HRP20150489T1 - Imidazo[4,5-c]kinolini kao inhibitori dna-pk - Google Patents
Imidazo[4,5-c]kinolini kao inhibitori dna-pk Download PDFInfo
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- HRP20150489T1 HRP20150489T1 HRP20150489TT HRP20150489T HRP20150489T1 HR P20150489 T1 HRP20150489 T1 HR P20150489T1 HR P20150489T T HRP20150489T T HR P20150489TT HR P20150489 T HRP20150489 T HR P20150489T HR P20150489 T1 HRP20150489 T1 HR P20150489T1
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- ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical class C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 29
- 150000003839 salts Chemical class 0.000 claims 17
- 125000004432 carbon atom Chemical group C* 0.000 claims 15
- 239000000203 mixture Substances 0.000 claims 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 5
- 125000004434 sulfur atom Chemical group 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 125000002950 monocyclic group Chemical group 0.000 claims 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims 4
- 125000002947 alkylene group Chemical group 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 206010070834 Sensitisation Diseases 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 230000008313 sensitization Effects 0.000 claims 2
- 102100030011 Endoribonuclease Human genes 0.000 claims 1
- 101710199605 Endoribonuclease Proteins 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- -1 carboxylic acid halide Chemical class 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000005865 ionizing radiation Effects 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
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- C07D471/00—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
- 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
- C07D471/04—Ortho-condensed systems
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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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
- A61P35/04—Antineoplastic agents specific for metastasis
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/38—Nitrogen atoms
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
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- C12Y207/11—Protein-serine/threonine kinases (2.7.11)
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Claims (15)
1. Spojevi s formulom (I)
[image]
naznačeni time da
R1 označava Y ili -(CY2)n-Ar,
R2 označava Y, -(CY2)p-(C[YR6])s-R7 ili -Alk-R7,
R3 označava Y ili CN,
R4 označava Y, Hal, -(CY2)p-COOY ili -(CY2)p-CO-NYY,
R5 označava A, Hal, -(CY2)p-OY, -(CY2)p-NYY, -(CY2)p-COOY, -(CY2)p-CO-NYY ili -(CY2)p-NY-COY,
R6 označava Y, Hal, -(CY2)n-NYY, -(CY2)n-NY-COO-(CY2)n-SiA3, -(CY2)n-COOY, -CO-NYY, -CO-NY-(CY2)n-OY, -CO-NY-(CY2)n-NYY ili SO2A,
R7 označava -(CY2)p-Ar ili -(CY2)p-Het1,
X označava CH2, O, S ili jednostruku vezu,
Y označava H ili A,
A označava nerazgranati ili razgranati alkil koji ima 1, 2, 3, 4, 5, 6, 7, 8, 9 ili 10 C atoma, gdje 1, 2, 3, 4, 5, 6 ili 7 H atoma može biti zamijenjeno, međusobno neovisno, s Hal,
Alk označava alkilen koji ima 1, 2, 3, 4, 5 ili 6 C atoma,
Ar označava fenil koji je nesupstituiran ili jednostruko-, dvostruko- ili trostruko- supstituiran s Hal, A, CN, -(CY2)p-OY, -(CY2)p-NYY, -(CY2)p-COOY, -(CY2)p-CO-NYY ili -(CY2)p-NY-COY,
Het1 označava mono- ili biciklički aromatski heterocikal koji ima 2, 3, 4, 5, 6, 7, 8 ili 9 C atoma i 1, 2, 3 ili 4 N, O i/ili S atoma, koji mogu biti nesupstituirani ili jednostruko-, dvostruko- ili trostruko- supstituirani s Hal, A, CN, -(CY2)p-OY, -(CY2)p-NYY, -(CY2)p-COOY, -(CY2)p-CO-NYY, -(CY2)p-NY-COY ili -SO2-Het2,
Het2 označava monociklički zasićeni heterocikal koji ima 2, 3, 4, 5, 6 ili 7 C atoma i 1, 2, 3 ili 4 N, O i/ili S atoma, koji mogu biti nesupstituirani ili jednostruko supstituirani sa A,
Hal označava F, Cl, Br ili I,
m označava 0, 1, 2, 3 ili 4, i
n, p, s, međusobno neovisno, označavaju 0, 1, 2, 3, 4, 5 ili 6,
i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
2. Spojevi prema zahtjevu 1 koji imaju pod-formulu (IA)
[image]
naznačeni time da
R2 označava Y ili -(CY2)p-C(YR6)-R7,
R5 označava Y ili Hal,
R6 označava Y, -(CY2)n-NYY, -CO-NYY ili -CO-NY-(CY2)n-OY,
R7 označava Ar ili Het1,
Y označava H ili A,
A označava nerazgranati ili razgranati alkil koji ima 1, 2, 3 ili 4 C atoma, gdje 1, 2 ili 3 H atoma može biti zamijenjeno, međusobno neovisno, s Hal,
Ar označava fenil koji je nesupstituiran ili jednostruko- ili dvostruko- supstituiran s Hal,
Het1 označava mono- ili biciklički aromatski heterocikal koji ima 2, 3, 4, 5, 6, 7, 8 ili 9 C atoma i 1, 2 ili 3 N i/ili S atoma, koji mogu biti nesupstituirani ili jednostruko- ili dvostruko- supstituirani s Hal, A, OY ili -SO2-Het2,
Het2 označava monociklički zasićeni heterocikal koji ima 3, 4 ili 5 C atoma i 1 ili 2 N i/ili O atoma,
Hal označava F, Cl, Br ili I, te
n, p, međusobno neovisno, označavaju 0, 1, 2 ili 3,
i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
3. Spojevi prema zahtjevu 1 koji imaju pod-formulu (IB)
[image]
naznačeni time da
R2 označava R7, -Alk-Ar ili -Alk-Het1,
R5 označava Y ili Hal,
R7 označava -(CY2)p-Ar ili -(CY2)p-Het1,
Y označava H ili A,
A označava nerazgranati ili razgranati alkil koji ima 1, 2, 3 ili 4 C atoma, gdje 1, 2 ili 3 H atoma može biti zamijenjeno, međusobno neovisno, s Hal,
Alk označava alkilen koji ima 1, 2 ili 3 C atoma,
Ar označava fenil koji je nesupstituiran ili jednostruko- ili dvostruko- supstituiran s Hal,
Het1 označava mono- ili biciklički aromatski heterocikal koji ima 2, 3, 4, 5, 6, 7, 8 ili 9 C atoma i 1, 2 ili 3 N i/ili S atoma, koji mogu biti nesupstituirani ili jednostruko- ili dvostruko- supstituirani s Hal, A, OY ili -SO2-Het2,
Het2 označava monociklički zasićeni heterocikal koji ima 3, 4 ili 5 C atoma i 1 ili 2 N i/ili O atoma,
Hal označava F, Cl, Br ili I, te
p označava 0, 1, 2 ili 3,
i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
4. Spojevi prema zahtjevu 3 koji imaju pod-formulu (IB-1)
[image]
naznačeni time da
R2 označava R7, -Alk-Ar ili -Alk-Het1,
R5 označava Hal,
R7 označava Ar ili Het1,
A označava nerazgranati ili razgranati alkil koji ima 1, 2, 3 ili 4 C atoma, gdje 1, 2 ili 3 H atoma može biti zamijenjeno, međusobno neovisno, s Hal,
Alk označava alkilen koji ima 1 ili 2 C atoma,
Ar označava fenil koji je nesupstituiran ili jednostruko supstituiran s Hal,
Het1 označava mono- ili biciklički aromatski heterocikal koji ima 2, 3, 4, 5, 6, 7, 8 ili 9 C atoma i 1, 2 ili 3 N i/ili S atoma, koji mogu biti nesupstituirani ili jednostruko- ili dvostruko- supstituirani s Hal ili A, i
Hal označava F, Cl, Br ili I,
i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
5. Spojevi prema jednom zahtjevu od 1 do 4, naznačeni time da su odabrani iz skupine:
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
6. Intermedijarni spojevi formule (II)
[image]
naznačeni time da
R3 označava CN,
R8 označava NO2 ili NYY, te
R1, R2, R5, Y i m imaju značenje navedeno u zahtjevu 1,
i/ili njihove soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
7. Intermedijarni spojevi prema zahtjevu 6 naznačeni time da
R1 označava A,
R2 označava A ili -(CH2)p-(CH2)s-Ar,
R3 označava CN,
R5 označava Hal,
R8 označava NH2,
A označava nerazgranati ili razgranati alkil koji ima 1, 2, 3 ili 4 C atoma, gdje 1, 2 ili 3 H atoma može biti zamijenjeno, međusobno neovisno, s Hal,
Ar označava fenil koji je nesupstituiran ili jednostruko- ili dvostruko- supstituiran s Hal,
Hal označava F, Cl, Br ili I, i
m, p, s, međusobno neovisno, označavaju 0, 1 ili 2,
i/ili njihove soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima.
8. Postupak za dobivanje spojeva s formulom (I) prema zahtjevu 1, njihovih pod-formula i/ili njihovih fiziološki prihvatljivih soli, tautomera i/ili stereoizomera, uključujući njihove smjese u svim omjerima, naznačen time da sadrži slijedeće korake:
(a) reakciju spoja formule (II)
[image]
u kojoj R1, R2, R3, R5, R8 i m imaju značenje navedeno u zahtjevu 7,
sa halidom karboksilne kiseline i s organskom bazom u otapalu,
da se dobiju spojevi pod-formule (IC)
[image]
u kojoj R1, R2, R3, R5 i m imaju značenje navedeno u zahtjevu 7,
te proizvoljno
(b') reakciju spojeva pod-formule (IC) sa spojem Hal-R4, u kojem R4 i Hal imaju značenje navedeno u zahtjevu 1,
da se dobiju spojevi pod-formule (ID)
[image]
[image]
u kojoj R1, R2, R3, R5 i m imaju značenje navedeno u zahtjevu 7, i R4 ima značenje navedeno u zahtjevu 1,
(b") pretvaranje R1, -O-R2, R3, R4 i/ili R5 spojeva pod-formule (ID) i/ili dodavanje barem jednog R5 koji ima značenje navedeno u zahtjevu 1 na fenilni prsten spojeva pod-formule (ID) da se dobiju spojevi formule (I)
[image]
u kojoj R1, R2, R3, R4, R5, X i m imaju značenje navedeno u zahtjevu 1,
i/ili
(b"') pretvaranje baze ili kiseline spojeva formule (I) ili pod-formule (IC) ili (ID) u jednu od njihovih fiziološki prihvatljivih soli.
9. Postupak za dobivanje intermedijarnih spojeva formule (II) prema zahtjevu 6 i/ili njihovih soli, tautomera i/ili stereoizomera, uključujući njihove smjese u svim omjerima, naznačen time da sadrži slijedeće korake:
(a) reakciju spoja formule (III)
[image]
u kojoj
Hal označava F, Cl, Br ili I, i
R1, R2 i R8 imaju značenje navedeno u zahtjevu 6,
sa spojem formule (IV)
[image]
u kojoj R3, R5 i m imaju značenje navedeno u zahtjevu 6,
da se dobiju spojevi formule (II)
[image]
u kojoj R1, R2, R3, R5, R8 i m imaju značenje navedeno u zahtjevu 6,
te proizvoljno
(b) pretvaranje baze ili kiseline spojeva formule (II) u jednu od njihovih soli.
10. Uporaba spojeva prema jednom od zahtjeva 1 do 5 i/ili njihovih fiziološki prihvatljivih soli, tautomera i/ili stereoizomera, uključujući njihove smjese u svim omjerima, naznačena time da je za in vitro inhibiciju serin/treonin protein kinaza, poželjno PIKK i/ili ATM, naročito poželjno DNA-PK.
11. Uporaba najmanje jednog spoja prema jednom od zahtjeva 1 do 5 i/ili njihovih fiziološki prihvatljivih soli, tautomera i/ili stereoizomera, uključujući njihove smjese u svim omjerima, naznačena time da je za senzibilizaciju stanica raka na sredstvo protiv raka i/ili ionizirajuće zračenje, uz uvjet da se senzibilizacija ne provodi na ljudskom ili životinjskom tijelu.
12. Medikament naznačen time da sadrži najmanje jedan spoj prema jednom od zahtjeva 1 do 5 i/ili njihove fiziološki prihvatljive soli, tautomere i/ili stereoizomere, uključujući njihove smjese u svim omjerima.
13. Farmaceutski pripravak naznačen time da sadrži, kao aktivni spoj, učinkovitu količinu najmanje jednog spoja prema jednom od zahtjeva 1 do 5 i/ili njegove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima, zajedno s farmaceutski podnošljivom pomoćnom tvari, u kombinaciji s najmanje jednim sredstvom protiv raka.
14. Spojevi prema jednom od zahtjeva 1 do 5 i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima, naznačeni time da su za uporabu za sprečavanje, terapiju i/ili kontrolu napredovanja raka, tumora, metastaza i/ili poremećaja angiogeneze, u kombinaciji s radioterapijom i/ili s najmanje jednim sredstvom protiv raka.
15. Spojevi prema jednom od zahtjeva 1 do 5 i/ili njihove fiziološki prihvatljive soli, tautomeri i/ili stereoizomeri, uključujući njihove smjese u svim omjerima, naznačeni time da su za uporabu za senzibilizaciju stanica raka na sredstvo protiv raka i/ili na ionizirajuće zračenje.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DE102010035744A DE102010035744A1 (de) | 2010-08-28 | 2010-08-28 | Imidazolonylchinoline |
EP11748260.4A EP2609082B1 (de) | 2010-08-28 | 2011-07-26 | Imidazo[4,5-c]chinoline als dna-pk-inhibitoren |
PCT/EP2011/003744 WO2012028233A1 (de) | 2010-08-28 | 2011-07-26 | Imidazo [4,5-c]chinoline als dna-pk-inhibitoren |
Publications (1)
Publication Number | Publication Date |
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HRP20150489T1 true HRP20150489T1 (hr) | 2015-06-05 |
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HRP20150489TT HRP20150489T1 (hr) | 2010-08-28 | 2015-05-07 | Imidazo[4,5-c]kinolini kao inhibitori dna-pk |
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US (3) | US9000153B2 (hr) |
EP (1) | EP2609082B1 (hr) |
JP (1) | JP5882329B2 (hr) |
KR (1) | KR101912475B1 (hr) |
CN (1) | CN103068803B (hr) |
AR (1) | AR082728A1 (hr) |
AU (1) | AU2011298013B9 (hr) |
BR (1) | BR112013004613B1 (hr) |
CA (1) | CA2809553C (hr) |
CY (1) | CY1116281T1 (hr) |
DE (1) | DE102010035744A1 (hr) |
DK (1) | DK2609082T3 (hr) |
EA (1) | EA022095B1 (hr) |
ES (1) | ES2536313T3 (hr) |
HK (1) | HK1184154A1 (hr) |
HR (1) | HRP20150489T1 (hr) |
HU (1) | HUE025692T2 (hr) |
IL (1) | IL224903A (hr) |
MX (1) | MX338150B (hr) |
PL (1) | PL2609082T3 (hr) |
PT (1) | PT2609082E (hr) |
RS (1) | RS54038B1 (hr) |
SG (1) | SG187954A1 (hr) |
SI (1) | SI2609082T1 (hr) |
WO (1) | WO2012028233A1 (hr) |
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CN106977495B (zh) | 2012-04-24 | 2020-08-04 | 沃泰克斯药物股份有限公司 | Dna-pk抑制剂 |
ES2900061T3 (es) | 2013-03-12 | 2022-03-15 | Vertex Pharma | Inhibidores de DNA-PK |
EP3424920B1 (en) | 2013-10-17 | 2020-04-15 | Vertex Pharmaceuticals Incorporated | Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors |
NO2714752T3 (hr) | 2014-05-08 | 2018-04-21 | ||
ES2946507T3 (es) * | 2015-04-02 | 2023-07-20 | Merck Patent Gmbh | Imidazolonilquinolinas y su uso como inhibidores de ATM cinasa |
GB201516504D0 (en) | 2015-09-17 | 2015-11-04 | Astrazeneca Ab | Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer |
US11110108B2 (en) | 2016-09-27 | 2021-09-07 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA-damaging agents and DNA-PK inhibitors |
WO2018183868A1 (en) * | 2017-03-31 | 2018-10-04 | Bioventures, Llc | Inhibitors of dna pk and uses thereof |
ES2925801T3 (es) * | 2017-08-11 | 2022-10-19 | Merck Patent Gmbh | Preparación farmacéutica que comprende 3-fluoro-4-[7-metoxi-3-metil-8-(1-metil-1H-pirazol-4-il)-2-oxo-2,3-dihidro-imidazo[4,5-c]quinolin-1-il]-benzonitrilo |
WO2019177971A1 (en) * | 2018-03-12 | 2019-09-19 | Mavupharma, Inc. | Ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1) inhibitors and uses thereof |
EP3765019A1 (en) | 2018-03-14 | 2021-01-20 | Merck Patent GmbH | Compounds and uses thereof to treat tumors in a subject |
TWI820146B (zh) | 2018-06-15 | 2023-11-01 | 瑞典商阿斯特捷利康公司 | 嘌呤酮化合物及其在治療癌症中之用途 |
CN111909144A (zh) * | 2019-05-10 | 2020-11-10 | 山东轩竹医药科技有限公司 | 喹唑啉类dna-pk抑制剂 |
MX2022000358A (es) | 2019-07-10 | 2022-02-03 | Merck Patent Gmbh | Preparacion farmaceutica. |
US20230014730A1 (en) | 2019-09-23 | 2023-01-19 | Nanjing Zhengxiang Pharmaceuticals Co., Ltd. | Phosphodiesterase inhibitors and use |
US20230044248A1 (en) | 2019-11-01 | 2023-02-09 | Ares Trading S.A. | COMBINED INHIBITION OF PD-1, TGFBeta AND ATM TOGETHER WITH RADIOTHERAPY FOR THE TREATMENT OF CANCER |
US20230226041A1 (en) | 2020-06-18 | 2023-07-20 | Merck Patent Gmbh | Compounds for the treatment of viral infections |
CN116194109A (zh) | 2020-06-24 | 2023-05-30 | 阿斯利康(英国)有限公司 | 抗体-药物缀合物和atm抑制剂的组合 |
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ES2074867T3 (es) | 1990-11-06 | 1995-09-16 | Pfizer | Derivados de quinazolina para potenciar la actividad antitumoral. |
WO2000061186A1 (en) | 1999-04-08 | 2000-10-19 | Arch Development Corporation | Use of anti-vegf antibody to enhance radiation in cancer therapy |
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NZ540826A (en) * | 2002-12-20 | 2008-07-31 | 3M Innovative Properties Co | Aryl / hetaryl substituted imidazoquinolines |
NZ545412A (en) * | 2003-08-27 | 2008-12-24 | Coley Pharm Group Inc | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
BRPI0414856A (pt) * | 2003-10-03 | 2006-11-21 | 3M Innovative Properties Co | imidazoquinolinas alcóxi-substituìdas |
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CA2763821A1 (en) * | 2009-06-04 | 2010-12-09 | Novartis Ag | 1h-imidazo[4,5-c]quinolinone derivatives |
WO2011001212A1 (en) * | 2009-06-30 | 2011-01-06 | Piramal Life Sciences Limited | Imidazo [4,5-c]quinoline derivatives and their use in the treatment of tumors and/or inflammation |
-
2010
- 2010-08-28 DE DE102010035744A patent/DE102010035744A1/de not_active Withdrawn
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2011
- 2011-07-26 DK DK11748260.4T patent/DK2609082T3/en active
- 2011-07-26 CN CN201180041966.4A patent/CN103068803B/zh active Active
- 2011-07-26 PL PL11748260T patent/PL2609082T3/pl unknown
- 2011-07-26 SG SG2013013966A patent/SG187954A1/en unknown
- 2011-07-26 JP JP2013526334A patent/JP5882329B2/ja active Active
- 2011-07-26 KR KR1020137006794A patent/KR101912475B1/ko active IP Right Grant
- 2011-07-26 RS RS20150330A patent/RS54038B1/en unknown
- 2011-07-26 EP EP11748260.4A patent/EP2609082B1/de active Active
- 2011-07-26 US US13/819,488 patent/US9000153B2/en active Active
- 2011-07-26 ES ES11748260.4T patent/ES2536313T3/es active Active
- 2011-07-26 SI SI201130493T patent/SI2609082T1/sl unknown
- 2011-07-26 EA EA201300288A patent/EA022095B1/ru not_active IP Right Cessation
- 2011-07-26 CA CA2809553A patent/CA2809553C/en active Active
- 2011-07-26 AU AU2011298013A patent/AU2011298013B9/en active Active
- 2011-07-26 HU HUE11748260A patent/HUE025692T2/en unknown
- 2011-07-26 PT PT117482604T patent/PT2609082E/pt unknown
- 2011-07-26 WO PCT/EP2011/003744 patent/WO2012028233A1/de active Application Filing
- 2011-07-26 BR BR112013004613-9A patent/BR112013004613B1/pt active IP Right Grant
- 2011-07-26 MX MX2013002259A patent/MX338150B/es active IP Right Grant
- 2011-08-26 AR ARP110103113A patent/AR082728A1/es active IP Right Grant
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2013
- 2013-02-25 IL IL224903A patent/IL224903A/en active IP Right Grant
- 2013-10-17 HK HK13111720.9A patent/HK1184154A1/zh unknown
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2015
- 2015-04-01 US US14/676,125 patent/US9598408B2/en active Active
- 2015-05-07 HR HRP20150489TT patent/HRP20150489T1/hr unknown
- 2015-05-14 CY CY20151100429T patent/CY1116281T1/el unknown
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2017
- 2017-02-27 US US15/443,349 patent/US20170166567A1/en not_active Abandoned
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