HRP20240293T1 - Derivati kinazolina kao protutumorska sredstva - Google Patents
Derivati kinazolina kao protutumorska sredstva Download PDFInfo
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- HRP20240293T1 HRP20240293T1 HRP20240293TT HRP20240293T HRP20240293T1 HR P20240293 T1 HRP20240293 T1 HR P20240293T1 HR P20240293T T HRP20240293T T HR P20240293TT HR P20240293 T HRP20240293 T HR P20240293T HR P20240293 T1 HRP20240293 T1 HR P20240293T1
- Authority
- HR
- Croatia
- Prior art keywords
- yloxy
- triazolo
- pyrimidin
- methylphenyl
- amine
- Prior art date
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- 239000002246 antineoplastic agent Substances 0.000 title claims 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 46
- 229920006395 saturated elastomer Polymers 0.000 claims 44
- 125000000217 alkyl group Chemical group 0.000 claims 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims 34
- 150000001875 compounds Chemical class 0.000 claims 22
- 229910052736 halogen Inorganic materials 0.000 claims 22
- 150000002367 halogens Chemical group 0.000 claims 22
- 125000003342 alkenyl group Chemical group 0.000 claims 18
- 125000000304 alkynyl group Chemical group 0.000 claims 18
- 150000003839 salts Chemical class 0.000 claims 17
- 125000003118 aryl group Chemical group 0.000 claims 14
- 125000002252 acyl group Chemical group 0.000 claims 13
- 125000001188 haloalkyl group Chemical group 0.000 claims 13
- 125000001072 heteroaryl group Chemical group 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 11
- 239000001257 hydrogen Substances 0.000 claims 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims 10
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 10
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 10
- 229910052760 oxygen Inorganic materials 0.000 claims 10
- 229910052717 sulfur Inorganic materials 0.000 claims 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 8
- 150000002431 hydrogen Chemical group 0.000 claims 8
- 229910052757 nitrogen Inorganic materials 0.000 claims 8
- 125000005842 heteroatom Chemical group 0.000 claims 7
- -1 nitro, hydroxyl Chemical group 0.000 claims 7
- 125000004404 heteroalkyl group Chemical group 0.000 claims 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 3
- ZKRGDRIWZDUEPQ-MDNUFGMLSA-N 5-[(1R,5R)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@@H]2CCN([C@@H]2C1)C)O[C@@H]1COCC1)C ZKRGDRIWZDUEPQ-MDNUFGMLSA-N 0.000 claims 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 2
- 206010027476 Metastases Diseases 0.000 claims 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- XZWQXDUAEYDLMF-SRDVKXRDSA-N (5S)-6-(difluoromethoxy)-5-(3,3-difluoro-1-methylpiperidin-4-yl)oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6H-quinazolin-5-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)N[C@@]1(C=2C=NC=NC=2C=CC1OC(F)F)OC1C(CN(CC1)C)(F)F)C XZWQXDUAEYDLMF-SRDVKXRDSA-N 0.000 claims 1
- XVWWYSCPCWFSKB-VOTSOKGWSA-N (E)-4-(dimethylamino)-N-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]but-2-enamide Chemical compound CC1=C(C=CC(=C1)NC2=NC=NC3=C2C(=C(C=C3)NC(=O)/C=C/CN(C)C)N4CC(C4)N(C)C)OC5=CC6=NC=NN6C=N5 XVWWYSCPCWFSKB-VOTSOKGWSA-N 0.000 claims 1
- XDEPOFKWJQCAOD-LZPATWBJSA-N (E)-N-[3-cyano-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound CC1=C(C=CC(=C1)NC2=C3C(=NC=C2C#N)C=CC(=C3O[C@@H]4CCN(CC4(F)F)C)NC(=O)/C=C/[C@H]5CCCN5C)OC6=CC7=NC=NN7C=N6 XDEPOFKWJQCAOD-LZPATWBJSA-N 0.000 claims 1
- KXZRACJXPFTXCJ-IQKOXAACSA-N (E)-N-[3-cyano-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound CC1=C(C=CC(=C1)NC2=C3C(=NC=C2C#N)C=CC(=C3O[C@@H]4CCN(CC4(F)F)C)NC(=O)/C=C/CN(C)C)OC5=CC6=NC=NN6C=N5 KXZRACJXPFTXCJ-IQKOXAACSA-N 0.000 claims 1
- JTNGBYUNJKTYFT-PMPXQKCGSA-N (E)-N-[3-cyano-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound CCOC1=C(C(=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OC4=CC5=NC=NN5C=N4)C)C#N)O[C@@H]6CCN(CC6(F)F)C)NC(=O)/C=C/[C@H]7CCCN7C JTNGBYUNJKTYFT-PMPXQKCGSA-N 0.000 claims 1
- YRHMDFJNKYQMLD-UWSNOUECSA-N (E)-N-[3-cyano-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound CCOC1=C(C(=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OC4=CC5=NC=NN5C=N4)C)C#N)O[C@@H]6CCN(CC6(F)F)C)NC(=O)/C=C/CN(C)C YRHMDFJNKYQMLD-UWSNOUECSA-N 0.000 claims 1
- LVUHOOHMDJWZHA-NQOLIALDSA-N (E)-N-[5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound CC1=C(C=CC(=C1)NC2=NC=NC3=C2C(=C(C=C3)NC(=O)/C=C/[C@H]4CCCN4C)O[C@@H]5CCN(CC5(F)F)C)OC6=CC7=NC=NN7C=N6 LVUHOOHMDJWZHA-NQOLIALDSA-N 0.000 claims 1
- ZNZLYQXLYDJAMP-XALOKNAFSA-N (E)-N-[5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound CCOC1=C(C(=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)OC4=CC5=NC=NN5C=N4)C)O[C@@H]6CCN(CC6(F)F)C)NC(=O)/C=C/[C@H]7CCCN7C ZNZLYQXLYDJAMP-XALOKNAFSA-N 0.000 claims 1
- CHXBHABTRUNWBN-DIJOXEGBSA-N (E)-N-[5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound CCOC1=C(C(=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)OC4=CC5=NC=NN5C=N4)C)O[C@@H]6CCN(CC6(F)F)C)NC(=O)/C=C/CN(C)C CHXBHABTRUNWBN-DIJOXEGBSA-N 0.000 claims 1
- AIWKOBLDEVRENR-ZRGXPQFDSA-N (E)-N-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound CC1=C(C=CC(=C1)NC2=NC=NC3=C2C(=C(C=C3)NC(=O)/C=C/[C@H]4CCCN4C)N5CC(C5)N(C)C)OC6=CC7=NC=NN7C=N6 AIWKOBLDEVRENR-ZRGXPQFDSA-N 0.000 claims 1
- OOFIFMBWTZZRRM-UHFFFAOYSA-N 1-[4-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-3,6-dihydro-2H-pyridin-1-yl]prop-2-en-1-one Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)C=1CCN(CC=1)C(C=C)=O)C OOFIFMBWTZZRRM-UHFFFAOYSA-N 0.000 claims 1
- SCSVJBGTAYSBRS-UHFFFAOYSA-N 1-[4-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-7-yl]-3,6-dihydro-2H-pyridin-1-yl]prop-2-en-1-one Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC(=CC(=C12)N1CC(C1)N(C)C)C=1CCN(CC=1)C(C=C)=O)C SCSVJBGTAYSBRS-UHFFFAOYSA-N 0.000 claims 1
- JOWVFZSEIHHQAE-UHFFFAOYSA-N 1-[5-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl]-3,6-dihydro-2H-pyridin-1-yl]prop-2-en-1-one Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)C1=CCCN(C1)C(C=C)=O)C JOWVFZSEIHHQAE-UHFFFAOYSA-N 0.000 claims 1
- CKOFGCXDBATTOY-UHFFFAOYSA-N 1-[5-[5-[3-(dimethylamino)azetidin-1-yl]-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-7-yl]-3,6-dihydro-2H-pyridin-1-yl]prop-2-en-1-one Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC(=CC(=C12)N1CC(C1)N(C)C)C1=CCCN(C1)C(C=C)=O)C CKOFGCXDBATTOY-UHFFFAOYSA-N 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- NSQIBSJKZMXNTE-UHFFFAOYSA-N 5-(2-cyclopropyl-2,6-diazabicyclo[3.2.0]heptan-6-yl)-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C2CCN(C2C1)C1CC1)OC)C NSQIBSJKZMXNTE-UHFFFAOYSA-N 0.000 claims 1
- XBOGWTVNNYYDGG-UHFFFAOYSA-N 5-(7,7-difluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CC(C2)(F)F)C)OC)C XBOGWTVNNYYDGG-UHFFFAOYSA-N 0.000 claims 1
- XBOGWTVNNYYDGG-HPRDVNIFSA-N 5-(7,7-difluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CC(C2)(F)F)C)OC([2H])([2H])[2H])C XBOGWTVNNYYDGG-HPRDVNIFSA-N 0.000 claims 1
- YRRGTHJHIGWEMW-NRFANRHFSA-N 5-(7,7-difluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CC(C2)(F)F)C)O[C@@H]1COCC1)C YRRGTHJHIGWEMW-NRFANRHFSA-N 0.000 claims 1
- SMJRRAAHDXKYCQ-UHFFFAOYSA-N 5-(8-methyl-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=CC(=C12)N1CC2(C1)OCCN(C2)C)C SMJRRAAHDXKYCQ-UHFFFAOYSA-N 0.000 claims 1
- JXQKQNNMNCWTIW-RSJQNUHWSA-N 5-[(1R,5R)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@@H]2CCN([C@@H]2C1)C)OC([2H])([2H])[2H])C JXQKQNNMNCWTIW-RSJQNUHWSA-N 0.000 claims 1
- IAMGOGVQPSKQQH-FGZHOGPDSA-N 5-[(1R,5R)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-propan-2-yloxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@@H]2CCN([C@@H]2C1)C)OC(C)C)C IAMGOGVQPSKQQH-FGZHOGPDSA-N 0.000 claims 1
- MQGBVXUNEXCWHU-SFTDATJTSA-N 5-[(1S,5S)-2-(2-fluoroethyl)-2,6-diazabicyclo[3.2.0]heptan-6-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)CCF)OC)C MQGBVXUNEXCWHU-SFTDATJTSA-N 0.000 claims 1
- JXQKQNNMNCWTIW-JVBJWZIXSA-N 5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)OC([2H])([2H])[2H])C JXQKQNNMNCWTIW-JVBJWZIXSA-N 0.000 claims 1
- ZKRGDRIWZDUEPQ-PMVMPFDFSA-N 5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)O[C@@H]1COCC1)C ZKRGDRIWZDUEPQ-PMVMPFDFSA-N 0.000 claims 1
- IAMGOGVQPSKQQH-VXKWHMMOSA-N 5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-propan-2-yloxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)OC(C)C)C IAMGOGVQPSKQQH-VXKWHMMOSA-N 0.000 claims 1
- IQSYFGKEPBJGRP-LJQANCHMSA-N 5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C[C@@H](CC1)N(C)C)OC)C IQSYFGKEPBJGRP-LJQANCHMSA-N 0.000 claims 1
- UOQMXHXCLGTRJC-UYAOXDASSA-N 5-[(3R,4R)-3-(dimethylamino)-4-fluoropyrrolidin-1-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C[C@H]([C@@H](C1)F)N(C)C)OC)C UOQMXHXCLGTRJC-UYAOXDASSA-N 0.000 claims 1
- JHNVZIXDACFDHW-WIYYLYMNSA-N 5-[(3R,4R)-3-fluoro-1-methylpiperidin-4-yl]oxy-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1[C@@H](CN(CC1)C)F)OC)C JHNVZIXDACFDHW-WIYYLYMNSA-N 0.000 claims 1
- UOQMXHXCLGTRJC-AZUAARDMSA-N 5-[(3R,4S)-3-(dimethylamino)-4-fluoropyrrolidin-1-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C[C@H]([C@H](C1)F)N(C)C)OC)C UOQMXHXCLGTRJC-AZUAARDMSA-N 0.000 claims 1
- IQSYFGKEPBJGRP-IBGZPJMESA-N 5-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C[C@H](CC1)N(C)C)OC)C IQSYFGKEPBJGRP-IBGZPJMESA-N 0.000 claims 1
- PTKRHBXNNDLRPO-LTGPVEHVSA-N 5-[(4R)-3,3-difluoro-1-(trideuteriomethyl)piperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C([2H])([2H])[2H])(F)F)OC([2H])([2H])[2H])C PTKRHBXNNDLRPO-LTGPVEHVSA-N 0.000 claims 1
- GHGBEAPNWAOSDX-HSZRJFAPSA-N 5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-6-methoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinoline-3-carbonitrile Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=C(C=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC)C#N)C GHGBEAPNWAOSDX-HSZRJFAPSA-N 0.000 claims 1
- UWNQDRKSOGNBTH-XMMPIXPASA-N 5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-7-methoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinoline-3-carbonitrile Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=C(C=NC2=CC(=CC(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC)C#N)C UWNQDRKSOGNBTH-XMMPIXPASA-N 0.000 claims 1
- PTKRHBXNNDLRPO-CREDLSHTSA-N 5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC([2H])([2H])[2H])C PTKRHBXNNDLRPO-CREDLSHTSA-N 0.000 claims 1
- JYPFZIHUICGFBF-HXUWFJFHSA-N 5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trifluoromethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC(F)(F)F)C JYPFZIHUICGFBF-HXUWFJFHSA-N 0.000 claims 1
- SEKCYDQOHRZQLQ-GBXCKJPGSA-N 5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)O[C@@H]1COCC1)C SEKCYDQOHRZQLQ-GBXCKJPGSA-N 0.000 claims 1
- KNMIRDATSJAIPW-HXUWFJFHSA-N 5-[(4R)-3,3-difluoropiperidin-4-yl]oxy-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CNCC1)(F)F)OC)C KNMIRDATSJAIPW-HXUWFJFHSA-N 0.000 claims 1
- PTKRHBXNNDLRPO-CZHKOJODSA-N 5-[(4S)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trideuteriomethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@@H]1C(CN(CC1)C)(F)F)OC([2H])([2H])[2H])C PTKRHBXNNDLRPO-CZHKOJODSA-N 0.000 claims 1
- JYPFZIHUICGFBF-FQEVSTJZSA-N 5-[(4S)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-(trifluoromethoxy)quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@@H]1C(CN(CC1)C)(F)F)OC(F)(F)F)C JYPFZIHUICGFBF-FQEVSTJZSA-N 0.000 claims 1
- SEKCYDQOHRZQLQ-RDPSFJRHSA-N 5-[(4S)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@@H]1C(CN(CC1)C)(F)F)O[C@@H]1COCC1)C SEKCYDQOHRZQLQ-RDPSFJRHSA-N 0.000 claims 1
- JRYLIHMRXPLXCQ-GOSISDBHSA-N 5-[(7R)-7-fluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(C[C@@H](C2)F)C)OC)C JRYLIHMRXPLXCQ-GOSISDBHSA-N 0.000 claims 1
- JRYLIHMRXPLXCQ-SFHVURJKSA-N 5-[(7S)-7-fluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(C[C@H](C2)F)C)OC)C JRYLIHMRXPLXCQ-SFHVURJKSA-N 0.000 claims 1
- YHOXAOXMRAKRBS-IBGZPJMESA-N 5-[(8S)-8-fluoro-5-methyl-2,5-diazaspiro[3.5]nonan-2-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CC[C@@H](C2)F)C)OC)C YHOXAOXMRAKRBS-IBGZPJMESA-N 0.000 claims 1
- FXPULUWIDCEJPG-UHFFFAOYSA-N 5-[2-(2,2-difluoroethyl)-2,6-diazabicyclo[3.2.0]heptan-6-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C2CCN(C2C1)CC(F)F)OC)C FXPULUWIDCEJPG-UHFFFAOYSA-N 0.000 claims 1
- HOXNBDRKOWZPGJ-UHFFFAOYSA-N 5-[3-(dimethylamino)azetidin-1-yl]-6-(2-fluoroethoxy)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)OCCF)C HOXNBDRKOWZPGJ-UHFFFAOYSA-N 0.000 claims 1
- JFFXGCPGUQZSLO-UHFFFAOYSA-N 5-[3-(dimethylamino)azetidin-1-yl]-6-N-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-4-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazoline-4,6-diamine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)NC=1OCC(N=1)(C)C)C JFFXGCPGUQZSLO-UHFFFAOYSA-N 0.000 claims 1
- AHJJWEILIIBSLU-UHFFFAOYSA-N 5-[3-(dimethylamino)azetidin-1-yl]-6-ethoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)OCC)C AHJJWEILIIBSLU-UHFFFAOYSA-N 0.000 claims 1
- HPKDOXLDGGGXFV-UHFFFAOYSA-N 5-[3-(dimethylamino)azetidin-1-yl]-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC(C1)N(C)C)OC)C HPKDOXLDGGGXFV-UHFFFAOYSA-N 0.000 claims 1
- OMUGBGGTLOVNDN-UHFFFAOYSA-N 5-[3-(dimethylamino)cyclopentyl]oxy-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)OC1CC(CC1)N(C)C)OC)C OMUGBGGTLOVNDN-UHFFFAOYSA-N 0.000 claims 1
- OTCROUTUWVSCAR-UHFFFAOYSA-N 5-[4-(dimethylamino)cyclohexyl]oxy-6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)OC1CCC(CC1)N(C)C)OC)C OTCROUTUWVSCAR-UHFFFAOYSA-N 0.000 claims 1
- SETXXABQPISDAP-UHFFFAOYSA-N 6-(difluoromethoxy)-5-(7,7-difluoro-5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CC(C2)(F)F)C)OC(F)F)C SETXXABQPISDAP-UHFFFAOYSA-N 0.000 claims 1
- SKUBYBNMCXOSOK-OALUTQOASA-N 6-(difluoromethoxy)-5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)OC(F)F)C SKUBYBNMCXOSOK-OALUTQOASA-N 0.000 claims 1
- UAGDXSOSAVYDMC-HXUWFJFHSA-N 6-(difluoromethoxy)-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC(F)F)C UAGDXSOSAVYDMC-HXUWFJFHSA-N 0.000 claims 1
- JWYUXLONVOYXON-FGZHOGPDSA-N 6-cyclopropyloxy-5-[(1R,5R)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@@H]2CCN([C@@H]2C1)C)OC1CC1)C JWYUXLONVOYXON-FGZHOGPDSA-N 0.000 claims 1
- JWYUXLONVOYXON-VXKWHMMOSA-N 6-cyclopropyloxy-5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)OC1CC1)C JWYUXLONVOYXON-VXKWHMMOSA-N 0.000 claims 1
- XVTAQYVEQSIBAJ-HSZRJFAPSA-N 6-cyclopropyloxy-5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@H]1C(CN(CC1)C)(F)F)OC1CC1)C XVTAQYVEQSIBAJ-HSZRJFAPSA-N 0.000 claims 1
- XVTAQYVEQSIBAJ-QHCPKHFHSA-N 6-cyclopropyloxy-5-[(4S)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)O[C@@H]1C(CN(CC1)C)(F)F)OC1CC1)C XVTAQYVEQSIBAJ-QHCPKHFHSA-N 0.000 claims 1
- ROATUQDMUFXUDZ-UHFFFAOYSA-N 6-methoxy-5-(1-methylpiperidin-4-yl)oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)OC1CCN(CC1)C)OC)C ROATUQDMUFXUDZ-UHFFFAOYSA-N 0.000 claims 1
- KEIXAGCSTFTMCE-UHFFFAOYSA-N 6-methoxy-5-(1-methylpyrrolidin-3-yl)oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)OC1CN(CC1)C)OC)C KEIXAGCSTFTMCE-UHFFFAOYSA-N 0.000 claims 1
- POOTUMJKGCKHDZ-UHFFFAOYSA-N 6-methoxy-5-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2CN(CC2C1)C)OC)C POOTUMJKGCKHDZ-UHFFFAOYSA-N 0.000 claims 1
- AFRWAVVZFSRJTD-UHFFFAOYSA-N 6-methoxy-5-(3-methyl-3,6-diazabicyclo[3.2.0]heptan-6-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C2CN(CC2C1)C)OC)C AFRWAVVZFSRJTD-UHFFFAOYSA-N 0.000 claims 1
- RIENFGUJMFHGDJ-UHFFFAOYSA-N 6-methoxy-5-(3-methyl-3,7-diazabicyclo[4.2.0]octan-7-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C2CCN(CC2C1)C)OC)C RIENFGUJMFHGDJ-UHFFFAOYSA-N 0.000 claims 1
- MTXFCUIHSQTZQB-UHFFFAOYSA-N 6-methoxy-5-(4-methyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazin-6-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2OCCN(C2C1)C)OC)C MTXFCUIHSQTZQB-UHFFFAOYSA-N 0.000 claims 1
- DTLJNHFWGFMZSW-UHFFFAOYSA-N 6-methoxy-5-(4-methyl-3,3a,5,6,7,7a-hexahydro-2H-pyrrolo[3,2-b]pyridin-1-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CCC2N(CCCC21)C)OC)C DTLJNHFWGFMZSW-UHFFFAOYSA-N 0.000 claims 1
- BPSSFAOHFNPNAN-UHFFFAOYSA-N 6-methoxy-5-(4-methylpiperazin-1-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CCN(CC1)C)OC)C BPSSFAOHFNPNAN-UHFFFAOYSA-N 0.000 claims 1
- FPVKZTXDFNGSJV-UHFFFAOYSA-N 6-methoxy-5-(5-methyl-8-oxa-2,5-diazaspiro[3.5]nonan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)N(CCOC2)C)OC)C FPVKZTXDFNGSJV-UHFFFAOYSA-N 0.000 claims 1
- BSKQBFZXCDWRIR-UHFFFAOYSA-N 6-methoxy-5-(6-methyl-2,6-diazabicyclo[3.2.0]heptan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1C2CN(C2CC1)C)OC)C BSKQBFZXCDWRIR-UHFFFAOYSA-N 0.000 claims 1
- KJJCJDQFVDAFSG-UHFFFAOYSA-N 6-methoxy-5-(7-methyl-2,7-diazaspiro[3.4]octan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)CN(CC2)C)OC)C KJJCJDQFVDAFSG-UHFFFAOYSA-N 0.000 claims 1
- MSZHNSKBDCRBTM-UHFFFAOYSA-N 6-methoxy-5-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)CCN(CC2)C)OC)C MSZHNSKBDCRBTM-UHFFFAOYSA-N 0.000 claims 1
- BOLINYJVWIJFES-UHFFFAOYSA-N 6-methoxy-5-(8-methyl-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CC2(C1)OCCN(C2)C)OC)C BOLINYJVWIJFES-UHFFFAOYSA-N 0.000 claims 1
- JXQKQNNMNCWTIW-WOJBJXKFSA-N 6-methoxy-5-[(1R,5R)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@@H]2CCN([C@@H]2C1)C)OC)C JXQKQNNMNCWTIW-WOJBJXKFSA-N 0.000 claims 1
- JXQKQNNMNCWTIW-PMACEKPBSA-N 6-methoxy-5-[(1S,5S)-2-methyl-2,6-diazabicyclo[3.2.0]heptan-6-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C)OC)C JXQKQNNMNCWTIW-PMACEKPBSA-N 0.000 claims 1
- COBMGUYEAKMSGR-PMACEKPBSA-N 6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-5-[(1S,5S)-2-(2,2,2-trifluoroethyl)-2,6-diazabicyclo[3.2.0]heptan-6-yl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)CC(F)(F)F)OC)C COBMGUYEAKMSGR-PMACEKPBSA-N 0.000 claims 1
- JXQKQNNMNCWTIW-YOCWRRKESA-N 6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-5-[(1S,5S)-2-(trideuteriomethyl)-2,6-diazabicyclo[3.2.0]heptan-6-yl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1[C@H]2CCN([C@H]2C1)C([2H])([2H])[2H])OC)C JXQKQNNMNCWTIW-YOCWRRKESA-N 0.000 claims 1
- OEKIZKJCCSEQRO-UHFFFAOYSA-N 6-methoxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]-5-morpholin-4-ylquinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C(=C12)N1CCOCC1)OC)C OEKIZKJCCSEQRO-UHFFFAOYSA-N 0.000 claims 1
- PTTYKDRAMIVLJB-UHFFFAOYSA-N 7-methoxy-5-(1-methylpiperidin-4-yl)oxy-N-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound N=1C=NN2C=NC(=CC2=1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC(=CC(=C12)OC1CCN(CC1)C)OC)C PTTYKDRAMIVLJB-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- ALDFLMRHGPRKDW-ZTDHTWSHSA-N [5-[(4R)-3,3-difluoro-1-methylpiperidin-4-yl]oxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-c]pyrimidin-7-yloxy)anilino]quinazolin-6-yl] 2,4-dimethylpiperazine-1-carboxylate Chemical compound CC1CN(CCN1C(=O)OC2=C(C3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OC5=CC6=NC=NN6C=N5)C)O[C@@H]7CCN(CC7(F)F)C)C ALDFLMRHGPRKDW-ZTDHTWSHSA-N 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 229960004117 capecitabine Drugs 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 229960001612 trastuzumab emtansine Drugs 0.000 claims 1
Classifications
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- C07D487/04—Ortho-condensed systems
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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Claims (15)
1. Spoj, naznačen time, da ima formulu (I):
[image]
ili njegova farmaceutski prihvatljiva sol, pri čemu:
G je C(R5) ili N;
A je CH ili N;
B je CH ili N;
svaki X1, X2, X3, X4, X5, X6 i X7 je neovisno CH ili N, uz uvjet da X6 i X7 nisu svi CH ili N;
E je O, NH ili S;
L je odabran iz skupine koju čine O, S i N(R6);
svaki R1 neovisno je odabran iz skupine koju čine vodik, halogen, cijano, nitro, hidroksil, alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkinil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, aril, N(R7)(R8) i O(R9), pri čemu su navedeni cikloalkil i heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, cijano, nitro, hidroksil, karboksi, karbamoil, acil, alkil, alkenil, alkinil i haloalkil;
R2 je odabran iz skupine koju čine alkil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, pri čemu su navedeni alkil, cikloalkil i heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, cijano, nitro, hidroksil, karboksi, karbamoil, alkil, alkenil, alkinil, haloalkil, zasićeni ili djelomično nezasićeni cikloalkil i N(R10)(R11);
R6 je vodik ili alkil; ili
kada L je N(R6), R2 i R6 zajedno s atomom dušika na koji su vezani tvore 3- do 10-člani zasićeni ili djelomično nezasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O i S, pri čemu je navedeni 3- do 10-člani heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, cijano, nitro, karboksi, karbamoil, alkil, alkenil, alkinil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil, i N(R10)(R11);
svaki R3 i R4 neovisno su odabrani iz skupine koju čine vodik, halogen, cijano, nitro, alkil, alkenil, alkinil i alkoksil;
R5 je odabran iz skupine koju čine vodik, halogen i cijano;
svaki R7 i R8 neovisno su odabrani iz skupine koju čine vodik, alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkinil, acil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, cikloalkilalkil, aril, arilalkil, heteroaril, heteroarilalkil ili heterociklilalkil, pri čemu su navedeni alkil, alkenil, alkinil, acil, cikloalkil, heterociklil, cikloalkilalkil, aril, arilalkil, heteroaril, heteroarilalkil i heterociklilalkil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkinil, alkilamino, zasićeni i djelomično nezasićeni cikloalkil, zasićeni i djelomično nezasićeni heterociklil po izboru supstituiran s alkilom, arilom i heteroarilom; ili
R7 i R8 zajedno s atomom na koji su vezani tvore 3- do 10-člani zasićeni ili djelomično nezasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O, S, SO, SO2 i NR12, pri čemu je navedeni heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine okso, halogen, alkil, alkenil, alkinil, zasićeni i djelomično nezasićeni cikloalkil, zasićeni i djelomično nezasićeni heterociklil, cikloalkilalkil, cijano, nitro, haloalkil, haloalkoksi, azido, aril, heteroaril, arilalkil, heteroarilalkil i heterociklilalkil;
R9 je odabran iz skupine koja se sastoji od alkila, alkenila, alkinila, acila, zasićenog ili djelomično nezasićenog cikloalkila, zasićenog ili djelomično nezasićenog heterociklila, pri čemu su navedeni alkil, alkenil, alkinil, acil, cikloalkil, heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil, alkenil, alkinil, alkoksil, acil, zasićeni i djelomično nezasićeni cikloalkil, zasićeni i djelomično nezasićeni heterociklil, cikloalkilalkil, cijano, nitro, haloalkil, haloalkoksi, azido, aril, heteroaril, arilalkil, heteroarilalkil i heterociklilalkil;
svaki R10 i R11 neovisno su odabrani iz skupine koju čine vodik, alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkinil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, cikloalkilalkil, aril, arilalkil, heteroaril, heteroarilalkil ili heterociklilalkil, pri čemu su navedeni alkil, alkenil, alkinil, cikloalkil, heterociklil, cikloalkilalkil, aril, arilalkil, heteroaril, heteroarilalkil i heterociklilalkil po izboru supstituirani s jednom ili više skupina neovisno odabranih između alkila, alkenila, alkinila, heteroalkila, heteroalkenila, heteroalkinila, zasićenog i djelomično nezasićenog cikloalkila, zasićenog i djelomično nezasićenog heterociklila, arila i heteroarila; ili
R10 i R11 zajedno s atomom na koji su vezani tvore 3- do 10-člani zasićeni ili djelomično nezasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O, S, SO, SO2 i NR12, pri čemu je navedeni heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine okso, halogen, alkil, alkenil, alkinil, zasićeni i djelomično nezasićeni cikloalkil, zasićeni i djelomično nezasićeni heterociklil, cikloalkilalkil, cijano, nitro, haloalkil, haloalkoksi, azido, aril, heteroaril, arilalkil, heteroarilalkil i heterociklilalkil;
R12 je odabran iz skupine koju čine vodik, alkil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, aril, arilalkil, heteroaril, heteroarilalkil ili heterociklilalkil, pri čemu su navedeni alkil, cikloalkil, heterociklil, aril, arilalkil, heteroaril, heteroarilalkil i heterociklilalkil po izboru supstituirani s jednom ili više skupina neovisno odabranih između halogena, alkila, alkenila, alkinila, zasićenog i djelomično nezasićenog cikloalkila, zasićenog i djelomično nezasićenog heterociklila, cikloalkilalkila, cijano, nitro, arila, heteroarila, arilalkila, heteroarilalkila i heterociklilalkila;
n je 0, 1 ili 2.
2. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1, naznačen time, da spoj ima formulu:
[image]
3. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1 ili 2, naznačen time, da X1 je CH.
4. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1, naznačen time, da jedan od X2, X3, X4 i X5 je N; ili pri čemu dva od X2, X3, X4 i X5 su N.
5. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1, naznačen time, da X6 je N i X7 je CH; ili pri čemu X6 je CH i X7 je N.
6. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od prethodnih patentnih zahtjeva, pri čemu G je N, pri čemu po izboru A je CH i B je N; i/ili pri čemu E je O.
7. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je R1 odabran između vodika, N(R7)(R8), O(R9), ili zasićenog ili djelomično nezasićenog heterociklila po izboru supstituiranog acilom, pri čemu je R3 po izboru odabran između halogena ili alkila; i/ili pri čemu R4 je vodik.
8. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da L je N(R6), a R2 i R6 zajedno s atomom dušika na koji su vezani tvore 3- do 10-člani zasićeni ili djelomično nezasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O i S, pri čemu je navedeni 3- do 10-člani heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil, i N(R10)(R11), pri čemu je poželjno da R2 i R6 zajedno s atomom dušika na koji su vezani tvore 4- do 9-člani zasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O i S, pri čemu je navedeni 4- do 9-člani zasićeni heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil, i N(R10)(R11); i/ili pri čemu R2 i R6 zajedno s atomom dušika na koji su vezani tvore:
[image]
[image]
ili
[image]
od kojih je svaki po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil, N(R10)(R11), pri čemu p je 1, 2 ili 3, a q je 1, 2 ili 3.
9. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od patentnih zahtjeva od 1 do 7, naznačen time, da L je O, a R2 je odabran između zasićenog ili djelomično nezasićenog cikloalkila i zasićenog ili djelomično nezasićenog heterociklila, pri čemu su navedeni cikloalkil i heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil i N(R10)(R11), pri čemu je poželjno da je R2 odabran između C4−6 zasićenog cikloalkila ili 5- do 6-članog zasićenog heterociklila, pri čemu su navedeni C4−6 zasićeni cikloalkil i 5- do 6-člani zasićeni heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil i N(R10)(R11).
10. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1 ili 2, naznačen time, da:
G je N;
A je CH;
B je N;
X1 je CH;
X6 je N;
X7 je CH;
E je O;
L je odabran između O ili N(R6);
R1 je O(R9), N(R7)(R8) ili djelomično nezasićeni heterociklil koji je po izboru supstituiran s acilom;
R2 je odabran između C4−6 zasićenog cikloalkila ili 5- do 6-članog zasićenog heterociklila, pri čemu su navedeni C4−6 zasićeni cikloalkil i 5- do 6-člani zasićeni heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil i N(R10)(R11); ili
R2 i R6 zajedno s atomom dušika na koji su vezani tvore 4- do 9-člani zasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O i S, pri čemu je navedeni 4- do 9-člani zasićeni heterociklilni prsten po izboru supstituiran s jednom ili više skupina neovisno odabranih iz skupine koju čine halogen, alkil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil i N(R10)(R11);
R3 je odabran između halogena ili alkila;
R4 i R5 su vodik;
svaki R7 i R8 neovisno su odabrani između vodika, acila ili zasićenog ili djelomično nezasićenog heterociklila, pri čemu su navedeni acil i heterociklil po izboru supstituirani s jednom ili više skupina odabranih između alkila, alkilaminoa, zasićenog i djelomično nezasićenog heterociklila;
R9 je odabran iz skupine koju čine alkil, acil, C3-7 zasićeni ili djelomično nezasićeni cikloalkil i 4- do 6-člani zasićeni ili djelomično nezasićeni heterociklil, pri čemu su navedeni alkil, acil, cikloalkil i heterociklil po izboru supstituirani s jednom ili više skupina neovisno odabranih između halogena, alkila, acila i alkoksila;
R10 i R11 su alkil; i
n je 1.
11. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1 ili 2, naznačen time, da spoj ima formulu odabranu iz skupine koju čine:
[image]
pri čemu, poželjno
L je N(R6);
R1 je odabran iz skupine koju čine halogen, cijano, nitro, hidroksil, alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkinil, zasićeni ili djelomično nezasićeni cikloalkil, zasićeni ili djelomično nezasićeni heterociklil, aril, N(R7)(R8) i O(R9); i
R2 i R6 zajedno s atomom dušika na koji su vezani tvore 4- do 9-člani zasićeni heterociklilni prsten koji po izboru sadrži jedan ili više dodatnih heteroatoma odabranih između N, O i S, pri čemu je navedeni 4- do 9-člani zasićeni heterociklilni prsten po izboru supstituiran s jednom ili viša skupina neovisno odabranih iz skupine koju čine halogen, alkil, haloalkil, zasićeni i djelomično nezasićeni cikloalkil i N(R10)(R11).
12. Spoj ili njegova farmaceutski prihvatljiva sol, prema patentnom zahtjevu 1 ili 2, naznačen time, da spoj ima formulu odabranu iz skupine koju čine:
[image]
13. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je spoj odabran iz skupine koju čine:
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)azetidin-1-il)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)pirolidin-1-il)-6-metoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)pirolidin-1-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-morfolinokinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1-metilpiperidin-4-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1-metilpirolidin-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)ciklobutoksi)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3-(dimetilamino)ciklopentil)oksi)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((4-(dimetilamino)cikloheksil)oksi)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(4-metilpiperazin-1-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)azetidin-1-il)-6-etoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(3-(dimetilamino)azetidin-1-il)-6-(2-fluoroetoksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-(difluorometoksi)-5-((1S,5S)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((1R,5R)-2-metil-2,6- diazabiciklo[3.2.0]heptan-6-il)-6-(((S)-tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
cis-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3-fluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
trans-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3-fluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(difluorometoksi)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(difluorometoksi)kinazolin-5-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((1S,5S)-2-metil-2,6- diazabiciklo[3.2.0]heptan-6-il)-6-(((S)-tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((1R,5R)-2-metil-2,6- diazabiciklo[3.2.0]heptan-6-il)-6-(((S)-tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(((R)-3,3-difluoro-1-metilpiperidin -4-il)oksi)-6-(((S)-tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(((S)-3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(((S)-tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-ciklopropoksi-5-((1S,5S)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-ciklopropoksi-5-((1R,5R)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-izopropoksi-5-((1S,5S)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-izopropoksi-5-((1R,5R)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-ciklopropoksi-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-ciklopropoksi-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-izopropoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-izopropoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-klorofenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-klorofenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-(metil-d3)piperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(metoksi-d3)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(metoksi-d3)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(8-metil-5-oksa-2,8-diazaspiro[3.5]nonan-2-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3R,4S)-3-(dimetilamino)-4-fluoropirolidin-1-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3R,4R)-3-(dimetilamino)-4-fluoropirolidin-1-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(5-metil-8-oksa-2,5-diazaspiro[3.5]nonan-2-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(4-metilheksahidropirolo[3,4-b][1,4]oksazin-6(2H)-il)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7-fluoro-5-metil-2,5-diazaspiro[3.4]oktan-2-il)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7-fluoro-5-metil-2,5-diazaspiro[3.4]oktan-2-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1S,5S)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1R,5R)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(8-fluoro-5-metil-2,5-diazaspiro[3.5]nonan-2-il)-6-metoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(8-fluoro-5-metil-2,5-diazaspiro[3.5]nonan-2-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(6-metil-2,6-diazaspiro[3.4]oktan-2-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(7-metil-2,7-diazaspiro[3,5]nonan-2-il)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-7-metoksi-5-((1-metilpiperidin-4-il)oksi)kinazolin-4-amin;
N4-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-N6-(4,4-dimetil-4,5-dihidrooksazol-2- il)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-4,6-diamin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(8-metil-5-oksa-2,8-diazaspiro[3,5]nonan-2-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-(metoksi-d3)-5-((1S,5S)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-(metoksi-d3)-5-((1R,5R)-2-metil-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7,7-difluoro-5-metil-2,5-diazaspiro[3.4]oktan-2-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7,7-difluoro-5-metil-2,5- diazaspiro[3.4]oktan-2-il)-6-(difluorometoksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7,7-difluoro-5-metil-2,5-diazaspiro[3.4]oktan-2-il)-6-(metoksi-d3)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(7,7-difluoro-5-metil-2,5-diazaspiro[3.4]oktan-2-il)-6-((tetrahidrofuran-3-il)oksi)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(6-metil-2,6-diazabiciklo[3.2.0]heptan-2-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(5-metilheksahidropirolo[3,4-c]pirol-2(1H)-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(4-metiloktahidro-1H-pirolo[3,2-b]piridin-1-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(3-metil-3,7-diazabiciklo[4.2.0]oktan-7-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-(3-metil-3,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(2-ciklopropil-2,6-diazabiciklo[3.2.0]heptan-6-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-(2-(2,2-difluoroetil)-2,6-diazabiciklo[3.2.0]heptan-6-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1S,5S)-2-(metil-d3)-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((1S,5S)-2-(2-fluoretil)-2,6-diazabiciklo[3.2.0]heptan-6-il)-6-metoksikinazolin-4-amin;
N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-6-metoksi-5-((1S,5S)-2-(2,2,2-trifluoroetil)-2,6-diazabiciklo[3.2.0]heptan-6-il)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(trifluorometoksi)kinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-(trifluorometoksi)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((4,4-difluoro-1-metilpirolidin-3-il)oksi)-6-metoksikinazolin-4-amin;
(S)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((4,4-difluoro-1-metilpirolidin-3-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoropiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-(metil-d3)piperidin-4-il)oksi)-6-(metoksi-d3)kinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-izopropilpiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((1-ciklopropil-3,3-difluoropiperidin-4-il)oksi)-6-metoksikinazolin-4-amin;
1-(4-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-6-il)-3,6-dihidropiridin-1(2H)-il)prop-2-en-1-on;
(R)-1-(4-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-6-il)-3,6-dihidropiridin-1(2H)-il)prop-2-en-1-on;
1-(5-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-6-il)-3,6-dihidropiridin-1(2H)-il)prop-2-en-1-on;
1-(4-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-7-il)-3,6-dihidropiridin-1(2H)-il)prop-2-en-1-on;
1-(5-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-7-il)-3,6-dihidropiridin-1(2H)-il)prop-2-en-1-on;
1-(4-((4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)pirolidin-1-il)kinazolin-6-il)oksi)piperidin-1-il)prop-2-en-1-on;
(R)-4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6-metoksikinolin-3-karbonitril;
(R)-4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-metoksikinolin-3-karbonitril;
4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(((R)-3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-6-il 2,4-dimetilpiperazin-1-karboksilat;
(R,E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-3-cijano-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)kinolin-6-il)-4-(dimetilamino)but-2-enamid;
(R,E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-3-cijano-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-etoksikinolin-6-il)-4-(dimetilamino)but-2-enamid;
(R,E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-etoksikinazolin-6-il)-4-(dimetilamino)but-2-enamid;
(R,E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-6-il)-4-(dimetilamino)but-2-enamid;
(E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-3-cijano-5-(((R)-3,3-difluoro-1-metilpiperidin-4-il)oksi)kinolin-6-il)-3-((R)-1-metilpirolidin-2-il)akrilamid;
(E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-3-cijano-5-(((R)-3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-etoksikinolin-6-il)-3-((R)-1-metilpirolidin-2-il)akrilamid;
(E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(((R)-3,3-difluoro-1-metilpiperidin-4-il)oksi)kinazolin-6-il)-3-((R)-1-metilpirolidin-2-il)akrilamid;
(E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(((R)-3,3-difluoro-1-metilpiperidin-4-il)oksi)-7-etoksikinazolin-6-il)-3-((R)-1-metilpirolidin-2-il)akrilamid;
(E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-6-il)-4-(dimetilamino)but-2-enamid;
(R,E)-N-(4-((4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)amino)-5-(3-(dimetilamino)azetidin-1-il)kinazolin-6-il)-3-(1-metilpirolidin-2-il)akrilamid; i
(R)-N-(4-([1,2,4]triazolo[1,5-c]pirimidin-7-iloksi)-3-metilfenil)-5-((3,3-difluoro-1-metilpiperidin-4-il)oksi)-6,7-dimetoksikinazolin-4-amin.
14. Farmaceutski pripravak, naznačen time, da sadrži spoj ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od prethodnih patentnih zahtjeva, i najmanje jednu farmaceutski prihvatljivu pomoćnu tvar, po izboru, pri čemu farmaceutski pripravak ne sadrži sredstvo za olakšavanje ulaska BBB.
15. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od patentnih zahtjeva 1 do 13, naznačen time, da je za upotrebu u postupku liječenja bolesti ili stanja povezanih s HER2 kod ispitanika kojemu je to potrebno, koji obuhvaća davanje ispitaniku terapijski učinkovite količine spoja ili njegove farmaceutski prihvatljive soli, pri čemu su bolesti ili stanja povezani s HER2 prvenstveno rak, kao što je rak dojke, rak želuca, mCRC, NSCLC ili njihove metastaze, gdje je prvenstveno metastaza u mozgu, pri čemu je bolje da je spoj ili njegova farmaceutski prihvatljiva sol sposobna za ulazak BBB u odsutnosti sredstva za olakšavanje ulaska BBB; i/ili
spoj se daje istovremeno, odvojeno ili uzastopno s jednim ili više kemoterapijskih sredstava, kao što je kapecitabin, T-DM1, radioterapija i anti-HER2 protutijelo.
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PCT/CN2019/106233 WO2020057511A1 (en) | 2018-09-18 | 2019-09-17 | Quinazoline derivatives as antitumor agents |
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CN111377850B (zh) * | 2018-12-31 | 2022-10-18 | 艾琪康医药科技(上海)有限公司 | 一种手性n-取代-3,3-二氟-4-羟基哌啶衍生物及其制备方法 |
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