JP2016501844A - MoGAT−2阻害剤として有用な新規のベンジルスルホンアミド化合物 - Google Patents
MoGAT−2阻害剤として有用な新規のベンジルスルホンアミド化合物 Download PDFInfo
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- 0 C[C@](c1ccc(CNC[C@@]2Oc3ncccc3OC2)cc1)NS(C)(=*)=O Chemical compound C[C@](c1ccc(CNC[C@@]2Oc3ncccc3OC2)cc1)NS(C)(=*)=O 0.000 description 2
- YUXQSZNZGIKWCP-OVWNDWIMSA-N CC(C)(C)[S@@](N[C@H](C(F)(F)F)c(cc1)ccc1Br)=O Chemical compound CC(C)(C)[S@@](N[C@H](C(F)(F)F)c(cc1)ccc1Br)=O YUXQSZNZGIKWCP-OVWNDWIMSA-N 0.000 description 1
- PGKFBBLLXMBLJX-UHFFFAOYSA-N CN(C1=CCCC=C1O1)C1=O Chemical compound CN(C1=CCCC=C1O1)C1=O PGKFBBLLXMBLJX-UHFFFAOYSA-N 0.000 description 1
- DFTOYQQXJJQNSK-PXYINDEMSA-N CO[C@@H](COC1OCC1)c1ccccc1 Chemical compound CO[C@@H](COC1OCC1)c1ccccc1 DFTOYQQXJJQNSK-PXYINDEMSA-N 0.000 description 1
- NMJSAKBGLNPHTD-CJNGLKHVSA-N C[C@H](c1ccc(CNC[C@@H]2Oc3ncccc3OC2)cc1)NS(C)(O)=O Chemical compound C[C@H](c1ccc(CNC[C@@H]2Oc3ncccc3OC2)cc1)NS(C)(O)=O NMJSAKBGLNPHTD-CJNGLKHVSA-N 0.000 description 1
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Abstract
Description
(Aの式中、Tは、CH2、NHおよびOから選択され;Uは、CH2、NHおよびOから選択され;Vは、CH2、C=O、NH、N−CH3およびOから選択され、ただしT、UおよびVの少なくとも1つはCH2であるが全てではなく、かつUがOの場合は、それぞれのTおよびVはOまたはN以外であるとし;Wは、CH2およびOから選択され;Xは、CHおよびNから選択され;ただしWがCH2の場合は、XはNであり、WがOの場合は、XはCHであるとし;Yは、CH2、N−C6H5およびOから選択され;Zは、CH2およびOから選択され;R2は、Hおよびハロゲンから選択され;R3は、H、シクロプロピルおよびフェニルから選択され;R4は、Hおよびフェニルから選択される
(式中、
本明細書で使用する場合、以下の語は示される意味を有する:「ACN」はアセトニトリルを指し、「DCM」はジクロロメタンを指し、「DEA」はジエチルアミンを指し、「DMEA」はジメチルエチルアミンを指し、「DMF」はジメチルホルムアミドを指し、「ee」は鏡像体過剰率を指し、「EtOAc」は酢酸エチルを指し、「EtOH」はエタノールを指し、「IPA」はイソプロピルアルコールを指し、「IPA」はイソプロピルアミンを指し、「異性体1」は本明細書で除外した条件下での第1の溶出異性体を指し、「異性体2」は本明細書で除外した条件下での第2の溶出異性体を指し、「LC/MS」は液体クロマトグラフィーとそれに続く質量分析を指し、「MeOH」はメタノールを指し、「MS」は質量分析を指し、「NMR」は核磁気共鳴を指し、「Prep」は調製を指し、「SFC」は超臨界流体クロマトグラフィーを指し、「THF」はテトラヒドロフランを指す。
N−{(1S)−1−[4−({[(3S)−2,3−ジヒドロ[1,4]ジオキシノ[2,3−b]ピリジン−3−イルメチル]アミノ}メチル)フェニル]−2,2,2−トリフルオロエチル}メタンスルホンアミド塩酸塩
N−{(1S)−2,2,2−トリフルオロ−1−[4−({[2−(1−オキソ−3,4−ジヒドロイソキノリン−2(1H)−イル)エチル]アミノ}メチル)フェニル]エチル}メタンスルホンアミド塩酸塩
N−{(1S)−2,2,2−トリフルオロ−1−[4−({[2−(2−オキソ−1,3−ベンゾオキサゾール−3(2h)−イル)エチル]アミノ}メチル)フェニル]エチル}メタンスルホンアミド塩酸塩
本アッセイにおいてヒトMoGAT−2に対する化合物のインビトロでの阻害活性を評価する。MoGAT−2は、腸管トリグリセリド再合成経路においてオレオイル基をオレオイル−CoAからモノオレオイル−グリセロール(「MAG」)に転移してジオレオイル−グリセロール(「DAG」)を形成する。本アッセイは、疎水性分子を親水性分子よりも選択的に抽出して14C−オレオイル−CoAを14C−DAGから分離する、Microscint E抽出を利用する。
本アッセイにおいて細胞環境におけるヒトMoGAT−2に対する化合物の阻害活性を評価する。Caco−2は、ヒト結腸がん細胞株であり、腸上皮細胞のためのモデルとしてしばしば用いられる。Caco−2は、MoGAT−2を発現せず、したがって、ヒトMoGAT−2は、安定的なトランスフェクションによって細胞株内に組み込まれる。MAG類似体である、2−O−ヘキサデシルグリセロール(HDG)は、HDGが加水分解されず、得られる生成物は質量分析法によって容易に観察できるので、細胞のMoGAT−2活性を検出するために利用される。基質は、超音波処理した小胞の形態のDOPCとの混合物として用いて細胞に送達される。
小腸で見つかるMoGAT−2を阻害することは、過度の脂肪摂取量に起因する高トリグリセリド血症を治療するために有用であり得る。MoGAT−2の阻害は、トリグリセリドの再合成を妨害し、これは腸からのトリグリセリドの分泌を減少させる。したがって、MoGAT−2阻害は、身体を通る最終的な循環のための腸へのトリグリセリドの分泌に至る特異的なプロセスを妨げる。血液系において測定されるようなMoGAT−2によって誘発される腸へのTAG分泌を阻害する1種または複数の例示された化合物の能力を評価するために、以下の手順に従ってもよい:
Claims (26)
- 下式の化合物:
Lは、−CH2−および−CH2CH2−から選択され、
R1は、−CH3および−CF3から選択され、
Aは、
(式中、
Tは、CH2、NHおよびOから選択され、
Uは、CH2、NHおよびOから選択され、
Vは、CH2、C=O、NH、N−CH3およびOから選択され、
但しT、UおよびVの少なくとも1つはCH2であるが全部ではなく、かつUがOである場合はTおよびVのそれぞれはOまたはN以外であり、
Wは、CH2およびOから選択され、
Xは、CHおよびNから選択され、但しWがCH2の場合、XはNであり、WがOの場合、XはCHであり、
Yは、CH2、N−C6H5およびOから選択され、
Zは、CH2およびOから選択され、
R2は、Hおよびハロゲンから選択され、
R3は、H、シクロプロピルおよびフェニルから選択され、
R4は、Hおよびフェニルから選択され、
およびその薬学的に許容可能な塩。 - Lは−CH2−である、請求項1または2に記載の化合物。
- R1は−CH3である、請求項1から3のいずれか一項に記載の化合物。
- R1は−CF3である、請求項1から3のいずれか一項に記載の化合物。
- TはOまたはNであり、
UはCH2であり、かつ
VはOまたはNである、
請求項7に記載の化合物。 - TおよびVは共にOである、請求項1から8のいずれか一項に記載の化合物。
- TはOかつVはNである、請求項1から8のいずれか一項に記載の化合物。
- TおよびVは共にCH2でありかつUはOである、請求項1から7のいずれか一項に記載の化合物。
- R2はHである、請求項1から11のいずれか一項に記載の化合物。
- 請求項1から21のいずれか一項に記載の化合物またはその薬学的に許容可能な塩および薬学的に許容可能な担体、希釈剤もしくは賦形剤のうちの少なくとも1種を含む、医薬組成物。
- 高トリグリセリド血症の治療を必要とする患者を治療する方法であって、有効量の請求項1から21のいずれか一項に記載の化合物またはその薬学的に許容可能な塩を患者に投与するステップを含む、方法。
- 療法における使用のための、請求項1から21のいずれか一項に記載の化合物またはその薬学的に許容可能な塩。
- 高トリグリセリド血症の治療における使用のための、請求項1から21のいずれか一項に記載の化合物またはその薬学的に許容可能な塩。
- 高トリグリセリド血症を治療する薬品の製造における、請求項1から21のいずれか一項に記載の化合物またはその薬学的に許容可能な塩の使用。
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EP12382431 | 2012-11-06 | ||
EP12382431.0 | 2012-11-06 | ||
US201361748935P | 2013-01-04 | 2013-01-04 | |
US61/748,935 | 2013-01-04 | ||
PCT/US2013/067466 WO2014074365A1 (en) | 2012-11-06 | 2013-10-30 | Novel benzyl sulfonamide compounds useful as mogat-2 inhibitors |
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JP2016501844A true JP2016501844A (ja) | 2016-01-21 |
JP2016501844A5 JP2016501844A5 (ja) | 2016-11-24 |
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US (1) | US9416138B2 (ja) |
EP (1) | EP2917194B1 (ja) |
JP (1) | JP2016501844A (ja) |
KR (1) | KR20150063519A (ja) |
CN (1) | CN104768941B (ja) |
AU (1) | AU2013341584A1 (ja) |
BR (1) | BR112015009567A2 (ja) |
CA (1) | CA2886831A1 (ja) |
EA (1) | EA201590696A1 (ja) |
MX (1) | MX2015005739A (ja) |
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WO2013112323A1 (en) | 2012-01-23 | 2013-08-01 | Eli Lilly And Company | Phenyl methanesulfonamide derivatives useful as mgat - 2 inhibitors |
ES2571577T3 (es) | 2012-01-31 | 2016-05-26 | Lilly Co Eli | Derivados novedosos de morfolinilo útiles como inhibidores de MOGAT-2 |
EP3395798A4 (en) | 2015-12-21 | 2019-07-17 | Shionogi & Co., Ltd | NON-AROMATIC HETEROCYCLIC DERIVATIVE HAVING MGAT2 INHIBITORY ACTIVITY |
TWI782056B (zh) | 2017-07-14 | 2022-11-01 | 日商鹽野義製藥股份有限公司 | 具有mgat2抑制活性的縮合環衍生物 |
KR20210114001A (ko) | 2019-01-11 | 2021-09-17 | 시오노기 앤드 컴파니, 리미티드 | Mgat2 저해 활성을 갖는 다이하이드로피라졸로피라지논 유도체 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10510512A (ja) * | 1994-10-04 | 1998-10-13 | 藤沢薬品工業株式会社 | 尿素誘導体とacat阻害剤としての用途 |
JP2005516061A (ja) * | 2002-01-29 | 2005-06-02 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | タンパク質チロシンホスファターゼの調節因子としての置換メチレンアミド誘導体 |
JP2007533752A (ja) * | 2004-04-20 | 2007-11-22 | トランス テック ファーマ,インコーポレイテッド | メラノコルチン受容体の調節因子としての置換チアゾール及びピリミジン誘導体 |
JP2012524121A (ja) * | 2009-04-20 | 2012-10-11 | アボット・ラボラトリーズ | 新規アミドおよびアミジン誘導体ならびにこれらの使用 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9702194D0 (en) | 1997-02-04 | 1997-03-26 | Lilly Co Eli | Sulphonide derivatives |
EP1659113A1 (en) * | 2004-11-08 | 2006-05-24 | Evotec AG | Inhibitors of 11beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) |
EP1655283A1 (en) * | 2004-11-08 | 2006-05-10 | Evotec OAI AG | 11beta-HSD1 Inhibitors |
EP2078719A4 (en) * | 2006-09-28 | 2009-11-11 | Dainippon Sumitomo Pharma Co | COMPOUND WITH BICYCLIC PYRIMIDINE STRUCTURE AND THE COMPOUND CONTAINING PHARMACEUTICAL COMPOSITION |
TW200831092A (en) * | 2006-12-21 | 2008-08-01 | Astrazeneca Ab | Therapeutic agents |
CA2751244A1 (en) | 2009-02-23 | 2010-08-26 | Msd K.K. | Pyrimidin-4(3h)-one derivatives |
EP2243479A3 (en) * | 2009-04-20 | 2011-01-19 | Abbott Laboratories | Novel amide and amidine derivates and uses thereof |
WO2013112323A1 (en) | 2012-01-23 | 2013-08-01 | Eli Lilly And Company | Phenyl methanesulfonamide derivatives useful as mgat - 2 inhibitors |
ES2571577T3 (es) | 2012-01-31 | 2016-05-26 | Lilly Co Eli | Derivados novedosos de morfolinilo útiles como inhibidores de MOGAT-2 |
TW201343629A (zh) | 2012-01-31 | 2013-11-01 | Lilly Co Eli | 可作為mogat-2抑制劑之新穎芐磺醯胺衍生物 |
-
2013
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- 2013-10-30 KR KR1020157011222A patent/KR20150063519A/ko not_active Application Discontinuation
- 2013-10-30 EP EP13789443.2A patent/EP2917194B1/en active Active
- 2013-10-30 JP JP2015540743A patent/JP2016501844A/ja not_active Ceased
- 2013-10-30 EA EA201590696A patent/EA201590696A1/ru unknown
- 2013-10-30 BR BR112015009567A patent/BR112015009567A2/pt not_active IP Right Cessation
- 2013-10-30 CN CN201380057789.8A patent/CN104768941B/zh not_active Expired - Fee Related
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- 2013-10-30 MX MX2015005739A patent/MX2015005739A/es unknown
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10510512A (ja) * | 1994-10-04 | 1998-10-13 | 藤沢薬品工業株式会社 | 尿素誘導体とacat阻害剤としての用途 |
JP2005516061A (ja) * | 2002-01-29 | 2005-06-02 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | タンパク質チロシンホスファターゼの調節因子としての置換メチレンアミド誘導体 |
JP2007533752A (ja) * | 2004-04-20 | 2007-11-22 | トランス テック ファーマ,インコーポレイテッド | メラノコルチン受容体の調節因子としての置換チアゾール及びピリミジン誘導体 |
JP2012524121A (ja) * | 2009-04-20 | 2012-10-11 | アボット・ラボラトリーズ | 新規アミドおよびアミジン誘導体ならびにこれらの使用 |
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CA2886831A1 (en) | 2014-05-15 |
BR112015009567A2 (pt) | 2017-07-04 |
CN104768941A (zh) | 2015-07-08 |
EP2917194B1 (en) | 2017-09-27 |
US9416138B2 (en) | 2016-08-16 |
CN104768941B (zh) | 2016-08-24 |
KR20150063519A (ko) | 2015-06-09 |
MX2015005739A (es) | 2015-09-16 |
AU2013341584A1 (en) | 2015-04-30 |
EA201590696A1 (ru) | 2015-08-31 |
WO2014074365A1 (en) | 2014-05-15 |
EP2917194A1 (en) | 2015-09-16 |
US20150284404A1 (en) | 2015-10-08 |
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