DK2183254T3 - Hæmmere af proteintyrosinkinaseaktivitet - Google Patents
Hæmmere af proteintyrosinkinaseaktivitet Download PDFInfo
- Publication number
- DK2183254T3 DK2183254T3 DK08800252.2T DK08800252T DK2183254T3 DK 2183254 T3 DK2183254 T3 DK 2183254T3 DK 08800252 T DK08800252 T DK 08800252T DK 2183254 T3 DK2183254 T3 DK 2183254T3
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- DK
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- alkyl
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- aryl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Claims (8)
- HÆMMERE AF PROTEINTYROSINKINASEAKTIVITET1. Forbindelse med formlen (I):og farmaceutisk acceptable salte deraf, og racemiske og scalemiske blandinger, diastereomerer og enantiomerer deraf, hvori D er udvalgt fra gruppen bestående af: (1) et 6-leddet heteroaromatisk ringsystem, furanyl, tetrahydropyridyl, thienyl eller pyrazolyl, som hver er substitueret med 1 eller 2 uafhængigt udvalgte R38-grupper, hvori hver R er uafhængigt udvalgt fra gruppen bestående af halo, -C(0)NR R , -C(0)0-(CH2)nNR36R39, -(CH2)jNR39(CH2)iS(0)j(C1-C6 alkyl), -(CH2)jNR39(CH2)R36, -C(0)(CH2)jNR39(CH2)nR36, -(CH2)nP(=0)(CrC6alkyl)2, -(CH2)jNR39CH2(CH2)nP(=0)(C1-C6alkyl)2, NRl3C(X1)NRl3-arylP(=OXC1-C.6alkyl)2, NR^CfX^NR13-hetemarylP( =0)(C.1-C6alkyl)2, -(CH2)jNR39(CH2)i[0(CH2)i]x(CH2)jR99, -(CH^NR^CH^SO^. 2)(CH2)1[0(CH2)i]j(CH2)j R" og -((Ή2),ΝΡ39(αΐ2)^100, hvori hvert j er et heltal der uafhængigt ligger i området fra 0 til 4, n er et heltal, der ligger i området fra 0 to 6, x er et heltal, der ligger i området fra 1-6, hvert i er et heltal, der uafhængigt ligger i området fra 1 til 3, og -(CH2)i og -(CH2)n-delene af de foregående R38-grupper valgfrit omfatter en carbon-carbon dobbelt- eller tripelbinding, hvor n er et heltal mellem 2 og 6; R36 er udvalgt fra gruppen bestående af H, -OH, C1-C6 alkyl, C3-C10 cycloalkyl, -(CII2)n(C6-Ci0 aryl), -(CII2)„(5-10-leddet heterocyclyl) og -(CH2)nA4R37, hvori hvert n er et heltal, der uafhængigt ligger i området fra 0 til 6, A4 er udvalgt fra gruppen bestående af O, S, SO og S02; og (2) imidazolyl substitueret med (VCealkyl og -(CH2)jNR39(CH2)nR36, hvori j er et heltal fra 0 til 4, n er et heltal fra 0 til 6, og R36 er -(CH2)n3OR37, hvori n3 er et heltal, der ligger i området fra 0 til 6, hvori R37 er CVC6 alkyl, og R39 er H; M erΖ er -0-; Ar er et 6-leddet aromatisk ringsystem, som er substitueret med 0 til 4 R2-grupper; og G erR37 er uafhængigt udvalgt fra H, -0-Ci-C6 alkyl, -O-C3-C10 cycloalkyl, -O-(CH2)n(C6-Ci0 aryl), -O-(CH2)n(5-10-leddet heterocyclyl), Q-Q alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, -0-(CH2)nA4-C1-C6 alkyl, -0-(CH2)nA4-C2-C6 alkenyl, -0-(CH2)nA4-C2-C6 alkynyl og -O-(CH2)nA4-C3-Ci0cycloalkyl; R39 er udvalgt fra gruppen bestående af H, -OH, Q-Q alkyl, -C(0)-Ci-C6alkyl, -S02-Ci-C6alkyl, -C(0)-0-Ci-C6alkyl-aryl og en beskyttende gruppe, der anvendes til at beskytte sekundære aminogrupper, med den forudsætning, at når R36 og R39 begge er forbundet med samme nitrogen, er R36 og R39 ikke begge bundet til nitrogenet direkte gennem et oxygen; R99 ved hver forekomst er uafhængigt udvalgt fra gruppen bestående af -H, halogen, trihalomethyl, -CN, -N02, -NH2, -OR3, -NR3R4, -S(O)0-2R3, -S(0)2NR3R3, -C(0)0R3, -C(0)NR3R3, -N(R3)S02R3, -N(R3)C(0)R3, -N(R3)C02R3, P(=0)(0H)2, -P(=0)(Ci-C6alkyl)2, -SO3H, -C(0)R3, C1-C4 alkoxy, C1-C4 alkylthio, -O(CH2)0_6aryl, -O(CH2)0-6heteroaryl, -(CH2)0. 5(aryl), -(CH2)0-5(heteroaryl), Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CH2(CH2)0-4-T2; R100 er en 12 til 24-leddet heteroalicyclicsk macrocyclus indeholdende 4 til 8 oxygenatomer; R2 ved hver forekomst er uafhængigt udvalgt fra gruppen bestående af -H, halogen, trihalomethyl, -CN, -N02, -NH2, -OR3, -NR3R4, -S(O)0.2R3, -S(0)2NR3R3, -C(0)0R3, -C(0)NR3R3, -N(R3)S02R3, -N(R3)C(0)R3, -N(R3)C02R3, -C(0)R3, C1-C4 alkoxy, CrC4 alkylthio, -O(CH2)0-6aryl, -O(CH2)0-6heteroaryl, -(CH2)o-5(aryl), -(CH2)0-5(heteroaryl), Ci-C6 alkyl, C2-Cé alkenyl, C2-Ce alkynyl, -CH2(CH2)0-4-T2; T2 er uafhængigt udvalgt fra gruppen bestående af -OH, -OMe, -OEt, -NH2, -NHMe, -NMe2, -NHEt og -NEt2; hver R3 er uafhængigt udvalgt fra gruppen bestående af -H og R4; R4 er udvalgt fra gruppen bestående af en (C|-C6)alkyl, en aryl, en lavere arylalkyl, en heterocyclyl og en lavere helerocyclylalkyl, eller R3 og R4, tilsammen med et fælles nitrogen, hvormed de er forbundet, danner en fem- til syvleddet heterocyclyl, hvilken fem- til syvleddede heterocyclyl valgfrit indeholder mindst ét yderligere ringformet heteroatom udvalgt fra gruppen bestående af N, O, S og P; hver R13 uafhængigt er udvalgt fra gruppen bestående af -H, halogen, trihalomethyl, -CN, -N02, -NH2, -OR3, -NR3R4, -S(0)o-2R\ -S(0)2NR3R3, -C(0)OR\ -C(0)NR3R\ -N(R3)S02R\ -N(R3)C(0)R3, -N(R3)C02R3, -C(0)R3, -C(0)SR3, CrC4 alkoxy, Cx-C4 alkylthio, -O(CH2)0.6aryl, -O(CH2)0-6heteroaryl, (CH2)0_5(aryl), -(CH2)0-5(heteroaryl), (CH2)0-5(cycloalkyl), Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CH2(CH2)0-4-T2, Ci_4 alkylcarbonyl og en mættet eller umættet tre- til syvleddet carbocyclisk eller heterocyclisk gruppe; eller to R13, sammen med det atom eller de atomer, hvormed de er forbundet, kan kombineres, så de danner en heteroalicyclisk valgfrit substitueret med mellem tre og fire R60, hvori den heteroalicycliske kan have op til fire ringformede heteroatomer, og den heteroalicycliske kan have en aryl eller heteroaryl kondenseret dertil, i hvilket fald arylen eller heteroarylen er valgfrit substitueret med en yderligere en til fire R60; R60 er udvalgt fra gruppen bestående af -H, halogen, trihalomethyl, -CN, -N02, -NH2, -OR3, -NR3R4, -S(0)o-2R3, -S02NR3R3, -C02R3, -C(0)NR3R3, -N(R3)S02R3, -N(R3)C(0)R3, -N(R3)C02R3, -C(0)R3, (Ci^falkyl, aryl, heteroarylalkyl og arylalkyl; eller to R60, når forbundet med en ikke-aromatisk carbon, kan være oxo; Q er Ci-Cealkyl eller et tre- til tileddet ringsystem, valgfrit substitueret med mellem nul og fire R20; hver R20 uafhængigt er udvalgt fra gruppen bestående af -H, halogen, trihalomethyl, -O-trihalomethyl, oxo, -CN, -N02, -NH2, -OR3, -OCF3, -NR3R4, -S(O)0.2R3, -S(0)2NR3R3, -C(0)0R3, -C(0)NR3R3, -N(R3)S02R3, -N(R3)C(0)R3, -N(R3)C(0)0R3, -C(0)R3, -C(0)SR3, Q-C4 alkoxy, C1-C4 alkylthio, -0(CH2)o.6aryl, -O(CH2)0.6heteroaryl, -(CH2)0-5(aryl), -(CH2)0. 5(heteroaryl), Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CH2(CH2)0.4-T2, C44 alkylcarbonyl, Ci. 4 alkoxy, en amino valgfrit substitueret af Ci_4 alkyl valgfrit substitueret af C44 alkoxy og en mættet eller umættet tre- til syvleddet carbocyclisk eller heterocyclisk gruppe; X1 er udvalgt fra gruppen bestående af O, S, CH2, N-CN, N-O-alkyl, NH og N(C!-C6alkyl); og X3 og X4 hver uafhængigt er udvalgt fra gruppen bestående af -H, halogen, cyano, nitro, Ci-Ce alkyl, eller X3 og X4 sammen med det atom, hvormed de er forbundet, danner en C3-C4 cycloalkyl.
- 2. Forbindelse ifølge krav 1, hvori D er pyridinyl substitueret med 1 eller 2 valgfrit udvalgte R38-grupper.
- 3. Forbindelse ifølge krav 1, som har en af de følgende strukturer:
- 4. Forbindelse ifølge krav 3, som har en af de følgende strukturer:
- 5. Forbindelse ifølge krav 3, som har en af de følgende strukturer:
- 6. Forbindelse ifølge krav 3, som har en af de følgende strukturer:
- 7. Sammensætning omfattende en forbindelse ifølge et hvilket som helst af kravene 1 til 6 og en farmaceutisk acceptabel bærer.
- 8. Forbindelse ifølge et hvilket som helst af kravene 1 til 6 til anvendelse i en metode til behandling af en øjensygdom hos en patient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96867307P | 2007-08-29 | 2007-08-29 | |
| PCT/CA2008/001538 WO2009026717A1 (en) | 2007-08-29 | 2008-08-28 | Inhibitors of protein tyrosine kinase activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2183254T3 true DK2183254T3 (da) | 2017-09-11 |
Family
ID=40386626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK08800252.2T DK2183254T3 (da) | 2007-08-29 | 2008-08-28 | Hæmmere af proteintyrosinkinaseaktivitet |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US8404846B2 (da) |
| EP (1) | EP2183254B1 (da) |
| JP (1) | JP5656634B2 (da) |
| KR (1) | KR101556269B1 (da) |
| CN (3) | CN101932586A (da) |
| AR (1) | AR068066A1 (da) |
| AU (1) | AU2008293038B2 (da) |
| BR (1) | BRPI0816064B8 (da) |
| CA (1) | CA2697795C (da) |
| DK (1) | DK2183254T3 (da) |
| ES (1) | ES2635131T3 (da) |
| IL (1) | IL204192A (da) |
| MX (1) | MX2010002427A (da) |
| MY (1) | MY156536A (da) |
| PL (1) | PL2183254T3 (da) |
| RU (1) | RU2495044C2 (da) |
| TW (1) | TWI571468B (da) |
| WO (1) | WO2009026717A1 (da) |
| ZA (1) | ZA201001512B (da) |
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