP2)阻害剤
(45)ホスホグリカン
(46)ガルパラン(Galparan);
(47)レセプトロン(Receptron);
(48)島細胞成熟因子;
(49)インスリン増強因子(IPFもしくはインスリン増強因子−1);
(50)結合タンパク質と共役されるソマトメジンC(IGF−BP3、IGF−BP3、ソマトカインとしてもまた知られる);
(51)バイオテック ホールディングス リミテッド(Biotech Holdings Ltd.)もしくはボルケ ファーマシューティカル(Volque Pharmaceutical)により製造される、ダイアブ(Diab)II(V−411として知られる)もしくはグルカニン(Glucanin);
(52)グルコース−6ホスファターゼ阻害剤;
(53)脂肪酸グルコース輸送タンパク質;
(54)糖質コルチコイド受容体アンタゴニスト;および
(55)グルタミン:フルクトース−6−リン酸アミドトランスフェラーゼ(GFAT)モジュレーター
を挙げることができる。
(C)肝のグルコース産生を減少させかつグルコースの取り込みを増大させるビグアニド。例は:
(1)1,1−ジメチルビグアニド(例えば、メトホルミン−デポメド(DepoMed)、メトホルミン−バイオヴェイル コーポレーション(BioVail Corporation)、もしくはメトホルミン(METFORMIN)GR(メトホルミン胃保持ポリマー));および
(2)メトホルミン塩酸塩(LA 6023、BMS 207150、グルコファージ(GLUCOPHAGE)もしくはグルコファージ(GLUCOPHAGE)XRとしてもまた知られる、N,N−ジメチルイミドジカルボンイミドジアミド一塩酸塩
のようなメトホルミンを包含する。
(D)α−グルコシダーゼを阻害するα−グルコシダーゼ阻害剤。α−グルコシダーゼはフルクトースをグルコースに転化して、それにより炭水化物の消化を遅延させる。消化されない炭水化物はその後腸で分解されて、食後のグルコースのピークを低下させる。例は、限定されるものでないが:
(1)アカルボース(AG−5421、Bay−g−542、BAY−g−542、グルコバイ(GLUCOBAY)、プレコース(PRECOSE)、グルコール(GLUCOR)、プランデース(PRANDASE)、グルミダ(GLUMIDA)もしくはアスカロース(ASCAROSE)としてもまた知られる、D−グルコース、O−4,6−ジデオキシ−4−(((1S−(1α,4α,5β,6α))−4,5,6−トリヒドロキシ−3−(ヒドロキシメチル)−2−シクロヘキセン−1−イル)アミノ)−α−D−グルコピラノシル−(1−4)−O−α−D−グルコピラノシル−(1−4)−);
(2)ミグリトール(BAY 1099、BAY M 1099、BAY−m−1099、バイグリトール(BAYGLITOL)、ダイアスタボール(DIASTABOL)、グリセット(GLYSET)、ミグリバイ(MIGLIBAY)、ミトルバイ(MITOLBAY)、プルマロール(PLUMAROL)としてもまた知られる、3,4,5−ピペリジントリオール、1−(2−ヒドロキシエチル)−2−(ヒドロキシメチル)−、(2R(2α,3β,4α,5β))−もしくは(2R,3R,4R,5S)−1−(2−ヒドロキシエチル)−2−(ヒドロキシメチル−3,4,5−ピペリジントリオール);
(3)CKD−711(0−4−デオキシ−4−((2,3−エポキシ−3−ヒドロキシメチル−4,5,6−トリヒドロキシシクロヘキサン−1−イル)アミノ)−α−b−グルコピラノシル−(1−4)−α−D−グルコピラノシル−(1−4)−D−グルコピラノース);
(4)エミグリテート(BAY o 1248もしくはMKC 542としてもまた知られる、4−(2−((2R,3R,4R,5S)−3,4,5−トリヒドロキシ−2−(ヒドロキシメチル)−1−ピペリジニル)エトキシ)安息香酸エチルエステル);
(5)MOR 14(N−メチルデオキシノジリマイシンもしくはN−メチルモラノリンとしてもまた知られる、3,4,5−ピペリジントリオール、2−(ヒドロキシメチル)−1−メチル−、(2R−(2α,3β,4α,5β))−);および
(6)ボグリボース(A71100、AO 128、ベイスン(BASEN)、グルスタット(GLUSTAT)、ボグリスタット(VOGLISTAT)としてもまた知られる、3,4−ジデオキシ−4−((2−ヒドロキシ−1−(ヒドロキシメチル)エチル)アミノ)−2−C−(ヒドロキシメチル)−D−エピ−イノシトール、もしくはD−エピ−イノシトール、3,4−ジデオキシ−4−((2−ヒドロキシ−1−(ヒドロキシメチル)エチル)アミノ−2−C−(ヒドロキシメチル)−
を挙げることができる。
(E)インスリンは、通常のもしくは短時間作用型、中間作用型および長時間作用型インスリン、注入不可能もしくは吸入型インスリン、組織選択的インスリン、グリコホスホキニン(D−カイロイノシトール)、天然のアミノ酸配列中に小さな差異を伴うインスリン分子のようなインスリン類似物およびインスリンの小分子模倣物(インスリン模倣物)、ならびにエンドソームモジュレーターを包含する。例は、限定されるものでないが:
(1)ビオタ(Biota);
(2)LP 100;
(3)(SP−5−21)−オキソビス(1−ピロリジンカルボジチオエート−S,S’)バナジウム、
(4)インスリン アスパルト(insulin aspart)(インスリンX14、INA−X14、ノボラピッド(NOVORAPID)、ノボミックス(NOVOMIX)もしくはノボログ(NOVOLOG)としてもまた知られる、ヒトインスリン(28B−L−アスパラギン酸)もしくはB28−Asp−インスリン);
(5)インスリン デテミール(insulin detemir)(ヒト29B−(N6−(1−オキソテトラデシル)−L−リシン)−(1A−21A)、(1B−29B)−インスリン、もしくはNN 304);
(6)インスリン リスプロ(insulin lispro)(lys−proインスリン、LY 275585、ヒューマログ(HUMALOG)、ヒューマログ ミックス(HUMALOG MIX)75/25もしくはヒューマログ ミックス(HUMALOG MIX)50/50としてもまた知られる、「28B−L−リシン−29B−L−プロリンヒトインスリン、もしくはLys(28B)、Pro(B29)ヒトインスリン類似物);
(7)インスリン グラルギン(insulin glargine)(ランタス(LUNTAS)、オプチスリン(OPTISULIN)としてもまた知られる、ヒト(A21−グリシン、B31−アルギニン、B32−アルギニン)インスリン HOE 901);
(8)ヒュームリン(HUMULIN)Uもしくはウルトラレンテ(ULTRALENTE)としてもまた知られる、インスリン亜鉛懸濁液、持続型(ウルトラレンテ(Ultrarente));
(9)レンテ イレチン(LENTE ILETIN)II、ヒュームリン(HUMULIN)Lもしくはノボリン(NOVOLIN)Lとしてもまた知られる、インスリン亜鉛懸濁液(レンテ(Lente))、70%結晶および30%無定形インスリン懸濁液、;
(10)ヒュームリン(HUMULIN)50/50(50%イソフェンインスリンおよび50%インスリン注射剤);
(11)ノボリン(NOVOLIN)70/30、ノボリン(NOVOLIN)70/30 ペンフィル(PenFill)、ノボリン(NOVOLIN)70/30 充填済(Prefilled)としてもまた知られる、ヒュームリン(HUMULIN)70/30(70%イソフェンインスリンNPHおよび30%インスリン注射剤);
(12)NPH イレチン(ILETIN)II、ノボリン(NOVOLIN)N、ノボリン(NOVOLIN)N ペンフィル(PenFill)、ノボリン(NOVOLIN)N 充填済(Prefilled)、ヒュームリン(HUMULIN)Nのようなインスリンイソフェン懸濁液;
(13)イレチン(ILETIN)II レギュラー(Regular)、ノボリン(NOVOLIN)R、ベロスリン(VELOSULIN)BR、ノボリン(NOVOLIN)R ペンフィル(PenFill)、ノボリン(NOVOLIN)R 充填済(Prefilled)、ヒュームリン(HUMULIN)R、もしくはレギュラー(Regular)U−500(濃縮)のような通常型(regular)インスリン注射剤;
(14)アリアッド(ARIAD);
(15)LY 197535;
(16)L−783281;および
(17)TE−17411
を挙げることができる。
(F)(1)グルカゴン様ペプチド−1(GLP−1)およびその模倣物;
(2)グルコースインスリン分泌刺激ペプチド(GIP)およびその模倣物;
(3)エキセンジンおよびその模倣物;
(4)(4a)DPP−728もしくはLAF 237(NVP−DPP−728、DPP−728A、LAF−237として知られる、2−ピロリジンカルボニトリル、1−(((2−((5−シアノ−2−ピリジニル)アミノ)エチル)アミノ)アセチル);
(4b)P 3298もしくはP32/98(ジ−(3N−((2S,3S)−2−アミノ−3−メチル−ペンタノイル)−1,3−チアゾリジン)フマレート);
(4c)TSL 225(トリプトフィル−1,2,3,4−テトラヒドロイソキノリン−3−カルボン酸);
(4d)バリンピロリジド(valpyr);
(4e)1−アミノアルキルイソキノリノン−4−カルボキシレートおよびそれらの類似物;
(4f)SDZ 272−070(1−(L−バリル)ピロリジン);
(4g)TMC−2A、TMC−2BもしくはTMC−2C;
(4h)ジペプチドニトリル(2−シアノピロロジド);
(4i)CD26阻害剤;ならびに
(4j)SDZ 274−444
のようなジペプチルプロテアーゼ(DPPもしくはDPPIV)阻害剤;
(5)AY−279955のようなグルカゴンアンタゴニスト;ならびに
(6)限定されるものでないがプラムリンチド(AC−137、シムリン(Symlin)、トリプロアミリンもしくはプラムリンチドアセテート)を挙げることができるアミリンアゴニスト
のようなインスリン分泌モジュレーター。
(G)(1)アスミチグリニド(ミツグリミドカルシウム水和物、KAD 1229もしくはS 21403としてもまた知られる、(2(S)−cis)−オクタヒドロ−γ−オキソ−α−(フェニルメチル)−2H−イソインドール−2−ブタン酸、カルシウム塩);
(2)Ro 34563;
(3)ナテグリニド(A 4166、AY 4166、YM 026、FOX 988、DJN 608、SDZ DJN608、スターリックス(STARLIX)、スターシス(STARSIS)、ファスティック(FASTIC)、トラゼック(TRAZEC)としてもまた知られる、trans−N−((4−(1−メチルエチル)シクロヘキシル)カルボニル)−D−フェニルアラニン);
(4)JTT 608(trans−4−メチル−γ−オキソシクロヘキサンブタン酸);
(5)(5a)クロルプロパミド(ダイアビニース(DIABINESE)としてもまた知られる、1−[(p−クロロフェニル)スルホニル]−3−プロピル尿素);
(5b)トラザミド(トリネース(TOLINASE)もしくはトラネース(TOLANASE));
(5c)トルブタミド(オリネース(ORINASE)もしくはラスチノン(RASTINON));
(5d)グリブリド(グリベンクラミド(Glibenclamide)、ダイアベータ(DIABETA)、ミクロネース(MICRONASE)、グリネース(GLYNASE)プレスタブ(PresTab)もしくはダオニル(DAONIL)としてもまた知られる、1−[[p−[2−(5−クロロ−o−アニスアミド)エチル]フェニル]スルホニル]−3−シクロヘキシル尿素);
(5e)グリピジド(グルコトロール(GLUCOTROL)、グルコトロール(GLUCOTROL)XL、ミノダイアブ(MINODIAB)もしくはグリベニース(GLIBENESE)としてもまた知られる、1−シクロヘキシル−3−[[p−[2−(5−エチルピラジンカルボキサミド)エチル]フェニル]スルホニル]尿素);
(5f)グリメピリド(Hoe−490もしくはアマリル(AMARYL)としてもまた知られる、1H−ピロール−1−カルボキサミド、3−エチル−2,5−ジヒドロ−4−メチル−N−[2−[4−[[[[(4−メチルシクロヘキシル)アミノ]カルボニル]アミノ]スルホニル]フェニル]エチル]−2−オキソ−、trans−);
(5g)アセトへキサミド(ダイメロール(DYMELOR));
(5h)グリクラジド(ダイアミクロン(DIAMICRON));
(5i)グリペンチド(スタチカム(STATICUM));
(5j)グリキドン(グルレノーム(GLURENORM));および
(5k)グリソラミド(ダイアベノール(DIABENOR))
のようなスルホニル尿素;
(6)限定されるものでないが、
(6a)レパグリニド(AGEE 623、AGEE 623 ZW、NN 623、プランジン(PRANDIN)もしくはノボノーム(NovoNorm)としてもまた知られる、(S)−2−エトキシ−4−(2−((3−メチル−1−(2−(1−ピペリジニル)フェニル)ブチル)アミノ)−2−オキソエチル)安息香酸);
(6b)イミダゾリジン;および
(6c)α−2アドレナリン受容体アンタゴニスト
のようなメグリチニドを挙げることができるK+チャンネル遮断薬;
(7)下垂体アデニル酸シクラーゼ活性化ポリペプチド(PAcAP);
(8)血管作動性腸ペプチド(VIP);
(9)アミノ酸類似物;ならびに
(10)グルコキナーゼ活性化物質
のような、膵β細胞を刺激することによりインスリン産生を増大させるインスリン分泌刺激物質(secretagogues)。
(H)(1)インスリン様増殖因子(IGF−1、IGF−2);
(2)小分子ニューロトロフィン:
(3)ソマトスタチン;
(4)成長ホルモン放出ペプチド(GHRP);
(5)成長ホルモン放出因子(GHRF);および
(6)ヒト成長ホルモンフラグメント
のような成長因子。
(I)(1)ワクチン;
(2)T細胞阻害剤
(3)モノクローナル抗体;
(4)インターロイキン−1(IL−1)アンタゴニスト;および
(5)BDNF
のような免疫モジュレーター。
(J)他の抗糖尿病薬:
(1)rHu−グルカゴン;
(2)DHEA類似物;
(3)カルニチンパルミトイルトランスフェラーゼ(CPT)阻害剤;
(4)島神経発生;
(5)膵βアミロイド阻害剤;ならびに
(6)UCP(脱共役タンパク質)−2およびUCP−3モジュレーター。
E.組合せ剤
本発明は、糖尿病もしくはシンドロームX、またはそれらの関連する症状もしくは合併症の治療のための、SGLT阻害剤のようなグルコース再吸収阻害剤を投与すること、およびPPARモジュレーターを投与することを含んで成る併用療法の方法を特徴とする。NIDDMの多数のモデルにおけるSGLT阻害剤の立証された有効性は、ヒトにおけるNIDDMの治療のためのこの薬物単独の利用性を実証する。グルコース再吸収阻害剤はPPARモジュレーターのものと別個の作用機序を有するため、PPARモジュレーターとの開示される組合せ剤は、いずれかの薬物単独の使用に関して組合せられた治療的もしくは製薬学的有効性を達成するのに必要ないずれの薬物の量も低下させるという利点を有し、それにより、体重増加、浮腫、心肥大、肝肥大、低血糖もしくは肝毒性、またはそれらのいずれかの組合せをしばしば包含する1種もしくはそれ以上の有害な副作用を減少させる。
Arはアリールもしくはヘテロアリールであり;
OXは場合によっては保護されるヒドロキシ基であり;
Yは水素もしくはアルキルであり;ならびに
Zは、その1個もしくはそれ以上のヒドロキシ基が、α−D−グルコピラノシル、アルカノイル、アルコキシカルボニルおよび置換アルキルから選択される1個もしくはそれ以上の基で場合によっては置換されていてもよいグルコピラノシルである]
の化合物である。
F.投与、製剤および投薬量
グルコースおよび脂質代謝における障害を治療するための開示される化合物、組成物および組合せ剤の利用性は、当該技術分野で公知の手順(下に列挙される参考文献を参照されたい)、ならびに米国特許第5424406号、同第5731292号、同第5767094号、同第5830873号および同第6048842号明細書(引用することにより本明細書に組み込まれる)に記述される手順に従って決定することができる。該化合物は、限定されるものでないが、静脈内、経口、皮下、筋肉内、皮内および非経口投与を挙げることができるいずれかの慣習的な投与経路により患者に投与してよい。好ましくは、製剤は経口投与のためである。
実施例1
血漿グルコース、血漿インスリン、血漿トリグリセリド、肝重量、心重量および体重に対する影響
PPARγアゴニストと組合せのT−1095の効果を検査するために、雌性db/dbマウス(6〜7週齢/ジャクソン ラブス(Jackson Labs)、メーン州)を、ベヒクル(0.5%メチルセルロース)、ロシグリタゾン(0.1mpk〜10mpk、アバンジア(Avandia))、T−1095(100mpk)、もしくはロシグリタゾンおよびT−1095(100mpk)で、連日、11日間治療した。マウス(1群あたりn=8匹の動物)は、10ml/kg体重の容量の経口強制栄養により試験化合物もしくはベヒクルを受領した。体重を第1日(投与前)、ならびに第4、8および11日に記録した。最終投与18時間後にマウスを重量測定し、そしてCO2/O2(70:30)で麻酔した。その後、マウスを、眼窩後洞穿刺により、氷上の2mLヘパリン処理ポリプロピレン管中に採血した。
実施例2
血漿グルコース、血漿インスリン、血漿トリグリセリド、肝重量、心重量および体重に対する影響
PPARγアゴニストと組合せのT−1095の効果を検査するために、雌性db/dbマウス(6〜7週齢/ジャクソン ラブス(Jackson Labs)、メーン州)を、ベヒクル(0.5%メチルセルロース)、ロシグリタゾンのようなPPARγアゴニスト(10mpk、アバンジア(Avandia))、T−1095(3、10、30もしくは100mpk)、またはロシグリタゾンおよびT−1095で、連日、11日間治療した。マウス(1群あたりn=8匹の動物)は、10ml/kg体重の容量の経口強制栄養により試験化合物もしくはベヒクルを受領した。体重を第1日(投与前)、ならびに第4、8および11日に記録した。最終投与18時間後にマウスを重量測定し、そしてCO2/O2(70:30)で麻酔した。その後、マウスを、眼窩後洞穿刺により、氷上の2mLヘパリン処理ポリプロピレン管中に採血した。血漿サンプルをその後、トラインダー(Tringer)試薬(シグマ ディアグノスティックス(Sigma Diagnostics))、Elisa(アルプコ(Alpco))およびGPO−トラインダー(Trinder)(シグマ ディアグノスティックス(Sigma Diagnostics))を使用して、それぞれグルコース、インスリンおよびトリグリセリドについてアッセイした。肝および心を摘出し、重量測定しかつ凍結させた。結果を表5に示す。
実施例3
血漿グルコース、HbA1c、ヘマトクリット、血漿インスリン、血漿トリグリセリド、血漿薬物濃度、肝重量、心重量、脂肪含量および体重に対する影響
PPARγアゴニストと組合せのT−1095の効果を検査するために、雄性ZDFラット(8週齢/GMI)を、ベヒクル(0.5%メチルセルロース)、ロシグリタゾンのようなPPARγアゴニスト(0.1mg/kg〜10mg/kg、アバンジア(AVANDIA))、T−1095(3〜100mg/kg)、もしくはT−1095と組合せられたロシグリタゾンで、連日、28日間治療する。ラット(1群あたりn=8匹の動物)は、2ml/kg体重の容量の経口強制栄養により試験化合物もしくはベヒクルを受領する。体重を第1日(投与前)、および試験の期間の間週2回記録する。最終投与の前日に動物を一夜絶食させる。最終投与後1時間に、ラットを重量測定し、そしてCO2/O2(70:30)で麻酔する。その後、ラットを、眼窩後洞穿刺により氷上の2mLヘパリン処理ポリプロピレン管中に採血する。ラットはその後グルコース攻撃(2g/kg p.o)を受領し、かつ、尿収集のため代謝ケージに入れる(4時間)。その後、動物を殺し、そして精巣上体脂肪パッド、肝および心を摘出し、重量測定しかつ組織学的検査のため凍結させる。血漿サンプルをその後、グルコース、HbA1c、インスリン、ヘマトクリット、血漿薬物濃度およびトリグリセリドについてアッセイする。尿容量および尿グルコース、タンパク質、オスモル濃度、電解質(Na、K、Cl)、BUN、クレアチニンを測定する。
実施例4
血漿グルコース、HbA1c、血漿インスリン、血漿トリグリセリド、血漿薬物濃度、肝重量、心重量および体重に対する影響
PPARγアゴニストと組合せのT−1095の効果を検査するために、雄性db/dbマウス(6週齢/ジャクソン ラブス(Jackson Labs)、メーン州)を、ベヒクル(0.5%メチルセルロース)、MCC−555のようなPPARγアゴニスト(3mg/kg〜30mg/kg)、T−1095(3〜100mg/kg)、もしくはMCC−555およびT−1095で、連日、28日間治療した。マウス(1群あたりn=8匹の動物)は、10ml/kg体重の容量の経口強制栄養により試験化合物もしくはベヒクルを受領した。体重を第1日(投与前)、および試験の期間の間週2回記録した。最終投与1時間後にマウスを重量測定し、そしてCO2/O2(70:30)で麻酔した。その後、マウスを、眼窩後洞穿刺により、氷上の2mLヘパリン処理ポリプロピレン管中に採血した。マウスをその後一夜絶食させ、そしてグルコース攻撃(2g/kg p.o.)を受領する前に尾部クリップにより採血した。血液は攻撃後30、60、120および180分に収集した。動物をその後殺し、そして精巣上体脂肪パッド、肝および心を摘出し、重量測定しかつ組織学的検査のため凍結させた。その後、血漿サンプルを、グルコース、HbA1c、インスリンおよびトリグリセリドについてアッセイした。結果を表8および表9に示す。
Claims (12)
- (a) 式(V)
塩であるグルコース吸収阻害剤であって、上式中
Arはアリールもしくはヘテロアリールであり;
OXは場合によっては保護されるヒドロキシ基であり;
Yは水素もしくはアルキルであり;ならびに
Zはグルコピラノシルであり、ここでその1個もしくはそれ以上のヒドロキシ基がβ−D−グルコピラノシル、アルカノイル、アルコキシカルボニルおよび置換アルキルから選択される1個もしくはそれ以上の基で場合によっては置換されていてもよい、
であるグルコース再吸収阻害剤、
(b) (i) ロシグリタゾン、および(ii)イサグリタゾン、から成る群から選択されるPPARモジュレーター、および、
(c) 製薬学的に許容できる担体、
を含んで成る、糖尿病又は糖尿病に起因する疾患を予防又は治療するための製薬学的組成物。 - PPARモジュレーターがロシグリタゾンである、請求項1記載の製薬学的組成物。
- PPARモジュレーターがイサグリタゾンである、請求項1記載の製薬学的組成物。
- 糖尿病又は糖尿病に起因する疾患を予防又は治療するための医薬の製造のために、
(a) 式(V)
OXは場合によっては保護されるヒドロキシ基であり;
Yは水素もしくはアルキルであり;ならびに
Zはグルコピラノシルであり、ここでその1個もしくはそれ以上のヒドロキシ基がβ−D−グルコピラノシル、アルカノイル、アルコキシカルボニルおよび置換アルキルから選択される1個もしくはそれ以上の基で場合によっては置換されていてもよい]
の化合物である、1種もしくはそれ以上のグルコース再吸収阻害剤を、
(b) (i) ロシグリタゾン、および(ii)イサグリタゾン、から成る群から選択されるPPARモジュレーターとともに混合することを含んで成る、
糖尿病又は糖尿病に起因する疾患を予防又は治療するための製薬学的組成物の製造方法。 - PPARモジュレーターがロシグリタゾンである、請求項7記載の方法。
- PPARモジュレーターがイサグリタゾンである、請求項7記載の方法。
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Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60233655D1 (de) * | 2001-04-04 | 2009-10-22 | Ortho Mcneil Janssen Pharm | R und retinoid x rezeptorenmodulatoren |
US20030045553A1 (en) | 2001-04-04 | 2003-03-06 | Bussolari Jacqueline C. | Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators |
US20090162342A1 (en) * | 2001-06-07 | 2009-06-25 | Sanomune Inc. | Therapeutic uses of glandular kallikrein |
EP1388352A1 (en) * | 2002-08-08 | 2004-02-11 | Laboratoires Fournier S.A. | Use of a ppar-alpha agonist to treat patients suffering from weight gain associated with a ppar-gamma agonist treatment |
DE10258007B4 (de) * | 2002-12-12 | 2006-02-09 | Sanofi-Aventis Deutschland Gmbh | Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
DE10258008B4 (de) * | 2002-12-12 | 2006-02-02 | Sanofi-Aventis Deutschland Gmbh | Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
JP2004300102A (ja) * | 2003-03-31 | 2004-10-28 | Kissei Pharmaceut Co Ltd | 縮合複素環誘導体、それを含有する医薬組成物およびその医薬用途 |
WO2004108126A1 (en) * | 2003-06-06 | 2004-12-16 | Snowden Pharmaceuticals, Llc | Fibric acid derivatives for the treatment of irritable bowel syndrome |
JP2007506649A (ja) * | 2003-06-27 | 2007-03-22 | ドクター レディーズ リサーチ ファンデーション | バラグリタゾンとさらなる抗糖尿病化合物とを含む組成物 |
WO2005027661A1 (en) * | 2003-09-23 | 2005-03-31 | Dsm Ip Assets B.V. | Compositions for the treatment and prevention of diabetes mellitus |
US20050239706A1 (en) * | 2003-10-31 | 2005-10-27 | Washington University In St. Louis | Modulation of fiaf and the gastrointestinal microbiota as a means to control energy storage in a subject |
JPWO2005070413A1 (ja) * | 2004-01-23 | 2007-09-06 | 独立行政法人科学技術振興機構 | レチノイン酸を含有する糖尿病治療薬 |
US20070197602A1 (en) * | 2004-02-09 | 2007-08-23 | Hashime Kanazawa | Combined pharmaceutical composition |
CA2601278C (en) | 2004-03-17 | 2014-06-10 | Lars Michael Larsen | Prevention of retinopathy by inhibition of the visual cycle |
CA2572793C (en) | 2004-07-21 | 2015-11-03 | Kissei Pharmaceutical Co., Ltd. | Progression inhibitor for disease attributed to abnormal accumulation of liver fat |
JP2008531707A (ja) * | 2005-03-03 | 2008-08-14 | スミスクライン ビーチャム コーポレーション | 医薬品 |
JP2009509539A (ja) * | 2005-09-30 | 2009-03-12 | パーレジェン サイエンシーズ, インコーポレイテッド | 血糖調節の障害のスクリーニングおよび処置のための方法および組成物 |
EP1785133A1 (en) * | 2005-11-10 | 2007-05-16 | Laboratoires Fournier S.A. | Use of fenofibrate or a derivative thereof for preventing diabetic retinopathy |
DE102006028862A1 (de) | 2006-06-23 | 2007-12-27 | Merck Patent Gmbh | 3-Amino-imidazo[1,2-a]pyridinderivate |
WO2008096769A1 (ja) * | 2007-02-08 | 2008-08-14 | Daiichi Sankyo Company, Limited | 置換されたセルコスポラミド誘導体を含有する医薬 |
DE102007008420A1 (de) | 2007-02-21 | 2008-08-28 | Merck Patent Gmbh | Benzimidazolderivate |
US8666671B2 (en) * | 2007-07-05 | 2014-03-04 | Enhanced Pharmaceuticals, Inc. | Method for determining drug-molecular combinations that modulate and enhance the therapeutic safety and efficacy of biological or pharmaceutical drugs |
DE102007048716A1 (de) | 2007-10-11 | 2009-04-23 | Merck Patent Gmbh | Imidazo[1,2-a]pyrimidinderivate |
JP5302900B2 (ja) | 2008-01-31 | 2013-10-02 | アステラス製薬株式会社 | 脂肪性肝疾患の治療用医薬組成物 |
DE102008017590A1 (de) | 2008-04-07 | 2009-10-08 | Merck Patent Gmbh | Glucopyranosidderivate |
RS52236B (en) * | 2008-08-28 | 2012-10-31 | Pfizer Inc. | DIOKASA-BICYCLE DERIVATIVES (3.2.1) OCTOBER-2,3,4-TRIOLA |
DK2601949T3 (da) | 2009-04-16 | 2015-01-05 | Taisho Pharmaceutical Co Ltd | Farmaceutisk sammensætning med (1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol og et insulin-sekretionsfremkaldende stof |
EP2451455A4 (en) * | 2009-07-10 | 2013-01-16 | Univ Case Western Reserve | RXR AGONIST COMPOUNDS AND METHODS |
AU2010302642A1 (en) | 2009-10-02 | 2012-04-26 | Sanofi | Use of compounds with SGLT-1/SGLT-2 inhibitor activity for producing medicaments for treatment of bone diseases |
US8163704B2 (en) | 2009-10-20 | 2012-04-24 | Novartis Ag | Glycoside derivatives and uses thereof |
CA2777857C (en) | 2009-11-02 | 2014-12-02 | Pfizer Inc. | Dioxa-bicyclo[3.2.1]octane-2,3,4-triol derivatives |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
PL2543357T3 (pl) * | 2011-07-07 | 2018-08-31 | Holy Stone Healthcare Co.,Ltd. | Kompozycja do zastosowania w leczeniu i zapobieganiu zaburzeniom związanym ze stanem zapalnym |
US9451987B2 (en) | 2011-11-16 | 2016-09-27 | K2M, Inc. | System and method for spinal correction |
US20130315891A1 (en) | 2012-05-25 | 2013-11-28 | Matthew Charles | Formulations of human tissue kallikrein-1 for parenteral delivery and related methods |
PL2854841T3 (pl) | 2012-06-04 | 2017-08-31 | Diamedica Inc. | Izoformy glikozylacji ludzkiej kalikreiny tkankowej 1 |
CN102727477B (zh) * | 2012-06-14 | 2014-07-16 | 合肥博太医药生物技术发展有限公司 | 视黄酸及其衍生物在制备防治糖尿病药物中的应用 |
EP2774619B1 (de) | 2013-03-04 | 2016-05-18 | BioActive Food GmbH | Zusammensetzung zur Behandlung von hyperglykämischen Erkrankungen |
EP2944311A1 (de) | 2014-05-16 | 2015-11-18 | BioActive Food GmbH | Kombination von biologisch aktiven Substanzen zur Behandlung von hyperglykämischen Erkrankungen |
AU2018230478A1 (en) | 2017-03-09 | 2019-09-12 | Diamedica Inc. | Dosage forms of tissue kallikrein 1 |
JP7253805B2 (ja) * | 2017-12-28 | 2023-04-07 | 国立大学法人福井大学 | 白内障の予防剤および/または治療剤、白内障の予防および/または治療のための医薬組成物、ならびにこれらを製造するためのppar活性化剤の使用 |
Family Cites Families (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
DE10199003I1 (de) * | 1987-09-04 | 2003-06-12 | Beecham Group Plc | Substituierte Thiazolidinionderivate |
JPH0253573A (ja) * | 1988-08-11 | 1990-02-22 | Nippon Riki Kk | ラチェットレンチの製造法 |
US5731299A (en) * | 1992-05-29 | 1998-03-24 | The Procter & Gamble Company | Phosphonosulfonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
JP2762903B2 (ja) | 1992-11-12 | 1998-06-11 | 田辺製薬株式会社 | ジヒドロカルコン誘導体及びその製法 |
US5731292A (en) * | 1992-11-12 | 1998-03-24 | Tanabe Seiyaku Co., Ltd. | Dihydrochalcone derivatives which are hypoglycemic agents |
CA2102591C (en) * | 1992-11-12 | 2000-12-26 | Kenji Tsujihara | Hypoglycemic agent |
JP2795162B2 (ja) | 1993-02-18 | 1998-09-10 | 田辺製薬株式会社 | ジヒドロカルコン誘導体及びその製法 |
JP2906978B2 (ja) | 1993-02-25 | 1999-06-21 | 田辺製薬株式会社 | 血糖降下剤 |
US6046222A (en) * | 1993-09-15 | 2000-04-04 | Warner-Lambert Company | Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus |
JP2847695B2 (ja) * | 1994-05-11 | 1999-01-20 | 田辺製薬株式会社 | 血糖降下剤 |
US5830873A (en) * | 1994-05-11 | 1998-11-03 | Tanabe Seiyaku Co., Ltd. | Propiophenone derivative and a process for preparing the same |
EP1426048A3 (en) | 1995-09-18 | 2004-06-16 | Ligand Pharmaceuticals, Inc. | Treating hypertriglyceridemia with RXR agonists in combination with a PPARgamma agonist |
JP3059088B2 (ja) | 1995-11-07 | 2000-07-04 | 田辺製薬株式会社 | プロピオフェノン誘導体およびその製法 |
CN1230114A (zh) * | 1996-07-12 | 1999-09-29 | 史密丝克莱恩比彻姆有限公司 | Leptine抵抗的新疗法 |
JP3055135B2 (ja) * | 1996-12-26 | 2000-06-26 | 田辺製薬株式会社 | プロピオフェノン誘導体及びその製法 |
ES2176600T3 (es) | 1996-12-26 | 2002-12-01 | Tanabe Seiyaku Co | Derivado de la propiofenona y procedimientos para su preparacion. |
US6153632A (en) * | 1997-02-24 | 2000-11-28 | Rieveley; Robert B. | Method and composition for the treatment of diabetes |
JP4100734B2 (ja) | 1997-04-30 | 2008-06-11 | Sabicイノベーティブプラスチックスジャパン合同会社 | 熱可塑性樹脂組成物 |
AU8799998A (en) | 1997-06-18 | 1999-01-04 | Smithkline Beecham Plc | Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor |
JP2000080041A (ja) | 1998-03-09 | 2000-03-21 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
CZ20011763A3 (cs) * | 1998-11-20 | 2001-10-17 | Mitsubishi Chemical Corporation | Krystaly 5-[{6-(2-fluorbenzyl)oxy-2-naftyl}methyl]-2,4-thiazolidindionu |
US6337426B1 (en) | 1998-11-23 | 2002-01-08 | Nalco/Exxon Energy Chemicals, L.P. | Antifoulant compositions and processes |
US6548529B1 (en) | 1999-04-05 | 2003-04-15 | Bristol-Myers Squibb Company | Heterocyclic containing biphenyl aP2 inhibitors and method |
TWI249401B (en) | 1999-04-14 | 2006-02-21 | Takeda Chemical Industries Ltd | Agent for improving ketosis |
AU4649600A (en) | 1999-04-22 | 2000-11-10 | Joel F. Habener | Bridge-1, a transcription factor |
AR035016A1 (es) | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
CN1145635C (zh) | 1999-08-31 | 2004-04-14 | 橘生药品工业株式会社 | 吡喃葡糖氧基吡唑衍生物、含该衍生物的药物组合物及其制备中的中间体 |
CA2384194A1 (en) | 1999-08-31 | 2001-03-08 | David P. M. Pleynet | Benzylidene-thiazolidinediones and analogues and their use in the treatment of inflammation |
PE20010580A1 (es) | 1999-09-03 | 2001-05-25 | Takeda Chemical Industries Ltd | Composicion farmaceutica para tratar la diabetes |
US6515117B2 (en) * | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
PH12000002657B1 (en) * | 1999-10-12 | 2006-02-21 | Bristol Myers Squibb Co | C-aryl glucoside SGLT2 inhibitors |
JP2001192375A (ja) * | 1999-10-29 | 2001-07-17 | Takeda Chem Ind Ltd | オキシイミノアルカン酸誘導体の結晶 |
TW558554B (en) | 1999-10-29 | 2003-10-21 | Takeda Chemical Industries Ltd | Crystals of oxyiminoalkanoic acid derivative |
CZ20021604A3 (cs) | 1999-11-10 | 2002-09-11 | Takeda Chemical Industries, Ltd. | Pětičlenné N-heterocyklické sloučeniny, farmaceutický přípravek a činidlo je obsahující a jejich použití |
US6683056B2 (en) * | 2000-03-30 | 2004-01-27 | Bristol-Myers Squibb Company | O-aryl glucoside SGLT2 inhibitors and method |
US6555519B2 (en) * | 2000-03-30 | 2003-04-29 | Bristol-Myers Squibb Company | O-glucosylated benzamide SGLT2 inhibitors and method |
AU2002253838B2 (en) * | 2000-10-30 | 2006-11-09 | Ortho-Mcneil Pharmaceutical, Inc. | Combination therapy comprising anti-diabetic and anticonvulsant agents |
SK287786B6 (sk) * | 2000-12-28 | 2011-09-05 | Kissei Pharmaceutical Co., Ltd. | Glukopyranosyloxypyrazolový derivát, farmaceutická kompozícia alebo kombinácia s jeho obsahom a ich použitie |
US20030045553A1 (en) | 2001-04-04 | 2003-03-06 | Bussolari Jacqueline C. | Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators |
DE60233655D1 (de) * | 2001-04-04 | 2009-10-22 | Ortho Mcneil Janssen Pharm | R und retinoid x rezeptorenmodulatoren |
-
2002
- 2002-04-03 US US10/115,827 patent/US20030045553A1/en not_active Abandoned
- 2002-04-03 CN CN02811137A patent/CN100577175C/zh not_active Expired - Lifetime
- 2002-04-03 EP EP02717766A patent/EP1381361B1/en not_active Expired - Lifetime
- 2002-04-03 WO PCT/US2002/010538 patent/WO2002080936A1/en active Application Filing
- 2002-04-03 CA CA2442917A patent/CA2442917C/en not_active Expired - Lifetime
- 2002-04-03 DE DE60231295T patent/DE60231295D1/de not_active Expired - Lifetime
- 2002-04-03 JP JP2002578975A patent/JP4590159B2/ja not_active Expired - Fee Related
- 2002-04-03 EP EP09075012A patent/EP2065044A1/en not_active Withdrawn
- 2002-04-03 ES ES02717766T patent/ES2321815T3/es not_active Expired - Lifetime
- 2002-04-03 AT AT02717766T patent/ATE423559T1/de not_active IP Right Cessation
- 2002-04-04 TW TW091106918A patent/TWI330084B/zh not_active IP Right Cessation
- 2002-04-04 MY MYPI20021224A patent/MY180762A/en unknown
-
2003
- 2003-03-24 US US10/395,502 patent/US20030199557A1/en not_active Abandoned
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Also Published As
Publication number | Publication date |
---|---|
EP1381361A1 (en) | 2004-01-21 |
US20030199557A1 (en) | 2003-10-23 |
JP2004529915A (ja) | 2004-09-30 |
ES2321815T3 (es) | 2009-06-12 |
CA2442917A1 (en) | 2002-10-17 |
CN100577175C (zh) | 2010-01-06 |
EP2065044A1 (en) | 2009-06-03 |
WO2002080936A1 (en) | 2002-10-17 |
US8278268B2 (en) | 2012-10-02 |
DE60231295D1 (de) | 2009-04-09 |
US20030045553A1 (en) | 2003-03-06 |
CN1568190A (zh) | 2005-01-19 |
TWI330084B (en) | 2010-09-11 |
ATE423559T1 (de) | 2009-03-15 |
US20080096802A1 (en) | 2008-04-24 |
CA2442917C (en) | 2011-02-01 |
EP1381361B1 (en) | 2009-02-25 |
MY180762A (en) | 2020-12-08 |
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