AU2002306596B2 - Analogs of thalidomide as potential angiogenesis inhibitors - Google Patents
Analogs of thalidomide as potential angiogenesis inhibitors Download PDFInfo
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- AU2002306596B2 AU2002306596B2 AU2002306596A AU2002306596A AU2002306596B2 AU 2002306596 B2 AU2002306596 B2 AU 2002306596B2 AU 2002306596 A AU2002306596 A AU 2002306596A AU 2002306596 A AU2002306596 A AU 2002306596A AU 2002306596 B2 AU2002306596 B2 AU 2002306596B2
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- Prior art keywords
- pharmaceutically acceptable
- substituted
- compound
- alkyl
- hydrogen
- Prior art date
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
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| ES (1) | ES2338534T3 (enExample) |
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| US7629360B2 (en) * | 1999-05-07 | 2009-12-08 | Celgene Corporation | Methods for the treatment of cachexia and graft v. host disease |
| US6458810B1 (en) | 2000-11-14 | 2002-10-01 | George Muller | Pharmaceutically active isoindoline derivatives |
| AU2002253795B2 (en) * | 2000-11-30 | 2007-02-01 | The Children's Medical Center Corporation | Synthesis of 4-Amino-Thalidomide enantiomers |
| JP4361273B2 (ja) | 2001-02-27 | 2009-11-11 | アメリカ合衆国 | 潜在的な血管形成阻害剤としてのサリドマイド類似体 |
| US20100129363A1 (en) * | 2002-05-17 | 2010-05-27 | Zeldis Jerome B | Methods and compositions using pde4 inhibitors for the treatment and management of cancers |
| US7323479B2 (en) * | 2002-05-17 | 2008-01-29 | Celgene Corporation | Methods for treatment and management of brain cancer using 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-methylisoindoline |
| US7393862B2 (en) | 2002-05-17 | 2008-07-01 | Celgene Corporation | Method using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for treatment of certain leukemias |
| USRE48890E1 (en) | 2002-05-17 | 2022-01-11 | Celgene Corporation | Methods for treating multiple myeloma with 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione after stem cell transplantation |
| CN1668296A (zh) * | 2002-05-17 | 2005-09-14 | 细胞基因公司 | 使用选择性细胞因子抑制性药物用于治疗和控制癌症和其它疾病的方法及组合物 |
| US7968569B2 (en) * | 2002-05-17 | 2011-06-28 | Celgene Corporation | Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione |
| US8404717B2 (en) * | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes using lenalidomide |
| CN1713905A (zh) * | 2002-10-15 | 2005-12-28 | 细胞基因公司 | 用于治疗骨髓增生异常综合征的选择性细胞因子抑制药 |
| US8404716B2 (en) * | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
| US7189740B2 (en) | 2002-10-15 | 2007-03-13 | Celgene Corporation | Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes |
| US11116782B2 (en) | 2002-10-15 | 2021-09-14 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
| US20050203142A1 (en) * | 2002-10-24 | 2005-09-15 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
| US20040091455A1 (en) * | 2002-10-31 | 2004-05-13 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment and management of macular degeneration |
| US7563810B2 (en) * | 2002-11-06 | 2009-07-21 | Celgene Corporation | Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases |
| KR20090048520A (ko) | 2002-11-06 | 2009-05-13 | 셀진 코포레이션 | 암 및 다른 질환의 치료 및 관리를 위한 선택적 시토킨 억제 약물의 사용 방법 및 그 조성물 |
| US8034831B2 (en) * | 2002-11-06 | 2011-10-11 | Celgene Corporation | Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies |
| UA83504C2 (en) | 2003-09-04 | 2008-07-25 | Селджин Корпорейшн | Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione |
| US8952895B2 (en) | 2011-06-03 | 2015-02-10 | Apple Inc. | Motion-based device operations |
| CA2538864C (en) | 2003-09-17 | 2013-05-07 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Thalidomide analogs as tnf-alpha modulators |
| US20080027113A1 (en) * | 2003-09-23 | 2008-01-31 | Zeldis Jerome B | Methods of Using and Compositions Comprising Immunomodulatory Compounds for Treatment and Management of Macular Degeneration |
| US7612096B2 (en) * | 2003-10-23 | 2009-11-03 | Celgene Corporation | Methods for treatment, modification and management of radiculopathy using 1-oxo-2-(2,6-dioxopiperidin-3yl)-4-aminoisoindoline |
| US20050100529A1 (en) * | 2003-11-06 | 2005-05-12 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of asbestos-related diseases and disorders |
| US20070208057A1 (en) * | 2003-11-06 | 2007-09-06 | Zeldis Jerome B | Methods And Compositions Using Thalidomide For The Treatment And Management Of Cancers And Other Diseases |
| US20050143344A1 (en) * | 2003-12-30 | 2005-06-30 | Zeldis Jerome B. | Methods and compositions using immunomodulatory compounds for the treatment and management of central nervous system disorders or diseases |
| CA2560221C (en) * | 2004-03-22 | 2010-12-07 | Celgene Corporation | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of skin diseases or disorders |
| US20050222209A1 (en) * | 2004-04-01 | 2005-10-06 | Zeldis Jerome B | Methods and compositions for the treatment, prevention or management of dysfunctional sleep and dysfunctional sleep associated with disease |
| BRPI0418743A (pt) * | 2004-04-14 | 2007-09-18 | Celgene Corp | métodos de tratamento, prevenção ou controle de uma sìndrome mielodisplásica, de redução ou evitação de um efeito adverso associado com a administração de um segundo ingrediente ativo em um paciente sofrendo de uma sìndrome mielodisplásica, composição farmacêutica, forma de dosagem unitária única, e, kit |
| EA014429B1 (ru) * | 2004-04-14 | 2010-12-30 | Селджин Корпорейшн | Композиции, содержащие иммуномодулирующие соединения для лечения и управления течением миелодиспластических синдромов, и способы с их использованием |
| ZA200609226B (en) * | 2004-04-23 | 2008-06-25 | Celgene Corp | Methods of using and compositions comprising immuno-modulatory compounds for the treatment and management of pulmonary hypertension |
| CN101102771A (zh) * | 2004-11-23 | 2008-01-09 | 细胞基因公司 | 用免疫调节化合物治疗和控制中枢神经系统损伤的方法和组合物 |
| CN100383139C (zh) | 2005-04-07 | 2008-04-23 | 天津和美生物技术有限公司 | 可抑制细胞释放肿瘤坏死因子的哌啶-2，6-二酮衍生物 |
| US20060270707A1 (en) * | 2005-05-24 | 2006-11-30 | Zeldis Jerome B | Methods and compositions using 4-[(cyclopropanecarbonylamino)methyl]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione for the treatment or prevention of cutaneous lupus |
| US20080138295A1 (en) * | 2005-09-12 | 2008-06-12 | Celgene Coporation | Bechet's disease using cyclopropyl-N-carboxamide |
| US20070155791A1 (en) * | 2005-12-29 | 2007-07-05 | Zeldis Jerome B | Methods for treating cutaneous lupus using aminoisoindoline compounds |
| EP2004614B1 (en) | 2006-04-13 | 2016-10-19 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Tetrahalogenated compounds useful as inhibitors of angiogenesis |
| CL2007002218A1 (es) * | 2006-08-03 | 2008-03-14 | Celgene Corp Soc Organizada Ba | Uso de 3-(4-amino-1-oxo-1,3-dihidro-isoindol-2-il)-piperidina 2,6-diona para la preparacion de un medicamento util para el tratamiento de linfoma de celula de capa. |
| US8877780B2 (en) | 2006-08-30 | 2014-11-04 | Celgene Corporation | 5-substituted isoindoline compounds |
| US7893045B2 (en) | 2007-08-07 | 2011-02-22 | Celgene Corporation | Methods for treating lymphomas in certain patient populations and screening patients for said therapy |
| GB0914330D0 (en) | 2009-08-17 | 2009-09-30 | Univ Dublin City | A method of predicting response to thalidomide in multiple myeloma patients |
| RU2013115747A (ru) | 2010-09-09 | 2014-10-20 | ТРИФОЙЛИУМ АпС | Введение антиангиогенных агентов в дыхательные пути |
| US8877899B2 (en) | 2010-09-27 | 2014-11-04 | Morphosys Ag | Anti-CD38 antibody and lenalidomide or bortezomib for the treatment of multipe myeloma and NHL |
| EA035454B1 (ru) * | 2011-11-30 | 2020-06-18 | Ф.Хоффманн-Ля Рош Аг | Бициклические производные дигидроизохинолин-1-она |
| US8927725B2 (en) | 2011-12-02 | 2015-01-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Thio compounds |
| CA2900529A1 (en) | 2013-02-08 | 2014-08-14 | Institute For Myeloma & Bone Cancer Research | Improved diagnostic, prognostic, and monitoring methods for multiple myeloma, chronic lymphocytic leukemia, and b-cell non-hodgkin lymphoma |
| JP6778114B2 (ja) * | 2014-04-14 | 2020-10-28 | アルビナス・オペレーションズ・インコーポレイテッドＡｒｖｉｎａｓ Ｏｐｅｒａｔｉｏｎｓ， Ｉｎｃ． | イミド系タンパク質分解モジュレーター及び関連する使用方法 |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| EP4233870A3 (en) | 2014-05-28 | 2024-01-24 | Onco Tracker, Inc. | Anti-cancer effects of jak2 inhibitors in combination with thalidomide derivatives and glucocorticoids |
| KR102524920B1 (ko) | 2014-07-22 | 2023-04-25 | 아폴로믹스 인코포레이티드 | 항-pd-1 항체 |
| ES2987034T3 (es) | 2014-08-05 | 2024-11-13 | Apollomics Inc | Anticuerpos anti-PD-L1 |
| EP3925609B1 (en) | 2014-08-22 | 2025-07-30 | Celgene Corporation | Methods of treating multiple myeloma with immunomodulatory compounds in combination with antibodies |
| EP3313818B1 (en) | 2015-06-26 | 2023-11-08 | Celgene Corporation | Methods for the treatment of kaposi's sarcoma or kshv-induced lymphoma using immunomodulatory compounds, and uses of biomarkers |
| MX2018000999A (es) | 2015-07-24 | 2018-11-09 | Oncotracker Inc | Moduladores de gamma secretasa para el tratamiento de disfuncion del sistema inmunologico. |
| US11698369B2 (en) | 2016-01-12 | 2023-07-11 | Oncotracker, Inc. | Methods for monitoring immune status of a subject |
| ES2878156T3 (es) | 2016-05-30 | 2021-11-18 | Morphosys Ag | Métodos para predecir el beneficio terapéutico de una terapia anti-CD19 en pacientes |
| KR20190104528A (ko) | 2016-12-03 | 2019-09-10 | 주노 쎄러퓨티크스 인코퍼레이티드 | Car-t 세포들 투여를 결정하는 방법 |
| MA46961A (fr) | 2016-12-03 | 2019-10-09 | Juno Therapeutics Inc | Procédés de modulation de lymphocytes t modifiés par car |
| CN106806366B (zh) * | 2016-12-29 | 2020-02-11 | 兰州大学 | 一种异吲哚-1，3-二酮类化合物的新用途 |
| AU2018263887B2 (en) | 2017-05-01 | 2025-04-24 | Juno Therapeutics, Inc. | Combination of a cell therapy and an immunomodulatory compound |
| AU2018275894B2 (en) | 2017-06-02 | 2025-04-24 | Juno Therapeutics, Inc. | Articles of manufacture and methods for treatment using adoptive cell therapy |
| US11635435B2 (en) | 2017-06-13 | 2023-04-25 | Oncotracker, Inc. | Diagnostic, prognostic, and monitoring methods for solid tumor cancers |
| AU2018291032A1 (en) | 2017-06-29 | 2020-01-16 | Juno Therapeutics, Inc. | Mouse model for assessing toxicities associated with immunotherapies |
| KR20200086278A (ko) | 2017-10-18 | 2020-07-16 | 노파르티스 아게 | 선택적 단백질 분해를 위한 조성물 및 방법 |
| CN111511370A (zh) | 2017-11-01 | 2020-08-07 | 朱诺治疗学股份有限公司 | 对b细胞成熟抗原具有特异性的抗体和嵌合抗原受体 |
| US12031975B2 (en) | 2017-11-01 | 2024-07-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| WO2019109053A1 (en) | 2017-12-01 | 2019-06-06 | Juno Therapeutics, Inc. | Methods for dosing and for modulation of genetically engineered cells |
| WO2019118937A1 (en) | 2017-12-15 | 2019-06-20 | Juno Therapeutics, Inc. | Anti-cct5 binding molecules and methods of use thereof |
| IL282886B2 (en) | 2018-11-08 | 2025-07-01 | Juno Therapeutics Inc | Methods and combinations for T-cell therapy and modulation |
| JP2022513062A (ja) | 2018-11-16 | 2022-02-07 | ジュノー セラピューティクス インコーポレイテッド | Ｂ細胞悪性腫瘍を処置するために、操作されたｔ細胞を投薬する方法 |
| KR20210117260A (ko) | 2018-11-30 | 2021-09-28 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법을 사용한 치료방법 |
| JP7709378B2 (ja) | 2018-12-03 | 2025-07-16 | ダナ－ファーバー キャンサー インスティテュート，インコーポレイテッド | Ｈｅｌｉｏｓの低分子分解誘導剤および使用方法 |
| CN113365660A (zh) | 2019-01-29 | 2021-09-07 | 朱诺治疗学股份有限公司 | 对受体酪氨酸激酶样孤儿受体1(ror1)具特异性的抗体及嵌合抗原受体 |
| US20220251152A1 (en) | 2019-04-24 | 2022-08-11 | Novartis Ag | Compositions and methods for selective protein degradation |
| WO2020225196A1 (en) | 2019-05-03 | 2020-11-12 | Morphosys Ag | Anti-cd19 therapy in patients having a limited number of nk cells |
| IL317199A (en) | 2019-10-31 | 2025-01-01 | Morphosys Ag | Anti-CD19 therapy in combination with lenalidomide for the treatment of leukemia or lymphoma |
| WO2021084064A1 (en) | 2019-10-31 | 2021-05-06 | Morphosys Ag | Sequential anti-cd19 therapy |
| WO2023250400A1 (en) | 2022-06-22 | 2023-12-28 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
| EP4611798A1 (en) | 2022-11-02 | 2025-09-10 | Celgene Corporation | Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy |
| WO2025076472A1 (en) | 2023-10-06 | 2025-04-10 | Juno Therapeutics, Inc. | Combination therapies with a cell therapy expressing a gprc5d-targeting car and related methods and uses |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998003502A1 (en) * | 1996-07-24 | 1998-01-29 | Celgene Corporation | Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and method of reducing tnf-alpha levels |
| US6110941A (en) * | 1997-02-01 | 2000-08-29 | Gruenenthal Gmbh | Compounds analogous to thalidomide from the class comprising piperidine-2,6-diones |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2830991A (en) * | 1954-05-17 | 1958-04-15 | Gruenenthal Chemie | Products of the amino-piperidine-2-6-dione series |
| GB962857A (en) | 1961-12-04 | 1964-07-08 | Distillers Co Yeast Ltd | Process for the production of imides |
| GB1049283A (en) | 1962-04-14 | 1966-11-23 | Distillers Co Yeast Ltd | Substituted butyro-lactones and -thiolactones |
| US3320270A (en) * | 1963-10-08 | 1967-05-16 | Tri Kem Corp | Certain 2-acylimidothiazole compounds |
| US3314953A (en) * | 1964-03-16 | 1967-04-18 | Richardson Merrell Inc | 1-substituted-3-phthalimido-2, 5-dioxopyrrolidines |
| US3560495A (en) * | 1965-05-08 | 1971-02-02 | Ernst Frankus | 1-heterocyclic amino methyl or 1-heterocyclic hydrazino methyl-3-phthalimido or (3',6'-dithia-3',4',5',6'-tetrahydrophthalimido)-pyrrolidinediones-2,5 or piperidinediones-2,6 |
| IL25595A (en) | 1965-05-08 | 1971-01-28 | Gruenenthal Chemie | New history of cyclic amide compounds and process for the production of these compounds |
| GB1324718A (en) * | 1970-11-10 | 1973-07-25 | Nehezvegyipari Kutato Intezet | Phthalimido triazines |
| US4067718A (en) * | 1975-11-12 | 1978-01-10 | American Cyanamid Company | Method for controlling the relative stem growth of plants |
| US4291048A (en) * | 1978-07-06 | 1981-09-22 | Joseph Gold | Method of treating tumors and cancerous cachexia with L-tryptophan |
| DE3332633A1 (de) | 1983-09-09 | 1985-04-04 | Luitpold-Werk Chemisch-pharmazeutische Fabrik GmbH & Co, 8000 München | Substituierte carbonsaeurederivate, verfahren zu ihrer herstellung, und arzneimittel |
| GB9311281D0 (en) * | 1993-06-01 | 1993-07-21 | Rhone Poulenc Rorer Ltd | Novel composition of matter |
| HK1005188A1 (en) | 1991-04-17 | 1998-12-24 | Grunenthal Gmbh | New thalidomide derivatives, method of manufacture and use thereof in medicaments |
| US6096768A (en) * | 1992-01-28 | 2000-08-01 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| US5629327A (en) * | 1993-03-01 | 1997-05-13 | Childrens Hospital Medical Center Corp. | Methods and compositions for inhibition of angiogenesis |
| US20010056114A1 (en) * | 2000-11-01 | 2001-12-27 | D'amato Robert | Methods for the inhibition of angiogenesis with 3-amino thalidomide |
| US6228879B1 (en) * | 1997-10-16 | 2001-05-08 | The Children's Medical Center | Methods and compositions for inhibition of angiogenesis |
| US5434170A (en) * | 1993-12-23 | 1995-07-18 | Andrulis Pharmaceuticals Corp. | Method for treating neurocognitive disorders |
| US5443824A (en) | 1994-03-14 | 1995-08-22 | Piacquadio; Daniel J. | Topical thalidomide compositions for surface or mucosal wounds, ulcerations, and lesions |
| DE4422237A1 (de) | 1994-06-24 | 1996-01-04 | Gruenenthal Gmbh | Verwendung von Lactamverbindungen als pharmazeutische Wirkstoffe |
| US5789434A (en) * | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| JP3251796B2 (ja) * | 1994-12-28 | 2002-01-28 | 株式会社日本自動車部品総合研究所 | セラミック圧電材料 |
| US6429221B1 (en) | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
| RU2164514C2 (ru) | 1994-12-30 | 2001-03-27 | Селджин Корпорейшн | Имид/амидные простые эфиры, фармацевтическая композиция на их основе и способ снижения уровня фнока у млекопитающих |
| US5783605A (en) * | 1995-02-27 | 1998-07-21 | Kuo; Sheng-Chu | Helper inducers for differentiation therapy and chemoprevention of cancer |
| AUPN278795A0 (en) | 1995-05-05 | 1995-05-25 | Neumann, Gregory Carl Heinrich | Animated displays |
| US5728844A (en) | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
| CA2251060C (en) | 1996-04-09 | 2006-09-12 | Grunenthal Gmbh | Acylated n-hydroxy methyl thalidomide prodrugs with immunomodulator action |
| DE19613976C1 (de) * | 1996-04-09 | 1997-11-20 | Gruenenthal Gmbh | Thalidomid-Prodrugs mit immunmodulatorischer Wirkung |
| EP0914123A4 (en) | 1996-05-29 | 2000-10-11 | Prototek Inc | THALIDOMIDE PRODUCTS AND METHODS OF USING SAID PRODUCTS AS T CELL MODIFIERS |
| US5635517B1 (en) * | 1996-07-24 | 1999-06-29 | Celgene Corp | Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines |
| JPH10109975A (ja) | 1996-08-16 | 1998-04-28 | Ishihara Sangyo Kaisha Ltd | 医薬組成物 |
| US6429212B1 (en) * | 1996-08-16 | 2002-08-06 | Ishihara Sangyo Kaisha Ltd. | Medicinal composition |
| ES2313154T3 (es) | 1996-11-05 | 2009-03-01 | The Children's Medical Center Corporation | Composiciones que comprenden talodimina y dexametasona para el tratamiento de cancer. |
| CA2274958A1 (en) | 1996-12-13 | 1998-06-18 | Gerald Wayne Becker | Inhibitors of the enzymatic activity of psa |
| RU2108786C1 (ru) | 1997-09-15 | 1998-04-20 | Клавдия Степановна Евланенкова | Средство для лечения онкологических больных |
| DE19743968C2 (de) | 1997-10-06 | 2002-07-11 | Gruenenthal Gmbh | Intravenöse Applikationsform von Thalidomid zur Therapie immunologischer Erkrankungen |
| EP1091726A2 (en) | 1998-05-11 | 2001-04-18 | EntreMed, Inc. | Analogs of 2-phthalimidinoglutaric acid and their use as inhibitors of angiogenesis |
| JP2003505337A (ja) | 1998-05-15 | 2003-02-12 | アストラゼネカ アクチボラグ | サイトカインにより仲介される疾病を処置するためのベンズアミド誘導体 |
| DE19843793C2 (de) * | 1998-09-24 | 2000-08-03 | Gruenenthal Gmbh | Substituierte Benzamide |
| US20030013739A1 (en) * | 1998-12-23 | 2003-01-16 | Pharmacia Corporation | Methods of using a combination of cyclooxygenase-2 selective inhibitors and thalidomide for the treatment of neoplasia |
| DE50001522D1 (de) | 1999-03-31 | 2003-04-30 | Gruenenthal Gmbh | Stabile wässrige Lösung von 3-(1-oxo-1,3-dihydro-isoindol-2-yl)-piperidin-2,6-dion |
| US6310360B1 (en) * | 1999-07-21 | 2001-10-30 | The Trustees Of Princeton University | Intersystem crossing agents for efficient utilization of excitons in organic light emitting devices |
| US20010041716A1 (en) * | 1999-12-02 | 2001-11-15 | Laing Timothy J. | Compositions and methods for locally treating inflammatory diseases |
| WO2001074362A1 (en) | 2000-03-31 | 2001-10-11 | Celgene Corporation | Inhibition of cyclooxygenase-2 activity |
| US6458810B1 (en) * | 2000-11-14 | 2002-10-01 | George Muller | Pharmaceutically active isoindoline derivatives |
| AU2002253795B2 (en) | 2000-11-30 | 2007-02-01 | The Children's Medical Center Corporation | Synthesis of 4-Amino-Thalidomide enantiomers |
| JP4361273B2 (ja) | 2001-02-27 | 2009-11-11 | アメリカ合衆国 | 潜在的な血管形成阻害剤としてのサリドマイド類似体 |
| NZ531294A (en) | 2001-08-06 | 2005-11-25 | Childrens Medical Center | Synthesis and anti-tumor activity of nitrogen substituted thalidomide analogs |
| EP1336602A1 (en) | 2002-02-13 | 2003-08-20 | Giovanni Scaramuzzino | Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases |
| EP2105135B1 (en) | 2002-05-17 | 2014-10-22 | Celgene Corporation | Pharmaceutical compositions for treating cancer |
| CN100488959C (zh) | 2003-03-27 | 2009-05-20 | 天津和美生物技术有限公司 | 水溶性的酞胺哌啶酮衍生物 |
| EP1530570A2 (en) | 2003-06-03 | 2005-05-18 | Teva Pharmaceutical Industries Limited | CRISTALLINE ZIPRASIDONE HCl AND PROCESSES FOR PREPARATION THEREOF |
| WO2005016326A2 (en) | 2003-07-11 | 2005-02-24 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Analogs of thalidomide as potential angiogenesis inhibitors |
-
2002
- 2002-02-26 JP JP2002567927A patent/JP4361273B2/ja not_active Expired - Fee Related
- 2002-02-26 CA CA2439410A patent/CA2439410C/en not_active Expired - Fee Related
- 2002-02-26 ES ES02780964T patent/ES2338534T3/es not_active Expired - Lifetime
- 2002-02-26 EP EP02780964A patent/EP1389203B8/en not_active Expired - Lifetime
- 2002-02-26 AU AU2002306596A patent/AU2002306596B2/en not_active Ceased
- 2002-02-26 US US10/469,359 patent/US7320991B2/en not_active Expired - Fee Related
- 2002-02-26 AT AT02780964T patent/ATE450529T1/de not_active IP Right Cessation
- 2002-02-26 WO PCT/US2002/005868 patent/WO2002068414A2/en not_active Ceased
- 2002-02-26 DE DE60234585T patent/DE60234585D1/de not_active Expired - Lifetime
-
2007
- 2007-07-19 US US11/880,404 patent/US8716315B2/en not_active Expired - Fee Related
-
2009
- 2009-06-16 JP JP2009143087A patent/JP2009263376A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998003502A1 (en) * | 1996-07-24 | 1998-01-29 | Celgene Corporation | Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and method of reducing tnf-alpha levels |
| US6110941A (en) * | 1997-02-01 | 2000-08-29 | Gruenenthal Gmbh | Compounds analogous to thalidomide from the class comprising piperidine-2,6-diones |
Non-Patent Citations (1)
| Title |
|---|
| Teubert, U., Zwingenberger, K., Wnendt, S., Eger, K. Arch. Pharm. Pharm. Med. Chem 1998, 331, 7-12 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2338534T3 (es) | 2010-05-10 |
| CA2439410A1 (en) | 2002-09-06 |
| WO2002068414A3 (en) | 2002-10-17 |
| EP1389203B8 (en) | 2010-03-10 |
| EP1389203A2 (en) | 2004-02-18 |
| US8716315B2 (en) | 2014-05-06 |
| JP4361273B2 (ja) | 2009-11-11 |
| CA2439410C (en) | 2011-09-06 |
| JP2004523561A (ja) | 2004-08-05 |
| DE60234585D1 (enExample) | 2010-01-14 |
| US7320991B2 (en) | 2008-01-22 |
| US20040077685A1 (en) | 2004-04-22 |
| JP2009263376A (ja) | 2009-11-12 |
| WO2002068414A2 (en) | 2002-09-06 |
| EP1389203B1 (en) | 2009-12-02 |
| ATE450529T1 (de) | 2009-12-15 |
| US20070293519A1 (en) | 2007-12-20 |
| WO2002068414A8 (en) | 2010-02-25 |
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