SK285405B6 - Bicyklické heteroaromatické zlúčeniny, spôsob ichprípravy, farmaceutický prostriedok s ich obsahoma ich použitie - Google Patents
Bicyklické heteroaromatické zlúčeniny, spôsob ichprípravy, farmaceutický prostriedok s ich obsahoma ich použitie Download PDFInfo
- Publication number
- SK285405B6 SK285405B6 SK1050-2000A SK10502000A SK285405B6 SK 285405 B6 SK285405 B6 SK 285405B6 SK 10502000 A SK10502000 A SK 10502000A SK 285405 B6 SK285405 B6 SK 285405B6
- Authority
- SK
- Slovakia
- Prior art keywords
- methyl
- ethyl
- amino
- fluorobenzyloxy
- quinazolinamine
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
- -1 Bicyclic heteroaromatic compounds Chemical class 0.000 title claims description 138
- 238000004519 manufacturing process Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 13
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 13
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 39
- 239000012453 solvate Substances 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
- 108060006698 EGF receptor Proteins 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 3
- MNHCZHFLNIOWQH-UHFFFAOYSA-N n-[3-fluoro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(F)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 MNHCZHFLNIOWQH-UHFFFAOYSA-N 0.000 claims description 3
- QEHYWVNDAWPVRJ-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=CC(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=C1 QEHYWVNDAWPVRJ-UHFFFAOYSA-N 0.000 claims description 3
- RZEMPBRXCDBLDH-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 RZEMPBRXCDBLDH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- ZADGIWJEHDJLCZ-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-7-fluoro-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1Br)=CC=C1OCC1=CC=CC=C1 ZADGIWJEHDJLCZ-UHFFFAOYSA-N 0.000 claims description 2
- NKLDCSQPJCETMA-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-7-methoxy-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3OC(CNCCS(C)(=O)=O)=CC=3)C(OC)=CC2=NC=NC=1NC(C=C1Br)=CC=C1OCC1=CC=CC=C1 NKLDCSQPJCETMA-UHFFFAOYSA-N 0.000 claims description 2
- AXVKGZLOECWENV-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 AXVKGZLOECWENV-UHFFFAOYSA-N 0.000 claims description 2
- NOJHSHOVOCTOHJ-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-7-fluoro-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 NOJHSHOVOCTOHJ-UHFFFAOYSA-N 0.000 claims description 2
- UTGTXIQFRUQSMS-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-7-methoxy-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3N=C(CNCCS(C)(=O)=O)SC=3)C(OC)=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 UTGTXIQFRUQSMS-UHFFFAOYSA-N 0.000 claims description 2
- GITHWNVRQPKFEJ-UHFFFAOYSA-N n-(3-fluoro-4-phenylmethoxyphenyl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1F)=CC=C1OCC1=CC=CC=C1 GITHWNVRQPKFEJ-UHFFFAOYSA-N 0.000 claims description 2
- GFRIWQBALIBSCZ-UHFFFAOYSA-N n-(3-fluoro-4-phenylmethoxyphenyl)-7-methoxy-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3OC(CNCCS(C)(=O)=O)=CC=3)C(OC)=CC2=NC=NC=1NC(C=C1F)=CC=C1OCC1=CC=CC=C1 GFRIWQBALIBSCZ-UHFFFAOYSA-N 0.000 claims description 2
- FVRXRENVHJBKFO-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-7-fluoro-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1Br)=CC=C1OCC1=CC=CC(F)=C1 FVRXRENVHJBKFO-UHFFFAOYSA-N 0.000 claims description 2
- QLHIYBDUQPWZAA-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-7-fluoro-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 QLHIYBDUQPWZAA-UHFFFAOYSA-N 0.000 claims description 2
- WIDSGQVCKXSTPB-UHFFFAOYSA-N n-[3-fluoro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(F)C(OCC=5C=C(F)C=CC=5)=CC=4)=C3C=2)=C1 WIDSGQVCKXSTPB-UHFFFAOYSA-N 0.000 claims description 2
- YAPPGADRBQSUIE-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]-3-methoxyphenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound C=1C=C(OCC=2C=C(F)C=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C1=CSC(CNCCS(C)(=O)=O)=N1 YAPPGADRBQSUIE-UHFFFAOYSA-N 0.000 claims description 2
- ZUPCLUORSUOTAD-UHFFFAOYSA-N 4-[2-[(3-fluorophenyl)methoxy]phenyl]-6-[4-[(2-methylsulfonylethylamino)methyl]furan-2-yl]-1h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound CS(=O)(=O)CCNCC1=COC(C=2N=CC3=C(C(N=CN3)(N)C=3C(=CC=CC=3)OCC=3C=C(F)C=CC=3)C=2)=C1 ZUPCLUORSUOTAD-UHFFFAOYSA-N 0.000 claims 1
- CMPYWDJZUOBIIO-UHFFFAOYSA-N 7-fluoro-n-(3-fluoro-4-phenylmethoxyphenyl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1F)=CC=C1OCC1=CC=CC=C1 CMPYWDJZUOBIIO-UHFFFAOYSA-N 0.000 claims 1
- YOHWLAPRGKJAEL-UHFFFAOYSA-N 7-fluoro-n-[3-fluoro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(C(=CC1=NC=N2)F)=CC1=C2NC(C=C1F)=CC=C1OCC1=CC=CC(F)=C1 YOHWLAPRGKJAEL-UHFFFAOYSA-N 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- HMWAXNWFVBPMKK-UHFFFAOYSA-N CCNCC1=NC(=CS1)C2=NC=C3C(=C2)C(=NC=N3)NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl Chemical compound CCNCC1=NC(=CS1)C2=NC=C3C(=C2)C(=NC=N3)NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl HMWAXNWFVBPMKK-UHFFFAOYSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- MNNXRVSQOABRRP-UHFFFAOYSA-N N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-4-thiazolyl]-4-quinazolinamine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=C1 MNNXRVSQOABRRP-UHFFFAOYSA-N 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
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- HQHSVSSDBPWQBD-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(Br)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 HQHSVSSDBPWQBD-UHFFFAOYSA-N 0.000 claims 1
- LPHALCCJJMLFMZ-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(Cl)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 LPHALCCJJMLFMZ-UHFFFAOYSA-N 0.000 claims 1
- WVPMKVVGRCIEBV-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-3-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 WVPMKVVGRCIEBV-UHFFFAOYSA-N 0.000 claims 1
- INOHEVIDYKGWNH-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-7-methoxy-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3OC(CNCCS(C)(=O)=O)=CC=3)C(OC)=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 INOHEVIDYKGWNH-UHFFFAOYSA-N 0.000 claims 1
- RPBYFFUZCIDSBL-UHFFFAOYSA-N n-(3-fluoro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(F)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 RPBYFFUZCIDSBL-UHFFFAOYSA-N 0.000 claims 1
- IVNDWQOKRSEWBH-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Br)C(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=C1 IVNDWQOKRSEWBH-UHFFFAOYSA-N 0.000 claims 1
- OKOQGGNYPJNMTO-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Br)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 OKOQGGNYPJNMTO-UHFFFAOYSA-N 0.000 claims 1
- UODLBPXYHJNREK-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-7-methoxy-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3OC(CNCCS(C)(=O)=O)=CC=3)C(OC)=CC2=NC=NC=1NC(C=C1Br)=CC=C1OCC1=CC=CC(F)=C1 UODLBPXYHJNREK-UHFFFAOYSA-N 0.000 claims 1
- QKXNWCXDCUQVGR-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 QKXNWCXDCUQVGR-UHFFFAOYSA-N 0.000 claims 1
- HNCNTMHPAYQWSL-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-7-fluoro-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C(=CC3=NC=NC(NC=4C=C(Cl)C(OCC=5C=C(F)C=CC=5)=CC=4)=C3C=2)F)=C1 HNCNTMHPAYQWSL-UHFFFAOYSA-N 0.000 claims 1
- LNFFTZLZPLIOIX-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-7-methoxy-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=12C=C(C=3OC(CNCCS(C)(=O)=O)=CC=3)C(OC)=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 LNFFTZLZPLIOIX-UHFFFAOYSA-N 0.000 claims 1
- KOUKAMXSEWAFHF-UHFFFAOYSA-N n-[3-fluoro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1F)=CC=C1OCC1=CC=CC(F)=C1 KOUKAMXSEWAFHF-UHFFFAOYSA-N 0.000 claims 1
- CJGPKVRBUPRPTR-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]-3-methoxyphenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=1C=C(OCC=2C=C(F)C=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C1=CC=C(CNCCS(C)(=O)=O)O1 CJGPKVRBUPRPTR-UHFFFAOYSA-N 0.000 claims 1
- CAORRJWMBDQDQW-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-5-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1)=CC=C1OCC1=CC=CC(F)=C1 CAORRJWMBDQDQW-UHFFFAOYSA-N 0.000 claims 1
- IZSWEZTZKROPAX-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-5-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 IZSWEZTZKROPAX-UHFFFAOYSA-N 0.000 claims 1
- FLWJDTAEWRNVFU-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[4-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound CS(=O)(=O)CCNCC1=CSC(C=2N=CC3=NC=NC(NC=4C=CC(OCC=5C=C(F)C=CC=5)=CC=4)=C3C=2)=N1 FLWJDTAEWRNVFU-UHFFFAOYSA-N 0.000 claims 1
- MJIYTTGQKXMTKS-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[4-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]quinazolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=CSC(C=2C=C3C(NC=4C=CC(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=N1 MJIYTTGQKXMTKS-UHFFFAOYSA-N 0.000 claims 1
- BOKWTLKKZRQINZ-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=CN=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1)=CC=C1OCC1=CC=CC(F)=C1 BOKWTLKKZRQINZ-UHFFFAOYSA-N 0.000 claims 1
- 208000000649 small cell carcinoma Diseases 0.000 claims 1
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- 238000002560 therapeutic procedure Methods 0.000 claims 1
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- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 16
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 7
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9800569.7A GB9800569D0 (en) | 1998-01-12 | 1998-01-12 | Heterocyclic compounds |
| PCT/EP1999/000048 WO1999035146A1 (en) | 1998-01-12 | 1999-01-08 | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK10502000A3 SK10502000A3 (sk) | 2001-08-06 |
| SK285405B6 true SK285405B6 (sk) | 2007-01-04 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1050-2000A SK285405B6 (sk) | 1998-01-12 | 1999-01-08 | Bicyklické heteroaromatické zlúčeniny, spôsob ichprípravy, farmaceutický prostriedok s ich obsahoma ich použitie |
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Families Citing this family (432)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| GB9800569D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| PT1119567E (pt) | 1998-10-08 | 2005-08-31 | Astrazeneca Ab | Derivados de quinazolina |
| GB2345486A (en) * | 1999-01-11 | 2000-07-12 | Glaxo Group Ltd | Heteroaromatic protein tyrosine kinase inhibitors |
| ES2242596T3 (es) | 1999-02-10 | 2005-11-16 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de la angiogenesis. |
| GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| CN1166645C (zh) | 1999-06-21 | 2004-09-15 | 贝林格尔英格海姆法玛两合公司 | 双环杂环化合物,含有该化合物的药物组合物,该化合物的用途及其制备方法 |
| ES2295035T3 (es) | 1999-07-09 | 2008-04-16 | Glaxo Group Limited | Anilinoquinazolinas como inhibidores de proteina tirosina quinasa. |
| US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| WO2001021596A1 (en) | 1999-09-21 | 2001-03-29 | Astrazeneca Ab | Quinazoline derivatives and their use as pharmaceuticals |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| AU2001228638A1 (en) | 2000-01-28 | 2001-08-07 | Astrazeneca Ab | Chemical compounds |
| GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
| US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
| AR035851A1 (es) * | 2000-03-28 | 2004-07-21 | Wyeth Corp | 3-cianoquinolinas, 3-ciano-1,6-naftiridinas y 3-ciano-1,7-naftiridinas como inhibidoras de proteina quinasas |
| US6462238B2 (en) | 2000-05-02 | 2002-10-08 | Array Biopharma, Inc. | Process for the reduction of cyano-substituted sulfones to aminoalkylene-substituted sulfones |
| DK1292591T3 (da) | 2000-06-22 | 2005-05-30 | Pfizer Prod Inc | Bicykliske derivater til behandling af abnorm cellevækst |
| CZ20024120A3 (cs) | 2000-06-28 | 2003-03-12 | Astrazeneca Ab | Substituované chinazolinové deriváty a jejich použití jako inhibitory |
| EP1792902A1 (en) * | 2000-06-30 | 2007-06-06 | Glaxo Group Limited | Processes for preparation of 5-(6-quinazolinyl)-furan-2-carbaldehydes |
| DE60126611T2 (de) * | 2000-06-30 | 2007-11-22 | Glaxo Group Ltd., Greenford | Ditosylatsalze von chinazolinverbindungen |
| IL153947A0 (en) | 2000-08-09 | 2003-07-31 | Astrazeneca Ab | Quinoline derivatives having vegf inhibiting activity |
| CN1474815A (zh) | 2000-09-20 | 2004-02-11 | Ĭ��ר���ɷ�����˾ | 4-氨基-喹唑啉 |
| CN101029022B (zh) | 2000-10-20 | 2011-01-12 | 卫材R&D管理有限公司 | 含氮芳环衍生物的制备方法 |
| US7776315B2 (en) | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
| AU2001295791A1 (en) | 2000-11-02 | 2002-05-15 | Astrazeneca Ab | 4-substituted quinolines as antitumor agents |
| WO2002044166A1 (en) | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| DK1399483T3 (da) | 2001-01-05 | 2010-08-02 | Pfizer | Antistoffer til insulinlignende vækstfaktorrecptor I |
| JP4458746B2 (ja) * | 2001-01-16 | 2010-04-28 | グラクソ グループ リミテッド | 癌の治療方法 |
| EP1488809A1 (en) | 2001-01-16 | 2004-12-22 | Glaxo Group Limited | Pharmaceutical combination containing a 4-quinazolineamine and another anti-neoplastic agent for the treatment of cancer |
| EP1377281A4 (en) * | 2001-03-15 | 2009-06-17 | Rhode Island Hospital | Taurine compounds |
| MY134783A (en) * | 2001-03-23 | 2007-12-31 | Bayer Healthcare Llc | Rho-kinase inhibitors |
| ATE353889T1 (de) * | 2001-03-23 | 2007-03-15 | Bayer Pharmaceuticals Corp | Rho-kinase inhibitoren |
| DE60212487T2 (de) | 2001-04-13 | 2006-12-21 | Pfizer Products Inc., Groton | Bizyklisch substituierte 4-Aminopyridopyrimidinderivate |
| WO2002092578A1 (en) * | 2001-05-14 | 2002-11-21 | Astrazeneca Ab | Quinazoline derivatives |
| AU2002345792A1 (en) | 2001-06-21 | 2003-01-08 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
| US20090197852A9 (en) * | 2001-08-06 | 2009-08-06 | Johnson Robert G Jr | Method of treating breast cancer using 17-AAG or 17-AG or a prodrug of either in combination with a HER2 inhibitor |
| US7829566B2 (en) | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
| AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| AU2003202263A1 (en) | 2002-01-10 | 2003-07-30 | Bayer Healthcare Ag | Roh-kinase inhibitors |
| WO2003062209A2 (en) | 2002-01-17 | 2003-07-31 | Neurogen Corporation | Substituted quinazolin-4-ylamine analogues as modulators of capsaicin |
| EP1470122B1 (en) | 2002-01-23 | 2007-12-19 | Bayer Pharmaceuticals Corporation | Rho-kinase inhibitors |
| CA2473510A1 (en) | 2002-01-23 | 2003-07-31 | Bayer Pharmaceuticals Corporation | Pyrimidine derivatives as rho-kinase inhibitors |
| ES2381781T3 (es) | 2002-02-01 | 2012-05-31 | Astrazeneca Ab | Compuestos de quinazolina |
| EP1481971B1 (en) * | 2002-02-06 | 2011-11-16 | Ube Industries, Ltd. | Process for producing 4-aminoquinazoline compound |
| JP2005534623A (ja) * | 2002-04-08 | 2005-11-17 | スミスクライン ビーチャム コーポレーション | Ｅｒｂファミリーの阻害剤並びにｒａｆ及び／又はｒａｓ阻害剤を投与することを含む癌の治療法 |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| EP1510221A4 (en) * | 2002-06-03 | 2009-04-29 | Mitsubishi Tanabe Pharma Corp | MEANS FOR THE PREVENTION AND / OR TREATMENT OF PERSONS EXPRESSING OR ACTIVATING HER2 AND / OR EGFR |
| UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
| US20040048887A1 (en) * | 2002-07-09 | 2004-03-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors |
| DE60327323D1 (de) | 2002-07-09 | 2009-06-04 | Astrazeneca Ab | Chinazoline derivative und ihre anwendung in der krebsbehandlung |
| GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
| CA2491191C (en) * | 2002-07-15 | 2014-02-04 | Exelixis, Inc. | Receptor-type kinase modulators and methods of use |
| GB0304367D0 (en) * | 2003-02-26 | 2003-04-02 | Pharma Mar Sau | Methods for treating psoriasis |
| GB0225579D0 (en) | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
| US8505468B2 (en) * | 2002-11-19 | 2013-08-13 | Sharp Kabushiki Kaisha | Substrate accommodating tray |
| JP2006515847A (ja) * | 2002-12-13 | 2006-06-08 | ニューロジェン・コーポレーション | カプサイシン受容体調節剤としてのカルボン酸、ホスフェート又はホスホネート置換キナゾリン−４−イルアミン類縁体 |
| ATE362928T1 (de) | 2002-12-19 | 2007-06-15 | Pfizer | 2-(1h-indazol-6-ylamino)- benzamid-verbindungen als protein kinase inhibitoren und deren verwendung zur behandlung von ophthalmischen krankheiten |
| AU2003292435A1 (en) * | 2002-12-23 | 2004-07-14 | Astrazeneca Ab | 4- (pyridin-4-ylamino) -quinazoline derivatives as anti-tumor agents |
| US20060167026A1 (en) * | 2003-01-06 | 2006-07-27 | Hiroyuki Nawa | Antipsychotic molecular-targeting epithelial growth factor receptor |
| US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| KR101106905B1 (ko) | 2003-02-26 | 2012-01-25 | 수젠, 인크. | 단백질 키나아제 억제제로서의 아미노헤테로아릴 화합물 |
| NZ543234A (en) | 2003-05-30 | 2009-04-30 | Astrazeneca Uk Ltd | Marker genes and uses thereof to identify cancer patients that will respond to erbb tyrosine kinase inhibitors |
| TW200510373A (en) | 2003-07-14 | 2005-03-16 | Neurogen Corp | Substituted quinolin-4-ylamine analogues |
| US7329664B2 (en) | 2003-07-16 | 2008-02-12 | Neurogen Corporation | Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues |
| MEP31408A (en) | 2003-07-18 | 2010-10-10 | Abgenix Inc | Specific binding agents to hepatocyte growth factor |
| WO2005011607A2 (en) | 2003-08-01 | 2005-02-10 | Smithkline Beecham Corporation | Treatment of cancers expressing p95 erbb2 |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| CA2536321A1 (en) | 2003-08-29 | 2005-03-10 | Pfizer Inc. | Thienopyridine-phenylacet amides and their derivatives useful as new anti-angiogenic agents |
| GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
| AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| ES2925655T3 (es) * | 2003-09-26 | 2022-10-19 | Exelixis Inc | Moduladores c-Met y métodos de uso |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| WO2005046678A1 (en) * | 2003-11-07 | 2005-05-26 | Smithkline Beecham (Cork) Limited | Cancer treatment method |
| WO2005044788A1 (ja) | 2003-11-11 | 2005-05-19 | Eisai Co., Ltd. | ウレア誘導体およびその製造方法 |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| AU2004298448B2 (en) * | 2003-12-18 | 2010-09-09 | Janssen Pharmaceutica N.V. | Pyrido- and pyrimidopyrimidine derivatives as anti- proliferative agents |
| GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
| WO2005105094A2 (en) * | 2004-04-16 | 2005-11-10 | Smithkline Beecham Corporation | Cancer treatment method |
| HRP20110958T1 (hr) | 2004-05-06 | 2012-01-31 | Warner-Lambert Company Llc | 4-fenilaminokinazolin-6-ilamidi |
| JP2008501690A (ja) * | 2004-06-03 | 2008-01-24 | スミスクライン ビーチャム （コーク） リミテッド | がんの治療方法 |
| CA2569404A1 (en) * | 2004-06-04 | 2005-12-22 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| RU2361589C2 (ru) * | 2004-06-04 | 2009-07-20 | Смитклайн Бичам (Корк) Лимитед | Способ лечения рака |
| US20100226931A1 (en) * | 2004-06-24 | 2010-09-09 | Nicholas Valiante | Compounds for immunopotentiation |
| WO2006002422A2 (en) * | 2004-06-24 | 2006-01-05 | Novartis Vaccines And Diagnostics Inc. | Compounds for immunopotentiation |
| NZ552091A (en) | 2004-07-16 | 2009-09-25 | Pfizer Prod Inc | Combination treatment for non-hematologic malignancies using an anti-IGF-1R antibody |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| ATE463486T1 (de) | 2004-08-26 | 2010-04-15 | Pfizer | Enantiomerenreine aminoheteroaryl-verbindungen als proteinkinasehemmer |
| DE602005013990D1 (de) | 2004-09-17 | 2009-05-28 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
| TW200621251A (en) | 2004-10-12 | 2006-07-01 | Neurogen Corp | Substituted biaryl quinolin-4-ylamine analogues |
| WO2006060318A2 (en) | 2004-11-30 | 2006-06-08 | Amgen Inc. | Quinolines and quinazoline analogs and their use as medicaments for treating cancer |
| GB0427131D0 (en) * | 2004-12-10 | 2005-01-12 | Glaxosmithkline Biolog Sa | Novel combination |
| US7947676B2 (en) | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
| ES2426007T3 (es) * | 2004-12-17 | 2013-10-18 | Smithkline Beecham (Cork) Limited | Método para el tratamiento del cáncer |
| ES2325035T3 (es) * | 2004-12-21 | 2009-08-24 | Smithkline Beecham Corporation | Inhibidores de quinasa erbb de 2-pirimidinil pirazolopiridina. |
| US7812022B2 (en) * | 2004-12-21 | 2010-10-12 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| AU2006204752A1 (en) * | 2005-01-14 | 2006-07-20 | Neurogen Corporation | Heteroaryl substituted quinolin-4-ylamine analogues |
| NZ560879A (en) | 2005-02-18 | 2010-04-30 | Abraxis Bioscience Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
| US8735394B2 (en) * | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
| US20060216288A1 (en) * | 2005-03-22 | 2006-09-28 | Amgen Inc | Combinations for the treatment of cancer |
| EP2444099A1 (en) | 2005-03-31 | 2012-04-25 | Agensys, Inc. | Antibodies and related molecules that bind to 161P2F10B proteins |
| DK1871347T3 (en) | 2005-04-19 | 2016-11-28 | Novartis Ag | pharmaceutical composition |
| KR101203328B1 (ko) | 2005-04-26 | 2012-11-20 | 화이자 인코포레이티드 | Ｐ-카드헤린 항체 |
| JP4989476B2 (ja) | 2005-08-02 | 2012-08-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を検定する方法 |
| EP3381945B1 (en) | 2005-09-07 | 2020-08-19 | Amgen Fremont Inc. | Human monoclonal antibodies to activin receptor-like kinase-1 |
| EP1926996B1 (en) | 2005-09-20 | 2011-11-09 | OSI Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2007034144A1 (en) | 2005-09-20 | 2007-03-29 | Astrazeneca Ab | 4- (ih-indazol-s-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
| UA96139C2 (uk) | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Антитіло до нейропіліну-1 (nrp1) |
| US8404697B2 (en) | 2005-11-11 | 2013-03-26 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| US7807673B2 (en) * | 2005-12-05 | 2010-10-05 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| CN101003514A (zh) | 2006-01-20 | 2007-07-25 | 上海艾力斯医药科技有限公司 | 喹唑啉衍生物、其制备方法及用途 |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| KR20080083046A (ko) * | 2006-01-31 | 2008-09-12 | 에프. 호프만-라 로슈 아게 | 7ｈ-피리도[3,4-ｄ]피리미딘-8-온, 이의 제조 및 단백질키나아제 억제제로서의 용도 |
| PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
| AR060358A1 (es) * | 2006-04-06 | 2008-06-11 | Novartis Vaccines & Diagnostic | Quinazolinas para la inhibicion de pdk 1 |
| US20090203718A1 (en) * | 2006-04-13 | 2009-08-13 | Smithkline Beecham (Cork) Ltd. | Cancer treatment method |
| JP2009534400A (ja) | 2006-04-19 | 2009-09-24 | ノバルティス アクチエンゲゼルシャフト | インダゾール化合物およびｃｄｃ７の阻害方法 |
| KR20090007792A (ko) | 2006-05-09 | 2009-01-20 | 화이자 프로덕츠 인크. | 시클로알킬아미노산 유도체 및 이들의 제약 조성물 |
| NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
| CN104706637A (zh) | 2006-05-18 | 2015-06-17 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
| ES2318616T3 (es) * | 2006-06-01 | 2009-05-01 | Cellzome Ag | Metodos para la identificacion de moleculas que interactuan con zap-70 y para la purificacion de zap-70. |
| ES2427924T3 (es) | 2006-06-30 | 2013-11-04 | Merck Sharp & Dohme Corp. | Biomarcador IGFBP2 |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| EP2054063A4 (en) * | 2006-08-22 | 2010-10-27 | Concert Pharmaceuticals Inc | 4-AMINOCHINAZOLINE DERIVATIVES AND METHOD FOR THEIR USE |
| US20110053964A1 (en) * | 2006-08-22 | 2011-03-03 | Roger Tung | 4-aminoquinazoline derivatives and methods of use thereof |
| KR101472600B1 (ko) | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
| KR20090074202A (ko) | 2006-09-18 | 2009-07-06 | 베링거 인겔하임 인터내셔날 게엠베하 | Ｅｇｆｒ 돌연변이를 갖는 암을 치료하는 방법 |
| CN101547922B (zh) * | 2006-10-04 | 2012-06-20 | 辉瑞产品公司 | 作为钙受体拮抗剂的吡啶并[4,3-d]嘧啶-4(3H)-酮衍生物 |
| JP5528807B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
| WO2008054633A1 (en) * | 2006-10-31 | 2008-05-08 | Janssen Pharmaceutica N.V. | Hydrazone derivatives as kinase inhibitors |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| WO2008076278A2 (en) | 2006-12-13 | 2008-06-26 | Schering Corporation | Methods of cancer treatment with igf1r inhibitors |
| EP2125781A2 (en) | 2006-12-20 | 2009-12-02 | Amgen Inc. | Substituted heterocycles and methods of use |
| ES2449482T3 (es) | 2007-01-09 | 2014-03-19 | Amgen Inc. | Derivados de bis-aril-amida útiles para el tratamiento de cáncer |
| EP2119707B1 (en) | 2007-01-29 | 2015-01-14 | Eisai R&D Management Co., Ltd. | Composition for treatment of undifferentiated-type of gastric cancer |
| CN101245050A (zh) * | 2007-02-14 | 2008-08-20 | 上海艾力斯医药科技有限公司 | 4-苯胺喹唑啉衍生物的盐 |
| JP2010519204A (ja) | 2007-02-16 | 2010-06-03 | アムジエン・インコーポレーテツド | 窒素含有複素環ケトン類およびそれらのｃ−Ｍｅｔ阻害薬としての使用 |
| JP5926487B2 (ja) | 2007-04-13 | 2016-05-25 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | ＥｒｂＢ療法に耐性である癌を治療するための方法 |
| AU2008249745B2 (en) * | 2007-05-09 | 2012-01-12 | Pfizer Inc. | Substituted heterocyclic derivatives and compositions and their pharmaceutical use as antibacterials |
| WO2008154469A1 (en) * | 2007-06-11 | 2008-12-18 | Smithkline Beecham (Cork) Limited | Quinazoline salt compounds |
| UY31137A1 (es) * | 2007-06-14 | 2009-01-05 | Smithkline Beecham Corp | Derivados de quinazolina como inhibidores de la pi3 quinasa |
| NZ583282A (en) | 2007-08-21 | 2012-09-28 | Amgen Inc | Human c-fms antigen binding proteins |
| CA2698287A1 (en) | 2007-09-07 | 2009-03-12 | Agensys, Inc. | Antibodies and related molecules that bind to 24p4c12 proteins |
| US20090215802A1 (en) * | 2007-09-13 | 2009-08-27 | Protia, Llc | Deuterium-enriched lapatinib |
| KR20100099128A (ko) * | 2007-10-19 | 2010-09-10 | 파르마 마르 에스.에이. | 개선된 항암치료 |
| EP2212432A4 (en) | 2007-10-22 | 2011-10-19 | Schering Corp | COMPLETELY HUMAN ANTI-VEGF ANTIBODIES AND USE PROCEDURES |
| EP2220054A2 (en) | 2007-10-29 | 2010-08-25 | Natco Pharma Limited | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents |
| AU2008325608B2 (en) | 2007-11-09 | 2013-03-14 | Eisai R & D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| UY31545A1 (es) | 2007-12-20 | 2009-08-03 | Nuevos derivados de 2-carboxamida cianoaminourea, sus sales y profarmacos farmacéuticamente aceptables, procesos de preparacion y aplicaciones | |
| CN101492445A (zh) * | 2008-01-22 | 2009-07-29 | 孙飘扬 | 杂芳族化合物、其制备方法以及其用途 |
| CA2713459A1 (en) * | 2008-01-30 | 2009-08-06 | Pharma Mar, S.A. | Improved antitumoral treatments |
| MX2010009782A (es) * | 2008-03-07 | 2010-09-30 | Pharma Mar Sa | Tratamientos antitumorales mejorados. |
| PL3269366T3 (pl) | 2008-03-18 | 2020-07-27 | Genentech, Inc. | Kombinacje koniugatu przeciwciało anty-HER2-lek i lapatinibu, i sposoby zastosowania |
| US8252805B2 (en) * | 2008-05-07 | 2012-08-28 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib ditosylate and processes for preparation thereof |
| WO2009140144A1 (en) * | 2008-05-15 | 2009-11-19 | Teva Pharmaceutical Industries Ltd. | Forms of crystalline lapatinib and processes for preparation thereof |
| CN101584696A (zh) * | 2008-05-21 | 2009-11-25 | 上海艾力斯医药科技有限公司 | 包含喹唑啉衍生物的组合物及制备方法、用途 |
| WO2010017387A2 (en) * | 2008-08-06 | 2010-02-11 | Teva Pharmaceutical Industries Ltd. | Lapatinib intermediates |
| EP2158912A1 (en) | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[3-fluorophenyl)methoxy)phenyl]6-[5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
| EP2158913A1 (en) | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[(3-fluorophenyl)methoxy]phenyl]6-(5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
| WO2010027848A2 (en) * | 2008-08-26 | 2010-03-11 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib compounds and processes for the preparation thereof |
| EP2334701A4 (en) | 2008-10-16 | 2014-01-08 | Univ Pittsburgh | FULLY HUMAN ANTIBODIES AGAINST ANTIGENES ASSOCIATED WITH MELANOMA OF HIGH MOLECULAR WEIGHT AND USES THEREOF |
| CA2740977A1 (en) | 2008-11-03 | 2010-06-03 | Natco Pharma Limited | A novel process for the preparation of lapatinib and its pharmaceutically acceptable salts |
| CA2742986C (en) | 2008-11-07 | 2015-03-31 | Triact Therapeutics, Inc. | Use of catecholic butane derivatives in cancer therapy |
| KR20250123237A (ko) | 2009-01-16 | 2025-08-14 | 엑셀리시스, 인코포레이티드 | 암의 치료를 위한 ｎ-（４-｛〔６，７-비스（메틸옥시）퀴놀린-4-일〕옥시｝페닐）-ｎ＇-（４-플루오로페닐）사이클로프로판-1,1-디카르복사미드의 말산염 및 그 결정형 |
| CN101787017A (zh) * | 2009-01-23 | 2010-07-28 | 岑均达 | 光学纯喹唑啉类化合物 |
| CN102307875A (zh) | 2009-02-09 | 2012-01-04 | 苏伯俭股份有限公司 | 吡咯并嘧啶基axl激酶抑制剂 |
| WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
| JP2012519170A (ja) | 2009-02-26 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 生体内の腫瘍細胞のｅｍｔステータスをモニターするためのｉｎｓｉｔｕ法 |
| US20100222381A1 (en) | 2009-02-27 | 2010-09-02 | Hariprasad Vankayalapati | Cyclopentathiophene/cyclohexathiophene DNA methyltransferase inhibitors |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2403339B1 (en) | 2009-03-06 | 2017-01-18 | Merck Sharp & Dohme Corp. | Combination cancer therapy with an akt inhibitor and other anticancer agents |
| US20120064072A1 (en) | 2009-03-18 | 2012-03-15 | Maryland Franklin | Combination Cancer Therapy Comprising Administration of an EGFR Inhibitor and an IGF-1R Inhibitor |
| TWI461211B (zh) | 2009-03-20 | 2014-11-21 | Genentech Inc | 抗－ｈｅｒ抗體 |
| WO2010120386A1 (en) | 2009-04-17 | 2010-10-21 | Nektar Therapeutics | Oligomer-protein tyrosine kinase inhibitor conjugates |
| US8816077B2 (en) | 2009-04-17 | 2014-08-26 | Nektar Therapeutics | Oligomer-protein tyrosine kinase inhibitor conjugates |
| US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
| HUE044629T2 (hu) | 2009-07-06 | 2019-11-28 | Boehringer Ingelheim Int | Eljárás BIBW2992, annak sói, valamint e hatóanyagot tartalmazó szilárd gyógyászati készítmények szárítására |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| JP5876827B2 (ja) | 2009-08-21 | 2016-03-02 | ノバルティス アーゲー | 癌を治療する方法 |
| JP2013503846A (ja) | 2009-09-01 | 2013-02-04 | ファイザー・インク | ベンズイミダゾール誘導体 |
| KR101648787B1 (ko) | 2009-09-28 | 2016-08-17 | 치루 파머수티컬 컴퍼니 리미티드 | 타이로신 키나제 억제제로서 유용한 4－（치환된 아닐리노）－퀴나졸린 유도체 |
| WO2011039759A1 (en) * | 2009-09-29 | 2011-04-07 | Natco Pharma Limited | A new process for the preparation of lapatinib and its pharmaceutically acceptable salts |
| EP2510110A1 (en) | 2009-11-13 | 2012-10-17 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| CN102079759B (zh) * | 2009-12-01 | 2014-09-17 | 天津药物研究院 | 6位取代的喹唑啉类衍生物、其制备方法和用途 |
| AR079256A1 (es) | 2009-12-04 | 2012-01-04 | Genentech Inc | Metodo para el tratamiento del cancer de mama metastasico con trastuzumab-mcc-dm1 |
| PH12012501361A1 (en) | 2009-12-31 | 2012-10-22 | Centro Nac De Investigaciones Oncologicas Cnio | Tricyclic compounds for use as kinase inhibitors |
| US9073927B2 (en) | 2010-01-22 | 2015-07-07 | Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii | Inhibitors of PI3 kinase |
| SG182533A1 (en) | 2010-02-12 | 2012-08-30 | Pfizer | Salts and polymorphs of 8-fluoro-2-{4-[(methylamino}methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one |
| SG183361A1 (en) | 2010-02-18 | 2012-09-27 | Ct Nac Investigaciones Oncologicas Cnio | Triazolo [4, 5 - b] pyridin derivatives |
| JP2013527748A (ja) | 2010-03-03 | 2013-07-04 | オーエスアイ・ファーマシューティカルズ，エルエルシー | インスリン様増殖因子１受容体キナーゼ阻害剤に対する抗癌反応の予測に役立つ生物学的マーカー |
| CA2783665A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| EP2550269B1 (en) | 2010-03-23 | 2016-03-23 | Scinopharm Taiwan Ltd. | Process and intermediates for preparing lapatinib |
| US8710221B2 (en) | 2010-03-23 | 2014-04-29 | Scinopharm Taiwan, Ltd. | Process and intermediates for preparing lapatinib |
| CA2793974A1 (en) | 2010-03-29 | 2011-10-06 | Abraxis Bioscience, Llc | Methods of treating cancer |
| CN107158389A (zh) | 2010-03-29 | 2017-09-15 | 阿布拉科斯生物科学有限公司 | 增强药物递送和治疗剂有效性的方法 |
| WO2011121317A1 (en) | 2010-04-01 | 2011-10-06 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Imidazo [2,1-b] [1,3,4] thiadiazoles as protein or lipid kinase inhibitors |
| ES2530755T3 (es) | 2010-05-21 | 2015-03-05 | Glaxosmithkline Llc | Terapia de combinación para el tratamiento del cáncer |
| JP2013526578A (ja) | 2010-05-21 | 2013-06-24 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 組合せ |
| KR20180049180A (ko) | 2010-06-04 | 2018-05-10 | 아브락시스 바이오사이언스, 엘엘씨 | 췌장암의 치료 방법 |
| ES2611479T3 (es) | 2010-06-16 | 2017-05-09 | University Of Pittsburgh- Of The Commonwealth System Of Higher Education | Anticuerpos contra endoplasmina y su uso |
| WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
| WO2011162343A1 (ja) | 2010-06-25 | 2011-12-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キナーゼ阻害作用を有する化合物の併用による抗腫瘍剤 |
| JP2013539962A (ja) | 2010-07-09 | 2013-10-31 | ジェネンテック， インコーポレイテッド | 抗ニューロピリン抗体及び使用方法 |
| CN102344444B (zh) * | 2010-07-23 | 2015-07-01 | 岑均达 | 光学纯喹唑啉类化合物 |
| CN102344445B (zh) * | 2010-07-23 | 2015-11-25 | 岑均达 | 光学纯喹唑啉类化合物 |
| AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
| SG187886A1 (en) | 2010-08-31 | 2013-04-30 | Genentech Inc | Biomarkers and methods of treatment |
| WO2012052948A1 (en) | 2010-10-20 | 2012-04-26 | Pfizer Inc. | Pyridine- 2- derivatives as smoothened receptor modulators |
| WO2012052745A1 (en) | 2010-10-21 | 2012-04-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Combinations of pi3k inhibitors with a second anti -tumor agent |
| EP2643351A1 (en) | 2010-11-24 | 2013-10-02 | Glaxo Group Limited | Multispecific antigen binding proteins targeting hgf |
| CN102558159A (zh) * | 2010-12-20 | 2012-07-11 | 天津药物研究院 | 4-取代间甲磺酰胺苯胺基-喹唑啉衍生物及其制备方法和用途 |
| CN102558160B (zh) * | 2010-12-20 | 2015-09-23 | 天津药物研究院 | 4-取代对甲磺酰胺苯胺基-喹唑啉衍生物及其制备方法和用途 |
| EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| EP2655364A4 (en) | 2010-12-23 | 2014-06-11 | Apotex Pharmachem Inc | PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS DITOSYLATE SALT |
| US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
| WO2012098387A1 (en) | 2011-01-18 | 2012-07-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | 6, 7-ring-fused triazolo [4, 3 - b] pyridazine derivatives as pim inhibitors |
| EA025011B1 (ru) | 2011-01-31 | 2016-11-30 | Новартис Аг | ПУРИНЫ, ПОЛЕЗНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR КИНАЗЫ, ИХ ИСПОЛЬЗОВАНИЕ И ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ |
| WO2012116040A1 (en) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
| SG192769A1 (en) | 2011-03-04 | 2013-09-30 | Glaxosmithkline Ip No 2 Ltd | Amino-quinolines as kinase inhibitors |
| JP6006242B2 (ja) | 2011-03-04 | 2016-10-12 | ニューゲン セラピューティクス， インコーポレイテッド | アルキン置換キナゾリン化合物および使用方法 |
| CA2829219C (en) | 2011-03-09 | 2021-03-16 | Richard G. Pestell | Prostate cancer cell lines, gene signatures and uses thereof |
| WO2012125913A1 (en) | 2011-03-17 | 2012-09-20 | The Trustees Of The University Of Pennsylvania | Methods and use of bifunctional enzyme-building clamp-shaped molecules |
| WO2012125904A1 (en) | 2011-03-17 | 2012-09-20 | The Trustees Of The University Of Pennsylvania | Mutation mimicking compounds that bind to the kinase domain of egfr |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| WO2012129344A1 (en) | 2011-03-23 | 2012-09-27 | Amgen Inc. | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
| KR20140025434A (ko) | 2011-04-01 | 2014-03-04 | 제넨테크, 인크. | Akt 억제제 화합물 및 화학요법제의 조합물, 및 사용 방법 |
| WO2012142164A1 (en) | 2011-04-12 | 2012-10-18 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii |
| CA2828946C (en) | 2011-04-18 | 2016-06-21 | Eisai R&D Management Co., Ltd. | Therapeutic agent for tumor |
| CA3019531A1 (en) | 2011-04-19 | 2012-10-26 | Pfizer Inc. | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| WO2012155339A1 (zh) * | 2011-05-17 | 2012-11-22 | 江苏康缘药业股份有限公司 | 4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途 |
| SG11201400681UA (en) | 2011-05-19 | 2014-08-28 | Ct Nac De Investigaciones Oncológicas Cnio | Macrocyclic compounds as protein kinase inhibitors |
| EP2524918A1 (en) | 2011-05-19 | 2012-11-21 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyrazines derivates as kinase inhibitors |
| ITMI20110894A1 (it) * | 2011-05-20 | 2012-11-21 | Italiana Sint Spa | Impurezza del lapatinib e suoi sali |
| JP5414739B2 (ja) | 2011-05-25 | 2014-02-12 | 三菱電機株式会社 | 半導体テスト治具 |
| EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| WO2013005041A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Tricyclic heterocyclic compounds as kinase inhibitors |
| WO2013005057A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | New compounds |
| WO2013004984A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Tricyclic compounds for use as kinase inhibitors |
| HUE052198T2 (hu) | 2011-07-21 | 2021-04-28 | Sumitomo Dainippon Pharma Oncology Inc | Heterociklusos protein kináz inhibitorok |
| US9499530B2 (en) * | 2011-08-01 | 2016-11-22 | Hangzhou Minsheng Institutes For Pharma Research | Quinazoline derivative, composition having the derivative, and use of the derivative in preparing medicament |
| WO2013025939A2 (en) | 2011-08-16 | 2013-02-21 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| BR112014004762A2 (pt) | 2011-08-31 | 2018-06-19 | Genentech Inc | métodos de determinação da sensibilidade de crescimento de célula tumoral á inibição por um inibidor de quinase de egfr, de identificação de um paciente com câncer que provavelmente irá se beneficiar do tratamento com um inibidor de efgr, de tratamento de um câncer em um paciente, de seleção de uma terapia para um paciente com câncer e de determinação de superexpressão de gene erbb2 em uma célula |
| EP2758402B9 (en) | 2011-09-22 | 2016-09-14 | Pfizer Inc | Pyrrolopyrimidine and purine derivatives |
| RU2014110228A (ru) | 2011-09-30 | 2015-11-10 | Дженентек, Инк. | Диагностические маркеры |
| US9783613B2 (en) | 2011-10-04 | 2017-10-10 | Igem Therapeutics Limited | IgE anti-HMW-MAA antibody |
| PL2771342T3 (pl) | 2011-10-28 | 2016-11-30 | Nowe pochodne puryny i ich zastosowanie w leczeniu chorób | |
| EP2776467A1 (en) | 2011-11-08 | 2014-09-17 | Pfizer Inc | Methods of treating inflammatory disorders using anti-m-csf antibodies |
| WO2013080218A1 (en) | 2011-11-28 | 2013-06-06 | Fresenius Kabi Oncology Ltd. | Novel intermediates and process for the preparation of lapatinib and its pharmaceutically acceptable salts |
| WO2013113796A1 (en) | 2012-01-31 | 2013-08-08 | Smithkline Beecham (Cork) Limited | Method of treating cancer |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| RU2660354C2 (ru) | 2012-04-03 | 2018-07-05 | Новартис Аг | Комбинированные продукты, содержащие ингибиторы тирозинкиназ, и их применение |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| HK1209673A1 (en) | 2012-05-14 | 2016-04-08 | Prostagene Llc | Using modulators of ccr5 for treating cancer |
| US10213432B2 (en) | 2012-05-16 | 2019-02-26 | Novartis Ag | Dosage regimen for a PI-3 kinase inhibitor |
| WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
| US9505749B2 (en) | 2012-08-29 | 2016-11-29 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| DK2909181T3 (da) | 2012-10-16 | 2017-11-20 | Tolero Pharmaceuticals Inc | PKM2-modulatorer og fremgangsmåder til anvendelse deraf |
| CZ2012712A3 (cs) | 2012-10-17 | 2014-04-30 | Zentiva, K.S. | Nový způsob výroby klíčového intermediátu výroby lapatinibu |
| CN102942561A (zh) * | 2012-11-06 | 2013-02-27 | 深圳海王药业有限公司 | 4-氨基喹唑啉杂环化合物及其用途 |
| US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
| KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
| CN103896889B (zh) * | 2012-12-27 | 2016-05-25 | 上海创诺制药有限公司 | 拉帕替尼中间体及其制备方法和应用 |
| WO2014127214A1 (en) | 2013-02-15 | 2014-08-21 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| EP2958552B1 (en) | 2013-02-19 | 2017-06-21 | Hexal AG | Pharmaceutical composition comprising n-[3-chloro-4-(3-fluorobenzyloxy)phenyl]-6-[5({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]quinazolin-4-amine or a pharmaceutically acceptable salt, solvate or solvated salt thereof |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| CN107915751A (zh) | 2013-02-20 | 2018-04-17 | 卡拉制药公司 | 治疗性化合物和其用途 |
| TWI630203B (zh) | 2013-02-21 | 2018-07-21 | 葛蘭素史克智慧財產發展有限公司 | 做為激酶抑制劑的喹唑啉類 |
| KR20150118159A (ko) | 2013-02-22 | 2015-10-21 | 에프. 호프만-라 로슈 아게 | 암의 치료 방법 및 약물 내성의 예방 방법 |
| JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス，インク． | 癌治療 |
| CN103159747A (zh) * | 2013-02-26 | 2013-06-19 | 常州鸿创高分子科技有限公司 | 一种二对甲苯磺酸拉帕替尼的合成方法 |
| US9468681B2 (en) | 2013-03-01 | 2016-10-18 | California Institute Of Technology | Targeted nanoparticles |
| HK1213180A1 (zh) | 2013-03-06 | 2016-06-30 | 豪夫迈‧罗氏有限公司 | 治疗和预防癌症药物抗性的方法 |
| RU2015139054A (ru) | 2013-03-14 | 2017-04-19 | Дженентек, Инк. | Способы лечения рака и профилактики лекарственной резистентности рака |
| KR20210149232A (ko) | 2013-03-14 | 2021-12-08 | 스미토모 다이니폰 파마 온콜로지, 인크. | Ｊａｋ2 및 ａｌｋ2 억제제 및 이들의 사용 방법 |
| MX2015011899A (es) | 2013-03-15 | 2016-05-05 | Genentech Inc | Metodos para el tratamiento de cáncer y prevención de resistencia a los fármacos para el cáncer. |
| WO2014147246A1 (en) | 2013-03-21 | 2014-09-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
| WO2014170910A1 (en) | 2013-04-04 | 2014-10-23 | Natco Pharma Limited | Process for the preparation of lapatinib |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| EP2997377B1 (en) | 2013-05-14 | 2018-07-18 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| HU231012B1 (hu) | 2013-05-24 | 2019-11-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Lapatinib sók |
| ES2784664T3 (es) * | 2013-07-18 | 2020-09-29 | Shanghai Fochon Pharmaceutical Co Ltd | Derivados de quinazolina, composiciones de los mismos y uso como productos farmacéuticos. |
| US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
| WO2015051302A1 (en) | 2013-10-04 | 2015-04-09 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2015066482A1 (en) | 2013-11-01 | 2015-05-07 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CN103554091B (zh) * | 2013-11-05 | 2016-05-18 | 沈阳工业大学 | 喹唑啉衍生物及其制备方法和用途 |
| UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
| PL3076969T3 (pl) | 2013-12-06 | 2022-01-17 | Novartis Ag | Schemat dawkowania selektywnego inhibitora 3-kinazy fosfatydynozytolu alfa-izoformy |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| RS59059B1 (sr) | 2014-01-24 | 2019-08-30 | Turning Point Therapeutics Inc | Diaril makrociklična jedinjenja kao modulatori protein kinaza |
| US20160361309A1 (en) | 2014-02-26 | 2016-12-15 | Glaxosmithkline Intellectual Property (No.2) Limited | Methods of treating cancer patients responding to ezh2 inhibitor gsk126 |
| EP3122900A1 (en) | 2014-03-24 | 2017-02-01 | F. Hoffmann-La Roche AG | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| EP2937346A1 (en) | 2014-04-24 | 2015-10-28 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Co-crystals of lapatinib |
| MA39926B1 (fr) | 2014-04-30 | 2019-12-31 | Pfizer | Dérivés de dihétérocycle liés à cycloalkyle |
| US9388239B2 (en) | 2014-05-01 | 2016-07-12 | Consejo Nacional De Investigation Cientifica | Anti-human VEGF antibodies with unusually strong binding affinity to human VEGF-A and cross reactivity to human VEGF-B |
| WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
| EP3473271B1 (en) | 2014-07-31 | 2022-07-20 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Human monoclonal antibodies against epha4 and their use |
| HUE059606T2 (hu) | 2014-08-28 | 2022-11-28 | Eisai R&D Man Co Ltd | Nagy tisztaságú kinolinszármazék és eljárás elõállítására |
| US20170252335A1 (en) | 2014-10-17 | 2017-09-07 | Novartis Ag | Combination of Ceritinib with an EGFR Inhibitor |
| US10206924B2 (en) * | 2014-12-15 | 2019-02-19 | The Regents Of The University Of Michigan | Small molecule inhibitors of EGFR and PI3K |
| WO2016097918A1 (en) | 2014-12-18 | 2016-06-23 | Pfizer Inc. | Pyrimidine and triazine derivatives and their use as axl inhibitors |
| KR20170095893A (ko) | 2014-12-24 | 2017-08-23 | 제넨테크, 인크. | 방광암에 대한 치료, 진단, 및 예후 방법 |
| CN105801565B (zh) * | 2014-12-30 | 2020-04-03 | 天津法莫西医药科技有限公司 | N-[3-氯-4-[(3-氟苯基)甲氧基]苯基]-6-[(5-甲酰基)呋喃-2-基]-4-喹唑啉胺制备方法 |
| EP3242934B1 (en) | 2015-01-08 | 2021-08-18 | The Board of Trustees of the Leland Stanford Junior University | Factors and cells that provide for induction of bone, bone marrow, and cartilage |
| MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
| US20180050993A1 (en) * | 2015-02-03 | 2018-02-22 | Trillium Therapeutics Inc. | Novel fluorinated derivatives as egfr inhibitors useful for treating cancers |
| AU2016224583B2 (en) | 2015-02-25 | 2021-06-03 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| AU2015384801B2 (en) | 2015-03-04 | 2022-01-06 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| US9901574B2 (en) | 2015-04-20 | 2018-02-27 | Tolero Pharmaceuticals, Inc. | Predicting response to alvocidib by mitochondrial profiling |
| CA2984421C (en) | 2015-05-01 | 2024-04-09 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
| ES2921350T3 (es) | 2015-05-18 | 2022-08-24 | Sumitomo Pharma Oncology Inc | Profármacos de alvocidib que tienen biodisponibilidad aumentada |
| CN106279307B (zh) * | 2015-05-19 | 2019-07-26 | 正大天晴药业集团股份有限公司 | 芳氨代葡萄糖衍生物、其制备方法及抗肿瘤用途 |
| JP6757959B2 (ja) | 2015-06-16 | 2020-09-23 | 株式会社 ＰＲＩＳＭ ＢｉｏＬａｂ | 抗がん剤 |
| ES2980216T3 (es) | 2015-07-01 | 2024-09-30 | California Inst Of Techn | Sistemas de administración basados en polímeros de ácido múcico catiónicos |
| MX2017017097A (es) | 2015-07-02 | 2018-05-23 | Tp Therapeutics Inc | Macrociclos diarílicos quirales como moduladores de proteínas quinasas. |
| PT3319969T (pt) | 2015-07-06 | 2024-06-17 | Turning Point Therapeutics Inc | Polimorfo de macrociclo de diarilo |
| WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
| BR112018001065A2 (pt) | 2015-07-21 | 2018-09-11 | Tp Therapeutics, Inc. | macrociclos diarila quirais e usos dos mesmos |
| MX2018001289A (es) | 2015-08-03 | 2018-04-30 | Tolero Pharmaceuticals Inc | Terapias de combinacion para el tratamiento del cancer. |
| EP3331919A1 (en) | 2015-08-07 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination therapy comprising anti ctla-4 antibodies |
| CA2994925C (en) | 2015-08-20 | 2023-08-29 | Eisai R&D Management Co., Ltd. | Tumor therapeutic agent |
| WO2017040982A1 (en) * | 2015-09-02 | 2017-03-09 | The Regents Of The University Of California | Her3 ligands and uses thereof |
| CN106632276B (zh) * | 2015-10-28 | 2021-06-15 | 上海天慈生物谷生物工程有限公司 | 一种治疗乳腺癌药物的制备方法 |
| CN108472289A (zh) | 2015-11-02 | 2018-08-31 | 诺华股份有限公司 | 磷脂酰肌醇3-激酶抑制剂的给药方案 |
| EP3383907B1 (en) | 2015-12-01 | 2022-02-23 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| WO2017096165A1 (en) | 2015-12-03 | 2017-06-08 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
| CA3017411C (en) | 2016-03-15 | 2024-06-25 | Oryzon Genomics, S.A. | Combinations of lsd1 inhibitors for use in the treatment of solid tumors |
| JP2019527230A (ja) | 2016-07-28 | 2019-09-26 | ターニング・ポイント・セラピューティクス・インコーポレイテッドＴｕｒｎｉｎｇ Ｐｏｉｎｔ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 大環状キナーゼ阻害剤 |
| EP3494140A1 (en) | 2016-08-04 | 2019-06-12 | GlaxoSmithKline Intellectual Property Development Ltd | Anti-icos and anti-pd-1 antibody combination therapy |
| AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US10392399B2 (en) | 2016-09-08 | 2019-08-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| AU2017324251A1 (en) | 2016-09-08 | 2019-03-21 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
| WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| US10132797B2 (en) | 2016-12-19 | 2018-11-20 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
| JOP20190154B1 (ar) | 2016-12-22 | 2022-09-15 | Amgen Inc | بنز أيزو ثيازول، أيزو ثيازولو [3، 4-b] بيريدين، كينازولين، فثالازين، بيريدو [2، 3-d] بيريدازين ومشتقات بيريدو [2، 3-d] بيريميدين على هيئة مثبطات kras g12c لمعالجة سرطان الرئة، أو سرطان البنكرياس أو سرطان القولون والمستقيم |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| BR112019014127A2 (pt) | 2017-02-08 | 2020-02-11 | Eisai R&D Management Co., Ltd. | Composição farmacêutica para tratamento de tumores |
| MX2019013014A (es) | 2017-05-16 | 2020-08-06 | Eisai R&D Man Co Ltd | Tratamiento de carcinoma hepatocelular. |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| PE20200700A1 (es) | 2017-07-28 | 2020-06-23 | Turning Point Therapeutics Inc | Compuestos macrociclicos y usos de los mismos |
| ES2985118T3 (es) | 2017-09-08 | 2024-11-04 | Amgen Inc | Inhibidores de KRAS G12C y métodos de uso de los mismos |
| US11497756B2 (en) | 2017-09-12 | 2022-11-15 | Sumitomo Pharma Oncology, Inc. | Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib |
| US20200237766A1 (en) | 2017-10-13 | 2020-07-30 | Tolero Pharmaceuticals, Inc. | Pkm2 activators in combination with reactive oxygen species for treatment of cancer |
| WO2019126136A2 (en) | 2017-12-18 | 2019-06-27 | Sterngreene, Inc. | Pyrimidine compounds useful as tyrosine kinase inhibitors |
| LT3728271T (lt) | 2017-12-19 | 2022-12-12 | Turning Point Therapeutics, Inc. | Makrocikliniai junginiai, skirti ligų gydymui |
| JP7266043B2 (ja) | 2018-05-04 | 2023-04-27 | アムジエン・インコーポレーテツド | ＫＲａｓ Ｇ１２Ｃ阻害剤及びそれを使用する方法 |
| WO2019213526A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| CA3099045A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
| AU2019278998B2 (en) | 2018-06-01 | 2023-11-09 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| WO2019241157A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
| JP7369719B2 (ja) | 2018-06-12 | 2023-10-26 | アムジエン・インコーポレーテツド | ＫＲａｓ Ｇ１２Ｃ阻害剤及びそれを使用する方法 |
| CA3099440A1 (en) | 2018-06-13 | 2019-12-19 | California Institute Of Technology | Nanoparticles for crossing the blood brain barrier and methods of treatment using the same |
| MY204443A (en) * | 2018-06-27 | 2024-08-28 | Oscotec Inc | Pyridopyrimidinone derivatives for use as axl inhibitors |
| CN112512597A (zh) | 2018-07-26 | 2021-03-16 | 大日本住友制药肿瘤公司 | 用于治疗与acvr1表达异常相关的疾病的方法以及用于此的acvr1抑制剂 |
| AU2019352741A1 (en) | 2018-10-04 | 2021-05-06 | Assistance Publique-Hôpitaux De Paris (Aphp) | EGFR inhibitors for treating keratodermas |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| EP3890749A4 (en) | 2018-12-04 | 2022-08-03 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 INHIBITORS AND POLYMORPHS THEREOF FOR USE AS AGENTS FOR THE TREATMENT OF CANCER |
| EP3898615A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| WO2020131627A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| AU2019403488B2 (en) | 2018-12-20 | 2025-07-24 | Amgen Inc. | KIF18A inhibitors |
| CR20210387A (es) | 2018-12-20 | 2021-08-19 | Amgen Inc | Inhibidores de kif18a |
| MA54546A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a |
| JP7676308B2 (ja) | 2018-12-20 | 2025-05-14 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| WO2020128981A1 (en) * | 2018-12-21 | 2020-06-25 | University Of Notre Dame Du Lac | Discovery of bd oxidase inhibitors for the treatment of mycobacterial diseases |
| EP3917963A1 (en) | 2019-02-01 | 2021-12-08 | GlaxoSmithKline Intellectual Property Development Limited | Belantamab mafodotin in combination with pembrolizumab for treating cancer |
| US11471456B2 (en) | 2019-02-12 | 2022-10-18 | Sumitomo Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
| US20230096028A1 (en) | 2019-03-01 | 2023-03-30 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| KR20210146287A (ko) | 2019-03-01 | 2021-12-03 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로아릴 화합물 및 이의 용도 |
| WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
| EP3941463A1 (en) | 2019-03-22 | 2022-01-26 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| KR20220011670A (ko) | 2019-05-21 | 2022-01-28 | 암젠 인크 | 고체 상태 형태 |
| BR112021025476A2 (pt) | 2019-06-26 | 2022-10-11 | Glaxosmithkline Ip Dev Ltd | Proteínas de ligação à il1rap |
| US20220372018A1 (en) | 2019-08-02 | 2022-11-24 | Amgen Inc. | Kif18a inhibitors |
| WO2021026098A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| US20220281843A1 (en) | 2019-08-02 | 2022-09-08 | Amgen Inc. | Kif18a inhibitors |
| WO2021046289A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and ipilimumab |
| WO2021043961A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and chemotherapy |
| WO2021081212A1 (en) | 2019-10-24 | 2021-04-29 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| MX2022005357A (es) | 2019-11-04 | 2022-06-02 | Revolution Medicines Inc | Inhibidores de ras. |
| CA3160142A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| US11566007B2 (en) | 2019-11-04 | 2023-01-31 | Revolution Medicines, Inc. | Ras inhibitors |
| PH12022551102A1 (en) | 2019-11-08 | 2023-11-20 | Revolution Medicines Inc | Bicyclic heteroaryl compounds and uses thereof |
| AR120456A1 (es) | 2019-11-14 | 2022-02-16 | Amgen Inc | Síntesis mejorada del compuesto inhibidor de g12c de kras |
| IL292315A (en) | 2019-11-14 | 2022-06-01 | Amgen Inc | Improved synthesis of kras g12c inhibitor compound |
| JP2023505100A (ja) | 2019-11-27 | 2023-02-08 | レボリューション メディシンズ インコーポレイテッド | 共有ｒａｓ阻害剤及びその使用 |
| AU2021206217A1 (en) | 2020-01-07 | 2022-09-01 | Revolution Medicines, Inc. | SHP2 inhibitor dosing and methods of treating cancer |
| EP4096718A1 (en) | 2020-01-28 | 2022-12-07 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
| CN115397514A (zh) * | 2020-03-02 | 2022-11-25 | 特普医药公司 | 大环化合物的治疗用途 |
| CA3183032A1 (en) | 2020-06-18 | 2021-12-23 | Mallika Singh | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
| KR20230081726A (ko) | 2020-09-03 | 2023-06-07 | 레볼루션 메디슨즈, 인크. | Shp2 돌연변이가 있는 악성 종양을 치료하기 위한 sos1 억제제의 용도 |
| CA3194067A1 (en) | 2020-09-15 | 2022-03-24 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202241885A (zh) | 2020-12-22 | 2022-11-01 | 大陸商上海齊魯銳格醫藥研發有限公司 | Ｓｏｓ１抑制劑及其用途 |
| WO2022140456A1 (en) | 2020-12-22 | 2022-06-30 | Mekanistic Therapeutics Llc | Substituted aminobenzyl heteroaryl compounds as egfr and/or pi3k inhibitors |
| WO2022221227A1 (en) | 2021-04-13 | 2022-10-20 | Nuvalent, Inc. | Amino-substituted heterocycles for treating cancers with egfr mutations |
| JP2024516450A (ja) | 2021-05-05 | 2024-04-15 | レボリューション メディシンズ インコーポレイテッド | 共有結合性ｒａｓ阻害剤及びその使用 |
| PE20240088A1 (es) | 2021-05-05 | 2024-01-16 | Revolution Medicines Inc | Inhibidores de ras |
| AR125787A1 (es) | 2021-05-05 | 2023-08-16 | Revolution Medicines Inc | Inhibidores de ras |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| CN119212994A (zh) | 2021-12-17 | 2024-12-27 | 建新公司 | 作为shp2抑制剂的吡唑并吡嗪化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| CN119998298A (zh) | 2022-06-10 | 2025-05-13 | 锐新医药公司 | 大环ras抑制剂 |
| EP4601644A1 (en) | 2022-10-14 | 2025-08-20 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
| TW202504611A (zh) | 2023-03-30 | 2025-02-01 | 美商銳新醫藥公司 | 用於誘導ｒａｓ ｇｔｐ水解之組合物及其用途 |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| US20240352036A1 (en) | 2023-04-14 | 2024-10-24 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| US20240352038A1 (en) | 2023-04-14 | 2024-10-24 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| WO2024229406A1 (en) | 2023-05-04 | 2024-11-07 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4074057A (en) | 1973-12-12 | 1978-02-14 | Takeda Chemical Co., Ltd. | 2-Halopropionic acid and its derivatives |
| US4166735A (en) | 1977-01-21 | 1979-09-04 | Shell Oil Company | Cycloalkanecarboxanilide derivative herbicides |
| EP0222839A4 (en) | 1985-05-17 | 1988-11-09 | Univ Australian | ANTI-MALARIA COMPOUNDS. |
| US5141941A (en) | 1988-11-21 | 1992-08-25 | Ube Industries, Ltd. | Aralkylamine derivatives, and fungicides containing the same |
| US5034393A (en) | 1989-07-27 | 1991-07-23 | Dowelanco | Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives |
| CA2039411A1 (en) | 1990-03-30 | 1991-10-01 | Ronnie Gerald Edie | Thienopyrimidine derivatives |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| DE4131924A1 (de) | 1991-09-25 | 1993-07-08 | Hoechst Ag | Substituierte 4-alkoxypyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel |
| GB9127252D0 (en) | 1991-12-23 | 1992-02-19 | Boots Co Plc | Therapeutic agents |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| WO1993018035A1 (en) | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
| WO1993017682A1 (en) | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
| US5326766A (en) | 1992-08-19 | 1994-07-05 | Dreikorn Barry A | 4-(2-(4-(2-pyridinyloxy)phenyl)ethoxy)quinazoline and analogues thereof |
| DE4308014A1 (de) | 1993-03-13 | 1994-09-15 | Hoechst Schering Agrevo Gmbh | Kondensierte Stickstoffheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide |
| GB9312891D0 (en) | 1993-06-22 | 1993-08-04 | Boots Co Plc | Therapeutic agents |
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| US5679683A (en) | 1994-01-25 | 1997-10-21 | Warner-Lambert Company | Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| AU2096895A (en) | 1994-03-07 | 1995-09-25 | Sugen, Incorporated | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (en:Method) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| DE69531558T2 (de) | 1995-06-07 | 2004-03-18 | Pfizer Inc. | Heterocyclische kondensierte pyrimidin-derivate |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| CA2209598C (en) | 1995-11-14 | 2005-06-07 | Pharmacia & Upjohn Spa | Aryl and heteroaryl purine compounds |
| GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| ID19430A (id) | 1996-07-13 | 1998-07-09 | Glaxo Group Ltd | Senyawa senyawa heterosiklik |
| ID19609A (id) | 1996-07-13 | 1998-07-23 | Glaxo Group Ltd | Senyawa-senyawa heterosiklik |
| HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
| GB9800569D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| DK1292591T3 (da) * | 2000-06-22 | 2005-05-30 | Pfizer Prod Inc | Bicykliske derivater til behandling af abnorm cellevækst |
| DE60126611T2 (de) * | 2000-06-30 | 2007-11-22 | Glaxo Group Ltd., Greenford | Ditosylatsalze von chinazolinverbindungen |
| JP4458746B2 (ja) * | 2001-01-16 | 2010-04-28 | グラクソ グループ リミテッド | 癌の治療方法 |
| ES2381781T3 (es) * | 2002-02-01 | 2012-05-31 | Astrazeneca Ab | Compuestos de quinazolina |
| US7488823B2 (en) * | 2003-11-10 | 2009-02-10 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
-
1998
- 1998-01-12 GB GBGB9800569.7A patent/GB9800569D0/en not_active Ceased
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