JP2005515210A5 - - Google Patents
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- JP2005515210A5 JP2005515210A5 JP2003552293A JP2003552293A JP2005515210A5 JP 2005515210 A5 JP2005515210 A5 JP 2005515210A5 JP 2003552293 A JP2003552293 A JP 2003552293A JP 2003552293 A JP2003552293 A JP 2003552293A JP 2005515210 A5 JP2005515210 A5 JP 2005515210A5
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Description
Z1, Z2又はZ3の1つは-Hであり、そして他の2つは、それらが置換されているベンゼン環からの2つの炭素原子及びそれらの間の結合と共に、S、N、及びOから選択された少なくとも1つのヘテロ原子を含む5−及び6−員の飽和環並びに5−及び6−員の不飽和環から選択された環を形成し、ここで
R1は、-F, -OCH3, -N(CH3)2, 及びS, N及びOから選択された少なくとも1つのヘテロ原子を含む不飽和5−員の環から選択され、
R2は、3−〜6−員の飽和環であり、そして
Y1及びY2は、-Cl, -Br, -NO2, -CN及び-CCHからそれぞれ独立して選択される]で表される化合物、及び医薬的に許容できるその塩及びエステルから選択された、少なくとも1つの化合物を提供する。
R1は、-F, -OCH3, -N(CH3)2, 及びS, N及びOから選択された少なくとも1つのヘテロ原子を含む不飽和5−員の環から選択され、
R2は、3−〜6−員の飽和環であり、そして
Y1及びY2は、-Cl, -Br, -NO2, -CN及び-CCHからそれぞれ独立して選択される]で表される化合物、及び医薬的に許容できるその塩及びエステルから選択された、少なくとも1つの化合物を提供する。
[式中、Z1, Z2及びZ3は、C1-C6アルコキシ、-CH2OCH3及び-CH2OCH2CH3からそれぞれ独立して選択されるか、あるいはZ1, Z2又はZ3の1つは-Hであり、そして他の2つは、C1-C6アルキル、C1-C6アルコキシ、-Cl、-Br、-F、-CF3、 -CH20CH3、-CH20CH2CH3、-OCH2CH2Rl、-CH2-モルホリノ、-OR2、-CH2R2、 -OCH2CF3、-OCH(CH3)CH20H 及び-COOQからそれぞれ独立して選択され、ここでQは-H及びC1-C6アルキルから選択され、又は
Z1, Z2又はZ3の1つは-Hであり、そして他の2つは、それらが置換されているベンゼン環からの2つの炭素原子及びそれらの間の結合と共に、S、N、及びOから選択された少なくとも1つのヘテロ原子を含む5−及び6−員の飽和環並びに5−及び6−員の不飽和環から選択された環を形成し、ここで
Z1, Z2又はZ3の1つは-Hであり、そして他の2つは、それらが置換されているベンゼン環からの2つの炭素原子及びそれらの間の結合と共に、S、N、及びOから選択された少なくとも1つのヘテロ原子を含む5−及び6−員の飽和環並びに5−及び6−員の不飽和環から選択された環を形成し、ここで
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34172901P | 2001-12-18 | 2001-12-18 | |
| US39087602P | 2002-06-21 | 2002-06-21 | |
| PCT/EP2002/013905 WO2003051360A1 (en) | 2001-12-18 | 2002-12-09 | Cis-imidazolines as mdm2 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005515210A JP2005515210A (ja) | 2005-05-26 |
| JP2005515210A5 true JP2005515210A5 (ja) | 2009-07-23 |
| JP4361798B2 JP4361798B2 (ja) | 2009-11-11 |
Family
ID=26992633
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003552293A Expired - Fee Related JP4361798B2 (ja) | 2001-12-18 | 2002-12-09 | Mdm2インヒビターとしてのシス−イミダゾリン |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US6617346B1 (ja) |
| EP (1) | EP1463501B1 (ja) |
| JP (1) | JP4361798B2 (ja) |
| KR (1) | KR100640707B1 (ja) |
| CN (1) | CN1604778A (ja) |
| AR (1) | AR037882A1 (ja) |
| AT (1) | ATE397925T1 (ja) |
| AU (1) | AU2002361986B2 (ja) |
| BR (1) | BR0215156A (ja) |
| CA (1) | CA2468783A1 (ja) |
| DE (1) | DE60227108D1 (ja) |
| ES (1) | ES2307822T3 (ja) |
| MX (1) | MXPA04005880A (ja) |
| PA (1) | PA8561801A1 (ja) |
| PE (1) | PE20030717A1 (ja) |
| PL (1) | PL370909A1 (ja) |
| RU (1) | RU2312101C2 (ja) |
| TW (1) | TW200301696A (ja) |
| UY (1) | UY27586A1 (ja) |
| WO (1) | WO2003051360A1 (ja) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7132421B2 (en) | 2003-06-17 | 2006-11-07 | Hoffmann-La Roche Inc. | CIS-imidazoles |
| AU2004253245B2 (en) * | 2003-06-17 | 2010-02-11 | F. Hoffmann-La Roche Ag | CIS-imidazolines as MDM2 inhibitors |
| EP1753727B1 (en) * | 2004-05-18 | 2008-11-19 | F.Hoffmann-La Roche Ag | Novel cis-imidazolines |
| JP2008500991A (ja) * | 2004-05-29 | 2008-01-17 | 7ティーエム ファーマ エイ/エス | 医学的使用のためのcrth2レセプターリガンド |
| US7893278B2 (en) * | 2004-06-17 | 2011-02-22 | Hoffman-La Roche Inc. | CIS-imidazolines |
| AU2006216780B8 (en) | 2005-02-22 | 2010-04-22 | The Regents Of The University Of Michigan | Small molecule inhibitors of MDM2 and uses thereof |
| NZ561215A (en) | 2005-02-22 | 2010-12-24 | Univ Michigan | Small molecule inhibitors of MDM2 and uses thereof |
| KR20100129331A (ko) | 2005-12-01 | 2010-12-08 | 에프. 호프만-라 로슈 아게 | 항암제로서 사용하기 위한 p53 및 mdm2 단백질 간 상호작용의 저해제로서의 2,4,5-트리페닐 이미다졸린 유도체 |
| WO2007082805A1 (en) * | 2006-01-18 | 2007-07-26 | F. Hoffmann-La Roche Ag | Cis-4, 5-biaryl-2-heterocyclic-imidazolines as mdm2 inhibitors |
| US8470785B2 (en) | 2006-07-28 | 2013-06-25 | St. Jude Children's Research Hospital | Method for treating ocular cancer |
| US8614192B2 (en) | 2006-07-28 | 2013-12-24 | Leiden University Medical Center | Method for treating ocular cancer |
| US8222288B2 (en) | 2006-08-30 | 2012-07-17 | The Regents Of The University Of Michigan | Small molecule inhibitors of MDM2 and the uses thereof |
| EP2103619A4 (en) | 2006-12-14 | 2011-11-23 | Daiichi Sankyo Co Ltd | IMIDAZOTHIAZOLDERIVATE |
| US7625895B2 (en) * | 2007-04-12 | 2009-12-01 | Hoffmann-Le Roche Inc. | Diphenyl-dihydro-imidazopyridinones |
| CA2701932C (en) * | 2007-10-09 | 2015-10-20 | F. Hoffmann-La Roche Ag | Chiral cis-imidazolines |
| WO2009070650A1 (en) * | 2007-11-26 | 2009-06-04 | The Research Foundation Of State University Of New York | Small molecule cancer treatments that cause necrosis in cancer cells but do not affect normal cells |
| WO2009151069A1 (ja) | 2008-06-12 | 2009-12-17 | 第一三共株式会社 | 4,7-ジアザスピロ[2.5]オクタン環構造を有するイミダゾチアゾール誘導体 |
| CN102356085A (zh) | 2009-01-16 | 2012-02-15 | 第一三共株式会社 | 具有脯氨酸环结构的咪唑并噻唑衍生物 |
| JP2013510860A (ja) | 2009-11-12 | 2013-03-28 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン | スピロ−オキシインドールmdm2アンタゴニスト |
| US10159669B2 (en) * | 2010-03-02 | 2018-12-25 | Ian H. Chan | Individual and combination of mdivi-1 and nutlin-3 for topical or intravitreal ophthalmic use |
| US20130225603A1 (en) * | 2010-09-27 | 2013-08-29 | Serrata Llc | Mdm2 inhibitors for treatment of ocular conditions |
| US9266860B2 (en) | 2010-09-30 | 2016-02-23 | St. Jude Children's Research Hospital | Aryl-substituted imidazoles |
| FR2967072B1 (fr) | 2010-11-05 | 2013-03-29 | Univ Dundee | Procede pour ameliorer la production de virus et semences vaccinales influenza |
| CA2817585A1 (en) | 2010-11-12 | 2012-05-18 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
| DK2684880T3 (en) | 2011-03-10 | 2018-05-22 | Daiichi Sankyo Co Ltd | DISPIROPYRROLIDINE DERIVATIVES |
| ES2624808T3 (es) | 2011-05-11 | 2017-07-17 | The Regents Of The University Of Michigan | Antagonistas de MDM2 espirooxindólicos |
| KR101384683B1 (ko) * | 2011-10-27 | 2014-04-11 | 한국생명공학연구원 | mdm2-결합 모티프를 포함하는 펩타이드 및 이의 용도 |
| CA2858565A1 (en) | 2011-12-07 | 2013-07-04 | Duke University | Methods of identifying and using mdm2 inhibitors |
| TWI586668B (zh) | 2012-09-06 | 2017-06-11 | 第一三共股份有限公司 | 二螺吡咯啶衍生物之結晶 |
| EP2935263B1 (en) | 2012-12-20 | 2018-12-05 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
| SG11201606239UA (en) | 2014-01-28 | 2016-08-30 | Buck Inst For Res On Aging | Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders |
| WO2015116735A1 (en) | 2014-01-28 | 2015-08-06 | Mayo Foundation For Medical Education And Research | Methods and combinations for killing senescent cells and for treating senescence-associated diseases and disorders |
| US10328058B2 (en) | 2014-01-28 | 2019-06-25 | Mayo Foundation For Medical Education And Research | Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques |
| US20190269675A1 (en) | 2014-01-28 | 2019-09-05 | Buck Institute for Research and Aging | Treatment of parkinson's disease and other conditions caused or mediated by senescent astrocytes using small molecule senolytic agents |
| TWI804010B (zh) * | 2015-08-03 | 2023-06-01 | 瑞士商諾華公司 | 作為血液學毒性生物標記之gdf-15 |
| JP7037500B2 (ja) | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Mdm2タンパク質分解剤 |
| AU2017246453A1 (en) | 2016-04-06 | 2018-11-08 | The Regents Of The University Of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
| CN118436801A (zh) | 2016-05-20 | 2024-08-06 | 豪夫迈·罗氏有限公司 | Protac抗体缀合物及其使用方法 |
| JP6848055B2 (ja) | 2017-06-16 | 2021-03-24 | ユニティ バイオテクノロジー インコーポレイテッド | 薬学的使用のための鏡像異性的に純粋なシス‐イミダゾリン化合物を生成するための合成方法 |
| WO2019195851A1 (en) | 2018-04-06 | 2019-10-10 | Oncolyze, Inc. | Compositions for use in lysis of selective cancer cells |
| MX2021003999A (es) | 2018-10-08 | 2021-06-23 | Univ Michigan Regents | Moleculas de bajo peso molecular degradadoras de la proteina mdm2. |
| IL296451B2 (en) | 2020-03-19 | 2026-05-01 | Kymera Therapeutics Inc | MDM2 joints and their uses |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1175431A (en) * | 1980-07-25 | 1984-10-02 | Alfred Sallmann | Tri-substituted imidazole derivatives, processes for their manufacture, pharmaceutical preparations containing them, and their use |
| JPH02101065A (ja) * | 1988-10-06 | 1990-04-12 | Tanabe Seiyaku Co Ltd | イミダゾリン誘導体及びその製法 |
| WO1992003421A2 (en) | 1990-08-17 | 1992-03-05 | E.I. Du Pont De Nemours And Company | Arthropodicidal pyrazolines, pyrazolidines and hydrazines |
| GB2351082A (en) * | 1999-06-18 | 2000-12-20 | Lilly Forschung Gmbh | Synthesis of Cyclic Substituted Amidines |
-
2002
- 2002-12-09 PL PL02370909A patent/PL370909A1/xx not_active Application Discontinuation
- 2002-12-09 MX MXPA04005880A patent/MXPA04005880A/es active IP Right Grant
- 2002-12-09 ES ES02796582T patent/ES2307822T3/es not_active Expired - Lifetime
- 2002-12-09 AU AU2002361986A patent/AU2002361986B2/en not_active Ceased
- 2002-12-09 CA CA002468783A patent/CA2468783A1/en not_active Abandoned
- 2002-12-09 CN CNA028252292A patent/CN1604778A/zh active Pending
- 2002-12-09 BR BR0215156-1A patent/BR0215156A/pt not_active IP Right Cessation
- 2002-12-09 DE DE60227108T patent/DE60227108D1/de not_active Expired - Lifetime
- 2002-12-09 EP EP02796582A patent/EP1463501B1/en not_active Expired - Lifetime
- 2002-12-09 AT AT02796582T patent/ATE397925T1/de not_active IP Right Cessation
- 2002-12-09 RU RU2004122404/04A patent/RU2312101C2/ru not_active IP Right Cessation
- 2002-12-09 JP JP2003552293A patent/JP4361798B2/ja not_active Expired - Fee Related
- 2002-12-09 KR KR1020047009612A patent/KR100640707B1/ko not_active Expired - Fee Related
- 2002-12-09 WO PCT/EP2002/013905 patent/WO2003051360A1/en not_active Ceased
- 2002-12-11 US US10/316,696 patent/US6617346B1/en not_active Expired - Fee Related
- 2002-12-13 PE PE2002001225A patent/PE20030717A1/es not_active Application Discontinuation
- 2002-12-17 AR ARP020104913A patent/AR037882A1/es not_active Application Discontinuation
- 2002-12-17 UY UY27586A patent/UY27586A1/es not_active Application Discontinuation
- 2002-12-17 PA PA20028561801A patent/PA8561801A1/es unknown
- 2002-12-18 TW TW091136524A patent/TW200301696A/zh unknown
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