CA2517020A1 - Dihydropteridinones, method for the production and use thereof in the form of drugs - Google Patents
Dihydropteridinones, method for the production and use thereof in the form of drugs Download PDFInfo
- Publication number
- CA2517020A1 CA2517020A1 CA002517020A CA2517020A CA2517020A1 CA 2517020 A1 CA2517020 A1 CA 2517020A1 CA 002517020 A CA002517020 A CA 002517020A CA 2517020 A CA2517020 A CA 2517020A CA 2517020 A1 CA2517020 A1 CA 2517020A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- denotes
- optionally
- cycloalkyl
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 3
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 239000003814 drug Substances 0.000 title 1
- 229940079593 drug Drugs 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims 14
- 229910052739 hydrogen Inorganic materials 0.000 claims 9
- 239000001257 hydrogen Substances 0.000 claims 9
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 5
- 125000005842 heteroatom Chemical group 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 4
- -1 piperazinylcarbonyl Chemical group 0.000 claims 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 3
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 150000002829 nitrogen Chemical group 0.000 claims 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 229920006395 saturated elastomer Polymers 0.000 claims 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 1
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000005592 polycycloalkyl group Polymers 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to new dihydropteridinones of general formula (I) (see formula I) wherein the groups L and R1- R5 have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropteridinones and the use thereof as pharmaceutical compositions.
Claims (12)
1) Compounds of general formula (I), wherein R1, R2 which may be identical or different, denote hydrogen or optionally substituted C1-C6-alkyl, or R1 and R2 together denote a 2- to 5-membered alkyl bridge which may contain 1 to 2 heteroatoms, R3 denotes hydrogen or a group selected from among optionally substituted C1-C12-alkyl, C2-C12-alkenyl, C2-C12-alkynyl and C6-C14-aryl, or a group selected from among optionally substituted and/or bridged C3-C12-cycloalkyl, C3-C12-cycloalkenyl, C7-C12-polycycloalkyl, C7-C12-polycycloalkenyl, C5-C12-spirocycloalkyl, C3-C12-heterocycloalkyl which contains 1 to 2 heteroatoms, and C3-C12-heterocycloalkenyl which contains 1 to 2 heteroatoms, or R1 and R3 or R2 and R3 together denote a saturated or unsaturated C3-C4-alkyl bridge which may contain 1 heteroatom, R4 denotes a group selected from among hydrogen, -CN, hydroxy, -NR6R7 and halogen, or a group selected from among optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C5-alkyloxy, C2-C5-alkenyloxy, C2-C5-alkynyloxy, C1-C6-alkylthio, C1-C6-alkylsulphoxo and C1-C6-alkylsulphonyl, L denotes a linker selected from among optionally substituted C2-C10-alkyl, C2-C10-alkenyl, C6-C14-aryl, -C2-C4-alkyl-C6-C14-aryl, -C6-C14-aryl-C1-C4-alkyl, optionally bridged C3-C12-cycloalkyl and heteroaryl which contains 1 or 2 nitrogen atoms, n denotes 0 or 1 m denotes 1 or 2 R5 denotes a group selected from among optionally substituted morpholinyl, piperidinyl, piperazinyl, piperazinylcarbonyl, pyrrolidinyl, tropenyl, R8-diketomethylpiperazinyl, sulphoxomorpholinyl, sulphonylmorpholinyl, thiomorpholinyl, -NR8R9 and azacycloheptyl, R6, R7 which may be identical or different, denote hydrogen or C1-C4-alkyl, and R8, R9 denote unsubstituted nitrogen substituents at R5, which may be identical or different, denote either hydrogen or a group selected from among C1-C6-alkyl, -C1-C4-alkyl-C3-C10-cycloalkyl, C3-C10-cycloalkyl, C6-C14-aryl, -C1-C4-alkyl-C6-C14-aryl, pyranyl, pyridinyl, pyrimidinyl, C1-C4-alkyloxycarbonyl, C6-C14-arylcarbonyl, C1-C4-alkylcarbonyl, C6-C14-arylmethyloxycarbonyl, C6-C14-arylsulphonyl, C1-C4-alkylsulphonyl and C6-C14-aryl-C1-C4-alkylsulphonyl, optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
2) Compounds of general formula (I), wherein R1 to R4, R6 and R7 are as hereinbefore defined, and L denotes a linker selected from among optionally substituted C2-C10-alkyl, C2-C10-alkenyl, C6-C14-aryl, -C2-C4-alkyl-C6-C14-aryl, -C6-C14-aryl-C1-C4-alkyl, optionally bridged C3-C12-cycloalkyl and heteroaryl which contains 1 or 2 nitrogen atoms n denotes 1 m denotes 1 or 2 R5 denotes a group which is bound to L via a nitrogen atom, selected from among optionally substituted morpholinyl, piperidinyl, R8-piperazinyl, pyrrolidinyl, tropenyl, R8-diketomethylpiperazinyl, sulphoxomorpholinyl, sulphonylmorpholinyl, thiomorpholinyl, -NR8R9 and azacycloheptyl, R8, R9 denote unsubstituted nitrogen substituents at R5, which may be identical or different, hydrogen or a group selected from among C1-C6-alkyl, -C1-C4-alkyl-C3-C10-cycloalkyl, C3-C10-cycloalkyl, C6-C14-aryl, -C1-C4-alkyl-C6-C14-aryl, pyranyl, pyridinyl, pyrimidinyl, C1-C4-alkyloxycarbonyl, C6-C14-arylcarbonyl, C1-C4-alkylcarbonyl, C6-C14-arylmethyloxycarbonyl, C6-C14-arylsulphonyl, C1-C4-alkylsulphonyl and C6-C14-aryl-C1-C4-alkylsulphonyl, optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
3) Compounds according to claim 1, wherein R1 to R4, R6 and R7 are as hereinbefore defined, L denotes a linker selected from among optionally substituted C2-C10-alkyl, C2-C10-alkenyl, C6-C14-aryl, -C2-C4-alkyl-C6-C14-aryl, -C6-C14-aryl-C1-C4-alkyl, optionally bridged C3-C12-cycloalkyl and heteroaryl which contains 1 or 2 nitrogen atoms n denotes 0 or 1 m denotes 1 or 2 R5 denotes a group which is bound to L via a carbon atom, selected from among R8 - piperidinyl, R8R9-piperazinyl, R8-pyrrolidinyl, R8-piperazinylcarbonyl, R8-tropenyl, R8-morpholinyl and R8-azacycloheptyl, and R8, R9 denote unsubstituted nitrogen substituents at R5, which may be identical or different, hydrogen or a group selected from among C1-C6-alkyl, -C1-C4-alkyl-C3-C10-cycloalkyl, C3-C10-cycloalkyl, C6-C14-aryl, -C1-C4-alkyl-C6-C14-aryl, pyranyl, pyridinyl, pyrimidinyl, C1-C4-alkyloxycarbonyl, C6-C14-arylcarbonyl, C1-C4-alkylcarbonyl, C6-C14-arylmethyloxycarbonyl, C6-C14-arylsulphonyl, C1-C4-alkylsulphonyl and C6-C14-aryl-C1-C4-alkylsulphonyl, optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
4) Compounds according to one of claims 1 to 3, wherein L, m, n and R3 to R9 are as hereinbefore defined, and R1, R2 which may be identical or different, denote a group selected from among hydrogen, Me, Et, Pr, or R1 and R2 together form a C2-C4-alkyl bridge, optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
5) Compounds according to one of claims 1 to 4, wherein R1, R2, m, n and R5 to R8 are as hereinbefore defined, and R3 denotes a group selected from among optionally substituted C1-C10-alkyl, C3-C7-cycloalkyl, C3-C6-heterocycloalkyl and C6-C14-aryl or R1 and R3 or R2 and R3 together denote a saturated or unsaturated C3-C4-alkyl bridge which may contain 1 to 2 heteroatoms, R4 denotes a group selected from among hydrogen, OMe, OH, Me, Et, Pr, OEt, NHMe, NH2, F, CL, Br, O-propargyl, O-butynyl, CN, SMe, NMe2, CONH2, ethynyl, propynyl, butynyl and allyl, and L denotes a linker selected from among optionally substituted phenyl, phenylmethyl, cyclohexyl and branched C1-C6-alkyl, optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
6) Compound of formula I according to one of claims 1 to 5 for use as a pharmaceutical composition.
7) Compound of formula I according to one of claims 1 to 5 for use as a pharmaceutical composition with an antiproliferative activity.
8) Use of a compound of formula I according to one of claims 1 to 5 for preparing a pharmaceutical composition for the treatment and/or prevention of cancer, infections, inflammatory and autoimmune diseases.
9) Method of treating and/or preventing cancer, infections, inflammatory and autoimmune diseases, characterised in that a patient is given an effective quantity of a compound of formula I according to claims 1 to 4.
10) Pharmaceutical preparations, containing as active substance one or more compounds of general formula (I) according to one of claims 1 to 4 or the physiologically acceptable salts thereof, optionally combined with conventional excipients and/or carriers.
11) Process for preparing a compound of general formula (I), wherein R1-R5,m ,n and L have the meanings given in claims 1 to 5, characterised in that a compound of general formula (II) wherein R1-R3 have the meanings given in claims 1 to 4 and A is a leaving group, is reacted with an optionally substituted compound of general formula (III), wherein R4 has the meanings given in claims 1 to 5 and R10 denotes OH, NH-L-R5, -O-methyl, -O-ethyl, and then optionally the product of general formula (IV) wherein R1 to R4 has the meanings given in claims 1 to 5 and R10 denotes OH, -NH-L-R5, -O-methyl or -O-ethyl, optionally after previous hydrolysis of the ester group -COR10, is reacted with an amine of general formula (V) NH2-L-R5m (V) wherein R5 has the meanings given in claims 1 to 5.
12) Compound of formula (II), wherein R1-R3 have the meanings given in claims 1 to 5 and A is a leaving group.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2003/001935 WO2004076454A1 (en) | 2003-02-26 | 2003-02-26 | Dihydropteridinones, method for the production and use thereof in the form of drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2517020A1 true CA2517020A1 (en) | 2004-09-10 |
| CA2517020C CA2517020C (en) | 2012-06-26 |
Family
ID=32921552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2517020A Expired - Fee Related CA2517020C (en) | 2003-02-26 | 2003-02-26 | Dihydropteridinones, method for the production and use thereof in the form of drugs |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP1599478B1 (en) |
| JP (1) | JP3876265B2 (en) |
| KR (1) | KR100983462B1 (en) |
| CN (2) | CN100537570C (en) |
| AT (1) | ATE361924T1 (en) |
| AU (1) | AU2003215591B2 (en) |
| BR (1) | BR0318145A (en) |
| CA (1) | CA2517020C (en) |
| CY (1) | CY1106752T1 (en) |
| DE (1) | DE50307267D1 (en) |
| DK (1) | DK1599478T3 (en) |
| EA (1) | EA008778B1 (en) |
| ES (1) | ES2287583T3 (en) |
| HK (1) | HK1089444A1 (en) |
| HR (1) | HRP20050735B1 (en) |
| IL (1) | IL170419A (en) |
| ME (1) | ME00376B (en) |
| MX (1) | MXPA05009068A (en) |
| NO (1) | NO332538B1 (en) |
| NZ (1) | NZ542498A (en) |
| PL (1) | PL226417B1 (en) |
| PT (1) | PT1599478E (en) |
| RS (1) | RS52386B (en) |
| SI (1) | SI1599478T1 (en) |
| TW (1) | TWI313600B (en) |
| UA (1) | UA80743C2 (en) |
| WO (1) | WO2004076454A1 (en) |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7414053B2 (en) | 2004-08-25 | 2008-08-19 | Boehringer Ingelheim International Gmbh | Dihydropteridione derivatives, process for their manufacture and their use as medicament |
| US7547780B2 (en) | 2004-08-25 | 2009-06-16 | Boehringer Ingelheim International Gmbh | Dihydropteridione intermediate compounds |
| US7709471B2 (en) | 2006-07-06 | 2010-05-04 | Astrazeneca Ab | Compounds |
| US7728134B2 (en) | 2004-08-14 | 2010-06-01 | Boehringer Ingelheim International Gmbh | Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament |
| US7750152B2 (en) | 2003-02-26 | 2010-07-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Intermediate compounds for making dihydropteridinones useful as pharmaceutical compositions and processes of making the same |
| US7759347B2 (en) | 2004-06-21 | 2010-07-20 | Boehringer Ingelheim International Gmbh | 2-benzylaminodihydropteridinones, process for their manufacture and use thereof as medicaments |
| US7759485B2 (en) | 2004-08-14 | 2010-07-20 | Boehringer Ingelheim International Gmbh | Process for the manufacture of dihydropteridinones |
| US8058270B2 (en) | 2004-08-14 | 2011-11-15 | Boehringer Ingelheim International Gmbh | Dihydropteridinones for the treatment of cancer diseases |
| USRE43115E1 (en) | 2004-12-02 | 2012-01-17 | Boehringer Ingelheim International Gmbh | Process for the manufacture of fused piperazin-2-one derivatives |
| CN101379064B (en) * | 2006-02-08 | 2012-01-25 | 贝林格尔·英格海姆国际有限公司 | Trihydrochloride forms of a dihydropteridinone derivative and processes for preparation |
| US8119655B2 (en) | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| US8143247B2 (en) | 2004-08-14 | 2012-03-27 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| US8193188B2 (en) | 2004-07-09 | 2012-06-05 | Boehringer Ingelheim International Gmbh | Methods of using pyridodihydropyrazinones |
| US8329695B2 (en) | 2007-08-03 | 2012-12-11 | Boehringer Ingelheim International Gmbh | Crystalline form of the free base N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7r)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)-6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide |
| US8410100B2 (en) | 2007-02-01 | 2013-04-02 | Boehringer Ingelheim International Gmbh | Pteridinone derivatives as PI3-kinases inhibitors |
| US8445675B2 (en) | 2004-08-14 | 2013-05-21 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
| US8546566B2 (en) | 2010-10-12 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Process for manufacturing dihydropteridinones and intermediates thereof |
| US9133199B2 (en) | 2007-09-28 | 2015-09-15 | Cyclacel Limited | Pyrimidine derivatives as protein kinase inhibitors |
| AU2012256410B2 (en) * | 2006-02-08 | 2016-04-28 | Boehringer Ingelheim International Gmbh | Trihydrochloride forms of a dihydropteridinone derivative and processes for preparation |
| US9358233B2 (en) | 2010-11-29 | 2016-06-07 | Boehringer Ingelheim International Gmbh | Method for treating acute myeloid leukemia |
| US9370535B2 (en) | 2011-05-17 | 2016-06-21 | Boehringer Ingelheim International Gmbh | Method for treatment of advanced solid tumors |
| US9867831B2 (en) | 2014-10-01 | 2018-01-16 | Boehringer Ingelheim International Gmbh | Combination treatment of acute myeloid leukemia and myelodysplastic syndrome |
| US9956225B2 (en) | 2013-07-26 | 2018-05-01 | Boehringer Ingelheim International Gmbh | Treatment of myelodysplastic syndrome |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1784406A1 (en) * | 2004-08-27 | 2007-05-16 | Boehringer Ingelheim International GmbH | Dihydropteridinones, process for their preparation and their use as drugs |
| US7713973B2 (en) | 2004-10-15 | 2010-05-11 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| JP2009515852A (en) | 2005-11-11 | 2009-04-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Combination therapy of cancer containing EGFR / HER2 inhibitor |
| WO2007095188A2 (en) | 2006-02-14 | 2007-08-23 | Vertex Pharmaceuticals Incorporated | Dihydrodiazepines useful as inhibitors of protein kinases |
| US20090312336A1 (en) * | 2006-05-19 | 2009-12-17 | Astrazeneca Ab | Dihydropteridine compounds as anti proliferative agents |
| MX2009003793A (en) | 2006-10-09 | 2009-12-14 | Takeda Pharmaceutical | Kinase inhibitors. |
| US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
| WO2008044045A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| ES2631003T3 (en) | 2006-10-19 | 2017-08-25 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, their compositions and methods of treatment with them |
| ATE497961T1 (en) | 2006-12-14 | 2011-02-15 | Vertex Pharma | COMPOUNDS SUITABLE AS PROTEIN KINASE INHIBITORS |
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