BG64825B1 - Бициклични хетероароматни съединения, метод за получаването им, фармацевтични състави и използването им като протеин тирозин киназни инхибитори - Google Patents

Бициклични хетероароматни съединения, метод за получаването им, фармацевтични състави и използването им като протеин тирозин киназни инхибитори Download PDF

Info

Publication number: BG64825B1
Authority: BG; Bulgaria
Prior art keywords: methyl; methanesulfonyl; benzyloxy; fluoro; ethyl
Prior art date: 1998-01-12

Application number

BG104668A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG104668A (en

Inventor

Malcolm Carter

George Cockerill

Stephen Guntrip

Karen LACKEY

Kathryn 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

2000-08-07

Publication date

2006-05-31

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=BG64825(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2000-08-07 Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited

2001-04-30 Publication of BG104668A publication Critical patent/BG104668A/xx

2006-05-31 Publication of BG64825B1 publication Critical patent/BG64825B1/bg

Links

-1 Bicyclic heteroaromatic compounds Chemical class 0.000 title claims abstract description 157
238000000034 method Methods 0.000 title claims abstract description 64
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
238000002360 preparation method Methods 0.000 title claims abstract description 15
230000008569 process Effects 0.000 title claims description 5
229940043355 kinase inhibitor Drugs 0.000 title 1
239000003757 phosphotransferase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 132
150000003839 salts Chemical class 0.000 claims abstract description 43
239000012453 solvate Substances 0.000 claims abstract description 30
238000011282 treatment Methods 0.000 claims abstract description 28
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 26
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 26
230000000694 effects Effects 0.000 claims abstract description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
206010028980 Neoplasm Diseases 0.000 claims abstract description 16
101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 12
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 12
201000011510 cancer Diseases 0.000 claims abstract description 10
208000035475 disorder Diseases 0.000 claims abstract description 10
239000003814 drug Substances 0.000 claims abstract description 10
201000004681 Psoriasis Diseases 0.000 claims abstract description 8
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 28
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
239000003153 chemical reaction reagent Substances 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 9
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
239000000460 chlorine Chemical group 0.000 claims description 8
210000000481 breast Anatomy 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Chemical group 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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 5
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
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 4
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
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 description 3
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 3
208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
SVBHUECJXOVMOM-UHFFFAOYSA-N 4-(5-bromo-5-fluoro-6-phenylmethoxycyclohexa-1,3-dien-1-yl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]-1h-quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(N)(C=4C(C(F)(Br)C=CC=4)OCC=4C=CC=CC=4)NC=NC3=CC=2)=C1 SVBHUECJXOVMOM-UHFFFAOYSA-N 0.000 claims description 2
BJSZCBORGGERAG-UHFFFAOYSA-N 4-(5-bromo-5-fluoro-6-phenylmethoxycyclohexa-1,3-dien-1-yl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]-1h-quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CNC2(C=3C(C(F)(Br)C=CC=3)OCC=3C=CC=CC=3)N)C2=C1 BJSZCBORGGERAG-UHFFFAOYSA-N 0.000 claims description 2
HRAXMJGGCFDZBT-UHFFFAOYSA-N 7-fluoro-n-(3-fluoro-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(=CC3=NC=NC(NC=4C=C(F)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)F)=C1 HRAXMJGGCFDZBT-UHFFFAOYSA-N 0.000 claims description 2
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 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
239000003085 diluting agent Substances 0.000 claims description 2
239000002552 dosage form Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
150000002240 furans Chemical class 0.000 claims description 2
PSLPNMRXSBQHQB-UHFFFAOYSA-N n-(3-bromo-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(Br)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 PSLPNMRXSBQHQB-UHFFFAOYSA-N 0.000 claims description 2
RRURVOSFXQLYQR-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-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=CC=CC=4)=CC=3)C2=C1 RRURVOSFXQLYQR-UHFFFAOYSA-N 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
IHZCJKWDMHPKAC-UHFFFAOYSA-N n-(3-bromo-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=C1Br)=CC=C1OCC1=CC=CC=C1 IHZCJKWDMHPKAC-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
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
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 description 2
RRONZTYLARBRBH-UHFFFAOYSA-N n-(3-fluoro-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(F)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 RRONZTYLARBRBH-UHFFFAOYSA-N 0.000 claims description 2
XURMGEAAVZEGOJ-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-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(F)=C1 XURMGEAAVZEGOJ-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
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 description 2
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 description 2
FFYLLKGJBBUFGL-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[4-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=COC(C=2C=C3C(NC=4C=CC(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)=C1 FFYLLKGJBBUFGL-UHFFFAOYSA-N 0.000 claims description 2
ZHQNAWZWCCTYIT-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 ZHQNAWZWCCTYIT-UHFFFAOYSA-N 0.000 claims description 2
210000002784 stomach Anatomy 0.000 claims description 2
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 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
GLYXYXYAEODHMV-UHFFFAOYSA-N 4-(5,5-difluoro-6-phenylmethoxycyclohexa-1,3-dien-1-yl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]-1h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=C(C(NC=N3)(N)C=3C(C(F)(F)C=CC=3)OCC=3C=CC=CC=3)C=2)=C1 GLYXYXYAEODHMV-UHFFFAOYSA-N 0.000 claims 1
239000000945 filler Substances 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
BOJBCNAHDOIFBE-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-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=CC=CC=5)=CC=4)=C3C=2)F)=C1 BOJBCNAHDOIFBE-UHFFFAOYSA-N 0.000 claims 1
VSCPXIGUZBDNSV-UHFFFAOYSA-N n-(3-fluoro-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(F)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 VSCPXIGUZBDNSV-UHFFFAOYSA-N 0.000 claims 1
SRUGAMVGSFQHCH-UHFFFAOYSA-N n-(3-fluoro-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=C1F)=CC=C1OCC1=CC=CC=C1 SRUGAMVGSFQHCH-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
UGLDUUSMNMDDMH-UHFFFAOYSA-N n-[3-bromo-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(Br)C(OCC=5C=C(F)C=CC=5)=CC=4)=C3C=2)F)=C1 UGLDUUSMNMDDMH-UHFFFAOYSA-N 0.000 claims 1
SGJFGVYDLIDRBD-UHFFFAOYSA-N n-[3-bromo-4-[(3-fluorophenyl)methoxy]phenyl]-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=C1Br)=CC=C1OCC1=CC=CC(F)=C1 SGJFGVYDLIDRBD-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
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 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
XHNANHFGZRZRAU-UHFFFAOYSA-N n-[3-fluoro-4-[(3-fluorophenyl)methoxy]phenyl]-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=C1F)=CC=C1OCC1=CC=CC(F)=C1 XHNANHFGZRZRAU-UHFFFAOYSA-N 0.000 claims 1
DXPUMHHTGDHAKK-UHFFFAOYSA-N n-[3-fluoro-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=C1F)=CC=C1OCC1=CC=CC(F)=C1 DXPUMHHTGDHAKK-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
239000000203 mixture Substances 0.000 description 47
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
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Classifications

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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
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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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Cardiology (AREA)
Dermatology (AREA)
Heart & Thoracic Surgery (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Communicable Diseases (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Immunology (AREA)
Oncology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Indole Compounds (AREA)
Steroid Compounds (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

BG104668A 1998-01-12 2000-08-07 Бициклични хетероароматни съединения, метод за получаването им, фармацевтични състави и използването им като протеин тирозин киназни инхибитори BG64825B1 (bg)

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1998
- 1998-01-12 RS YUP-448/00A patent/RS49779B/sr unknown
- 1998-01-12 GB GBGB9800569.7A patent/GB9800569D0/en not_active Ceased
1999
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- 1999-01-08 EA EA200000637A patent/EA002455B1/ru not_active IP Right Cessation
- 1999-01-08 ES ES04076762T patent/ES2319119T3/es not_active Expired - Lifetime
- 1999-01-08 DK DK99902522T patent/DK1047694T3/da active
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- 1999-01-08 ME MEP-2000-448A patent/ME00757B/me unknown
- 1999-01-08 AP APAP/P/2000/001861A patent/AP1446A/en active
- 1999-01-08 KR KR1020007007635A patent/KR100569776B1/ko not_active Expired - Lifetime
- 1999-01-08 CA CA002317589A patent/CA2317589C/en not_active Expired - Lifetime
- 1999-01-08 DE DE69918528T patent/DE69918528T2/de not_active Expired - Lifetime
- 1999-01-08 MA MA25422A patent/MA26596A1/fr unknown
- 1999-01-08 EP EP99902522A patent/EP1047694B1/en not_active Expired - Lifetime
- 1999-01-08 DK DK04076761T patent/DK1460072T3/da active
- 1999-01-08 HU HU0100941A patent/HU227593B1/hu active Protection Beyond IP Right Term
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- 1999-01-08 DE DE69940128T patent/DE69940128D1/de not_active Expired - Lifetime
- 1999-01-08 AT AT04076761T patent/ATE322491T1/de active
- 1999-01-08 AU AU22783/99A patent/AU749549C/en not_active Revoked
- 1999-01-08 SI SI9930663T patent/SI1047694T1/xx unknown
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- 1999-01-08 CN CNB998038873A patent/CN1134438C/zh not_active Expired - Lifetime
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- 1999-01-08 WO PCT/EP1999/000048 patent/WO1999035146A1/en not_active Ceased
- 1999-01-08 DE DE122008000048C patent/DE122008000048I1/de active Pending
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2000
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2002
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2003
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2005
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2006
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2007
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2008
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2009
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2013
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2014
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2015
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2016
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Also Published As

Publication number	Publication date
YU44800A (sh)	2002-11-15
MA26596A1 (fr)	2004-12-20
FR08C0038I2 (fr)	2012-02-22
ATE270670T1 (de)	2004-07-15
US20160051551A1 (en)	2016-02-25
WO1999035146A1 (en)	1999-07-15
IL137041A (en)	2006-10-05
CN1292788A (zh)	2001-04-25
EE200000411A (et)	2001-12-17
EP1454907B1 (en)	2008-12-17
US20070015775A1 (en)	2007-01-18
HUP0100941A3 (en)	2002-09-30
JP3390741B2 (ja)	2003-03-31
DK1454907T3 (da)	2009-03-09
BG104668A (en)	2001-04-30
US20030176451A1 (en)	2003-09-18
CN1134438C (zh)	2004-01-14
AU749549B2 (en)	2002-06-27
AU2010276460A1 (en)	2011-02-17
US20020147205A1 (en)	2002-10-10
JP2002500225A (ja)	2002-01-08
RS49779B (sr)	2008-06-05
NO20003561D0 (no)	2000-07-11
NO20003561L (no)	2000-09-11
ATE417847T1 (de)	2009-01-15
DK1460072T3 (da)	2006-07-31
HU227593B1 (en)	2011-09-28
EP1460072B1 (en)	2006-04-05
EE04616B1 (et)	2006-04-17
US20130310562A1 (en)	2013-11-21
KR20010015902A (ko)	2001-02-26
CY1105618T1 (el)	2010-12-22
EP1454907A1 (en)	2004-09-08
EG24743A (en)	2010-07-14
DE69930773T2 (de)	2006-09-28
CO4820390A1 (es)	1999-07-28
CZ298047B6 (cs)	2007-06-06
EP1047694A1 (en)	2000-11-02
EP1047694B1 (en)	2004-07-07
NL300360I1 (nl)	2008-11-03
SK10502000A3 (sk)	2001-08-06
PL341595A1 (en)	2001-04-23
US8513262B2 (en)	2013-08-20
SK285405B6 (sk)	2007-01-04
CY2008015I1 (el)	2009-11-04
NO2008017I1 (no)	2008-12-01
BR9906904A (pt)	2000-10-17
AP2000001861A0 (en)	2000-09-30
AR066982A2 (es)	2009-09-23
CZ20002587A3 (en)	2001-05-16
KR100569776B1 (ko)	2006-04-11
AU2278399A (en)	1999-07-26
HK1031883A1 (en)	2001-06-29
NO316176B1 (no)	2003-12-22
PE20000230A1 (es)	2000-04-03
ES2262087T3 (es)	2006-11-16
IL137041A0 (en)	2001-06-14
TW477788B (en)	2002-03-01
DE69918528T2 (de)	2005-07-28
DK1047694T3 (da)	2004-11-08
GB9800569D0 (en)	1998-03-11
DE69930773D1 (de)	2006-05-18
BR9906904B1 (pt)	2011-05-03
AP1446A (en)	2005-07-19
US20150065527A1 (en)	2015-03-05
AR015507A1 (es)	2001-05-02
US20070238875A1 (en)	2007-10-11
HRP20060387A2 (en)	2008-02-29
AU749549C (en)	2003-03-20
HRP20000469A2 (en)	2001-06-30
DE69918528D1 (de)	2004-08-12
PL192746B1 (pl)	2006-12-29
US9199973B2 (en)	2015-12-01
NO2008017I2 (2)	2011-10-17
OA11444A (en)	2004-04-29
DE69940128D1 (de)	2009-01-29
ES2221354T3 (es)	2004-12-16
NZ505456A (en)	2003-06-30
ZA99172B (en)	2000-07-11
JP2002326990A (ja)	2002-11-15
CY2008015I2 (el)	2009-11-04
US20160339027A1 (en)	2016-11-24
SI1454907T1 (sl)	2009-04-30
IS5549A (is)	2000-06-27
US8912205B2 (en)	2014-12-16
FR08C0038I1 (2)	2008-11-14
DE122008000048I1 (de)	2009-01-02
PT1047694E (pt)	2004-11-30
IS2276B (is)	2007-09-15
MY124055A (en)	2006-06-30
ES2319119T3 (es)	2009-05-04
NL300360I2 (nl)	2009-02-02
GEP20022678B (en)	2002-04-25
CA2317589A1 (en)	1999-07-15
EA200000637A1 (ru)	2001-02-26
US6727256B1 (en)	2004-04-27
PT1454907E (pt)	2009-02-18
SI1047694T1 (en)	2005-02-28
EA002455B1 (ru)	2002-04-25
US20100120804A1 (en)	2010-05-13
LU91475I2 (fr)	2008-11-10
UA66827C2 (uk)	2004-06-15
LU91475I9 (2)	2019-01-02
US20050130996A1 (en)	2005-06-16
CA2317589C (en)	2007-08-07
TR200002015T2 (tr)	2001-01-22
ATE322491T1 (de)	2006-04-15
ME00757B (me)	2008-06-05
SI1460072T1 (sl)	2006-08-31
PT1460072E (pt)	2006-07-31
US6713485B2 (en)	2004-03-30
EP1460072A1 (en)	2004-09-22
HUP0100941A2 (hu)	2001-09-28
HRP20000469B1 (hr)	2007-05-31
CY1108859T1 (el)	2014-07-02
US7109333B2 (en)	2006-09-19

Publication	Publication Date	Title
BG64825B1 (bg)	2006-05-31	Бициклични хетероароматни съединения, метод за получаването им, фармацевтични състави и използването им като протеин тирозин киназни инхибитори
EP1506962B1 (en)	2008-07-02	Nitrogen-containing aromatic heterocycles
DE60037020T2 (de)	2008-08-21	Anilinochinazoline als protein-tyrosin-kinasehemmer
US6169091B1 (en)	2001-01-02	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
KR101028952B1 (ko)	2011-04-12	수용체 티로신 키나아제 억제제로서의 퀴나졸린 유사체
CZ8799A3 (cs)	1999-06-16	Bicyklické heteroaromatické sloučeniny, způsob jejich výroby a farmaceutický prostředek
HK1031883B (en)	2005-03-04	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
MXPA00006824A (en)	2001-07-31	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors