JP2007501204A - 新規な4,4’−ジチオビス−(3−アミノブタン−1−スルホン酸塩)の誘導体と、その誘導体を含む組成物 - Google Patents
新規な4,4’−ジチオビス−(3−アミノブタン−1−スルホン酸塩)の誘導体と、その誘導体を含む組成物 Download PDFInfo
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- JP2007501204A JP2007501204A JP2006522380A JP2006522380A JP2007501204A JP 2007501204 A JP2007501204 A JP 2007501204A JP 2006522380 A JP2006522380 A JP 2006522380A JP 2006522380 A JP2006522380 A JP 2006522380A JP 2007501204 A JP2007501204 A JP 2007501204A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/66—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfo, esterified sulfo or halosulfonyl groups, bound to the carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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Abstract
Description
- C1〜C6アルキル基、C2〜C6アルケニル基、C2〜C6アルキニル基、
- (CH2)nベンジル基(ただしnは0または1である)、
- (CH2)m(C3〜C6シクロアルキル)基(ただしmは0または1である)のいずれかを表わし、
アルキル基、アルケニル基、アルキニル基、ベンジル基、シクロアルキル基は、1つまたは2つの基Aで置換されている。
- カルボン酸基COOHまたはCOOR(ただしRは、C1〜C6アルキル基またはCH2フェニルである)、
- スルホン酸基SO3HまたはSO3R'(ただしR'は、C1〜C6アルキル基またはCH2フェニルである)、
- ホスホン酸基PO3H2またはPO3R"2R"'(ただしR"とR"'は、独立に、H、C1〜C6アルキル基、CH2フェニルのいずれかを表わす)を表わし;
それぞれの基R2は同じであって、C1〜C6アルキル基、C2〜C6アルケニル基、C2〜C6アルキニル基のいずれかを表わし、アルキル基、アルケニル基、アルキニル基は、それぞれ、そのままであるか基Bで置換されている。
- カルボン酸基COOHまたはCOOR(ただしRは、C1〜C6アルキル基またはCH2フェニルである)、
- そのままのフェニル基であるか、1つまたは複数の基で置換されたフェニル基(ここで置換基の選択は、水素原子、場合によっては保護されているヒドロキシル基、C1〜C4アルキル基、シアノ基、そのままのカルボキシル基、塩を形成したカルボキシル基、エステル化されたカルボキシル基、アミド基の中からなされる)を表わす。
以下の調製1〜5(方法A)では、記号a〜hは、可変基Rが以下のものである化合物を意味する。
a R=CH3
b R=Ph
c R=(CH3)2CHCH2-
d R=PhCH2-
e R=PhCH2CH2-
f R=4-MeOPhCH2CH2-
g R=2-MeOPhCH2CH2-
h R=4-Br-PhCH2CH2-
ただしPh=フェニル
10mlのジクロロメタンにN-ベンジルオキシカルボニル-α-ホスホノグリシンのトリメチルエステル12(5ミリモル、1.8g)を溶かした溶液に、0℃にて0.76ml(5ミリモル)のジアザビシクロウンデセン(DBU)を添加する。10分後、アルデヒド(5ミリモル)を添加する。この反応混合物を周囲温度にて一晩にわたって撹拌する。この反応混合物を30mlのジクロロメタンに溶かし、2×10mlのジクロロメタンで洗浄し、次いで2×10mlの飽和塩化ナトリウム溶液で洗浄する。有機相を硫酸ナトリウム上で乾燥させた後、減圧下で濃縮する。得られた油をシリカ(20g)上で濾過する。そのとき溶離液としてシクロヘキサン/酢酸エチル(9/1)を用いる。
化合物1(3ミリモル)と4-メトキシ-ベンジルメルカプタン(10ミリモル)を10mlの無水トルエンに溶かした溶液に、ピペリジンを200μl添加する。この混合物をアルゴン雰囲気下で24時間にわたって還流させる。溶媒を減圧下で除去する。カラム・クロマトグラフィ(溶離液はジクロロメタン)によって精製すると、油が得られる。
無水THF(4.5ml/ミリモル)にジエトキシホスホリルメタンスルホン酸ネオペンチル(2当量)を溶かした溶液に、-78℃にて、1.6Mのn-ブチルリチウムをヘキサン(2当量)に溶かした溶液を一滴ずつ添加する。30分間にわたって撹拌した後、化合物2(1当量)を無水THF(1ml/ミリモル)に溶かした溶液を添加した後、1.6Mの水素化ジイソブチルアルミニウムをトルエン(2当量)に溶かした溶液を一滴ずつ添加する。この反応混合物を4時間にわたって-78℃に維持した後、一晩かけて周囲温度に戻す。溶媒を減圧下で除去し、残留物に10ml/ミリモルのエーテルと5ml/ミリモルの2N HClを添加する。この混合物を30分間にわたって撹拌し、有機相を分離し、水相を対応する1容積のエーテルで2回抽出する。有機相を1つにまとめ、Na2SO4上で乾燥させ、減圧下で濃縮する。得られた油をシリカ上のクロマトグラフィによって精製する。溶媒を除去すると、生成物3が油として得られる。
化合物3(1当量)を無水エタノール(5ml/ミリモル)に溶かした溶液に、ホウ水素化ナトリウム(1当量)を添加する。この反応混合物を周囲温度にて一晩にわたって撹拌する。溶媒を減圧下で除去し、残留物に10ml/ミリモルの酢酸エチルと5ml/ミリモルの水を添加する。有機相を分離し、水相を対応する1容積の酢酸エチルで2回抽出する。有機相を1つにまとめ、Na2SO4上で乾燥させ、減圧下で濃縮する。得られた油を半分離用HPLCによって精製する。溶媒を除去すると、生成物16が油として得られる。
化合物4(1当量)にアニソール(5当量)とトリフルオロ酢酸(7ml/ミリモル)を添加する。この反応混合物をアルゴン雰囲気下で16時間にわたって還流させる。溶媒を減圧下で除去する。残留物を5ml/ミリモルのシクロヘキサンに懸濁させた後、そのシクロヘキサンを減圧下で除去する。この操作を2回繰り返して痕跡量のトリフルオロ酢酸を除去する。得られた油にエーテルに添加すると阻害剤5が沈澱するので、それを濾過した後、減圧下で乾燥させる。
(2E)-5-フェニル-ペント-2-エン酸エチル
32.6ml(164ミリモル、1.1当量)のホスホノ酢酸トリエチルを含む150mlの無水ジクロロメタンに、アルゴン雰囲気下で0℃にて24.7ml(164ミリモル、1.1当量)のジアザビシクロウンデセン(DBU)を一滴ずつ添加する。この反応物を30分間にわたって撹拌する。25℃に戻した後、19.6ml(149ミリモル、1当量)のヒドロシンナムアルデヒドを添加する。16時間にわたって反応させた後、反応媒体に150mlの1N HClを添加する。有機相を分離し、2×50mlの1N HClで洗浄し、次いで2×50mlの10%NaHCO3で洗浄する。有機相をNa2SO4上で乾燥させ、減圧下で濃縮する。生成物をシリカ上で濾過することによって精製する。無色の油が得られる。
50g(1.4g/ミリモル)のAD-ミックスと0.36g(3.7ミリモル、0.01g/ミリモル)のを160ml(4.5ml/ミリモル)のt-ブチルアルコールと160ml(4.5ml/ミリモル)の水の混合物に溶かした溶液に、25℃にて7.3g(35.7ミリモル、1当量)の(2Z)-5-フェニル-ペント-2-エン酸エチルを添加する。5時間にわたって反応させた後、45g(357ミリモル、1.3g/ミリモル、10当量)の亜硫酸ナトリウムを添加し、この混合物を30分間にわたって撹拌する。この反応媒体を150mlの酢酸エチルで希釈した後、有機相を分離し、Na2SO4上で乾燥させた後、減圧下で濃縮する。生成物をシリカ上で濾過することによって精製する。無色の油が得られる。
6.9g(29ミリモル、1当量)の化合物7と8ml(58ミリモル、2当量)トリエチルアミンを60ml(2ml/ミリモル)の無水ジクロロメタンに溶かした溶液に、0℃にて2.1ml(29ミリモル、1当量)の塩化チオニルを10分間かけて一滴ずつ添加する。この混合物を5分間にわたって撹拌し、40mlのエーテルで希釈し、30mlの水で洗浄する。溶媒を減圧下で除去し、残留物を、180mlの水と80mlのクロロホルムと80mlの四塩化炭素からなる混合物の中に懸濁させた後、9.6g(45ミリモル、1.5当量)の過ヨウ素酸ナトリウムと触媒量のRuCl3を添加する。25℃にて1時間にわたって撹拌した後、この混合物を150mlのエーテルで希釈し、セライト(登録商標)上で濾過する。有機相を40mlの10%NaHCO3で洗浄し、Na2SO4上で乾燥させた後、減圧下で濃縮する。生成物をシリカ上で濾過することによって精製する。無色の油が得られる。
3.3g(11ミリモル、1当量)の化合物8を110ml(10ml/ミリモル)の無水THFに溶かした溶液に、3.8g(44ミリモル、4当量)の臭化リチウムを添加する。この混合物を、25℃にて、化合物8が完全に消失するまで撹拌する。減圧下で濃縮した後、残留物を150mlのエーテルと20mlの水の中に入れた後、0.1mlの20%H2SO4を添加する。この溶液を4℃にて24時間にわたって撹拌する。有機相を分離し、3×20mlの10%NaHCO3で洗浄し、Na2SO4上で乾燥させた後、減圧下で濃縮する。生成物をシリカ上で濾過することによって精製する。無色の油が得られる。
1)1.2g(4ミリモル、1当量)の化合物8を24ml(6ミリモル)のアセトンと2.5ml(0.6ml/ミリモル)の水に溶かした溶液に、0.32g(5ミリモル、1.25当量)のアジ化ナトリウムを添加する。この混合物を、25℃にて、化合物8が完全に消失するまで撹拌する。減圧下で濃縮した後、残留物を50mlのエーテルと5mlの水の中に入れた後、1mlの20%H2SO4を添加する。この溶液を4℃にて24時間にわたって撹拌する。有機相を分離し、3×20mlの10%NaHCO3で洗浄し、Na2SO4上で乾燥させた後、減圧下で濃縮する。生成物をシリカ上で濾過することによって精製する。無色の油が得られる。
1.5g(5.7ミリモル、1当量)の化合物10を含む23ml(4ml/ミリモル)のアセトニトリルに、1.49g(5.7ミリモル、1当量)のトリフェニルホスフィンを添加する。この混合物を25℃にて1時間にわたって撹拌した後、5時間にわたって還流させる。反応媒体を減圧下で濃縮した後、得られた油をシリカ上で濾過することによって精製する。無色の油が得られる。
0.5g(2.3ミリモル、1当量)の化合物11を含む9ml(4ml/ミリモル)のピリジンに、1.14g(4.6ミリモル、2当量)のベンジルオキシカルボニルスクシンイミドと0.03g(0.24ミリモル、0.1当量)の4-ジメチルアミノピリジンを添加する。この混合物を4℃にて24時間にわたって撹拌する。この反応媒体を減圧下で濃縮した後、油をシリカ上で濾過することによって精製する。無色の油が得られる。
0.65g(1.8ミリモル、1当量)の化合物12を11ml(6ml/ミリモル)の無水ジクロロメタンに溶かして0℃に冷やした溶液に、1.0g(1ml、6.4ミリモル、3.6当量)の4-メトキシベンジルメルカプタンを添加し、それに続け、エーテルとの付加化合物にした0.7ml(5.5ミリモル、3当量)のBF3を一滴ずつ添加する。この混合物を4℃にて24時間にわたって撹拌する。18mlの10%NaHCO3(10ml/ミリモル)と18mlのジクロロメタンを添加した後、有機相を分離し、Na2SO4上で乾燥させ、減圧下で濃縮する。得られた油をシリカ上で濾過することによって精製する。無色の油が得られる。
ジエトキシホスホリルメタンスルホン酸ネオペンチル(2.0当量)を無水THF(4.5ml/ミリモル)に溶かした溶液に、-78℃にて、1.6Mのn-ブチルリチウムをヘキサン(2当量)に溶かした溶液を一滴ずつ添加する。30分後、撹拌しつつ、化合物2(1当量)を無水THF(1ml/ミリモル)に溶かした溶液を添加した後、1.6Mの水素化ジイソブチルアルミニウムをトルエン(2当量)に溶かした溶液を一滴ずつ添加する。この反応混合物を4時間にわたって-78℃に維持した後、一晩かけて周囲温度に戻す。溶媒を減圧下で除去し、残留物に10ml/ミリモルのエーテルと5ml/ミリモルの2N HClを添加する。この混合物を30分間にわたって撹拌し、有機相を分離し、水相を対応する1容積のエーテルで2回抽出する。有機相を1つにまとめ、Na2SO4上で乾燥させ、減圧下で濃縮する。得られた油をシリカ上のクロマトグラフィによって精製する。溶媒を除去すると、生成物3が油として得られる。
化合物3(1当量)を無水エタノール(5ml/ミリモル)に溶かした溶液に、ホウ水素化ナトリウム(1当量)を添加する。この反応混合物を25℃にて一晩にわたって撹拌する。溶媒を減圧下で除去し、残留物に10ml/ミリモルの酢酸エチルと5ml/ミリモルの水を添加する。有機相を分離し、水相を対応する1容積の酢酸エチルで2回抽出する。有機相を1つにまとめ、Na2SO4上で乾燥させ、減圧下で濃縮する。得られた油を半分離用HPLCによって精製する。溶媒を除去すると、生成物16が油として得られる。
化合物4(1当量)にアニソール(5当量)とトリフルオロ酢酸(7ml/ミリモル)を添加する。この反応混合物をアルゴン雰囲気下で16時間にわたって還流させる。溶媒を減圧下で除去する。残留物を5ml/ミリモルのシクロヘキサンに懸濁させた後、そのシクロヘキサンを減圧下で除去する。この操作を2回繰り返して痕跡量のトリフルオロ酢酸(TFA)を除去する。得られた油にエーテルに添加すると化合物5が沈澱するので、それを濾過した後、減圧下で乾燥させる。次に、化合物5を半分離用HPLCによって精製する。凍結乾燥させると、無色の固形物が得られる。
ダイマー化合物5eの合成
化合物5e(1当量)をエタノール(0.1ml/ミリモル)に溶かした溶液に、25℃にて撹拌しながら、着色した状態が続くようになるまで、0.1Mのヨウ素水溶液を一滴ずつ添加する。減圧下で濃縮した後、エーテルの存在下で油が結晶化する。この生成物を濾過した後、減圧下で乾燥させる。
化合物がAPAを阻害する阻害定数の決定
組み換えアミノペプチダーゼAに対する化合物5の作用を試験管内で調べ、その化合物のAPAに対する親和性を明らかにした。
試験管内では、APAは、カルシウム・イオンの存在下でα-L-グルタミル-β-ナフチルアミド(GluβNa)を加水分解してグルタミン酸塩とβ-ナフチルアミン(βNa)にする。酸性媒体中でジアゾ化反応させると、紫色の複合体が形成されることによってβ-ナフチルアミンの存在が明らかになる。そこで分光測光を行なうと形成された複合体の量を知ることができ、その結果をもとにして、β-ナフチルアミンの濃度を段階的に大きくしていった一連の基準と比較することにより、サンプルの酵素活性が求められる。
基質GluβNaとβ-ナフチルアミン(バケム社)をジメチルスルホキシドと0.1NのHClにそれぞれ溶かし、10-2Mの濃度で-20℃にて保管する。ジアゾ化反応は、亜硝酸ナトリウム(87mM)と、スルファミン酸アンモニウム(130mM)と、N-(1-ナフチル)エチレンジアミン二塩酸塩(23mM)の存在下で起こる。
この反応は、カルシウム(CaCl2、4mM)の存在下で、50mMのトリス-HCl緩衝液の中でpH7.4にて起こる。投与するサンプルは、基質(GluβNa、200μM)の存在下で、しかもテストするさまざまな濃度の阻害剤の不在下または存在下で、最終体積を100μlにして37℃にてインキュベートする。10μlの3N HClを添加することによって反応を停止させる。酸性媒体(10μlの0.1N HClを添加)にβ-ナフチルアミンが含まれた一連の基準を並行して作る。
それぞれのウエルに、以下のものを添加する:
- 亜硝酸ナトリウムを25μl(混合し、周囲温度にて5分間待つ)、
- スルファミン酸アンモニウムを50μl(撹拌し、周囲温度にて5分間待つ)、
- 23mMのN-(1-ナフチル)エチレンジアミン二塩酸塩を25μl(混合し、紫色が安定するのを37℃にて約30分間待つ)。
出願WO 04/007441に記載されている化合物RB 150(4,4'-ジチオビス-3-アミノブタン-1-スルホン酸)のモノマーである化合物EC33(出願WO 99/36066に記載されている(S)-3-アミノ-4-メルカプトブチルスルホン酸)が、参照化合物として役立つ。
Claims (12)
- 一般式(I):
・それぞれの基R1は同じであって、
- C1〜C6アルキル基、C2〜C6アルケニル基、C2〜C6アルキニル基、
- (CH2)nベンジル基(ただしnは0または1である)、
- (CH2)m(C3〜C6シクロアルキル)基(ただしmは0または1である)のいずれかを表わし、
アルキル基、アルケニル基、アルキニル基、ベンジル基、シクロアルキル基は、1つまたは2つの基Aで置換されており;
・基Aは、
- カルボン酸基COOHまたはCOOR(ただしRは、C1〜C6アルキル基またはCH2フェニルである)、
- スルホン酸基SO3HまたはSO3R'(ただしR'は、C1〜C6アルキル基またはCH2フェニルである)、
- ホスホン酸基PO3H2またはPO3R"2R"'(ただしR"とR"'は、独立に、H、C1〜C6アルキル基、CH2フェニルのいずれかを表わす)を表わし;
・それぞれの基R2は同じであって、C1〜C6アルキル基、C2〜C6アルケニル基、C2〜C6アルキニル基のいずれかを表わし、アルキル基、アルケニル基、アルキニル基は、それぞれ、そのままであるか基Bで置換されており;
・基Bは、
- カルボン酸基COOHまたはCOOR(ただしRは、C1〜C6アルキル基またはCH2フェニルである)、
- そのままのフェニル基であるか、1つまたは複数の基で置換されたフェニル基(ここで置換基の選択は、水素原子、場合によっては保護されているヒドロキシル基、C1〜C4アルキル基、シアノ基、そのままのカルボキシル基、塩を形成したカルボキシル基、エステル化されたカルボキシル基、アミド基の中からなされる)を表わし;
・それぞれの基R3は同じであって、水素原子を表わす。}で表される化合物。 - R1が、C1〜C6アルキル基、C2〜C6アルケニル基、ベンジル基からなる群から選択されており、そのそれぞれの基は、請求項1に規定した1つまたは2つの基Aで置換されている、請求項1に記載の化合物。
- R2が、C1〜C6アルキル基とC2〜C6アルケニル基の中から選択されており、そのそれぞれの基は、請求項1に規定した1つまたは2つの基Bで置換されている、請求項1または2に記載の化合物。
- R1が、そのままの、または塩を形成した、またはエステル化されたスルホン基、ホスホン基、カルボキシル基のいずれかで置換されたエチル基を表わし、R2が、そのままのフェニル基で置換されたエチル基、または置換されたフェニル基で置換されたエチル基を表わす、請求項1〜3のいずれか1項に記載の化合物。
- 4,4'-ジチオビス-(3,3'-アミノ-6,6'-フェニル-1,1'-ヘキサン)スルホン酸である、請求項1〜4のいずれか1項に記載の化合物。
- 4(S),4'(S),3(S),3'(S)-4'-ジチオビス-(3,3'-アミノ-6,6'-フェニル-1,1'-ヘキサン)スルホン酸である、請求項5に記載の化合物。
- 治療薬として使用される、請求項1〜6のいずれか1項に記載の化合物。
- 請求項1〜6のいずれか1項に記載の化合物を含む医薬組成物。
- アミノペプチダーゼAの選択的阻害剤として使用される、請求項1〜6のいずれか1項に記載の化合物。
- 請求項1〜6のいずれか1項に記載の化合物を用いて製造した病気の治療薬であって、動脈性高血圧と、それに直接または間接に関係した病気とを治療するための薬。
- 請求項1〜6のいずれか1項に記載の化合物を用いて製造した病気の治療薬であって、原発性および二次性の動脈性高血圧、心臓発作、心筋虚血、心不全、腎不全、心筋梗塞、末梢血管疾患、糖尿病性蛋白尿、X症候群、緑内障、神経変性疾患、記憶障害の中から選択した病気を治療するための薬。
- 請求項1〜6のいずれか1項に記載の化合物を用いて製造した病気の治療薬であって、アミノペプチダーゼAが関与する虚血および腫瘍を治療するための薬。
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PCT/FR2004/002106 WO2005014535A1 (fr) | 2003-08-06 | 2004-08-06 | Derives de 4,4’-dithiobis-(3-aminobutane-1-sulfonates) nouveaux et compositions les contenant |
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JP2014500238A (ja) * | 2010-10-07 | 2014-01-09 | クァンタム ジェノミック | (3s,3s’)4,4’−ジスルファンジイルビス(3−アミノブタン−1−スルホン酸)を調製する方法 |
JP2015506338A (ja) * | 2011-12-21 | 2015-03-02 | クァンタム ジェノミックQuantum Genomics | (3s,3s’)4,4’−ジスルファンジイルビス(3−アミノブタン1−スルホン酸)および第2の抗高血圧剤の組合せ |
JP2022520494A (ja) * | 2019-03-11 | 2022-03-30 | クワンタム・ゲノミクス | 高血圧又は心不全を処置するための化合物及びそれらを含む組成物 |
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FR2931151A1 (fr) * | 2008-05-13 | 2009-11-20 | Pharmaleads Soc Par Actions Si | Nouveaux derives d'amino-acides, leur procede de preparation et leur utilisation therapeutique |
WO2010014943A2 (en) * | 2008-08-01 | 2010-02-04 | Bioxiness Pharmaceutics, Inc. | Methionine analogs and methods of using same |
EP2722327A1 (en) | 2012-10-22 | 2014-04-23 | Quantum Genomics | Crystalline phase of (3S,3S') 4,4'-disulfanediylbis (3-aminobutane 1-sulfonic acid) with L-lysine |
WO2016061555A2 (en) * | 2014-10-17 | 2016-04-21 | University Of Florida Research Foundation | Novel small molecule anticancer agents |
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JP2014500238A (ja) * | 2010-10-07 | 2014-01-09 | クァンタム ジェノミック | (3s,3s’)4,4’−ジスルファンジイルビス(3−アミノブタン−1−スルホン酸)を調製する方法 |
JP2015506338A (ja) * | 2011-12-21 | 2015-03-02 | クァンタム ジェノミックQuantum Genomics | (3s,3s’)4,4’−ジスルファンジイルビス(3−アミノブタン1−スルホン酸)および第2の抗高血圧剤の組合せ |
JP2017222696A (ja) * | 2011-12-21 | 2017-12-21 | クァンタム ジェノミックQuantum Genomics | (3s,3s’)4,4’−ジスルファンジイルビス(3−アミノブタン 1−スルホン酸)および第2の抗高血圧剤の組合せ |
JP2022520494A (ja) * | 2019-03-11 | 2022-03-30 | クワンタム・ゲノミクス | 高血圧又は心不全を処置するための化合物及びそれらを含む組成物 |
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