DK2086972T3 - Forbindelser, som modulerer c-fms-og/eller c-kit-aktivitet, og anvendelser hertil - Google Patents
Forbindelser, som modulerer c-fms-og/eller c-kit-aktivitet, og anvendelser hertil Download PDFInfo
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- DK2086972T3 DK2086972T3 DK07864681.7T DK07864681T DK2086972T3 DK 2086972 T3 DK2086972 T3 DK 2086972T3 DK 07864681 T DK07864681 T DK 07864681T DK 2086972 T3 DK2086972 T3 DK 2086972T3
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- pyridin
- ylmethyl
- pyrrolo
- chloro
- amine
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Claims (16)
1. Forbindelse med den kemiske struktur af formel III
eller et salt, en tautomer eller stereoisomer deraf, hvor: l_4 er -CH2-, -CH2CH2-, -CH(R40)-, -C(O)- eller -C(0)NH-; R81 er chlor; R82 er udvalgt fra gruppen, bestående af hydrogen, C-i-3 alkyl, fluor-substitueret C2.3 alkyl, OH, C-1-3 alkoxy og fluor-substitueret C-1-3 alkoxy; R83 er heterocykloalkyl, heteroaryl, eller
indikerer bindingspunktet af R83 til L4 af formel III, hvor heterocykloalkyl eller heteroaryl eventuelt er substitueret med en eller flere substituenter, udvalgt fra gruppen, bestående af halogen, alkyl, fluor-substitueret alkyl, cycloalkylamino, -NHR41, -NR41R41, -OR41 og -S(0)2R41; R92, R93, R94, R95, og R96 uafhængigt er udvalgt fra gruppen, bestående af hydrogen, halogen, alkyl, fluor-substitueret Ci-6 alkyl, cycloalkylamino, -NHS(0)2R41, -NHC(0)R41, -NHR41, -NR41R41, -OR41 og -S(0)2R41; R40 er udvalgt fra gruppen, bestående af Ci-6 alkyl og fluor-substitueret Ci-6 al kyl; R41 ved hver forekomst uafhængigt er udvalgt fra gruppen, bestående af Ci-6 alkyl, cycloalkyl, heterocycloalkyl, aryl og heteroaryl, hvor Ci-6 alkyl eventuelt er substitueret med en eller flere substituenter, der er udvalgt fra gruppen, bestående af fluor, C^e alkoxy, fluor-substitueret Ci-6 alkoxy, Ci-6 alkylthio, fluor-substitueret alkylthio, mono-alkylamino, di-alkylamino, cycloalkyl, heterocycloalkyl, aryl og heteroaryl, og hvor cycloalkyl, heterocycloalkyl, aryl og heteroaryl som R41 eller som substituenter af Ci-6 alkyl eventuelt er substi tueret med en eller flere substituenter, der er udvalgt fra gruppen, bestående af -OH, -NH2, -CN, -N02j -S(0)2NH2, -C(0)NH2j -OR42, -SR42, -NHR42, -NR42R42, -NR39C (O)R42, -NR39S(0)2R42, -S(0)2R42, halogen, alkyl, fluor-substitueret C1-6 alkyl og cycloalkylamino; og R42 ved hver forekomst uafhængigt er udvalgt fra gruppen, bestående af C^e alkyl, heterocykloalkyl og heteroaryl, hvor Ci-6 alkyl eventuelt er substitueret med en eller flere substituenter, udvalgt fra gruppen, bestående af fluor, C-i-6 alkoxy, fluor-substitueret Ci-6 alkoxy, Ci-6 alkylthio, fluor-substitueret Ci-6 al-kylthio, mono-alkylamino, di-alkylamino og cycloalkylamino, og hvor hetero-cycloalkyl og heteroaryl eventuelt er substitueret med en eller flere substituenter, udvalgt fra gruppen, bestående af halogen, -CN, Ci-6 alkyl, fluorsubstitueret C-i-6 alkyl, Ci-6 alkoxy og fluor-substitueret Ci-6 alkoxy; dog under forudsætning af, at forbindelsen ikke er
2. Forbindelse ifølge krav 1, hvilken forbindelse er udvalgt fra gruppen, bestående af: (3-chlor-pyridin-4-ylmethyl)-[5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)- pyridin-2-yl]-amin, propan-1 -sulfonsyre (3-{[5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]-methyl}-2,4-difluor-phenyl)-amid, [5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-methoxy-pyridin-3-ylmethyl)-amin, (2-chlor-benzyl)-[5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]- amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-fluor-benzyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluormethyl-pyridin-3-ylmethyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-trifluormethyl-benzyl)-amin, [5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2,6-difluor- benzyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2,5-difluor-benzyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(5-fluor-pyridin-3-ylmethyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-difluormethoxy-benzyl)-amin eller [5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2-trifluor-ethoxy)-pyridin-3-ylmethyl]-amin; eller et salt, en tautomer eller stereoisomer deraf.
3. Forbindelse ifølge krav 1, hvilken forbindelse er udvalgt fra gruppen, bestående af: [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluormethyl-pyridin-3-ylmethyl)-amin, (3-chlor-pyridin-4-ylmethyl)-[5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-fluor-benzyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-trifluormethyl-benzyl)-amin, [5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2,6-difluor- benzyl)-amin, (2-chlor-benzyl)-[5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amin, [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-methoxy-pyridin-3-ylmethyl)-amin; eller et salt, en tautomer eller stereoisomer deraf.
4. Forbindelse ifølge krav 1, hvor forbindelsen er (3-chlor-pyridin-4-ylmethyl)-[5-(5-chlor-1 FI-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amin.
5. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-fluor-benzyl)-amin.
6. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluormethyl-pyridin-3-ylmethyl)-amin.
7. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-trifluormethyl-benzyl)-amin.
8. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2,6-difluor-benzyl)-amin.
9. Forbindelse ifølge krav 1, hvor forbindelsen er (2-chlor-benzyl)-[5-(5-chlor-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amin.
10. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amin.
11. Forbindelse ifølge krav 1, hvor forbindelsen er [5-(5-chlor-1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-methoxy-pyridin-3-ylmethyl)-amin.
12. Sammensætning, omfattende en farmaceutisk acceptabel bærer og en forbindelse ifølge et hvilket som helst af kravene 1-11.
13. Forbindelse ifølge et hvilket som helst af kravene 1-11 eller sammensætning ifølge krav 12 til anvendelse ved en fremgangsmåde til behandling af et individ, der lider af eller er i risiko for en c-kit- og/eller c-fms-medieret sygdom eller tilstand, hvilken fremgangsmåde omfatter indgivelse af en virksom mængde af forbindelsen eller sammensætningen i individet, hvor sygdommen eller tilstanden er udvalgt fra gruppen, bestående af mastcelletumorer, småcellet lungekræft, testi kel kræft, gastrointestinale stromale tumorer, glioblastom, astrocytom, neuroblastom, karcinomer i den kvindelige genitalvej, sarkomer af neuroektodermal oprindelse, kolorektalt karcinom, carcinoma in situ, Schwann-celleneoplasi associeret med neurofibromatose, akut myeloid leukæmi, akut lymfocytær leukæmi, kronisk myelogen leukæmi, multipelt myelom, mastocytose, melanom, brystkræft, æggestokkræft, prostata- kræft, mastcelletumorer hos hunde, metastase af kræft i knogle eller andre væv, hypertrofi, astma, reumatoid arthritis, allergisk rhinitis, multipel sklerose, inflammatorisk tarmsyndrom, transplantatafstødning, systemisk lupus erythematose, ulcerøs kolit, Crohns sygdom, kronisk obstruktiv lungesygdom, emfysem, aterosklerose, type l-diabetes, type ll-diabetes, insulinresistens, hyperglykæmi, lipolyse, hypereosinofili, osteoporose, øget frakturrisi-ko, Pagets sygdom, hyperkalcæmi, glomerulonephritis, interstitiel nephritis, lupus nephritis, tubulær nekrose, diabetisk nefropati, slagtilfælde, Alzheimers sygdom, Parkinsons sygdom, inflammatorisk smerte, kronisk smerte og knoglesmerter.
14. Forbindelse eller sammensætning til anvendelse ifølge krav 13, hvor forbindelsen er godkendt til indgivelse i et menneske.
15. Kit, omfattende en sammensætning ifølge krav 12.
16. Kit ifølge krav 15, hvor sammensætningen er godkendt til en medicinsk indikation, udvalgt fra gruppen, bestående af mastcelletumorer, småcellet lungekræft, testi kel kræft, gastrointestinale stromale tumorer, gliobalstom, astrocytom, neuroblastom, karcinomer i den kvindelige genitalvej, sarkomer af neuroektodermal oprindelse, kolorektalt karcinom, carcinoma in situ, Schwann-celleneoplasi associeret med neurofibromatose, akut myeloid leukæmi, akut lymfocytær leukæmi, kronisk myelogen leukæmi, multipelt my-elom, mastocytose, melanom, brystkræft, æggestokkræft, prostatakræft, mastcelletumorer hos hunde, metastase af kræft i knogle eller andre væv, hypertrofi, astma, reumatoid arthritis, allergisk rhinitis, multipel sklerose, inflammatorisk tarmsyndrom, transplantatafstødning, systemisk lupus erythematose, ulcerøs kolit, Crohns sygdom, kronisk obstruktiv lungesygdom, emfysem, aterosklerose, type l-diabetes, type ll-diabetes, insulinresistens, hyperglykæmi, lipolyse, hypereosinofili, osteoporose, øget frakturrisiko, Pagets sygdom, hyperkalcæmi, glomerulonephritis, interstitiel nephritis, lupus nephritis, tubulær nekrose, diabetisk nefropati, slagtilfælde, Alzheimers sygdom, Parkinsons sygdom, inflammatorisk smerte, kronisk smerte og knoglesmerter.
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