CA2458699A1 - Novel dihydropteridinones, method for producing the same and the use thereof as medicaments - Google Patents
Novel dihydropteridinones, method for producing the same and the use thereof as medicaments Download PDFInfo
- Publication number
- CA2458699A1 CA2458699A1 CA002458699A CA2458699A CA2458699A1 CA 2458699 A1 CA2458699 A1 CA 2458699A1 CA 002458699 A CA002458699 A CA 002458699A CA 2458699 A CA2458699 A CA 2458699A CA 2458699 A1 CA2458699 A1 CA 2458699A1
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- alkyl
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- group selected
- optionally substituted
- cycloalkyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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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]
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention relates to novel dihydropteridinones of general formula (I), wherein the groups X, R1, R2, R3, R4, R5 and R7 are defined as per the claim s and the description, to the isomers thereof, to a method for producing said dihydropteridinones and to the use thereof as medicaments.
Claims (12)
1 ) Compounds of general formula (I), wherein R1 denotes a group selected from among hydrogen, NH2, XH, halogen and a C1-C3-alkyl group optionally substituted by one or more halogen atoms, R2 denotes a group selected from among hydrogen, CHO, XH, -X-C1-C2-alkyl and an optionally substituted C1-C3-alkyl group, R3, R4 which may be identical or different denote a group selected from among optionally substituted C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, aryl, heteroaryl, C3-C8-cycloalkyl, C3-C8-heterocycloalkyl, -X-aryl, -X-heteroaryl, -X-cycloalkyl, -X-heterocycloalkyl, -NR8-aryl, -NR8-heteroaryl, -NR8-cycloalkyl, - and -NR8-heterocycloalkyl, or a group selected from among hydrogen, halogen, COXR8, CON(R8)2, COR8 and XR8, or R3 and R4 together denote a 2- to 5-membered alkyl bridge which may contain 1 to 2 heteroatoms, R5 denotes hydrogen or a group selected from among optionally substituted C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, aryl, heteroaryl and -C3-C6-cycloalkyl , or R3 and R5 or R4 and R5 together denote a saturated or unsaturated C3-C4-alkyl bridge which may contain 1 to 2 heteroatoms, R6 denotes optionally substituted aryl or heteroaryl, R7 denotes hydrogen or -CO-X-C1-C4-alkyl, and X in each case independently of one another denotes O or S, R8 in each case independently of one another denotes hydrogen or a group selected from among optionally substituted C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl and phenyl, 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 according to claim 1, wherein X and R6 have the meaning indicated, and R1 denotes hydrogen, R2 denotes a group selected from among a CHO, OH, and CH3 group, R3, R4 which may be identical or different denote a group selected from among hydrogen, optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-cycloalkyl, or R3 and R4 together denote a C2-C5-alkyl bridge , R5 denotes a group selected from among optionally substituted C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C6-cycloalkyl and C3-C6-cycloalkenyl, or R3 and R5 or R4 and R5 together denote a saturated or unsaturated C3-C4-alkyl bridge which may contain 1 to 2 heteroatoms, and R7 denotes hydrogen, 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 or 2, wherein R1-R5, R7, R8 and X have the meaning indicated, and R6 denotes a group of general formula wherein n denotes 1, 2, 3 or 4, R9 denotes a group selected from among optionally substituted C1-C6-alkyl, C2-alkenyl, C2-C6-alkynyl, -CONH-C1-C10-alkylene, -O-aryl, -O-heteroaryl, -O-cycloalkyl, -O-heterocycloalkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl or a group selected from among -O-C1-C6-alkyl-Q1, -CONR8-C1-C10-alkyl-Q1, -CONR8-C2-C10-alkenyl-Q1, -CONR8-Q2, halogen, OH, -SO2R8, -SO2N(R8)2, -COR8, -COOR8,-N(R8)2, -NHCOR8, CONR8OC1-C10 alkylQ1 and CONR8OQ2, Q1 denotes hydrogen, -NHCOR8, or a group selected from among an optionally substituted -NH-aryl, -NH-heteroaryl, aryl, heteroaryl, C3-C8-cycloalkyl- and heterocycloalkyl group, Q2 denotes hydrogen or a group selected from among an optionally substituted aryl, heteroaryl, C3-C8-heterocycloalkyl, C3-C8-cycloalkyl- and C1-C4-alkyl-C3-cycloalkyl group, R10 which may be identical or different denotes a group selected from among optionally substituted C1-C6-alkyl , C2-C6-alkenyl and C2-C6-alkynyl, -O-C1-C6-alkyl, -O-C2-C6-alkenyl, -O-C2-C6-alkynyl, C3-C6-heterocycloalkyl and C2-C6-cycloalkyl, or a group selected from among hydrogen, -CONH2, -COOR8, -OCON(R8)2, -N(R8)2, -NHCOR8, -NHCON(R8)2 , -NO2 and halogen, or adjacent groups R9 and R10 together denote a bridge of general formula Y denotes O, S or NR11, m denotes 0, 1 or 2 R11 denotes hydrogen or C1-C2-alkyl, and R12 denotes hydrogen or a group selected from among optionally substituted phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, -C1-C3-alkyl-phenyl, -C1-C3-alkyl-pyridyl, -C1-C3-alkyl-pyrazinyl, -C1-C3-alkyl-pyrimidinyl and -C1-C3-alkyl-pyridazinyl, R13 denotes 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.
4) Compounds according to one of claims 1 to 3, wherein R3-R6, R8 and X have the meaning indicated, and R1 denotes hydrogen, R2 denotes CH3 , and R7 denotes hydrogen, 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) Compound of formula I according to one of claims 1 to 4 for use as pharmaceutical compositions.
6) Compound of formula I according to one of claims 1 to 4 for use as pharmaceutical compositions with an antiproliferative activity.
7) Use of a compound of formula I for preparing a pharmaceutical composition for the treatment and/or prevention of cancer, infections, inflammatory and autoimmune diseases.
8) 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.
9) 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.
10) Process for preparing a compound of general formula (I), wherein R1-R7 and X have the meanings given in claims 1 to 4, characterised in that a compound of general formula (II) wherein R1-R5 and X have the meanings given in claims 1 to 4 and L is a leaving group, is reacted with an optionally substituted compound of general formula (III) wherein R6 and R7 have the meanings given in claims 1 to 4.
11) Compound of formula (II), wherein R1-R5 and X have the meanings given in claims 1 to 4.
12) Process for preparing a compound of general formula (1), wherein R6 denotes a group of general formula, R9 denotes an optionally substituted group -CONH-C1-C10-alkylene or a group selected from among -CONR8-C1-C10-alkyl-Q1, -CONR8-C2-C10-alkenyl-Q1, -CONR8-Q2, and -COOR8, and R1-R5, R7, R10, n and X are as defined as in claims 1 to 4, characterised in that a compound of general formula (IA) wherein R1 to R5, R7, R10 and n are as defined as in claims 1 to 4, and L denotes a leaving group, is reacted with a primary or secondary amine to form the corresponding amide or is reacted with an alcohol to form the corresponding ester.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10143272.0 | 2001-09-04 | ||
| DE10143272 | 2001-09-04 | ||
| PCT/EP2002/009728 WO2003020722A1 (en) | 2001-09-04 | 2002-08-30 | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2458699A1 true CA2458699A1 (en) | 2003-03-13 |
| CA2458699C CA2458699C (en) | 2010-10-19 |
Family
ID=7697637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2458699A Expired - Lifetime CA2458699C (en) | 2001-09-04 | 2002-08-30 | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
Country Status (30)
| Country | Link |
|---|---|
| EP (1) | EP1427730B1 (en) |
| JP (1) | JP3876254B2 (en) |
| KR (1) | KR100955589B1 (en) |
| CN (1) | CN1551881A (en) |
| AR (1) | AR036586A1 (en) |
| AT (1) | ATE332898T1 (en) |
| AU (1) | AU2002337047B2 (en) |
| BR (1) | BRPI0212137A2 (en) |
| CA (1) | CA2458699C (en) |
| CO (1) | CO5560575A2 (en) |
| CY (1) | CY1105337T1 (en) |
| DE (1) | DE50207522D1 (en) |
| DK (1) | DK1427730T3 (en) |
| EA (1) | EA007062B1 (en) |
| EC (1) | ECSP045003A (en) |
| ES (1) | ES2268093T3 (en) |
| HR (1) | HRP20040213A2 (en) |
| HU (1) | HUP0401293A3 (en) |
| IL (2) | IL160440A0 (en) |
| MX (1) | MXPA04002067A (en) |
| MY (1) | MY129751A (en) |
| NO (1) | NO328804B1 (en) |
| NZ (1) | NZ531928A (en) |
| PL (1) | PL369740A1 (en) |
| PT (1) | PT1427730E (en) |
| RS (1) | RS51012B (en) |
| UA (1) | UA76512C2 (en) |
| UY (1) | UY27427A1 (en) |
| WO (1) | WO2003020722A1 (en) |
| ZA (1) | ZA200401365B (en) |
Cited By (43)
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| WO2008051493A3 (en) * | 2006-10-19 | 2008-07-03 | Signal Pharm Llc | Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors |
| US7414053B2 (en) | 2004-08-25 | 2008-08-19 | Boehringer Ingelheim International Gmbh | Dihydropteridione derivatives, process for their manufacture and their use as medicament |
| US7439358B2 (en) | 2006-02-08 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Specific salt, anhydrous and crystalline form of a dihydropteridione derivative |
| US7547780B2 (en) | 2004-08-25 | 2009-06-16 | Boehringer Ingelheim International Gmbh | Dihydropteridione intermediate compounds |
| US20100099680A1 (en) * | 2007-02-01 | 2010-04-22 | Boehringer Ingelheim International Gmbh | Pteridinone derivatives as p13-kinases inhibitors |
| 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 |
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| US8445675B2 (en) | 2004-08-14 | 2013-05-21 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
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