RU2426729C2 - Ингибиторы митотического кинезина и способы их использования - Google Patents

Ингибиторы митотического кинезина и способы их использования Download PDF

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RU2426729C2
RU2426729C2 RU2007118632/04A RU2007118632A RU2426729C2 RU 2426729 C2 RU2426729 C2 RU 2426729C2 RU 2007118632/04 A RU2007118632/04 A RU 2007118632/04A RU 2007118632 A RU2007118632 A RU 2007118632A RU 2426729 C2 RU2426729 C2 RU 2426729C2
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Джереми ХАНС (US)
Джереми Ханс
Илай М. УОЛЛЕС (US)
Илай М. УОЛЛЕС
Квиан ЧЖАО (US)
Квиан ЧЖАО
Джозеф П. ЛИССИКАТОС (US)
Джозеф П. ЛИССИКАТОС
Том АЙЧЕР (US)
Том АЙЧЕР
Эллен ЛЭЙРД (US)
Эллен ЛЭЙРД
Джон РОБИНСОН (US)
Джон Робинсон
Шелли АЛЛЕН (US)
Шелли АЛЛЕН
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Эррэй Биофарма Инк.
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Abstract

Настоящее изобретение относится к новым соединениям формулы
Figure 00000169
а также к их разделенным энантиомерам, диастереомерам, рацемическим смесям и фармацевтически приемлемым солям, обладающим ингибиторной активностью в отношении митотического кинезина KSP и в отношении жизнедеятельности опухолевых клеток, к их применению для производства лекарственного средства и к фармацевтической композиции на их основе. В указанной формуле R является Z-NR2R3, Z-OH, Ar1 и Ar2 - независимо фенил, который является, при необходимости, замещенным одной или более группами, независимо выбранными из: F, Cl, Br, I, ОН, Z - алкилен, включающий от 1 до 6 атомов углерода, который является, при необходимости, замещенным С1-6алкилом, a R1 имеет значения, перечисленные в формуле изобретения. 3 н. и 13 з.п. ф-лы.

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Claims (16)

1. Соединение формулы
Figure 00000155

а также его разделенные энантиомеры, диастереомеры, рацемические смеси и фармацевтически приемлемые соли, где
R является Z-NR2R3, Z-OH;
R1 - С1-6алкил, замещенный при необходимости одной или более группами, выбранными независимо из С1-6алкила, фенила, -ORa, -OCH2C(=O)ORa, -NRbC(=O)Ra, -NRaRb; насыщенный С3-8циклоалкил; насыщенный гетероциклоалкил с количеством атомов от 5 до 6, в котором один или два кольцевых атома являются гетероатомами, выбранными из азота и кислорода; гетероарил, имеющий 6 атомов кольца и содержащий один гетероатом, выбранный из азота; -OR3; -NR4R5;
Ar1 и Ar2 - независимо фенил, где вышеуказанный фенил является при необходимости замещенным одной или более группами, независимо выбранными из F, Cl, Br, I, ОН;
R2 - водород, С1-6алкил;
R3 - водород, -C(=O)R4, С1-6алкил, где вышеуказанный С1-6алкил является при необходимости замещенным -ORa;
R4 и R5 - независимо H, ORa, С1-6алкил, насыщенный С3-8циклоалкил, гетероарил, имеющий 6 атомов кольца и содержащий один гетероатом, выбранный из азота, где вышеуказанный С1-6алкил является при необходимости замещенным -NRbC(=O)Ra или -ORa;
Ra - водород, С1-6алкил, где вышеуказанный C1-6алкил является при необходимости замещенным -NReRf;
Rb, Re, Rf - независимо являются водородом,
и
Z - алкилен, включающий от 1 до 6 атомов углерода, который является при необходимости замещенным С1-6алкилом.
2. Соединение по п.1, которое имеет формулу
Figure 00000156

где
Rx и Ry - независимо Н, С1-6алкил, насыщенный С3-8циклоалкил, где вышеуказанный С1-6алкил является при необходимости замещенным одной или несколькими группами, выбранными независимо из С1-6алкила, фенила, -OCH2C(=O)ORa, -NRbC(=O)Ra, -NRaRb.
3. Соединение по п.2, где по крайней мере один из Rx и Ry не является Н.
4. Соединение по п.3, где Ra является Н или С1-6алкилом.
5. Соединение по п.4, где Rx является С1-6алкилом.
6. Соединение по п.5, где R3 выбирают из водорода, С1-6алкила, где вышеуказанный С1-6алкил является при необходимости замещенным -ORa.
7. Соединение по п.1, где R4 и R5 независимо выбирают из Н, С1-6алкила, насыщенного С3-8циклоалкила, гетероарила, имеющего 6 атомов кольца и содержащего один гетероатом, выбранный из азота.
8. Соединение по п.1, имеющее следующие структуры
Figure 00000157

Figure 00000158

Figure 00000159

Figure 00000160

Figure 00000161

Figure 00000162
9. Соединение по п.1, имеющее структуру:
Figure 00000163

или его фармацевтически приемлемая соль.
10. Соединение по п.1, имеющее структуру:
Figure 00000164

или его фармацевтически приемлемая соль.
11. Соединение по п.1, имеющее структуру:
Figure 00000165

или его фармацевтически приемлемая соль.
12. Соединение по п.1, имеющее структуру:
Figure 00000166

или его фармацевтически приемлемая соль.
13. Соединение по п.1, имеющее структуру:
Figure 00000167

или его фармацевтически приемлемая соль.
14. Соединение по п.1, имеющее структуру:
Figure 00000168

или его фармацевтически приемлемая соль.
15. Применение соединения по любому из пп.1, 2, 8-14 для производства лекарственного средства, обладающего ингибиторной активностью в отношении митотического кинезина KSP, а также в отношении жизнедеятельности опухолевых клеток.
16. Фармацевтическая композиция, обладающая ингибиторной активностью в отношении митотического кинезина KSP, а также в отношении жизнедеятельности опухолевых клеток, содержащая эффективное количество соединения по любому из пп.1, 2, 8-14 в сочетании с фармацевтически приемлемым разбавителем или носителем.
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Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE480527T1 (de) * 2001-12-11 2010-09-15 Kyowa Hakko Kirin Co Ltd Thiadiazolinderivate zur krebsbehandlung
ATE537158T1 (de) 2003-04-18 2011-12-15 Kyowa Hakko Kirin Co Ltd M-stage-kinesin-inhibitor
US20070276017A1 (en) * 2003-06-10 2007-11-29 Chikara Murakata Thiadiazoline Derivative
US7723365B2 (en) * 2004-08-18 2010-05-25 Merck & Co., Inc. Mitotic kinesin inhibitors
US7449486B2 (en) * 2004-10-19 2008-11-11 Array Biopharma Inc. Mitotic kinesin inhibitors and methods of use thereof
JPWO2006101103A1 (ja) * 2005-03-22 2008-09-04 協和醗酵工業株式会社 造血器腫瘍治療剤
US20080194653A1 (en) * 2005-03-22 2008-08-14 Kyowa Hakko Kogyo Co., Ltd. Therapeutic Agent For Solid Tumor
UA95907C2 (en) 2005-05-02 2011-09-26 Эррей Биофарма Инк. Mitotic kinesin inhibitors and methods of use thereof
US7910611B2 (en) * 2005-06-24 2011-03-22 Kyowa Hakko Kirin Co., Ltd. Therapeutic agent for restenosis
EP2081918A2 (en) * 2006-10-03 2009-07-29 Array Biopharma, Inc. Mitotic kinesin inhibitors and methods of use thereof
WO2008070739A1 (en) * 2006-12-06 2008-06-12 Cytokinetics, Inc. Ksp activators
ES2565983T3 (es) * 2007-10-19 2016-04-08 Merck Sharp & Dohme Corp. Derivados de 1,3,4-tiadiazol espiro-condensados para inhibir la actividad quinesina de KSP
CL2008003062A1 (es) * 2007-11-09 2010-02-19 Schering Corp Compuestos derivados de pirazoles espiro conjugados, inhibidores de la actividad de ksp kinesina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de enfermedades proliferativas.
US9561214B2 (en) * 2008-10-16 2017-02-07 Array Biopharma Inc. Method of treatment using inhibitors of mitosis
PL2349259T3 (pl) * 2008-10-16 2016-07-29 Array Biopharma Inc Inhibitory mitozy do zwiększania apoptozy w terapii
US20120070370A1 (en) * 2009-05-13 2012-03-22 Siddiqui M Arshad Spiro 1,3,4-thiadiazoline derivatives as ksp inhibitors
KR101713452B1 (ko) 2010-03-12 2017-03-07 오메로스 코포레이션 Pde10 억제제 및 관련 조성물 및 방법
FR2991199B1 (fr) * 2012-05-30 2015-05-15 IFP Energies Nouvelles Procede de preparation d'un catalyseur mettant en oeuvre une etape de sechage rapide et son utilisation pour la synthese fischer-tropsch
MX2015002018A (es) 2012-08-13 2015-10-09 Array Biopharma Inc Arry-520 para uso en el tratamiento del cancer en un paciente con agg baja.
US20150045391A1 (en) 2013-08-08 2015-02-12 Array Biopharma Inc Filanesib combined with pomalidomide displays enhanced anti-tumor activity
DK3086814T3 (da) 2013-12-23 2020-09-14 Bayer Pharma AG Binder-konjugater (adcs) med ksp-inhibitorer
NZ716494A (en) 2014-04-28 2017-07-28 Omeros Corp Processes and intermediates for the preparation of a pde10 inhibitor
NZ716462A (en) 2014-04-28 2017-11-24 Omeros Corp Optically active pde10 inhibitor
US10485880B2 (en) 2014-12-15 2019-11-26 Bayer Pharma Aktiengesellschaft Antibody-drug conjugates (ADCs) of KSP inhibitors with aglycosylated anti-TWEAKR antibodies
JP2018513153A (ja) 2015-04-24 2018-05-24 オメロス コーポレーション Ｐｄｅ１０インヒビターならびに関連する組成物および方法
CN108025084A (zh) 2015-06-22 2018-05-11 拜耳医药股份有限公司 具有酶可裂解基团的抗体药物缀合物（adc）和抗体前药缀合物（apdc）
BR112017027811A2 (pt) * 2015-06-23 2018-08-28 Bayer Pharma AG conjugados específicos de inibidores de ksp
EP3313522A1 (de) 2015-06-23 2018-05-02 Bayer Pharma Aktiengesellschaft Antikörper-wirkstoff-konjugate (adcs) von ksp-inhibitoren mit anti-b7h3-antikörpern
WO2016207094A1 (de) 2015-06-23 2016-12-29 Bayer Pharma Aktiengesellschaft Antikörper-wirkstoff-konjugate (adcs) von ksp-inhibitoren mit anti-tweakr-antikörpern
WO2017079678A1 (en) 2015-11-04 2017-05-11 Omeros Corporation Solid state forms of a pde10 inhibitor
CN109310781A (zh) 2016-06-15 2019-02-05 拜耳制药股份公司 具有ksp抑制剂和抗-cd123-抗体的特异性抗体-药物-缀合物(adc)
CN110072556B (zh) 2016-12-21 2023-05-02 拜耳制药股份公司 具有ksp抑制剂的特异性抗体药物缀合物(adc)
AU2017380871A1 (en) 2016-12-21 2019-07-11 Bayer Aktiengesellschaft Antibody drug conjugates (ADCs) having enzymatically cleavable groups
SG11202012608VA (en) 2018-06-18 2021-02-25 Bayer Ag Binder/active agent conjugates directed against cxcr5, having enzymatically cleavable linkers and improved activity profile

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2702803A (en) * 1954-04-12 1955-02-22 Lilly Co Eli Substituted heterodiazoles
EP0217519B1 (en) * 1985-08-31 1992-02-05 FISONS plc 5-membered heterocyclic ring angiotensin converting enzyme inhibitors
US4762072A (en) * 1986-10-07 1988-08-09 Westinghouse Electric Corp. Desk and space dividing wall panel assembly
GB8625774D0 (en) 1986-10-28 1986-12-03 Reckitt & Colmann Prod Ltd Thiadiazole derivative
JPH0572686A (ja) 1991-09-11 1993-03-26 Konica Corp ハロゲン化銀写真感光材料
WO1993022311A1 (en) 1992-04-27 1993-11-11 E.I. Du Pont De Nemours And Company Fungicidal 1,3,4-oxadiazines and 1,3,4-thiadiazines
US6159938A (en) * 1994-11-21 2000-12-12 Cortech, Inc. Serine protease inhibitors comprising α-keto heterocycles
JPH10513443A (ja) * 1995-02-02 1998-12-22 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー ５ＨＴ▲下２ｃ▼レセプターアンタゴニスト活性を有する複素環化合物
US5958957A (en) * 1996-04-19 1999-09-28 Novo Nordisk A/S Modulators of molecules with phosphotyrosine recognition units
US5668159A (en) * 1996-05-08 1997-09-16 The Dupont Merck Pharmaceutical Company 1,3,4-thiadiazoles and 1,3,4-oxadiazoles as IIb/IIIa antagonists
HRP980093A2 (en) 1997-02-28 1998-12-31 Lilly Co Eli Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting "beta"-amyloid peptide release and/or its synthesis by use of such compounds
PT1045839E (pt) * 1997-12-16 2004-07-30 Warner Lambert Co Novas aminas como agentes farmaceuticos
US6235762B1 (en) * 1998-11-23 2001-05-22 American Cyanamid Company 2-aryl-Δ2-1,3,4-(oxa and thia)diazoline insecticidal and acaricidal agents
JP2000159756A (ja) 1998-11-23 2000-06-13 American Cyanamid Co ２―アリ―ル―δ２―１，３，４―（オキサおよびチア）ジアゾリン殺虫および殺ダニ剤
IL144215A0 (en) * 1999-01-13 2002-05-23 Warner Lambert Co 1-heterocycle substituted diarylamines
US6281217B2 (en) * 1999-03-25 2001-08-28 Dingwei Tim Yu Class of piperazino substituted thiazoles
US6545004B1 (en) * 1999-10-27 2003-04-08 Cytokinetics, Inc. Methods and compositions utilizing quinazolinones
AU2001234741A1 (en) 2000-02-04 2001-08-14 Biogen, Inc. Integrin antagonists
EP1419770A4 (en) * 2001-08-24 2005-08-03 Shionogi & Co AGENT ACC L RATION OF THE EXPRESSION OF APO AI
ATE480527T1 (de) 2001-12-11 2010-09-15 Kyowa Hakko Kirin Co Ltd Thiadiazolinderivate zur krebsbehandlung
DE60329990D1 (de) 2002-03-08 2009-12-24 Merck & Co Inc Mitotische kinesin-hemmer
AU2003246551A1 (en) 2002-06-25 2004-01-06 Dieter Borner Assembly for recording the use of rds radio receivers
US7294643B2 (en) * 2002-11-22 2007-11-13 Board Of Regents, The University Of Texas System UK-1 analogues: methods of preparation and use
US20050004186A1 (en) 2002-12-20 2005-01-06 Pfizer Inc MEK inhibiting compounds
US20040167188A1 (en) * 2003-02-14 2004-08-26 Zhili Xin Protein-tyrosine phosphatase inhibitors and uses thereof
ATE537158T1 (de) 2003-04-18 2011-12-15 Kyowa Hakko Kirin Co Ltd M-stage-kinesin-inhibitor
US7326790B2 (en) * 2003-05-02 2008-02-05 Rigel Pharmaceuticals, Inc. Diphenylisoxazole compounds and hydro isomers thereof
US7115642B2 (en) * 2003-05-02 2006-10-03 Rigel Pharmaceuticals, Inc. Substituted diphenyl isoxazoles, pyrazoles and oxadiazoles useful for treating HCV infection
US20050075375A1 (en) * 2003-05-14 2005-04-07 Anadys Pharmaceuticals, Inc. Heterocyclic compounds for treating hepatitis C virus
MXPA05012281A (es) * 2003-05-14 2006-05-19 Torreypines Therapeutics Inc Compuestos y uso de los mismos en la modulacion beta amiloide.
US20050009877A1 (en) * 2003-05-15 2005-01-13 Henry Lu Methods of identifying HCV NS5B polymerase inhibitors and their uses
US7220745B2 (en) 2003-05-15 2007-05-22 Rigel Pharmaceuticals Heterocyclic compounds useful to treat HCV
US20070276017A1 (en) 2003-06-10 2007-11-29 Chikara Murakata Thiadiazoline Derivative
WO2004111023A1 (ja) 2003-06-10 2004-12-23 Kyowa Hakko Kogyo Co., Ltd. チアジアゾリン－１－オキシド誘導体
EP1671957A4 (en) * 2003-10-10 2007-03-14 THIADIAZOLINDERIVATE
JP2005232016A (ja) 2004-02-17 2005-09-02 Kyowa Hakko Kogyo Co Ltd オキサジアゾリン誘導体
GB0406867D0 (en) 2004-03-26 2004-04-28 F2G Ltd Antifungal agents
US7723365B2 (en) 2004-08-18 2010-05-25 Merck & Co., Inc. Mitotic kinesin inhibitors
US7449486B2 (en) 2004-10-19 2008-11-11 Array Biopharma Inc. Mitotic kinesin inhibitors and methods of use thereof
FR2876586B1 (fr) 2004-10-20 2007-10-12 Persee Medica Composition pour prevenir ou traiter le stress, notamment les bouffees de stress chronique et permanent
JP2008150291A (ja) * 2005-03-22 2008-07-03 Kyowa Hakko Kogyo Co Ltd 乾癬治療剤
US20080194653A1 (en) * 2005-03-22 2008-08-14 Kyowa Hakko Kogyo Co., Ltd. Therapeutic Agent For Solid Tumor
JP2008137893A (ja) * 2005-03-22 2008-06-19 Kyowa Hakko Kogyo Co Ltd 関節炎治療剤
JPWO2006101103A1 (ja) * 2005-03-22 2008-09-04 協和醗酵工業株式会社 造血器腫瘍治療剤
JP2006265107A (ja) * 2005-03-22 2006-10-05 Kyowa Hakko Kogyo Co Ltd 緑内障治療剤
UA95907C2 (en) 2005-05-02 2011-09-26 Эррей Биофарма Инк. Mitotic kinesin inhibitors and methods of use thereof
US7910611B2 (en) * 2005-06-24 2011-03-22 Kyowa Hakko Kirin Co., Ltd. Therapeutic agent for restenosis
EP2081918A2 (en) 2006-10-03 2009-07-29 Array Biopharma, Inc. Mitotic kinesin inhibitors and methods of use thereof
TWI411395B (zh) 2007-12-24 2013-10-11 Syngenta Participations Ag 殺蟲化合物
US9561214B2 (en) 2008-10-16 2017-02-07 Array Biopharma Inc. Method of treatment using inhibitors of mitosis
MX2015002018A (es) 2012-08-13 2015-10-09 Array Biopharma Inc Arry-520 para uso en el tratamiento del cancer en un paciente con agg baja.
US20150045391A1 (en) 2013-08-08 2015-02-12 Array Biopharma Inc Filanesib combined with pomalidomide displays enhanced anti-tumor activity

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