JP2006523202A - 生体還元により活性化されるプロドラッグ - Google Patents
生体還元により活性化されるプロドラッグ Download PDFInfo
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- JP2006523202A JP2006523202A JP2006506035A JP2006506035A JP2006523202A JP 2006523202 A JP2006523202 A JP 2006523202A JP 2006506035 A JP2006506035 A JP 2006506035A JP 2006506035 A JP2006506035 A JP 2006506035A JP 2006523202 A JP2006523202 A JP 2006523202A
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- Prior art keywords
- unsubstituted
- alkyl
- group
- alkoxy
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229940002612 prodrug Drugs 0.000 title description 27
- 239000000651 prodrug Substances 0.000 title description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 135
- -1 morpholino, piperidino, piperazino Chemical group 0.000 claims abstract description 94
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 50
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
- 231100000433 cytotoxic Toxicity 0.000 claims abstract description 18
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 16
- 239000000824 cytostatic agent Substances 0.000 claims abstract description 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
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- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 13
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- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
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- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 6
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- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 3
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- 150000003893 lactate salts Chemical class 0.000 description 1
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- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- WFFQYWAAEWLHJC-UHFFFAOYSA-N mercaptopurine hydrate Chemical compound O.S=C1NC=NC2=C1NC=N2 WFFQYWAAEWLHJC-UHFFFAOYSA-N 0.000 description 1
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- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
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- OHNBINDOZFVTHK-UHFFFAOYSA-N n-[2-[3-[2-(5-nitrothiophen-2-yl)propan-2-yloxy]phenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=CC(OC(C)(C)C=2SC(=CC=2)[N+]([O-])=O)=C1 OHNBINDOZFVTHK-UHFFFAOYSA-N 0.000 description 1
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- 231100000587 neutral red assay Toxicity 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004999 nitroaryl group Chemical group 0.000 description 1
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 description 1
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- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 1
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- RJXQSIKBGKVNRT-UHFFFAOYSA-N phosphoramide mustard Chemical compound ClCCN(P(O)(=O)N)CCCl RJXQSIKBGKVNRT-UHFFFAOYSA-N 0.000 description 1
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- 229920000642 polymer Polymers 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
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- 230000001185 psoriatic effect Effects 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
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- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
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- 239000008174 sterile solution Substances 0.000 description 1
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- QULKDBMYSOOKMH-UHFFFAOYSA-N sulfo hydrogen carbonate Chemical compound OC(=O)OS(O)(=O)=O QULKDBMYSOOKMH-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/42—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
- C07D473/38—Sulfur atom attached in position 6
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0306907.7A GB0306907D0 (en) | 2003-03-26 | 2003-03-26 | Boireductively-activated prodrugs |
| PCT/GB2004/001330 WO2004085421A2 (en) | 2003-03-26 | 2004-03-26 | Bioreductively-activated prodrugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006523202A true JP2006523202A (ja) | 2006-10-12 |
| JP2006523202A5 JP2006523202A5 (https=) | 2007-05-24 |
Family
ID=9955527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006506035A Pending JP2006523202A (ja) | 2003-03-26 | 2004-03-26 | 生体還元により活性化されるプロドラッグ |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20070099871A1 (https=) |
| EP (1) | EP1613612A2 (https=) |
| JP (1) | JP2006523202A (https=) |
| CN (1) | CN1791591A (https=) |
| AU (1) | AU2004224070A1 (https=) |
| CA (1) | CA2519901A1 (https=) |
| GB (1) | GB0306907D0 (https=) |
| WO (1) | WO2004085421A2 (https=) |
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| EP2186811A1 (en) | 2002-08-23 | 2010-05-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CN1720332A (zh) * | 2002-10-03 | 2006-01-11 | 洛桑生态综合技术联合公司 | O6－烷基鸟嘌呤－dna烷基转移酶的底物 |
| ZA200507752B (en) | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
| GB0421296D0 (en) * | 2004-09-24 | 2004-10-27 | Angiogene Pharm Ltd | Bioreductively-activated prodrugs |
| EP1831225A2 (en) | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| EP1896040B1 (en) | 2005-06-29 | 2012-08-01 | Threshold Pharmaceuticals, Inc. | Phosphoramidate alkylator prodrugs |
| WO2007114926A2 (en) | 2006-04-04 | 2007-10-11 | The Regents Of The University Of California | Kinase antagonists |
| ES2884044T3 (es) | 2006-12-26 | 2021-12-10 | Immunogenesis Inc | Profármaco alquilante de fosforamidato para el tratamiento del cáncer |
| GB2467670B (en) | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| MX2010007419A (es) | 2008-01-04 | 2010-11-12 | Intellikine Inc | Ciertas entidades quimicas, composiciones y metodos. |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| EP2252293B1 (en) * | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| BRPI0915231A2 (pt) * | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| EP2358720B1 (en) | 2008-10-16 | 2016-03-02 | The Regents of The University of California | Fused ring heteroaryl kinase inhibitors |
| US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| JP5789252B2 (ja) | 2009-05-07 | 2015-10-07 | インテリカイン， エルエルシー | 複素環式化合物およびその使用 |
| NZ598220A (en) | 2009-08-17 | 2014-02-28 | Intellikine Llc | Heterocyclic compounds and uses thereof |
| WO2011047048A1 (en) | 2009-10-14 | 2011-04-21 | Gemmus Pharma, Inc. | Combination therapy treatment for viral infections |
| WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
| CA2799579A1 (en) | 2010-05-21 | 2011-11-24 | Intellikine, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| JP2013545749A (ja) | 2010-11-10 | 2013-12-26 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環化合物及びその使用 |
| ES2637113T3 (es) | 2011-01-10 | 2017-10-10 | Infinity Pharmaceuticals, Inc. | Procedimientos para preparar isoquinolinonas y formas sólidas de isoquinolinonas |
| US9295673B2 (en) | 2011-02-23 | 2016-03-29 | Intellikine Llc | Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof |
| AR088218A1 (es) | 2011-07-19 | 2014-05-21 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos utiles como inhibidores de pi3k |
| HK1198443A1 (en) | 2011-07-19 | 2015-04-24 | 无限药品股份有限公司 | Heterocyclic compounds and uses thereof |
| MX2014002542A (es) | 2011-08-29 | 2014-07-09 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos. |
| CA2846496C (en) | 2011-09-02 | 2020-07-14 | The Regents Of The University Of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
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| CA2122036C (en) * | 1991-10-23 | 2002-09-17 | Gillian Anlezark | Bacterial nitroreductase for the reduction of cb 1954 and analogues thereof to a cytotoxic form |
| AU2001296215A1 (en) * | 2000-07-17 | 2002-01-30 | Oxi-Gene, Inc. | Efficient method of synthesizing combretastatin a-4 prodrugs |
| EP1351912A2 (en) * | 2000-12-21 | 2003-10-15 | Cancer Research Ventures Limited | Substituted stilbenes, their reactions and anticancer activity |
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| WO2002030922A2 (en) * | 2000-10-13 | 2002-04-18 | Shire Biochem Inc. | Dioxolane analogs for improved inter-cellular delivery |
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