SI9600184A - Heterocyclic ring-fused pyrimidine derivatives - Google Patents

Heterocyclic ring-fused pyrimidine derivatives Download PDF

Info

Publication number: SI9600184A
Authority: SI; Slovenia
Prior art keywords: pyrimidin; amine; alkyl; pyrido; phenyl
Prior art date: 1995-06-07

Application number

SI9600184A

Other languages

English (en)

Slovenian (sl)

Inventor

Daniel Lee Arnold

Paul Mike Moyer

Beth Susan Sobolov-Jaynes

Original Assignee

Pfizer

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.)

1995-06-07

Filing date

1996-06-06

Publication date

1997-04-30

1996-06-06 Application filed by Pfizer filed Critical Pfizer

1997-04-30 Publication of SI9600184A publication Critical patent/SI9600184A/sl

Links

150000003230 pyrimidines Chemical class 0.000 title description 5
125000000623 heterocyclic group Chemical group 0.000 title description 2
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 147
230000003463 hyperproliferative effect Effects 0.000 claims abstract description 12
150000003839 salts Chemical class 0.000 claims abstract description 12
241000124008 Mammalia Species 0.000 claims abstract description 7
239000000651 prodrug Substances 0.000 claims abstract 2
229940002612 prodrug Drugs 0.000 claims abstract 2
-1 nitro, hydroxy, amino Chemical group 0.000 claims description 219
229910052757 nitrogen Inorganic materials 0.000 claims description 99
125000000217 alkyl group Chemical group 0.000 claims description 75
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 59
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
125000003282 alkyl amino group Chemical group 0.000 claims description 36
125000003545 alkoxy group Chemical group 0.000 claims description 33
150000001412 amines Chemical class 0.000 claims description 33
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
229910052799 carbon Inorganic materials 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 19
125000005236 alkanoylamino group Chemical group 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 17
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
125000005518 carboxamido group Chemical group 0.000 claims description 14
125000004414 alkyl thio group Chemical group 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 10
125000004423 acyloxy group Chemical group 0.000 claims description 9
125000005605 benzo group Chemical group 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
125000005596 alkyl carboxamido group Chemical group 0.000 claims description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000005494 pyridonyl group Chemical group 0.000 claims description 8
229910052727 yttrium Inorganic materials 0.000 claims description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
125000005530 alkylenedioxy group Chemical group 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
125000001589 carboacyl group Chemical group 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 6
SBAWIIKMDWKPAP-UHFFFAOYSA-N n-(3-chlorophenyl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=CC=CN=C3N=CN=2)=C1 SBAWIIKMDWKPAP-UHFFFAOYSA-N 0.000 claims description 6
GXHHNATXYAMTDG-UHFFFAOYSA-N n-phenylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C=NC2=CN=CC=C2C=1NC1=CC=CC=C1 GXHHNATXYAMTDG-UHFFFAOYSA-N 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
KAIRQZLXOKATIQ-UHFFFAOYSA-N 4-(3-ethynylanilino)-7h-pyrrolo[2,3-d]pyrimidine-5-carbonitrile Chemical compound C#CC1=CC=CC(NC=2C=3C(C#N)=CNC=3N=CN=2)=C1 KAIRQZLXOKATIQ-UHFFFAOYSA-N 0.000 claims description 5
VFUAAGBLFHOQAV-UHFFFAOYSA-N 5-bromo-n-(3-ethynylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(Br)=CNC2=NC=NC=1NC1=CC=CC(C#C)=C1 VFUAAGBLFHOQAV-UHFFFAOYSA-N 0.000 claims description 5
OGJKPEXQIVCSBG-UHFFFAOYSA-N CC1=CC(NC2=NC=NC3=C2C=NC=C3)=CC=C1 Chemical compound CC1=CC(NC2=NC=NC3=C2C=NC=C3)=CC=C1 OGJKPEXQIVCSBG-UHFFFAOYSA-N 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
BHPQVEMLECZBDB-UHFFFAOYSA-N n-(1h-indol-5-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C2C(NC=3C=C4C=CNC4=CC=3)=NC=NC2=C1 BHPQVEMLECZBDB-UHFFFAOYSA-N 0.000 claims description 5
NPMPBDSPHFHHMC-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-methylsulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(SC)=CNC2=NC=NC=1NC1=CC=CC(C#C)=C1 NPMPBDSPHFHHMC-UHFFFAOYSA-N 0.000 claims description 5
HDARLEDIXFDUNN-UHFFFAOYSA-N n-phenylpyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C=NC2=NC=CC=C2C=1NC1=CC=CC=C1 HDARLEDIXFDUNN-UHFFFAOYSA-N 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
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 5
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 5
125000004768 (C1-C4) alkylsulfinyl 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
DXZWKHBMXNTZOI-UHFFFAOYSA-N 4-(3-ethynylanilino)-7h-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid Chemical compound C=12C(C(=O)O)=CNC2=NC=NC=1NC1=CC=CC(C#C)=C1 DXZWKHBMXNTZOI-UHFFFAOYSA-N 0.000 claims description 4
OHKQCQFYJDTPBJ-UHFFFAOYSA-N ClC1=CC=C(CCN2C3=NC=NC4=C3C=NC=C4)C2=C1 Chemical compound ClC1=CC=C(CCN2C3=NC=NC4=C3C=NC=C4)C2=C1 OHKQCQFYJDTPBJ-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
125000003368 amide group Chemical group 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
125000001475 halogen functional group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
JXFAHPCDBDADEP-UHFFFAOYSA-N n-(3-ethynyl-4-fluorophenyl)-6-methylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(C)=CC2=C1NC1=CC=C(F)C(C#C)=C1 JXFAHPCDBDADEP-UHFFFAOYSA-N 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
UZZQOANSYKQBJS-UHFFFAOYSA-N 2-iodo-4-[(6-methylpyrido[3,4-d]pyrimidin-4-yl)amino]phenol hydrochloride Chemical compound Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=C(O)C(I)=C1 UZZQOANSYKQBJS-UHFFFAOYSA-N 0.000 claims description 3
LDZCYEOEHIAAHI-UHFFFAOYSA-N 4-(4-bromo-7-methyl-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC(C(=CC=C2C)Br)=C2N1C1=C2C=C(C)N=CC2=NC=N1 LDZCYEOEHIAAHI-UHFFFAOYSA-N 0.000 claims description 3
BGZUKOJRLCOJQL-UHFFFAOYSA-N 4-(6-bromo-5-fluoro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC(F)=C(Br)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 BGZUKOJRLCOJQL-UHFFFAOYSA-N 0.000 claims description 3
PQTYWQWATNSLSN-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC=C(Cl)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 PQTYWQWATNSLSN-UHFFFAOYSA-N 0.000 claims description 3
RKBKLXOJDZURGJ-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-7h-pyrrolo[2,3-d]pyrimidine;hydrochloride Chemical compound Cl.C12=CC(Cl)=CC=C2CCN1C1=NC=NC2=C1C=CN2 RKBKLXOJDZURGJ-UHFFFAOYSA-N 0.000 claims description 3
WMAOJUAPQNRXMN-UHFFFAOYSA-N 5-iodo-n-(3-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(NC=2C=3C(I)=CNC=3N=CN=2)=C1 WMAOJUAPQNRXMN-UHFFFAOYSA-N 0.000 claims description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
QMJOVHBPLRUCLQ-UHFFFAOYSA-N n-(1h-indazol-5-yl)-6-methylpyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C1=C2NN=CC2=CC(NC2=C3C=C(N=CC3=NC=N2)C)=C1 QMJOVHBPLRUCLQ-UHFFFAOYSA-N 0.000 claims description 3
CVPVAPRGSBCQRN-UHFFFAOYSA-N n-(1h-indazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C2C(NC=3C=C4C=NNC4=CC=3)=NC=NC2=C1 CVPVAPRGSBCQRN-UHFFFAOYSA-N 0.000 claims description 3
OUBTWUSFURPWEL-UHFFFAOYSA-N n-(1h-indazol-5-yl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(NC=3C=C4C=NNC4=CC=3)=NC=NC2=C1 OUBTWUSFURPWEL-UHFFFAOYSA-N 0.000 claims description 3
RAISXOMJIRTPRU-UHFFFAOYSA-N n-(1h-indol-5-yl)-7h-purin-6-amine;hydrochloride Chemical compound Cl.C=1C=C2NC=CC2=CC=1NC1=NC=NC2=C1N=CN2 RAISXOMJIRTPRU-UHFFFAOYSA-N 0.000 claims description 3
FGCYZSQHCWZARH-UHFFFAOYSA-N n-(1h-indol-5-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C=1C=C2NC=CC2=CC=1NC1=NC=NC2=C1C=CN2 FGCYZSQHCWZARH-UHFFFAOYSA-N 0.000 claims description 3
OAVGTUPPZGFJPZ-UHFFFAOYSA-N n-(1h-indol-5-yl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(NC=3C=C4C=CNC4=CC=3)=NC=NC2=C1 OAVGTUPPZGFJPZ-UHFFFAOYSA-N 0.000 claims description 3
BWXVBEQVOBGQHC-UHFFFAOYSA-N n-(3-bromophenyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C3=CC=NC=C3N=CN=2)=C1 BWXVBEQVOBGQHC-UHFFFAOYSA-N 0.000 claims description 3
KXQSONXECJTULQ-UHFFFAOYSA-N n-(3-bromophenyl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C3=CN=CC=C3N=CN=2)=C1 KXQSONXECJTULQ-UHFFFAOYSA-N 0.000 claims description 3
WMSTVSZIKRBBNP-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-methylpyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 WMSTVSZIKRBBNP-UHFFFAOYSA-N 0.000 claims description 3
CLWFLUMQGXDSSO-UHFFFAOYSA-N n-(3-chlorophenyl)-2h-triazolo[4,5-d]pyrimidin-7-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C=3NN=NC=3N=CN=2)=C1 CLWFLUMQGXDSSO-UHFFFAOYSA-N 0.000 claims description 3
HAWXKROVNIIVEX-UHFFFAOYSA-N n-(3-chlorophenyl)-7-methylpyrido[4,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C=12C=NC(C)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1 HAWXKROVNIIVEX-UHFFFAOYSA-N 0.000 claims description 3
ZKISXEYMMCKORH-UHFFFAOYSA-N n-(3-chlorophenyl)-7h-purin-6-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C=3N=CNC=3N=CN=2)=C1 ZKISXEYMMCKORH-UHFFFAOYSA-N 0.000 claims description 3
BCLXVHJHHBULCV-UHFFFAOYSA-N n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 BCLXVHJHHBULCV-UHFFFAOYSA-N 0.000 claims description 3
VMFOIJKDWCGYQN-UHFFFAOYSA-N n-(3-chlorophenyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=CC=NC=C3N=CN=2)=C1 VMFOIJKDWCGYQN-UHFFFAOYSA-N 0.000 claims description 3
UTDASZLSKTXCQQ-UHFFFAOYSA-N n-(3-chlorophenyl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=CN=CC=C3N=CN=2)=C1 UTDASZLSKTXCQQ-UHFFFAOYSA-N 0.000 claims description 3
DWNRTKDSVRXCDR-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-iodo-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(I)=CNC2=NC=NC=1NC1=CC=CC(C#C)=C1 DWNRTKDSVRXCDR-UHFFFAOYSA-N 0.000 claims description 3
YRRBOKHSOVSHSI-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C=12C(C)=CNC2=NC=NC=1NC1=CC=CC(C#C)=C1 YRRBOKHSOVSHSI-UHFFFAOYSA-N 0.000 claims description 3
XGPRAWMNWHDJKI-UHFFFAOYSA-N n-(3-ethynylphenyl)-6-methylpyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=CC(C#C)=C1 XGPRAWMNWHDJKI-UHFFFAOYSA-N 0.000 claims description 3
YFRSGDRAYOBDPX-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-(2-methoxyethyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(CCOC)C=CC2=C1NC1=CC=CC(C#C)=C1 YFRSGDRAYOBDPX-UHFFFAOYSA-N 0.000 claims description 3
HDNMPTXODRTFCR-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-[2-(2-methoxyethoxy)ethyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(CCOCCOC)C=CC2=C1NC1=CC=CC(C#C)=C1 HDNMPTXODRTFCR-UHFFFAOYSA-N 0.000 claims description 3
LOXLJUYFTDRFPO-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-methylpyrido[4,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C=12C=NC(C)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 LOXLJUYFTDRFPO-UHFFFAOYSA-N 0.000 claims description 3
NDKPPINOPXHVPF-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-methylpyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2N(C)C=CC2=C1NC1=CC=CC(C#C)=C1 NDKPPINOPXHVPF-UHFFFAOYSA-N 0.000 claims description 3
QFRDWIHAVDMHPE-UHFFFAOYSA-N n-(3-ethynylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C#CC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 QFRDWIHAVDMHPE-UHFFFAOYSA-N 0.000 claims description 3
HNGRZKXBWKRSCA-UHFFFAOYSA-N n-(3-ethynylphenyl)pyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C#CC1=CC=CC(NC=2C3=CC=NC=C3N=CN=2)=C1 HNGRZKXBWKRSCA-UHFFFAOYSA-N 0.000 claims description 3
IWJGFLQPYWJHAV-UHFFFAOYSA-N n-(3-ethynylphenyl)pyrido[4,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C#CC1=CC=CC(NC=2C3=CN=CC=C3N=CN=2)=C1 IWJGFLQPYWJHAV-UHFFFAOYSA-N 0.000 claims description 3
UIWSPJBKFSXXEY-UHFFFAOYSA-N n-(5-iodo-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-n-(3-methylphenyl)acetamide Chemical compound N=1C=NC=2NC=C(I)C=2C=1N(C(=O)C)C1=CC=CC(C)=C1 UIWSPJBKFSXXEY-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Chemical group 0.000 claims description 3
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 claims description 2
DKLGVCDKNBPBEQ-UHFFFAOYSA-N 1-[4-(3-methylanilino)pyrrolo[2,3-d]pyrimidin-7-yl]ethanone;hydrochloride Chemical compound Cl.N1=CN=C2N(C(=O)C)C=CC2=C1NC1=CC=CC(C)=C1 DKLGVCDKNBPBEQ-UHFFFAOYSA-N 0.000 claims description 2
CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 2
XWQYVWRXHMSKRB-UHFFFAOYSA-N 2-methyl-4-[(6-methylpyrido[3,4-d]pyrimidin-4-yl)amino]phenol dihydrochloride Chemical compound Cl.Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=C(O)C(C)=C1 XWQYVWRXHMSKRB-UHFFFAOYSA-N 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
FUYJBBSAMAELRK-UHFFFAOYSA-N 4-(6-bromo-7-methyl-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC=C(Br)C(C)=C2N1C1=C2C=C(C)N=CC2=NC=N1 FUYJBBSAMAELRK-UHFFFAOYSA-N 0.000 claims description 2
LOPBUDCQZDQIQH-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound ClC1=CC=C2CCN(C2=C1)C=1C2=C(N=CN=1)N=C(C2)O LOPBUDCQZDQIQH-UHFFFAOYSA-N 0.000 claims description 2
CXAPZNBQPOKHKN-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3CCC4=CC=C(C=C43)Cl)=NC=NC2=C1 CXAPZNBQPOKHKN-UHFFFAOYSA-N 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 2
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000003843 furanosyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
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Classifications

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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom

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SI9600184A 1995-06-07 1996-06-06 Heterocyclic ring-fused pyrimidine derivatives SI9600184A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
PCT/US1995/007881 WO1996040142A1 (en)	1995-06-07	1995-06-07	Heterocyclic ring-fused pyrimidine derivatives
HU9601559A HUP9601559A3 (en)	1995-06-07	1996-06-06	Heterocyclic ring-fused pyrimidine derivatives, pharmaceutical compositions containing the same and intermediates

Publications (1)

Publication Number	Publication Date
SI9600184A true SI9600184A (en)	1997-04-30

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SI9600184A SI9600184A (en)	1995-06-07	1996-06-06	Heterocyclic ring-fused pyrimidine derivatives

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AR (1)	AR002746A1 (cs)
AT (1)	ATE247469T1 (cs)
AU (1)	AU5479196A (cs)
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CA (1)	CA2223081C (cs)
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ES (1)	ES2203642T3 (cs)
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SI (1)	SI9600184A (cs)
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TR (1)	TR199600474A2 (cs)
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Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0682027B1 (de) *	1994-05-03	1997-10-15	Novartis AG	Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
TW321649B (cs) *	1994-11-12	1997-12-01	Zeneca Ltd
GB9424233D0 (en) *	1994-11-30	1995-01-18	Zeneca Ltd	Quinazoline derivatives
ES2150113T3 (es) *	1995-04-03	2000-11-16	Novartis Ag	Derivados de pirazol y procedimientos para la preparacion de los mismos.
GB9508537D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
GB9508565D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quiazoline derivative
GB9508538D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
GB9508535D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivative
WO1996033977A1 (en) *	1995-04-27	1996-10-31	Zeneca Limited	Quinazoline derivatives
MX9800215A (es) *	1995-07-06	1998-03-31	Novartis Ag	Pirrolopirimidas y procesos para su preparacion.
GB9624482D0 (en) *	1995-12-18	1997-01-15	Zeneca Phaema S A	Chemical compounds
ATE217873T1 (de) *	1996-01-23	2002-06-15	Novartis Erfind Verwalt Gmbh	Pyrrolopyrimidinen und verfahren zu deren herstellung
BR9707495A (pt)	1996-02-13	1999-07-27	Zeneca Ltd	Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente
GB9603097D0 (en) *	1996-02-14	1996-04-10	Zeneca Ltd	Quinazoline compounds
GB9603095D0 (en) *	1996-02-14	1996-04-10	Zeneca Ltd	Quinazoline derivatives
US6291455B1 (en)	1996-03-05	2001-09-18	Zeneca Limited	4-anilinoquinazoline derivatives
HU228446B1 (en)	1996-04-12	2013-03-28	Warner Lambert Co	Kinazoline derivatives as irreversible inhibitors of protein-kinase, pharmaceutical compositions containing these compounds and use thereof
GB9607729D0 (en) *	1996-04-13	1996-06-19	Zeneca Ltd	Quinazoline derivatives
AU3176297A (en) *	1996-06-25	1998-01-14	Novartis Ag	Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof
WO1998007726A1 (en)	1996-08-23	1998-02-26	Novartis Ag	Substituted pyrrolopyrimidines and processes for their preparation
US6251911B1 (en)	1996-10-02	2001-06-26	Novartis Ag	Pyrimidine derivatives and processes for the preparation thereof
US6225318B1 (en)	1996-10-17	2001-05-01	Pfizer Inc	4-aminoquinazolone derivatives
US6413971B1 (en)	1996-11-27	2002-07-02	Pfizer Inc	Fused bicyclic pyrimidine derivatives
EP1012151B1 (en)	1997-09-02	2002-08-07	Bristol-Myers Squibb Pharma Company	Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders
CA2309690A1 (en)	1997-11-11	1999-05-20	Pfizer Products Inc.	Thienopyrimidine and thienopyridine derivatives useful as anticancer agents
JPH11236333A (ja) *	1997-12-30	1999-08-31	Pfizer Prod Inc	抗ガン剤として有用なイミダゾリン−４−オン誘導体
RS49779B (sr)	1998-01-12	2008-06-05	Glaxo Group Limited,	Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze
US6187777B1 (en)	1998-02-06	2001-02-13	Amgen Inc.	Compounds and methods which modulate feeding behavior and related diseases
DE69943144D1 (de)	1998-03-31	2011-03-03	Kyowa Hakko Kirin Co Ltd	Stickstoffenthaltende heterocyclische verbindungen
BR9911365A (pt)	1998-06-19	2001-03-13	Pfizer Prod Inc	Compostos pirrolo[2,3-d]pirimidina
PA8474101A1 (es) *	1998-06-19	2000-09-29	Pfizer Prod Inc	Compuestos de pirrolo [2,3-d] pirimidina
WO2000023444A1 (en) *	1998-10-21	2000-04-27	Abbott Laboratories	5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds
US6174903B1 (en)	1998-12-28	2001-01-16	Pfizer Inc.	Imidazolidin-4-one derivatives useful as anticancer agents
JP3270834B2 (ja)	1999-01-27	2002-04-02	ファイザー・プロダクツ・インク	抗がん剤として有用なヘテロ芳香族二環式誘導体
UA71945C2 (en) *	1999-01-27	2005-01-17	Pfizer Prod Inc	Substituted bicyclic derivatives being used as anticancer agents
US6933299B1 (en)	1999-07-09	2005-08-23	Smithkline Beecham Corporation	Anilinoquinazolines as protein tyrosine kinase inhibitors
ATE377597T1 (de)	1999-07-09	2007-11-15	Glaxo Group Ltd	Anilinochinazoline als protein-tyrosin- kinasehemmer
US6432979B1 (en)	1999-08-12	2002-08-13	American Cyanamid Company	Method of treating or inhibiting colonic polyps and colorectal cancer
EP1409487A1 (en)	1999-09-15	2004-04-21	Warner-Lambert Company Llc	Pteridinones as kinase inhibitors
RU2264404C2 (ru) *	1999-10-21	2005-11-20	Ф.Хоффманн-Ля Рош Аг	Алкиламинозамещенные бициклические азотсодержащие гетероциклы и фармацевтическая композиция на их основе
GB9925958D0 (en) *	1999-11-02	1999-12-29	Bundred Nigel J	Therapeutic use
CZ301689B6 (cs)	1999-11-05	2010-05-26	Astrazeneca Ab	Derivát chinazolinu a farmaceutický prostredek, který ho obsahuje
JP2001142235A (ja)	1999-11-17	2001-05-25	Fuji Denki Gazo Device Kk	電子写真用感光体
EP1382339B1 (en)	1999-12-10	2007-12-05	Pfizer Products Inc.	Compositions containing pyrrolo ¬2,3-d pyrimidine derivatives
JP2003535867A (ja)	2000-06-06	2003-12-02	ファイザープロダクツインコーポレイテッド	抗癌剤として有用なチオフェン誘導体
IL152771A0 (en)	2000-06-26	2003-06-24	Pfizer Prod Inc	PYRROLO(2,3-d) PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS
WO2002024667A1 (en)	2000-09-20	2002-03-28	Merck Patent Gmbh	4-amino-quinazolines
DE60137273D1 (de)	2000-10-20	2009-02-12	Eisai R&D Man Co Ltd	Verfahren zur Herstellung von 4-Phenoxy chinolin Derivaten
ES2263743T3 (es)	2001-04-13	2006-12-16	Pfizer Products Inc.	Derivados de 4-aminopiridopirimidina sustituidos con un grupo biciclico.
AR035885A1 (es) *	2001-05-14	2004-07-21	Novartis Ag	Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica
US7301023B2 (en)	2001-05-31	2007-11-27	Pfizer Inc.	Chiral salt resolution
AU2002345792A1 (en)	2001-06-21	2003-01-08	Pfizer Inc.	Thienopyridine and thienopyrimidine anticancer agents
CZ294535B6 (cs) *	2001-08-02	2005-01-12	Ústav Experimentální Botaniky Avčr	Heterocyklické sloučeniny na bázi N6-substituovaného adeninu, způsoby jejich přípravy, jejich použití pro přípravu léčiv, kosmetických přípravků a růstových regulátorů, farmaceutické přípravky, kosmetické přípravky a růstové regulátory tyto sloučeniny obsahující
GB0121033D0 (en) *	2001-08-30	2001-10-24	Novartis Ag	Organic compounds
US7829566B2 (en)	2001-09-17	2010-11-09	Werner Mederski	4-amino-quinazolines
PY0228255A (es) *	2001-12-06	2004-06-01	Pfizer Prod Inc	Compuestos cristalinos novedosos
RU2289583C2 (ru) *	2001-12-27	2006-12-20	Ф.Хоффманн-Ля Рош Аг	Пиримидотриазины, способ их получения, фармацевтическая композиция на их основе и применение
DE60320933D1 (de) *	2002-01-10	2008-06-26	Bayer Healthcare Ag	Rho-kinase inhibitoren
CN1627944A (zh)	2002-01-17	2005-06-15	神经能质公司	取代的喹唑啉－4－基胺类似物作为辣椒辣素调节剂
MXPA04007196A (es)	2002-01-23	2005-06-08	Bayer Pharmaceuticals Corp	Inhibidores de rho-quinasa.
JP4469179B2 (ja)	2002-01-23	2010-05-26	バイエルファーマセチカルコーポレーション	Ｒｈｏキナーゼ阻害剤としてのピリミジン誘導体
JP2003238561A (ja)	2002-02-13	2003-08-27	Fuji Denki Gazo Device Kk	キノメタン化合物
BR0308162A (pt)	2002-03-01	2004-12-07	Pfizer	Derivados de indolil-uréia de tienopiridinas úteis como agentes antiangiogênicos e métodos para o seu uso
EP1485390B1 (en) *	2002-03-07	2008-10-08	F. Hoffman-la Roche AG	Bicyclic pyridine and pyrimidine p38 kinase inhibitors
UA77303C2 (en)	2002-06-14	2006-11-15	Pfizer	Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use
NZ539901A (en)	2002-11-26	2007-09-28	Pfizer Prod Inc	Method of treatment of transplant rejection
EP1592430A4 (en)	2003-01-17	2006-05-31	Threshold Pharmaceuticals Inc	TREATMENT OF GOOD PROSTATE HYPERPLASIA BY MEANS OF ENERGYSTIC ACTIVE SUBSTANCES
FR2851248B1 (fr) *	2003-02-18	2005-04-08	Aventis Pharma Sa	Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation
PT1636236E (pt)	2003-05-22	2013-12-16	Nerviano Medical Sciences Srl	Derivados de pirazol-quinazolina, processo para sua preparação e sua utilização como inibidores de cinase
EP1656378A4 (en) *	2003-08-15	2011-05-11	Irm Llc	COMPOUNDS AND COMPOSITIONS INHIBITING TYROSINE KINASE RECEPTOR ACTIVITY
US7338957B2 (en) *	2003-08-28	2008-03-04	Irm Llc	Compounds and compositions as protein kinase inhibitors
EP1660504B1 (en)	2003-08-29	2008-10-29	Pfizer Inc.	Thienopyridine-phenylacet amides and their derivatives useful as new anti-angiogenic agents
US7419978B2 (en)	2003-10-22	2008-09-02	Bristol-Myers Squibb Company	Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors
US7683172B2 (en)	2003-11-11	2010-03-23	Eisai R&D Management Co., Ltd.	Urea derivative and process for preparing the same
EA009994B1 (ru)	2003-12-23	2008-06-30	Пфайзер Инк.	Новые хинолиновые производные
US20080269238A1 (en) *	2004-04-01	2008-10-30	Takeda Pharmaceutical Company Limited	Thiazolopyrimidine Derivative
MXPA06013805A (es)	2004-05-27	2007-02-02	Pfizer Prod Inc	Derivados de pirrolopirimidina de utilidad en el tratamiento contra el cancer.
CN1993362B (zh) *	2004-06-02	2010-12-15	武田药品工业株式会社	稠合的杂环化合物
WO2005118588A1 (ja) *	2004-06-02	2005-12-15	Takeda Pharmaceutical Company Limited	縮合複素環化合物
JP2007161585A (ja) *	2004-06-25	2007-06-28	Taisho Pharmaceut Co Ltd	環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体
AU2005283422C1 (en)	2004-09-17	2017-02-02	Eisai R & D Management Co., Ltd.	Medicinal composition
EP1838712B8 (en) *	2004-12-14	2011-10-12	AstraZeneca AB	Pyrazolopyrimidine compounds as antitumor agents
CA2596830A1 (en) *	2005-02-03	2006-09-14	Vertex Pharmaceuticals Incorporated	Pyrrolopyrimidines useful as inhibitors of protein kinase
US7423043B2 (en)	2005-02-18	2008-09-09	Lexicon Pharmaceuticals, Inc.	4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine compounds
US20090111805A1 (en) *	2005-02-24	2009-04-30	Pfizer Inc.	Bicyclic heteroaromatic derivatives useful as anticancer agents
WO2006138714A2 (en) *	2005-06-17	2006-12-28	Janssen Pharmaceutica N.V.	Naphthyridine compounds
WO2007015578A1 (ja)	2005-08-02	2007-02-08	Eisai R & D Management Co., Ltd.	血管新生阻害物質の効果を検定する方法
US7915411B2 (en)	2005-12-21	2011-03-29	Abbott Laboratories	Anti-viral compounds
ATE475660T1 (de)	2005-12-21	2010-08-15	Abbott Lab	Antivirale verbindungen
CN101443334A (zh) *	2005-12-21	2009-05-27	艾博特公司	抗病毒化合物
EP1979348B1 (en) *	2005-12-21	2012-01-18	Abbott Laboratories	Anti-viral compounds
JP5255559B2 (ja) *	2006-03-31	2013-08-07	アボット・ラボラトリーズ	インダゾール化合物
WO2007114926A2 (en) *	2006-04-04	2007-10-11	The Regents Of The University Of California	Kinase antagonists
RU2448708C3 (ru)	2006-05-18	2017-09-28	Эйсай Ар Энд Ди Менеджмент Ко., Лтд.	Противоопухолевое средство против рака щитовидной железы
EP1889847A1 (en) *	2006-07-10	2008-02-20	DeveloGen Aktiengesellschaft	Pyrrolopyrimidines for pharmaceutical compositions
CN101511793B (zh)	2006-08-28	2011-08-03	卫材R&D管理有限公司	针对未分化型胃癌的抗肿瘤剂
EP2103620A1 (en) *	2006-12-12	2009-09-23	Takeda Pharmaceutical Company Limited	Fused heterocyclic compound
US8236950B2 (en)	2006-12-20	2012-08-07	Abbott Laboratories	Anti-viral compounds
CN101600694A (zh)	2007-01-29	2009-12-09	卫材R&D管理有限公司	未分化型胃癌治疗用组合物
KR101513326B1 (ko)	2007-11-09	2015-04-17	에자이 알앤드디 매니지먼트 가부시키가이샤	혈관 신생 저해 물질과 항종양성 백금 착물의 병용
AR070874A1 (es)	2008-03-12	2010-05-12	Takeda Pharmaceutical	Compuesto heterociclico fusionado, una composicion farmaceutica que lo comprende y su uso en el tratamiento del cancer.
AR073354A1 (es) *	2008-07-31	2010-11-03	Genentech Inc	Compuestos de pirimidina, composiciones farmaceuticas y su uso en el tratamiento del cancer.
JP4884570B2 (ja)	2008-08-20	2012-02-29	ファイザー・インク	ピロロ［２，３−ｄ］ピリミジン化合物
TW201014860A (en) *	2008-09-08	2010-04-16	Boehringer Ingelheim Int	New chemical compounds
KR101126736B1 (ko) *	2008-11-27	2012-04-12	주식회사 레고켐 바이오사이언스	티로신 키나아제 저해 화합물, 이의 이성질체 또는 이의 약학적으로 허용가능한 염 및 이를 포함하는 약학적 조성물
SG173014A1 (en)	2009-01-16	2011-08-29	Exelixis Inc	Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl)-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer
DE102009005193A1 (de) *	2009-01-20	2010-07-22	Merck Patent Gmbh	Neue heterocyclische Verbindungen als MetAP-2 Inhibitoren
JP5603883B2 (ja) *	2009-02-17	2014-10-08	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	Ｂ−Ｒａｆキナーゼを阻害するためのピリミドピリミジン誘導体
UA108618C2 (uk)	2009-08-07	2015-05-25		Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку
DK2468281T3 (en)	2009-08-19	2016-03-21	Eisai R&D Man Co Ltd	Quinolinderivatholdig pharmaceutical composition
WO2011058027A2 (en)	2009-11-12	2011-05-19	F. Hoffmann-La Roche Ag	N-9-substituted purine compounds, compositions and methods of use
CN102712642B (zh)	2009-11-12	2015-08-12	霍夫曼-拉罗奇有限公司	N-7取代的嘌呤和吡唑并嘧啶化合物、组合物和使用方法
JP2013518882A (ja) *	2010-02-05	2013-05-23	ファイザー・インク	ＪＡＫ阻害剤としてのピロロ［２，３−ｄ］ピリミジン尿素化合物
WO2011162343A1 (ja)	2010-06-25	2011-12-29	エーザイ・アール・アンド・ディー・マネジメント株式会社	キナーゼ阻害作用を有する化合物の併用による抗腫瘍剤
AU2011295441B2 (en) *	2010-08-27	2015-04-09	Merck Patent Gmbh	Furopyridine derivatives
EP2614065B1 (en)	2010-12-17	2017-04-19	Nerviano Medical Sciences S.r.l.	Substituted pyrazolo-quinazoline derivatives as kinase inhibitors
BR112013022552B1 (pt)	2011-03-04	2021-11-23	Newgen Therapeutics, Inc	Compostos de quinazolina substituídos com alcino, seu uso, composição farmacêutica, e kit
CN103402519B (zh)	2011-04-18	2015-11-25	卫材R&D管理有限公司	肿瘤治疗剂
JP6038128B2 (ja)	2011-06-03	2016-12-07	エーザイ・アール・アンド・ディー・マネジメント株式会社	レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー
AU2013224420B2 (en) *	2012-02-21	2016-12-15	Merck Patent Gmbh	Furopyridine derivatives
EP2900671A1 (en)	2012-09-26	2015-08-05	Bayer Pharma Aktiengesellschaft	Substituted indazol-pyrrolopyrimidines useful in the treatment of hyperproliferative diseases
JP2015531361A (ja)	2012-09-26	2015-11-02	バイエル・ファルマ・アクティエンゲゼルシャフト	過剰増殖性疾患の治療に有用な置換インダゾール−ピロロピリミジン
AU2013364953A1 (en)	2012-12-21	2015-04-30	Eisai R&D Management Co., Ltd.	Amorphous form of quinoline derivative, and method for producing same
JP2016506944A (ja) *	2013-02-01	2016-03-07	バイエル・ファルマ・アクティエンゲゼルシャフト	置換ピラゾロピリミジニルアミノ−インダゾール
WO2014145576A2 (en)	2013-03-15	2014-09-18	Northwestern University	Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer
EP2997377B1 (en)	2013-05-14	2018-07-18	Eisai R&D Management Co., Ltd.	Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds
HRP20220522T1 (hr)	2014-08-04	2022-06-10	Nuevolution A/S	Proizvoljno kondenzirani heterociklil-supstituirani derivati pirimidina koji su korisni za liječenje upalnih, metaboličkih, onkoloških i autoimunih bolesti
PT3524595T (pt)	2014-08-28	2022-09-19	Eisai R&D Man Co Ltd	Derivado de quinolina altamente puro e método para produção do mesmo
AU2016224583B2 (en)	2015-02-25	2021-06-03	Eisai R&D Management Co., Ltd.	Method for suppressing bitterness of quinoline derivative
KR102662228B1 (ko)	2015-03-04	2024-05-02	머크 샤프 앤드 돔 코포레이션	암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합
BR112017027227B1 (pt)	2015-06-16	2023-12-12	Eisai R&D Management Co., Ltd	Agente anti-câncer
JP6553726B2 (ja)	2015-08-20	2019-07-31	エーザイ・アール・アンド・ディー・マネジメント株式会社	腫瘍治療剤
GB201520499D0 (en) *	2015-11-20	2016-01-06	Medical Res Council Technology	Compounds
CN106831779B (zh) *	2015-11-28	2019-07-19	南昌弘益药业有限公司	一类jak激酶抑制剂的新化合物
JP6581320B2 (ja)	2017-02-08	2019-09-25	エーザイ・アール・アンド・ディー・マネジメント株式会社	腫瘍治療用医薬組成物
EP3624800A4 (en)	2017-05-16	2021-02-17	Eisai R&D Management Co., Ltd.	TREATMENT OF HEPATOCELLULAR CARCINOMA
NL2022471B1 (en)	2019-01-29	2020-08-18	Vationpharma B V	Solid state forms of oclacitinib
CN111825674A (zh) *	2019-04-22	2020-10-27	上海仕谱生物科技有限公司	嘧啶并五元杂环类化合物及其作为突变型idh2抑制剂的用途
MX2022007265A (es)	2019-12-20	2022-09-09	Nuevolution As	Compuestos activos frente a receptores nucleares.
US11685727B2 (en)	2019-12-20	2023-06-27	Nuevolution A/S	Compounds active towards nuclear receptors
EP4126874A1 (en)	2020-03-31	2023-02-08	Nuevolution A/S	Compounds active towards nuclear receptors
CA3174176A1 (en)	2020-03-31	2021-10-07	Sanne Schroder Glad	Compounds active towards nuclear receptors
EP4323356A1 (en)	2021-04-13	2024-02-21	Nuvalent, Inc.	Amino-substituted heterocycles for treating cancers with egfr mutations

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4012513A (en) *	1971-11-03	1977-03-15	Imperial Chemical Industries Limited	Indole derivatives for providing analgesic and anti-inflammatory effects
JPS58126887A (ja) *	1981-09-26	1983-07-28	Takeda Chem Ind Ltd	新規７−デアザプリン誘導体
JPS58157790A (ja) *	1982-03-16	1983-09-19	Takeda Chem Ind Ltd	７−デアザプリン誘導体およびその製造法
JPS60233080A (ja) *	1984-05-02	1985-11-19	Takeda Chem Ind Ltd	７−デアザプリン誘導体
CA1293727C (en) *	1986-08-26	1991-12-31	Catherine Rose Kostlan	9-deazaguanines
NO169490C (no) *	1988-03-24	1992-07-01	Takeda Chemical Industries Ltd	Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrrolopyrimidinderivater
JP2541702B2 (ja) *	1989-10-11	1996-10-09	帝人株式会社	二環性ピリミジン誘導体、その製造方法およびそれを有効成分とする医薬製剤
US5320663A (en) *	1992-07-02	1994-06-14	E. I. Du Pont De Nemours And Company	Method of obtaining lead and organolead from contaminated media using metal accumulating plants
ATE177101T1 (de) *	1992-12-17	1999-03-15	Pfizer	Pyrrolopyrimidine als crf antagonisten
WO1995001355A1 (en) *	1993-06-30	1995-01-12	Biocryst Pharmaceuticals, Inc.	9-deazahypoxanthines as pnp inhibitors

1995
- 1995-06-07 AT AT95924027T patent/ATE247469T1/de not_active IP Right Cessation
- 1995-06-07 DK DK95924027T patent/DK0831829T3/da active
- 1995-06-07 PT PT95924027T patent/PT831829E/pt unknown
- 1995-06-07 SK SK729-96A patent/SK72996A3/sk unknown
- 1995-06-07 EP EP95924027A patent/EP0831829B1/en not_active Expired - Lifetime
- 1995-06-07 DE DE69531558T patent/DE69531558T2/de not_active Expired - Fee Related
- 1995-06-07 WO PCT/US1995/007881 patent/WO1996040142A1/en not_active Ceased
- 1995-06-07 MX MX9709867A patent/MX9709867A/es not_active IP Right Cessation
- 1995-06-07 FI FI974443A patent/FI974443A7/fi unknown
- 1995-06-07 CA CA002223081A patent/CA2223081C/en not_active Expired - Fee Related
- 1995-06-07 ES ES95924027T patent/ES2203642T3/es not_active Expired - Lifetime
- 1995-06-07 JP JP50039097A patent/JP3290666B2/ja not_active Expired - Fee Related
1996
- 1996-05-09 AP APAP/P/1996/000805A patent/AP637A/en active
- 1996-05-22 AR ARP960102673A patent/AR002746A1/es unknown
- 1996-05-30 IL IL11848796A patent/IL118487A0/xx unknown
- 1996-06-03 MA MA24256A patent/MA26409A1/fr unknown
- 1996-06-05 SG SG1996009982A patent/SG45483A1/en unknown
- 1996-06-05 CN CN96108101A patent/CN1141298A/zh active Pending
- 1996-06-05 PL PL96314641A patent/PL314641A1/xx unknown
- 1996-06-06 SI SI9600184A patent/SI9600184A/sl unknown
- 1996-06-06 ZA ZA9604725A patent/ZA964725B/xx unknown
- 1996-06-06 NZ NZ286755A patent/NZ286755A/en unknown
- 1996-06-06 HR HR95/007,881A patent/HRP960269A2/hr not_active Application Discontinuation
- 1996-06-06 HU HU9601559A patent/HUP9601559A3/hu unknown
- 1996-06-06 NO NO962386A patent/NO962386L/no unknown
- 1996-06-06 AU AU54791/96A patent/AU5479196A/en not_active Abandoned
- 1996-06-06 TR TR96/00474A patent/TR199600474A2/xx unknown
- 1996-06-06 CZ CZ961641A patent/CZ164196A3/cs unknown
- 1996-06-07 BR BR9602695A patent/BR9602695A/pt active Search and Examination
- 1996-06-07 OA OA60838A patent/OA10460A/en unknown
- 1996-06-07 RU RU96111016A patent/RU2136683C1/ru active
- 1996-06-07 CO CO96029731A patent/CO4440628A1/es unknown

Also Published As

Publication number	Publication date
JP3290666B2 (ja)	2002-06-10
HUP9601559A3 (en)	1997-07-28
DK0831829T3 (da)	2003-12-15
AR002746A1 (es)	1998-04-29
BR9602695A (pt)	1998-10-06
PL314641A1 (en)	1996-12-09
CN1141298A (zh)	1997-01-29
MA26409A1 (fr)	2004-12-20
FI974443L (fi)	1997-12-05
OA10460A (en)	2002-03-28
NZ286755A (en)	1998-03-25
CA2223081A1 (en)	1996-12-19
HRP960269A2 (en)	1997-08-31
DE69531558D1 (de)	2003-09-25
EP0831829A1 (en)	1998-04-01
HU9601559D0 (en)	1996-08-28
ZA964725B (en)	1997-12-08
HUP9601559A2 (en)	1997-02-28
MX9709867A (es)	1998-03-31
SG45483A1 (en)	1998-01-16
DE69531558T2 (de)	2004-03-18
TR199600474A2 (tr)	1996-12-21
SK72996A3 (en)	1997-04-09
ES2203642T3 (es)	2004-04-16
IL118487A0 (en)	1996-09-12
CA2223081C (en)	2001-03-06
PT831829E (pt)	2003-12-31
FI974443A0 (fi)	1997-12-05
CZ164196A3 (en)	1996-12-11
EP0831829A4 (en)	1998-11-25
JPH10508875A (ja)	1998-09-02
AP9600805A0 (en)	1996-07-31
AU5479196A (en)	1996-12-19
NO962386L (no)	1996-12-09
ATE247469T1 (de)	2003-09-15
RU2136683C1 (ru)	1999-09-10
EP0831829B1 (en)	2003-08-20
FI974443A7 (fi)	1997-12-05
NO962386D0 (no)	1996-06-06
AP637A (en)	1998-04-08
CO4440628A1 (es)	1997-05-07
WO1996040142A1 (en)	1996-12-19

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