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 PDF

Info

Publication number: SK285405B6
Authority: SK; Slovakia
Prior art keywords: methyl; ethyl; amino; fluorobenzyloxy; quinazolinamine
Prior art date: 1998-01-12

Application number

SK1050-2000A

Other languages

English (en)

Slovak (sk)

Other versions

SK10502000A3 (sk

Inventor

Malcolm Clive Carter

George Stuart Cockerill

Stephen Barry Guntrip

Karen Elizabeth Lackey

Kathryn Jane Smith

Original Assignee

Glaxo Group Limited

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-01-12

Filing date

1999-01-08

Publication date

2007-01-04

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=10825153&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK285405(B6) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1999-01-08 Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited

2001-08-06 Publication of SK10502000A3 publication Critical patent/SK10502000A3/sk

2007-01-04 Publication of SK285405B6 publication Critical patent/SK285405B6/sk

Links

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
208000020816 lung neoplasm Diseases 0.000 claims 1
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
201000011549 stomach cancer Diseases 0.000 claims 1
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Classifications

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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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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SK1050-2000A 1998-01-12 1999-01-08 Bicyklické heteroaromatické zlúčeniny, spôsob ichprípravy, farmaceutický prostriedok s ich obsahoma ich použitie SK285405B6 (sk)

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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

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1999
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2007
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2008
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Also Published As

Publication number	Publication date
CY1105618T1 (el)	2010-12-22
PL341595A1 (en)	2001-04-23
US8513262B2 (en)	2013-08-20
EE200000411A (et)	2001-12-17
PE20000230A1 (es)	2000-04-03
CO4820390A1 (es)	1999-07-28
NO2008017I2 (2)	2011-10-17
NL300360I1 (nl)	2008-11-03
SK10502000A3 (sk)	2001-08-06
DE69918528D1 (de)	2004-08-12
EG24743A (en)	2010-07-14
JP3390741B2 (ja)	2003-03-31
GEP20022678B (en)	2002-04-25
IS5549A (is)	2000-06-27
US20160051551A1 (en)	2016-02-25
HUP0100941A2 (hu)	2001-09-28
SI1454907T1 (sl)	2009-04-30
CZ20002587A3 (en)	2001-05-16
AP1446A (en)	2005-07-19
AR015507A1 (es)	2001-05-02
EP1460072B1 (en)	2006-04-05
NO20003561D0 (no)	2000-07-11
DE69930773D1 (de)	2006-05-18
US20070238875A1 (en)	2007-10-11
AU749549C (en)	2003-03-20
KR100569776B1 (ko)	2006-04-11
US20130310562A1 (en)	2013-11-21
MA26596A1 (fr)	2004-12-20
US20030176451A1 (en)	2003-09-18
SI1460072T1 (sl)	2006-08-31
EA200000637A1 (ru)	2001-02-26
DK1047694T3 (da)	2004-11-08
YU44800A (sh)	2002-11-15
EP1047694A1 (en)	2000-11-02
BR9906904A (pt)	2000-10-17
US9199973B2 (en)	2015-12-01
DK1454907T3 (da)	2009-03-09
ME00757B (me)	2008-06-05
CA2317589A1 (en)	1999-07-15
EP1454907A1 (en)	2004-09-08
AU2010276460A1 (en)	2011-02-17
EP1460072A1 (en)	2004-09-22
US20100120804A1 (en)	2010-05-13
PT1460072E (pt)	2006-07-31
NO316176B1 (no)	2003-12-22
FR08C0038I2 (fr)	2012-02-22
US20160339027A1 (en)	2016-11-24
CZ298047B6 (cs)	2007-06-06
IL137041A0 (en)	2001-06-14
ES2319119T3 (es)	2009-05-04
DE69918528T2 (de)	2005-07-28
CY2008015I1 (el)	2009-11-04
AR066982A2 (es)	2009-09-23
EP1047694B1 (en)	2004-07-07
NZ505456A (en)	2003-06-30
EP1454907B1 (en)	2008-12-17
US8912205B2 (en)	2014-12-16
EE04616B1 (et)	2006-04-17
PL192746B1 (pl)	2006-12-29
CY2008015I2 (el)	2009-11-04
GB9800569D0 (en)	1998-03-11
US20020147205A1 (en)	2002-10-10
PT1454907E (pt)	2009-02-18
CY1108859T1 (el)	2014-07-02
IL137041A (en)	2006-10-05
CN1134438C (zh)	2004-01-14
JP2002326990A (ja)	2002-11-15
US6727256B1 (en)	2004-04-27
ATE270670T1 (de)	2004-07-15
DE122008000048I1 (de)	2009-01-02
US7109333B2 (en)	2006-09-19
WO1999035146A1 (en)	1999-07-15
TR200002015T2 (tr)	2001-01-22
ATE417847T1 (de)	2009-01-15
RS49779B (sr)	2008-06-05
HRP20000469B1 (hr)	2007-05-31
BG64825B1 (bg)	2006-05-31
KR20010015902A (ko)	2001-02-26
HU227593B1 (en)	2011-09-28
NO20003561L (no)	2000-09-11
CA2317589C (en)	2007-08-07
UA66827C2 (uk)	2004-06-15
BG104668A (en)	2001-04-30
LU91475I9 (2)	2019-01-02
LU91475I2 (fr)	2008-11-10
ZA99172B (en)	2000-07-11
NO2008017I1 (no)	2008-12-01
HRP20000469A2 (en)	2001-06-30
HUP0100941A3 (en)	2002-09-30
HK1031883A1 (en)	2001-06-29
US20050130996A1 (en)	2005-06-16
DE69940128D1 (de)	2009-01-29
OA11444A (en)	2004-04-29
AU749549B2 (en)	2002-06-27
CN1292788A (zh)	2001-04-25
EA002455B1 (ru)	2002-04-25
NL300360I2 (nl)	2009-02-02
DE69930773T2 (de)	2006-09-28
MY124055A (en)	2006-06-30
AU2278399A (en)	1999-07-26
ATE322491T1 (de)	2006-04-15
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US20070015775A1 (en)	2007-01-18
HRP20060387A2 (en)	2008-02-29
PT1047694E (pt)	2004-11-30
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US20150065527A1 (en)	2015-03-05
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US6713485B2 (en)	2004-03-30
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Publication	Publication Date	Title
SK285405B6 (sk)	2007-01-04	Bicyklické heteroaromatické zlúčeniny, spôsob ichprípravy, farmaceutický prostriedok s ich obsahoma ich použitie
US7157466B2 (en)	2007-01-02	Quinazoline ditosylate salt compounds
GB2345486A (en)	2000-07-12	Heteroaromatic protein tyrosine kinase inhibitors
CZ8799A3 (cs)	1999-06-16	Bicyklické heteroaromatické sloučeniny, způsob jejich výroby a farmaceutický prostředek
MXPA00006824A (en)	2001-07-31	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
HK1031883B (en)	2005-03-04	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors