HRP20040898A2 - 4-(n-phenylamino)-quinazolines/quinolines as tyrosine kinase inhibitors - Google Patents

4-(n-phenylamino)-quinazolines/quinolines as tyrosine kinase inhibitors Download PDF

Info

Publication number: HRP20040898A2
Authority: HR; Croatia
Prior art keywords: group; alkyl; amino; morpholin; oxo
Prior art date: 2002-03-30

Application number

HR20040898A

Other languages

English (en)

Croatian (hr)

Inventor

Himmelsbach Frank

Jung Birgit

Solca Flavio

Original Assignee

Boehringer Ingelheim Pharma Gmbh & Co.Kg.

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.)

2002-03-30

Filing date

2004-09-29

Publication date

2005-10-31

2002-03-30 Priority claimed from DE10214412A external-priority patent/DE10214412A1/de

2002-07-13 Priority claimed from DE2002131711 external-priority patent/DE10231711A1/de

2004-09-29 Application filed by Boehringer Ingelheim Pharma Gmbh & Co.Kg. filed Critical Boehringer Ingelheim Pharma Gmbh & Co.Kg.

2005-10-31 Publication of HRP20040898A2 publication Critical patent/HRP20040898A2/hr

Links

229940111121 antirheumatic drug quinolines Drugs 0.000 title 1
150000003248 quinolines Chemical class 0.000 title 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 title 1
239000005483 tyrosine kinase inhibitor Substances 0.000 title 1
-1 2-oxo-pyrrolidin-1-yl Chemical group 0.000 claims description 849
150000001875 compounds Chemical class 0.000 claims description 105
238000006243 chemical reaction Methods 0.000 claims description 84
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 62
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 62
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 44
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 31
238000002360 preparation method Methods 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 29
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
239000002253 acid Substances 0.000 claims description 18
229910052801 chlorine Inorganic materials 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 18
229910052740 iodine Inorganic materials 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
150000003254 radicals Chemical class 0.000 claims description 16
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 15
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
239000000460 chlorine Chemical group 0.000 claims description 14
229910052731 fluorine Inorganic materials 0.000 claims description 14
239000011737 fluorine Chemical group 0.000 claims description 14
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
125000003282 alkyl amino group Chemical group 0.000 claims description 13
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 11
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 8
229910052794 bromium Inorganic materials 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
238000000034 method Methods 0.000 claims description 8
125000002912 morpholin-4-ylsulfonyl group Chemical group O1C([H])([H])C([H])([H])N(S(=O)(=O)[*])C([H])([H])C1([H])[H] 0.000 claims description 8
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
125000006598 aminocarbonylamino group Chemical group 0.000 claims description 6
229910021529 ammonia Inorganic materials 0.000 claims description 6
125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 6
125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 4
125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 4
125000006599 (C1-C3) alkylaminocarbonylamino group Chemical group 0.000 claims description 4
125000006603 (C1-C3) alkylaminosulfonyl group Chemical group 0.000 claims description 4
125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 4
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
150000003973 alkyl amines Chemical class 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000005265 dialkylamine group Chemical class 0.000 claims description 4
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 4
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 4
125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
ISOQHYHPBKMXGJ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-piperidin-4-yloxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCNCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 ISOQHYHPBKMXGJ-UHFFFAOYSA-N 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
KCXAZEJYKXXQIS-UHFFFAOYSA-N 1-[4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-methoxyethanone Chemical compound C1CN(C(=O)COC)CCC1OC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=C(F)C(Cl)=C1 KCXAZEJYKXXQIS-UHFFFAOYSA-N 0.000 claims description 3
ZAQVAMIBXWWRPQ-NSHDSACASA-N 4-(3-chloro-4-fluoroanilino)-6-[(3S)-oxolan-3-yl]oxyquinazolin-7-ol Chemical compound C=12C=C(O[C@@H]3COCC3)C(O)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 ZAQVAMIBXWWRPQ-NSHDSACASA-N 0.000 claims description 3
JAFDYPYUQHLWBH-UHFFFAOYSA-N 4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carbonitrile Chemical compound C=12C=C(OC3CCN(CC3)C#N)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 JAFDYPYUQHLWBH-UHFFFAOYSA-N 0.000 claims description 3
CYBRSHQMQMRQGS-MQMHXKEQSA-N C=12C=C(O[C@@H]3CC[C@@H](N)CC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@@H](N)CC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 CYBRSHQMQMRQGS-MQMHXKEQSA-N 0.000 claims description 3
LACBJYAZTCFDGP-SAABIXHNSA-N C=12C=C(O[C@@H]3CC[C@H](CC3)NC(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@H](CC3)NC(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 LACBJYAZTCFDGP-SAABIXHNSA-N 0.000 claims description 3
PNFJQZSVQASXPY-XUTJKUGGSA-N C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)CCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)CCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 PNFJQZSVQASXPY-XUTJKUGGSA-N 0.000 claims description 3
CUELDVKCEKJXBE-KOMQPUFPSA-N C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 CUELDVKCEKJXBE-KOMQPUFPSA-N 0.000 claims description 3
OTLJXOJEXWTEBW-SAABIXHNSA-N C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@H](CC3)NS(=O)(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 OTLJXOJEXWTEBW-SAABIXHNSA-N 0.000 claims description 3
FJNIWTSYKPLARM-CTYIDZIISA-N C=12C=C(O[C@@H]3CC[C@H](CC3)NS(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@@H]3CC[C@H](CC3)NS(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 FJNIWTSYKPLARM-CTYIDZIISA-N 0.000 claims description 3
SGPQZLAIXLGTBH-UHFFFAOYSA-N [4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=12C=C(OC3CCN(CC3)C(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 SGPQZLAIXLGTBH-UHFFFAOYSA-N 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
210000004072 lung Anatomy 0.000 claims description 3
150000007522 mineralic acids Chemical class 0.000 claims description 3
AHPPMJNZFROCCT-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 AHPPMJNZFROCCT-UHFFFAOYSA-N 0.000 claims description 3
PHXCLARSPIPCKJ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-(1-morpholin-4-ylsulfonylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C=C(OC3CCN(CC3)S(=O)(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 PHXCLARSPIPCKJ-UHFFFAOYSA-N 0.000 claims description 3
WZBWYRUTRBGTAL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-(oxan-3-yloxy)quinazolin-4-amine Chemical compound C=12C=C(OC3COCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 WZBWYRUTRBGTAL-UHFFFAOYSA-N 0.000 claims description 3
XNHQKLXMYJHGPA-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C=12C=C(OC3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XNHQKLXMYJHGPA-UHFFFAOYSA-N 0.000 claims description 3
AMOWBTZSDREVRB-LBPRGKRZSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-6-[(3s)-oxolan-3-yl]oxyquinazolin-4-amine Chemical compound C=12C=C(O[C@@H]3COCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 AMOWBTZSDREVRB-LBPRGKRZSA-N 0.000 claims description 3
QDYICOKSXMTYPO-UHFFFAOYSA-N n-[2-[4-(3-chloro-4-fluoroanilino)-6-(oxan-4-yloxy)quinazolin-7-yl]oxyethyl]acetamide Chemical compound C=12C=C(OC3CCOCC3)C(OCCNC(=O)C)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 QDYICOKSXMTYPO-UHFFFAOYSA-N 0.000 claims description 3
YBTWSPCOMHYEKP-UHFFFAOYSA-N n-[2-[4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethyl]acetamide Chemical compound C=12C=C(OC3CCN(CCNC(C)=O)CC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 YBTWSPCOMHYEKP-UHFFFAOYSA-N 0.000 claims description 3
150000007524 organic acids Chemical class 0.000 claims description 3
235000005985 organic acids Nutrition 0.000 claims description 3
125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims description 2
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 2
125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims description 2
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
PNFJQZSVQASXPY-TYKWCNGQSA-N C=12C=C(O[C@H]3CC[C@H](CC3)NS(=O)(=O)CCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 Chemical compound C=12C=C(O[C@H]3CC[C@H](CC3)NS(=O)(=O)CCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 PNFJQZSVQASXPY-TYKWCNGQSA-N 0.000 claims description 2
230000010933 acylation Effects 0.000 claims description 2
238000005917 acylation reaction Methods 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
125000005002 aryl methyl group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 2
210000000013 bile duct Anatomy 0.000 claims description 2
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
238000007333 cyanation reaction Methods 0.000 claims description 2
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical group N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 2
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
210000000232 gallbladder Anatomy 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
YAHVBINRULXWJV-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-(2-methoxyethoxy)-6-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C=12C=C(OC3CCOCC3)C(OCCOC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 YAHVBINRULXWJV-UHFFFAOYSA-N 0.000 claims description 2
MWHCFCZAROGOAF-UHFFFAOYSA-N n-[2-[4-(3-chloro-4-fluoroanilino)-6-(oxan-4-yloxy)quinazolin-7-yl]oxyethyl]methanesulfonamide Chemical compound C=12C=C(OC3CCOCC3)C(OCCNS(=O)(=O)C)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 MWHCFCZAROGOAF-UHFFFAOYSA-N 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
125000004673 propylcarbonyl group Chemical group 0.000 claims description 2
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
125000005554 pyridyloxy group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
238000005932 reductive alkylation reaction Methods 0.000 claims description 2
210000002345 respiratory system Anatomy 0.000 claims description 2
230000006103 sulfonylation Effects 0.000 claims description 2
238000005694 sulfonylation reaction Methods 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
241000221535 Pucciniales Species 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 405
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 246
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Classifications

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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems

HR20040898A 2002-03-30 2004-09-29 4-(n-phenylamino)-quinazolines/quinolines as tyrosine kinase inhibitors HRP20040898A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE10214412A DE10214412A1 (de)	2002-03-30	2002-03-30	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE2002131711 DE10231711A1 (de)	2002-07-13	2002-07-13	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
PCT/EP2003/003062 WO2003082290A1 (de)	2002-03-30	2003-03-25	4- ( n-phenylamino ) -chinazoline/chinoline als tyrosinkinaseinhibitoren

Publications (1)

Publication Number	Publication Date
HRP20040898A2 true HRP20040898A2 (en)	2005-10-31

Family

ID=28676040

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20040898A HRP20040898A2 (en)	2002-03-30	2004-09-29	4-(n-phenylamino)-quinazolines/quinolines as tyrosine kinase inhibitors

Country Status (24)

Country	Link
EP (1)	EP1492536B1 (zh)
JP (1)	JP4776882B2 (zh)
KR (1)	KR101064530B1 (zh)
CN (1)	CN1642552B (zh)
AR (1)	AR039187A1 (zh)
AT (1)	ATE557008T1 (zh)
AU (1)	AU2003226705B2 (zh)
BR (1)	BR0308902A (zh)
CA (1)	CA2476008C (zh)
EA (2)	EA200701302A1 (zh)
HK (1)	HK1079095A1 (zh)
HR (1)	HRP20040898A2 (zh)
IL (1)	IL164167A0 (zh)
ME (1)	MEP47208A (zh)
MX (1)	MXPA04009536A (zh)
MY (1)	MY127771A (zh)
NO (1)	NO329271B1 (zh)
NZ (1)	NZ536114A (zh)
PE (1)	PE20040169A1 (zh)
PL (1)	PL371188A1 (zh)
RS (1)	RS85404A (zh)
TW (2)	TW201024269A (zh)
UY (1)	UY27737A1 (zh)
WO (1)	WO2003082290A1 (zh)

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Publication number	Publication date
AR039187A1 (es)	2005-02-09
CA2476008A1 (en)	2003-10-09
ATE557008T1 (de)	2012-05-15
KR20040094898A (ko)	2004-11-10
JP2005529090A (ja)	2005-09-29
TW200406211A (en)	2004-05-01
NO329271B1 (no)	2010-09-20
EA009300B1 (ru)	2007-12-28
UY27737A1 (es)	2003-10-31
CN1642552B (zh)	2010-05-12
CN1642552A (zh)	2005-07-20
NO20043997L (no)	2004-10-27
MXPA04009536A (es)	2005-01-25
CA2476008C (en)	2011-12-13
MY127771A (en)	2006-12-29
NZ536114A (en)	2007-11-30
TW201024269A (en)	2010-07-01
JP4776882B2 (ja)	2011-09-21
EA200401191A1 (ru)	2005-04-28
AU2003226705B2 (en)	2008-11-06
HK1079095A1 (en)	2006-03-31
MEP47208A (en)	2011-02-10
EA200701302A1 (ru)	2007-12-28
AU2003226705A1 (en)	2003-10-13
KR101064530B1 (ko)	2011-09-14
PE20040169A1 (es)	2004-05-24
RS85404A (en)	2007-02-05
EP1492536B1 (de)	2012-05-09
TWI331604B (en)	2010-10-11
PL371188A1 (en)	2005-06-13
BR0308902A (pt)	2005-01-04
EP1492536A1 (de)	2005-01-05
IL164167A0 (en)	2005-12-18
WO2003082290A1 (de)	2003-10-09

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Publication	Publication Date	Title
HRP20040898A2 (en)	2005-10-31	4-(n-phenylamino)-quinazolines/quinolines as tyrosine kinase inhibitors
US7119084B2 (en)	2006-10-10	Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
JP3754617B2 (ja)	2006-03-15	二環式複素環化合物、その化合物を含む医薬組成物、及び製法
JP4834282B2 (ja)	2011-12-14	二環式複素環、それを含む医薬組成物、その使用及びその製造方法
US7456189B2 (en)	2008-11-25	Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation
US20020082270A1 (en)	2002-06-27	Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases
US20070135463A1 (en)	2007-06-14	Bicyclic heterocycles, drugs containing said compounds, the use thereof and method for preparing same
HRP20030504A2 (en)	2005-06-30	Quinazoline derivatives, medicaments containing said compounds, their utilization and method for the production thereof
US20100234371A1 (en)	2010-09-16	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof
US7998949B2 (en)	2011-08-16	Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof
DE10326186A1 (de)	2004-12-23	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
EP2298305A1 (de)	2011-03-23	4-(N-phenylamino)-chinazoline/chinoline als tyrosinkinaseinhibitoren
CA2540501C (en)	2012-05-22	Quinoline derivatives and quinazoline derivatives, medicaments containing said compounds, use thereof, and method for the production thereof
JP2007507445A6 (ja)	2007-07-12	キノリン及びキナゾリン誘導体、これを含む薬物、その使用及びその調製方法