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 PDFInfo
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- BG64825B1 BG64825B1 BG104668A BG10466800A BG64825B1 BG 64825 B1 BG64825 B1 BG 64825B1 BG 104668 A BG104668 A BG 104668A BG 10466800 A BG10466800 A BG 10466800A BG 64825 B1 BG64825 B1 BG 64825B1
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- BG
- Bulgaria
- Prior art keywords
- methyl
- methanesulfonyl
- benzyloxy
- fluoro
- ethyl
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- -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
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
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Classifications
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- 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
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- 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
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- 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
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- 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
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- 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
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9800569.7A GB9800569D0 (en) | 1998-01-12 | 1998-01-12 | Heterocyclic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BG104668A BG104668A (en) | 2001-04-30 |
| BG64825B1 true BG64825B1 (bg) | 2006-05-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG104668A BG64825B1 (bg) | 1998-01-12 | 2000-08-07 | Бициклични хетероароматни съединения, метод за получаването им, фармацевтични състави и използването им като протеин тирозин киназни инхибитори |
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Families Citing this family (435)
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2003
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2005
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2007
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2014
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2015
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