JP2022036285A - ピペリジニルノシセプチン受容体化合物 - Google Patents
ピペリジニルノシセプチン受容体化合物 Download PDFInfo
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- JP2022036285A JP2022036285A JP2022004411A JP2022004411A JP2022036285A JP 2022036285 A JP2022036285 A JP 2022036285A JP 2022004411 A JP2022004411 A JP 2022004411A JP 2022004411 A JP2022004411 A JP 2022004411A JP 2022036285 A JP2022036285 A JP 2022036285A
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- substituted
- alkyl
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- heteroalkyl
- aryl
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Abstract
Description
本発明は、アメリカ合衆国保健福祉省(U.S.Department of Human Health and Services)、国立衛生研究所(National Institutes of Health)により与えられた助成番号R01DA014026、R01DA027811、R43NS070664、R43HL115984、HHSN275201300005C及びHHSN275201500005Cの下で政府支援により為された。政府は、本発明に特定の権利を有する。
本出願は、その全体が参照により組み入れられる2015年12月2日出願の米国仮特許出願第62/261,871号明細書から、35U.S.C.§119(e)下の優先権を主張する。
Bは、水素であり;又は代替的に、A及びBは存在せず、それらが結合している炭素原子は、
特に定義しない限り、本明細書で使用される全ての技術及び科学用語は、本発明が属する分野の当業者が通常理解するものと同じ意味を有する。本明細書で1つの用語に複数の定義が存在する場合、特に言及されない限り、このセクションの定義が優先する。
本発明は、神経性疾病及び病状の処置に有用な、新規なピペリジニルノシセプチン受容体リガンドを提供し、それらのリガンドは、病状の負の効果を媒介する。そのような神経性疾病及び病状は、例えば、急性及び慢性疼痛、薬物乱用/依存症、アルコール中毒、不安、鬱病、睡眠障害、胃腸疾患、腎疾患、心血管疾患、及びパーキンソン病を含む。
Bは、水素であり;又は代替的に、A及びBは存在せず、それらが結合している炭素原子は、
式(I)のピペリジニル含有ノシセプチン受容体化合物、並びに式(II)、式(III)及び式(IV)で表される実施形態は、当業者が認識し得るような多数の合成経路を介して合成することができる。式(II)の化合物の例示的な合成方法は、図1~6及び10に示され、下記の実施例1~6及び10に記載されている。表1は、式IIの化合物の1H NMR又はTLCデータも提供する。
本明細書に提供する組成物は、本明細書に記載した疾病又は疾患の症状のうちの1つまたはそれ以上の予防、処置又は寛解に有用な治療的有効量の本明細書に提供した化合物のうちの1つまたはそれ以上、及びvehicleを含む。本明細書に提供した化合物の投与に好適なvehicleは、特定の投与モードに好適であるとして当業者に既知の任意の担体を含む。加えて、化合物は、組成物中の唯一の活性成分として配合されてもよく、又は他の活性成分と一緒にされてもよい。
感染性疾患の処置又は予防のための使用において、本明細書に記載した化合物又はその医薬組成物は、治療的有効量で投与又は適用される。ヒトの治療において、医師は、予防的又は治癒的処置に従って、また年齢、体重、疾病の段階及び処置される対象に特異的な他の因子に従って、最も適切な投与量レジメンを決定するであろう。感染性疾患の予防又は処置に有効となる本明細書に提供した製剤中の活性成分の量は、疾病又は病状の性質及び重篤さ、並びに活性成分が投与される経路により変動するであろう。頻度及び投与量はまた、投与される特定の治療法(例えば治療薬又は予防薬)、感染症の重篤さ、投与経路、並びに対象の年齢、身体、体重、応答、及び過去の病歴に応じて、各対象に特異的な因子に従って変動するであろう。
本明細書に記載した化合物及び組成物は、対象における神経性の病状及び他の疾患を処置又は予防するための非常に様々な用途に使用することができる。本方法は概して、治療的有効量の本明細書に開示した化合物又はその医薬組成物を対象に投与することを含む。
本明細書に開示した化合物及び組成物は、1つまたはそれ以上の他の活性成分との組み合わせで使用することもできる。特定の実施形態において、化合物は、他の一治療薬と組み合わせて、又は連続して投与することができる。そのような他の治療薬は、薬物中毒、疼痛、神経変性疾患、パーキンソン病、アルツハイマー病、精神疾患、腎疾患、胃腸疾患、及び心血管疾患に関連した1つ以上の症状の処置、予防、又は寛解に関して既知のものを含む。
スキームIは、この合成を示す。
ステップ1.N-Boc中間体(1.00当量)のCH2Cl2(0.25~0.30M)溶液を0℃に冷却し、次いでTFA(6~30当量)を数分間に亘って加えた。添加の完了後、氷浴を除去し、反応物を室温に温め、TLC(EtOAc:ヘキサン)により確認した。2時間後、反応が完了した。反応物を真空下で濃縮し、次いでEtOAcを加え、EtOAcは結果として真空下で除去された。次いで油残留物をEtOAcに溶解し、水性層が塩基性のままとなるまで飽和NaHCO3(aq.)を加えながら撹拌した。層を分離し、水性層中のUV活性が最小となるまで水性層をEtOAcで抽出した(3~8回)。EtOAc層を一緒にし、ブラインで洗浄し、MgSO4で乾燥し、ろ過し、真空下で濃縮してピペリジン中間体を提供した。
スキームIIは、この合成を示す。
i.一般的手順Aを参照。2-ヨードアニリン(15.0g、63.3mmol、1.00当量)、N-Boc-ピペリドン(18.5g、95.0mmol、1.50当量)、氷AcOH(8.40mL、146mmol、2.30当量)、STAB(30.9g、146mmol、2.30当量)、DCE(250mL、0.25M)。MgSO4は反応に使用しなかった。生成物を5:95 EtOAc:ヘキサンを使用したフラッシュクロマトグラフィーにより精製して、所望の二環式化合物を白色固体(収率75%)として提供し、次の反応に直接使用した。Rf=0.15(5:95 EtOAc:ヘキサン、UV)。
ステップ1.ヨードアニリン(1.00当量)及び末端アルキン(3.00~5.00当量)をDMF及びiPr2NEt(3:1、0.40M)に溶解した。PdCl2(PPh3)2(0.0400当量)及びCuI(0.100当量)を反応混合物に同時に加えた。3方向アダプターを有するアルゴンバルーンを反応容器の頂部に配置し、容器をパージし、次いでアルゴンで再充填した(全部で3回反復)。反応物をアルミ箔で覆い、周囲温度で一晩撹拌したままにした。反応物をTLC(EtOAc:ヘキサン:NH4OH(aq.))により確認した。反応が完了した後、反応物をEtOAc及びH2Oで希釈し、10分間撹拌した。二相を分離し、有機層をH2O、ブラインで2回洗浄し、MgSO4で乾燥し、ろ過し、真空下で濃縮した。得られた粗材料をフラッシュクロマトグラフィーにより精製し、次いで、更なる処理を行うことなく、次の反応に直接使用した。
スキームIIIは、この合成を示す。
スキームIVは、この合成を示す。
スキームVは、この合成を示す。
i.一般的手順Aを参照。4-フルオロ-2-ヨードアニリン(3.80g、16.0mmol、1.00当量)、N-Bocピペリドン(4.69g、24.0mmol、1.50当量)、MgSO4(3.80g、100重量%)、氷AcOH(2.11mL、36.8mmol、2.30当量)、STAB(7.80g、36.8mmol、2.30当量)、及びDCE(80.0mL、0.20M)。12:88 EtOAc:ヘキサンを使用したフラッシュクロマトグラフィーにより粗材料を精製して、所望の二環式中間体を白色固体(6.70g、収率99%)として提供し、次の反応に直接使用した。
スキームVIは、この合成を示す。
アルコール30(7.29g、20.6mmol、1.00当量)のCH2Cl2(138mL、0.15M)の溶液に、DMAP(503mg、4.12mmol、0.200当量)及びiPr2NEt(18.4mL、103mmol、5.00当量)を室温で加えた。続いて、(tBuCO)2O(6.70mL、33.0、1.60当量)を加え、反応物を一晩撹拌したままにした。TLC(30:70:3滴のEtOAc:ヘキサン:NH4OH(aq.))は反応が完了したことを示した。反応物を真空下で濃縮し、5:95:1.5 EtOAc:ヘキサン:NH4OH(aq.)を使用したフラッシュクロマトグラフィーにより粗油を精製して、35を白色固体(8.59g、95%)として提供した。Rf=0.70(30:70:3滴のEtOAc:ヘキサン:NH4OH(aq.)、UV);1H NMR(400MHz、CDCl3)δ 7.73(d、J=8.4Hz、1H)、7.60(d、J=8.0Hz、1H)、7.20(t、J=7.2Hz、1H)、7.09(t、J=7.2Hz、1H)、6.56(s、1H)、5.25(s、2H)、4.17(m、1H)、3.31(d、J=12.0Hz、2H)、2.78(q、J=12.0Hz、2H)、2.55(q、J=6.4Hz、1H)、2.32(t、J=11.6Hz、2H)、1.90(d、J=12.4Hz、2H)、1.80(m、2H)、1.64(m、5H)、1.43(m、2H)、1.22(s、9H)、1.20(m、1H)、0.92(d、J=6.4Hz、6H);MS(ESI)m/z:439.3[M+H]+。
スキームVIIは、この合成を示す。
スキームVIIIは、この合成を示す。
スキームIXは、この合成を示す。
スキームXは、この合成を示す。
AcCl(806μL、11.3mmol、6.00当量)をMeOH(19.0mL、0.10M)に0℃で加え、反応物を5分間撹拌した。次いでインドールX-2(1.10g、1.89mmol、1.00当量)を反応物に加えた。0℃で10分間撹拌した後、白色スラリーが形成した。次いで氷浴を除去し、反応物を室温に温め、4時間撹拌した。4時間後、TLC(10:90:3滴のiPrOH:CH2Cl2:NH4OH(aq.))は反応が完了したことを示した。EtOAc(約50mL)を撹拌反応物に加え、数分後、白色沈殿が形成した。この白色沈殿をろ過し、冷EtOAcで3回洗浄し、真空下で乾燥してインドール86のHCl塩を提供した。665mg(80%)の所望の塩を得た。Rf=0.10(10:90:3滴のiPrOH:CH2Cl2:NH4OH(aq.)、UV、I2);1H NMR(遊離塩基)(300MHz、CDCl3)δ 7.61(d、J=6.0Hz、1H)、7.35(d、J=6.3Hz、1H)、7.21(t、J=6.0Hz、1H)、7.11(m、2H)、4.18(m、1H)、3.19(d、J=8.7Hz、2H)、3.03(t、J=4.8Hz、2H)、2.93(t、J=4.8Hz、2H)、2.35(m、1H)、2.26(dt、J=8.4、1.8Hz、2H)、2.07(m、6H)、1.78-1.52(m、7H)、1.42(m、2H)、1.15(m、1H)、0.90(d、J=5.1Hz、6H);MS(ESI)m/z:368.5[M+H]+。
下記に記載するように、全化合物をノシセプチン(NOP)、μ及びκオピオイド受容体におけるそれらの結合親和性に関して試験した。結合アッセイは、迅速かつ単純であり、ヒトNOP又はオピオイド受容体をトランスフェクトしたチャイニーズハムスター卵巣細胞を使用する。これらのアッセイの結果を表4、5及び6に示し、これらの表は、式(II)、式(III)及び式(IV)の化合物のノシセプチン及びオピオイド受容体における一連の受容体結合親和性をそれぞれ提供する。
Claims (20)
- 構造式(I):
Aは、
Bは、水素であり;
又は代替的に、A及びBは存在せず、それらが結合している炭素原子は、
R1及びR2は、それらが結合している炭素原子と一緒になって、アリール、置換アリール、ヘテロアリール又は置換ヘテロアリールを形成し;
Xは、水素、-CH=NOR4、-C(O)NR5R6、アルキル、置換アルキル、アリール、置換アリール、アリールアルキル、置換アリールアルキル、ヘテロアルキル、置換ヘテロアルキル、ヘテロアリール、置換ヘテロアリール、ヘテロアリールアルキル又は置換ヘテロアリールアルキルであり;
Yは、水素、-CH=NOR7、-C(O)NR8R9、アルキル、置換アルキル、アリール、置換アリール、アリールアルキル、置換アリールアルキル、ヘテロアルキル、置換ヘテロアルキル、ヘテロアリール、置換ヘテロアリール、ヘテロアリールアルキル又は置換ヘテロアリールアルキルであり;
Tは、=NR10;=CR11R12-、-NR13R14-、置換アルキル、アリール、置換アリール、アリールアルキル、置換アリールアルキル、ヘテロアルキル、置換ヘテロアルキル、ヘテロアリール、置換ヘテロアリール、ヘテロアリールアルキル又は置換ヘテロアリールアルキルであり;
R3は、水素、アルキル、置換アルキル、アリール置換アリール、アリールアルキル、置換アリールアルキル、ヘテロアルキル、置換ヘテロアルキル、ヘテロアリール、置換ヘテロアリール、ヘテロアリールアルキル又は置換ヘテロアリールアルキルであるが;
但し、R1及びR2がフェニル環を形成し、Lが
R4は、水素、アルキル又は置換アルキルであり;
R5は、水素、アルキル又は置換アルキルであり;
R6は、水素、アルキル、置換アルキル又はOR15であり;
R7は、水素、アルキル又は置換アルキルであり;
R8及びR9は、独立して水素、アルキル又は置換アルキルであり;
R10は、水素、アルキル、置換アルキル、-OR16又は-NR17R18であり;
R11は、水素、アルキル、置換アルキル、-C(O)R19又は-CNであり;
R12は、水素、-C(O)R20、又は-CNであり;
R13は、水素又は-C(O)R21であり;
R14は、水素又は-C(O)R22であるが;
但し、R13及びR14の両方が水素ではないものとし;
R15は、水素、アルキル又は置換アルキルであり、
R16は、水素、アルキル又は置換アルキルであり;
R17は、水素又は-C(O)R23であり;
R18は、水素又は-C(O)R24であり;
R19及びR20は、独立して-NR25R26、-OR27、アルキル、置換アルキル、ヘテロアルキル又は置換ヘテロアルキルであり;
R21及びR22は、独立して-NR28R29、-OR30、アルキル、置換アルキル、ヘテロアルキル又は置換ヘテロアルキルであり;
R23及びR24は、独立してアルキル又は置換アルキルであり;
R25、R26、R27、R28、R29及びR30は、独立して、水素、アルキル又は置換アルキルであり;
Lは、(C3~C8)シクロアルキル、(C3~C8)置換シクロアルキル、(C3~C8)シクロヘテロアルキル、(C3~C8)置換シクロヘテロアルキル、
- R1及びR2は、それらが結合している炭素原子と一緒になって、フェニル、置換フェニル、ピリジル又は置換ピリジルを形成する、請求項1に記載の化合物。
- Lは、(C3~C8)シクロアルキル、(C3~C8)置換シクロアルキル又は(C3~C8)シクロヘテロアルキルである、請求項1に記載の化合物。
- Lは、置換シクロヘキシル基である、請求項1に記載の化合物。
- Zは、アルキル、置換アルキル、ヘテロアルキル又は置換ヘテロアルキルである、請求項6に記載の化合物。
- 請求項1に記載の化合物及び薬学的に許容可能なvehicleを含む医薬組成物。
- 患者におけるノシセプチン受容体介在性疾患の処置方法であって、前記処置を必要とする該患者に、請求項1に記載の化合物又は請求項16に記載の医薬組成物を投与することを含む、方法。
- ノシセプチン受容体の調節方法であって、請求項1に記載の化合物又は請求項16に記載の医薬組成物を投与することを含む、方法。
- 患者におけるパーキンソン病、心血管疾患、胃腸疾患、アルコール中毒、急性及び慢性疼痛、不安、鬱病、疼痛、睡眠障害並びに薬物乱用/依存症の処置又は予防方法であって、前記処置又は予防を必要とする前記患者に請求項1に記載の化合物又は請求項16に記載の医薬組成物を投与することを含む、方法。
- 患者におけるパーキンソン病、心血管疾患、胃腸疾患、アルコール中毒、急性及び慢性疼痛、不安、鬱病、疼痛、睡眠障害並びに薬物乱用/依存症を処置又は予防するためのノシセプチン受容体の調節方法であって、前記処置又は予防を必要とする前記患者に、請求項1に記載の化合物又は請求項16に記載の医薬組成物を投与することを含む、方法。
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CN117642402A (zh) * | 2021-07-14 | 2024-03-01 | 宜昌人福药业有限责任公司 | 一种螺哌啶环衍生物及其药物组合物、制备方法和用途 |
CN115611856A (zh) * | 2021-07-14 | 2023-01-17 | 宜昌人福药业有限责任公司 | 一种哌啶衍生物及其药物组合物、制备方法和用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10212290A (ja) * | 1997-01-30 | 1998-08-11 | F Hoffmann La Roche Ag | 8−置換−1,3,8−トリアザ−スピロ〔4.5〕デカン−4−オン誘導体 |
WO2003095427A1 (fr) * | 2002-05-10 | 2003-11-20 | Taisho Pharmaceutical Co.,Ltd. | Compose a noyau spiranique |
JP2007530656A (ja) * | 2004-03-29 | 2007-11-01 | ファイザー株式会社 | ORL1受容体拮抗薬としてのαアリールまたはヘテロアリールメチルβピペリジノプロパンアミド化合物 |
JP2008542375A (ja) * | 2005-06-02 | 2008-11-27 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Orl−1受容体モジュレーターとして有用な新規3−スピロ環式インドリル誘導体 |
JP2010523687A (ja) * | 2007-04-09 | 2010-07-15 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 不安及び鬱病の処置のためのorl−1受容体リガンドとしての1,3,8−三置換−1,3,8−トリアザ−スピロ[4.5]デカン−4−オン誘導体 |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2179650C (en) * | 1993-12-23 | 2007-10-30 | William Francis Heath, Jr. | Bisindolemaleimides and their use as protein kinase c inhibitors |
BR9913887A (pt) | 1998-09-18 | 2001-10-23 | Basf Ag | Composto, e, métodos de inibir a atividade de proteìna quinase, de tratar um paciente que tenha uma condição que seja mediada pela atividade da proteìna quinase e de diminuir a fertilidade em um paciente |
RU2230060C2 (ru) * | 2000-01-20 | 2004-06-10 | Эйсай Ко., Лтд. | Соединения, фармацевтическая композиция, способ предотвращения гибели нервных клеток, способ профилактики |
JP3966693B2 (ja) | 2000-01-20 | 2007-08-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 含窒素環化合物およびそれらを含んでなる医薬組成物 |
AU2000240570A1 (en) | 2000-03-29 | 2001-10-08 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
US7074794B2 (en) | 2000-08-10 | 2006-07-11 | Mitsubishi Pharma Corporation | Proline derivatives and the use thereof as drugs |
JP2005519921A (ja) * | 2002-01-28 | 2005-07-07 | ファイザー株式会社 | Orl−1受容体リガンドとしてのn置換スピロピペリジン化合物 |
KR20050043935A (ko) * | 2002-09-09 | 2005-05-11 | 얀센 파마슈티카 엔.브이. | Orl-1 수용체 매개 장애의 치료에 유용한 하이드록시 알킬 치환된 1,3,8-트리아자스피로[4.5]데칸-4-온 유도체 |
UA80171C2 (en) * | 2002-12-19 | 2007-08-27 | Pfizer Prod Inc | Pyrrolopyrimidine derivatives |
US20050228023A1 (en) * | 2003-12-19 | 2005-10-13 | Sri International | Agonist and antagonist ligands of the nociceptin receptor |
MX2009005252A (es) | 2006-11-17 | 2009-05-28 | Abbott Lab | Aminopirrolidinas como antagonistas del receptor de quimiocina. |
EP2141163A1 (de) * | 2008-07-02 | 2010-01-06 | Bayer Schering Pharma AG | Substituierte Thiazolidinone, deren Herstellung und Verwendung als Arzneimittel |
EP2475668A1 (en) | 2009-09-10 | 2012-07-18 | Novartis AG | Ether derivatives of bicyclic heteroaryls |
UY33227A (es) * | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
WO2014017659A1 (ja) | 2012-07-27 | 2014-01-30 | 独立行政法人理化学研究所 | 急性骨髄性白血病の治療又は再発抑制剤 |
WO2014102588A2 (en) * | 2012-12-27 | 2014-07-03 | Purdue Pharma L.P. | Indole and indoline-type piperidine compounds and uses thereof |
JP2016113366A (ja) * | 2013-03-29 | 2016-06-23 | 大鵬薬品工業株式会社 | アセトアミド基を有する1,2,4−トリアジン−6−カルボキサミド誘導体 |
TWI663166B (zh) * | 2013-04-24 | 2019-06-21 | 健生藥品公司 | 新化合物 |
CN105431436B (zh) * | 2013-05-14 | 2017-11-28 | 内尔维阿诺医学科学有限公司 | 吡咯并[2,3‑d]嘧啶衍生物,它们的制备方法和它们作为激酶抑制剂的用途 |
TWI627173B (zh) * | 2013-09-26 | 2018-06-21 | 比利時商健生藥品公司 | 作為NIK抑制劑的新穎3-(1H-吡唑-4-基)-1H-吡咯并[2,3-c]吡啶衍生物 |
ES2704738T3 (es) * | 2014-10-23 | 2019-03-19 | Janssen Pharmaceutica Nv | Nuevos derivados de tienopirimidina en calidad de inhibidores de nik |
MX371150B (es) * | 2014-10-23 | 2020-01-20 | Janssen Pharmaceutica Nv | NUEVOS DERIVADOS DE PIRAZOL EN CALIDAD DE INHIBIDORES DE LA CINASA INDUCTORA DE NF-kB (NIK). |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10212290A (ja) * | 1997-01-30 | 1998-08-11 | F Hoffmann La Roche Ag | 8−置換−1,3,8−トリアザ−スピロ〔4.5〕デカン−4−オン誘導体 |
WO2003095427A1 (fr) * | 2002-05-10 | 2003-11-20 | Taisho Pharmaceutical Co.,Ltd. | Compose a noyau spiranique |
JP2007530656A (ja) * | 2004-03-29 | 2007-11-01 | ファイザー株式会社 | ORL1受容体拮抗薬としてのαアリールまたはヘテロアリールメチルβピペリジノプロパンアミド化合物 |
JP2008542375A (ja) * | 2005-06-02 | 2008-11-27 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Orl−1受容体モジュレーターとして有用な新規3−スピロ環式インドリル誘導体 |
JP2010523687A (ja) * | 2007-04-09 | 2010-07-15 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 不安及び鬱病の処置のためのorl−1受容体リガンドとしての1,3,8−三置換−1,3,8−トリアザ−スピロ[4.5]デカン−4−オン誘導体 |
Non-Patent Citations (3)
Title |
---|
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 15, JPN6023001966, 2005, pages 5022 - 5026, ISSN: 0004974650 * |
JOURNAL OF CHEMICAL INFORMATION AND MODELING, vol. 54, JPN6023001968, 2014, pages 2732 - 2743, ISSN: 0004974649 * |
JOURNAL OF MEDICINAL CHEMISTRY, vol. 51(4), JPN6023001967, 2008, pages 1058 - 1062, ISSN: 0004974648 * |
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WO2017096323A1 (en) | 2017-06-08 |
IL259726A (en) | 2018-07-31 |
AU2016365400B2 (en) | 2022-04-07 |
KR20180094940A (ko) | 2018-08-24 |
AU2022202862B2 (en) | 2024-03-28 |
JP2024003167A (ja) | 2024-01-11 |
JP7011596B2 (ja) | 2022-02-10 |
CN108883103A (zh) | 2018-11-23 |
CA3006966A1 (en) | 2017-06-08 |
AU2016365400C1 (en) | 2022-11-10 |
JP2018536716A (ja) | 2018-12-13 |
JP7472175B2 (ja) | 2024-04-22 |
EP3383390A4 (en) | 2019-11-20 |
AU2016365400A1 (en) | 2018-06-21 |
IL259726B (en) | 2021-10-31 |
AU2022202862A1 (en) | 2022-05-19 |
EP3383390A1 (en) | 2018-10-10 |
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