OA10460A - Heterocyclic ring-fused pyrimidine derivatives - Google Patents

Heterocyclic ring-fused pyrimidine derivatives Download PDF

Info

Publication number: OA10460A
Authority: OA; OAPI
Prior art keywords: pyrimidin; amine; pyrido; phenyl; alkyl
Prior art date: 1995-06-07

Application number

OA60838A

Other languages

English (en)

Inventor

Daniel Arnold Lee

Paul Moyer Mikel

Beth Sobolov-Jaynes Susan

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

1996-06-07

Publication date

2002-03-28

1996-06-07 Application filed by Pfizer filed Critical Pfizer

2002-03-28 Publication of OA10460A publication Critical patent/OA10460A/en

Links

125000000623 heterocyclic group Chemical group 0.000 title description 2
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
150000003230 pyrimidines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 129
206010028980 Neoplasm Diseases 0.000 claims abstract description 25
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
238000011282 treatment Methods 0.000 claims abstract description 13
230000003463 hyperproliferative effect Effects 0.000 claims abstract description 12
201000010099 disease Diseases 0.000 claims abstract description 9
241000124008 Mammalia Species 0.000 claims abstract description 6
150000003839 salts Chemical class 0.000 claims abstract description 5
239000000651 prodrug Substances 0.000 claims abstract description 3
229940002612 prodrug Drugs 0.000 claims abstract description 3
-1 nitro, hydroxy, amino Chemical group 0.000 claims description 128
125000000217 alkyl group Chemical group 0.000 claims description 74
238000000034 method Methods 0.000 claims description 56
125000003545 alkoxy group Chemical group 0.000 claims description 55
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 40
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
125000003282 alkyl amino group Chemical group 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 19
125000005236 alkanoylamino group Chemical group 0.000 claims description 17
125000004414 alkyl thio group Chemical group 0.000 claims description 16
125000005518 carboxamido group Chemical group 0.000 claims description 16
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000004423 acyloxy group Chemical group 0.000 claims description 13
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
201000011510 cancer Diseases 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 11
125000005605 benzo group Chemical group 0.000 claims description 10
208000035475 disorder Diseases 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000005494 pyridonyl group Chemical group 0.000 claims description 8
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 8
125000005530 alkylenedioxy group Chemical group 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
210000000481 breast Anatomy 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
LNPZJAMDBWPNSF-UHFFFAOYSA-N n-(3-methylphenyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC=NC=C3N=CN=2)=C1 LNPZJAMDBWPNSF-UHFFFAOYSA-N 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
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
229910014585 C2-Ce Inorganic materials 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
125000001246 bromo group Chemical group Br* 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
230000002496 gastric effect Effects 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
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
210000004072 lung Anatomy 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
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 4
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 4
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 4
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 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
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 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000003368 amide group Chemical group 0.000 claims description 3
125000003118 aryl 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
210000004556 brain Anatomy 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
230000002440 hepatic effect Effects 0.000 claims description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
UGJFDWWKZWPKSZ-UHFFFAOYSA-N n-(1-benzothiophen-5-yl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(NC=3C=C4C=CSC4=CC=3)=NC=NC2=C1 UGJFDWWKZWPKSZ-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
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 3
239000001301 oxygen Chemical group 0.000 claims description 3
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 3
210000002307 prostate Anatomy 0.000 claims description 3
125000004760 (C1-C4) alkylsulfonylamino 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
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 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
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 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
MZJBVKCTGOKCHG-UHFFFAOYSA-N 4-(6-bromo-7-methyl-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.C1CC2=CC=C(Br)C(C)=C2N1C1=C2C=C(C)N=CC2=NC=N1 MZJBVKCTGOKCHG-UHFFFAOYSA-N 0.000 claims description 2
BSEIRHPCQJAJNT-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-ol Chemical compound C1CC2=CC=C(Cl)C=C2N1C1=C(NC(O)=C2)C2=NC=N1 BSEIRHPCQJAJNT-UHFFFAOYSA-N 0.000 claims description 2
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 2
OZMLAELAHCCJQD-UHFFFAOYSA-N 7-(benzenesulfonyl)-n-(3-ethynylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC2=C(NC=3C=C(C=CC=3)C#C)N=CN=C2N1S(=O)(=O)C1=CC=CC=C1 OZMLAELAHCCJQD-UHFFFAOYSA-N 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
239000005864 Sulphur Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
125000005596 alkyl carboxamido group Chemical group 0.000 claims description 2
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 2
125000004429 atom Chemical group 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
125000003843 furanosyl group Chemical group 0.000 claims description 2
125000002883 imidazolyl 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
150000004702 methyl esters Chemical class 0.000 claims description 2
QWBHMRAAZIJOEI-UHFFFAOYSA-N n-(1h-indol-5-yl)-6-methylpyrido[3,4-d]pyrimidin-4-amine Chemical compound C1=C2NC=CC2=CC(NC2=C3C=C(N=CC3=NC=N2)C)=C1 QWBHMRAAZIJOEI-UHFFFAOYSA-N 0.000 claims description 2
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 2
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 2
FJMBUNFCISVZGU-UHFFFAOYSA-N n-(1h-indol-5-yl)pyrido[4,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C1=NC=C2C(NC=3C=C4C=CNC4=CC=3)=NC=NC2=C1 FJMBUNFCISVZGU-UHFFFAOYSA-N 0.000 claims description 2
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 2
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 2
HYAREKYBZAMFCX-UHFFFAOYSA-N n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 HYAREKYBZAMFCX-UHFFFAOYSA-N 0.000 claims description 2
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 2
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 2
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 2
LVTUVRVZECNLGU-UHFFFAOYSA-N n-(3-ethynylphenyl)-7h-purin-6-amine Chemical compound C#CC1=CC=CC(NC=2C=3N=CNC=3N=CN=2)=C1 LVTUVRVZECNLGU-UHFFFAOYSA-N 0.000 claims description 2
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 2
KHEYWDNIEMRBQT-UHFFFAOYSA-N n-(4-fluoro-3-methylphenyl)-6-methylpyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=C(F)C(C)=C1 KHEYWDNIEMRBQT-UHFFFAOYSA-N 0.000 claims description 2
YSXXPSCMGXWKAH-UHFFFAOYSA-N n-(6-methyl-2,3-dihydroindol-1-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=CC(C)=CC=C2CCN1NC1=NC=NC2=C1C=CN2 YSXXPSCMGXWKAH-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003132 pyranosyl group Chemical group 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
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 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 1
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 1
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 1
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 1
YQACOZRQAQJJNS-UHFFFAOYSA-N 6-methyl-n-[3-(trifluoromethyl)phenyl]pyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(C)=CC2=C1NC1=CC=CC(C(F)(F)F)=C1 YQACOZRQAQJJNS-UHFFFAOYSA-N 0.000 claims 1
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 1
208000004403 Prostatic Hyperplasia Diseases 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
125000000304 alkynyl group Chemical group 0.000 claims 1
125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
210000003128 head Anatomy 0.000 claims 1
GLDRNGJKSCNHOB-UHFFFAOYSA-N n-(1-benzothiophen-5-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C2SC=CC2=CC=1NC1=NC=NC2=C1C=CN2 GLDRNGJKSCNHOB-UHFFFAOYSA-N 0.000 claims 1
BIPLYRLRZNBNNY-UHFFFAOYSA-N n-(1h-indazol-5-yl)-6-methylpyrido[3,4-d]pyrimidin-4-amine Chemical compound C1=C2NN=CC2=CC(NC2=C3C=C(N=CC3=NC=N2)C)=C1 BIPLYRLRZNBNNY-UHFFFAOYSA-N 0.000 claims 1
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 1
BHOIHXVTLUPUES-UHFFFAOYSA-N n-(1h-indazol-5-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C2NN=CC2=CC=1NC1=NC=NC2=C1C=CN2 BHOIHXVTLUPUES-UHFFFAOYSA-N 0.000 claims 1
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 1
ITTZBDQOYAADFL-UHFFFAOYSA-N n-(1h-indol-5-yl)-6-methylpyrido[3,4-d]pyrimidin-4-amine;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=C2NC=CC2=CC(NC2=C3C=C(N=CC3=NC=N2)C)=C1 ITTZBDQOYAADFL-UHFFFAOYSA-N 0.000 claims 1
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 1
RRCDEIQCICOTKZ-UHFFFAOYSA-N n-(3-chlorophenyl)pyrido[4,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C3=CN=CC=C3N=CN=2)=C1 RRCDEIQCICOTKZ-UHFFFAOYSA-N 0.000 claims 1
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 1
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 1
YNPDKOLXWRNDHX-UHFFFAOYSA-N n-(6-chloro-5-fluoro-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(NN3CCC=4C=C(C(=CC=43)Cl)F)=NC=NC2=C1 YNPDKOLXWRNDHX-UHFFFAOYSA-N 0.000 claims 1
210000003739 neck Anatomy 0.000 claims 1
AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 claims 1
IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims 1
208000020154 Acnes Diseases 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 124
239000000047 product Substances 0.000 description 63
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 61
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 56
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 31
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 28
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
238000004128 high performance liquid chromatography Methods 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
150000001412 amines Chemical class 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 20
229940073584 methylene chloride Drugs 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
238000004007 reversed phase HPLC Methods 0.000 description 19
239000000243 solution Substances 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 15
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
NNKQLUVBPJEUOR-UHFFFAOYSA-N 3-ethynylaniline Chemical group NC1=CC=CC(C#C)=C1 NNKQLUVBPJEUOR-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000012458 free base Substances 0.000 description 13
238000004519 manufacturing process Methods 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 11
108060006698 EGF receptor Proteins 0.000 description 11
102000001301 EGF receptor Human genes 0.000 description 11
229940093499 ethyl acetate Drugs 0.000 description 11
235000019439 ethyl acetate Nutrition 0.000 description 11
239000000463 material Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
239000000377 silicon dioxide Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
239000000725 suspension Substances 0.000 description 11
RWOCXEWKWNHSKH-UHFFFAOYSA-N 6-methyl-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(C)=C2 RWOCXEWKWNHSKH-UHFFFAOYSA-N 0.000 description 10
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
229910052938 sodium sulfate Inorganic materials 0.000 description 10
235000011152 sodium sulphate Nutrition 0.000 description 10
PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 9
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
UKTHPAHJCQLABU-UHFFFAOYSA-N 4-chloropyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(Cl)=NC=NC2=C1 UKTHPAHJCQLABU-UHFFFAOYSA-N 0.000 description 8
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
239000012442 inert solvent Substances 0.000 description 8
239000012071 phase Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
239000003513 alkali Substances 0.000 description 7
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
AQJMPQUAYYFZGY-UHFFFAOYSA-N n-(3-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 AQJMPQUAYYFZGY-UHFFFAOYSA-N 0.000 description 6
ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 5
OXLMTRZWMHIZBY-UHFFFAOYSA-N 5-bromo-4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C(Br)=CN2 OXLMTRZWMHIZBY-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
230000004913 activation Effects 0.000 description 5
150000008064 anhydrides Chemical class 0.000 description 5
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
235000017550 sodium carbonate Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
HJBCFHXEOPQFGF-UHFFFAOYSA-N 4-chloropyrido[2,3-d]pyrimidine Chemical compound C1=CC=C2C(Cl)=NC=NC2=N1 HJBCFHXEOPQFGF-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
102100033237 Pro-epidermal growth factor Human genes 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
230000001093 anti-cancer Effects 0.000 description 4
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
239000003701 inert diluent Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
102000027426 receptor tyrosine kinases Human genes 0.000 description 4
108091008598 receptor tyrosine kinases Proteins 0.000 description 4
229940001593 sodium carbonate Drugs 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
238000012360 testing method Methods 0.000 description 4
RADMRAMXLLLVGG-UHFFFAOYSA-N 1h-pyrido[4,3-d]pyrimidin-4-one Chemical compound C1=NC=C2C(=O)N=CNC2=C1 RADMRAMXLLLVGG-UHFFFAOYSA-N 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
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 description 3
HSLNYVREDLDESE-UHFFFAOYSA-N 6-chloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2CCNC2=C1 HSLNYVREDLDESE-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
101710098940 Pro-epidermal growth factor Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 3
239000012895 dilution Substances 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
230000014509 gene expression Effects 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
239000000758 substrate Substances 0.000 description 3
238000005694 sulfonylation reaction Methods 0.000 description 3
230000009466 transformation Effects 0.000 description 3
238000005406 washing Methods 0.000 description 3
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 2
DVXIUBGLTXOANK-UHFFFAOYSA-N 1-[4-(3-methylanilino)pyrrolo[2,3-d]pyrimidin-7-yl]ethanone Chemical compound N1=CN=C2N(C(=O)C)C=CC2=C1NC1=CC=CC(C)=C1 DVXIUBGLTXOANK-UHFFFAOYSA-N 0.000 description 2
XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 2
JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
OUDUMILAWSRWRY-UHFFFAOYSA-N 4-chloro-5-methylsulfanyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=NC(Cl)=C2C(SC)=CNC2=N1 OUDUMILAWSRWRY-UHFFFAOYSA-N 0.000 description 2
NEWCOPCSNFUQQY-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine-5-carbonitrile Chemical compound ClC1=NC=NC2=C1C(C#N)=CN2 NEWCOPCSNFUQQY-UHFFFAOYSA-N 0.000 description 2
LRWDLEGXXQAORM-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid Chemical compound C1=NC(Cl)=C2C(C(=O)O)=CNC2=N1 LRWDLEGXXQAORM-UHFFFAOYSA-N 0.000 description 2
ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 2
LSONQSDHHUUXOM-UHFFFAOYSA-N 7-methyl-1h-pyrido[4,3-d]pyrimidin-4-one Chemical compound C1=NC(O)=C2C=NC(C)=CC2=N1 LSONQSDHHUUXOM-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
229910052684 Cerium Inorganic materials 0.000 description 2
230000006820 DNA synthesis Effects 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
240000007817 Olea europaea Species 0.000 description 2
108700020796 Oncogene Proteins 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
208000024770 Thyroid neoplasm Diseases 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000009471 action Effects 0.000 description 2
150000001348 alkyl chlorides Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000006870 function Effects 0.000 description 2
230000012010 growth Effects 0.000 description 2
150000002391 heterocyclic compounds Chemical class 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
238000002513 implantation Methods 0.000 description 2
150000002475 indoles Chemical class 0.000 description 2
150000002476 indolines Chemical class 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 2
150000002828 nitro derivatives Chemical class 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
230000002611 ovarian Effects 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
102000020233 phosphotransferase Human genes 0.000 description 2
229910052697 platinum Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
230000004044 response Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000006103 sulfonylation Effects 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
230000004614 tumor growth Effects 0.000 description 2
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
XWAUDTLGRGKULT-UHFFFAOYSA-N 1-[5-amino-6-(6-chloro-2,3-dihydroindol-1-yl)pyrimidin-4-yl]propan-1-one Chemical compound CCC(=O)C1=NC=NC(N2C3=CC(Cl)=CC=C3CC2)=C1N XWAUDTLGRGKULT-UHFFFAOYSA-N 0.000 description 1
ZUPYTANKWDPRDP-UHFFFAOYSA-N 1-benzothiophen-5-amine Chemical compound NC1=CC=C2SC=CC2=C1 ZUPYTANKWDPRDP-UHFFFAOYSA-N 0.000 description 1
QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
ONADPSCFVJZVCN-UHFFFAOYSA-N 2-methyl-4-[(6-methyl-5h-pyrido[4,3-d]pyrimidin-4-yl)amino]phenol Chemical compound N1=CN=C2C=CN(C)CC2=C1NC1=CC=C(O)C(C)=C1 ONADPSCFVJZVCN-UHFFFAOYSA-N 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
KOWPUNQBGWIERF-UHFFFAOYSA-N 3-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Br)=C1 KOWPUNQBGWIERF-UHFFFAOYSA-N 0.000 description 1
YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
HWMVCSBQJWRQNF-UHFFFAOYSA-N 3-ethynyl-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C#C)=C1 HWMVCSBQJWRQNF-UHFFFAOYSA-N 0.000 description 1
SGLIJWXMPPZXRW-UHFFFAOYSA-N 4-(6,7-dimethyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.N1=CC=C2C(N3CCC4=CC=C(C(=C43)C)C)=NC=NC2=C1 SGLIJWXMPPZXRW-UHFFFAOYSA-N 0.000 description 1
QPEFVPDESAJGGO-UHFFFAOYSA-N 4-(6-bromo-5-fluoro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.C1CC2=CC(F)=C(Br)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 QPEFVPDESAJGGO-UHFFFAOYSA-N 0.000 description 1
GUGSDWSSHLBVST-UHFFFAOYSA-N 4-amino-2-iodophenol Chemical compound NC1=CC=C(O)C(I)=C1 GUGSDWSSHLBVST-UHFFFAOYSA-N 0.000 description 1
HDGMAACKJSBLMW-UHFFFAOYSA-N 4-amino-2-methylphenol Chemical compound CC1=CC(N)=CC=C1O HDGMAACKJSBLMW-UHFFFAOYSA-N 0.000 description 1
WUSQVMYMTQCNAV-UHFFFAOYSA-N 4-amino-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(N)=C(C(O)=O)C=N1 WUSQVMYMTQCNAV-UHFFFAOYSA-N 0.000 description 1
IASBMUIXBJNMDW-UHFFFAOYSA-N 4-aminonicotinic acid Chemical class NC1=CC=NC=C1C(O)=O IASBMUIXBJNMDW-UHFFFAOYSA-N 0.000 description 1
BPSAXYWIOCKHEM-UHFFFAOYSA-N 4-bromo-7-methyl-2,3-dihydro-1h-indole Chemical compound CC1=CC=C(Br)C2=C1NCC2 BPSAXYWIOCKHEM-UHFFFAOYSA-N 0.000 description 1
PAQRPFZPWLUCIM-UHFFFAOYSA-N 4-chloro-5-methyl-6,7-dihydropyrrolo[3,2-d]pyrimidine Chemical compound C1=NC(Cl)=C2N(C)CCC2=N1 PAQRPFZPWLUCIM-UHFFFAOYSA-N 0.000 description 1
NISJMYPRXDUYTF-UHFFFAOYSA-N 4-chloro-5-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=NC(Cl)=C2C(C)=CNC2=N1 NISJMYPRXDUYTF-UHFFFAOYSA-N 0.000 description 1
QEBYFYMAZXUKSU-UHFFFAOYSA-N 4-chloro-6-methylpyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(C)=CC2=C1Cl QEBYFYMAZXUKSU-UHFFFAOYSA-N 0.000 description 1
NYTHDOGSBSFBIR-UHFFFAOYSA-N 4-chloro-7-(2-methoxyethyl)pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2N(CCOC)C=CC2=C1Cl NYTHDOGSBSFBIR-UHFFFAOYSA-N 0.000 description 1
AZBRWKAPAHRLSV-UHFFFAOYSA-N 4-chloro-7-[2-(2-methoxyethoxy)ethyl]pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2N(CCOCCOC)C=CC2=C1Cl AZBRWKAPAHRLSV-UHFFFAOYSA-N 0.000 description 1
JWRIQTFDXVDHCR-UHFFFAOYSA-N 4-chloro-7-prop-2-enylpyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2CC=C JWRIQTFDXVDHCR-UHFFFAOYSA-N 0.000 description 1
MFUWUCHAQPUKDY-UHFFFAOYSA-N 4-chloropyrido[4,3-d]pyrimidine Chemical compound C1=NC=C2C(Cl)=NC=NC2=C1 MFUWUCHAQPUKDY-UHFFFAOYSA-N 0.000 description 1
OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 description 1
BXOBZGPEZABVEA-UHFFFAOYSA-N 5-amino-2-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=C(N)C=N1 BXOBZGPEZABVEA-UHFFFAOYSA-N 0.000 description 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
SVNDSMLMPVHWET-UHFFFAOYSA-N 6-bromo-5-fluoro-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(F)=CC2=C1NCC2 SVNDSMLMPVHWET-UHFFFAOYSA-N 0.000 description 1
JCTUCTVNFGEPHV-UHFFFAOYSA-N 6-bromo-7-methyl-2,3-dihydro-1h-indole Chemical compound C1=C(Br)C(C)=C2NCCC2=C1 JCTUCTVNFGEPHV-UHFFFAOYSA-N 0.000 description 1
MMGGSCIGUVFESP-UHFFFAOYSA-N 6-methyl-n-[3-(trifluoromethyl)phenyl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(C)=CC2=C1NC1=CC=CC(C(F)(F)F)=C1 MMGGSCIGUVFESP-UHFFFAOYSA-N 0.000 description 1
OEEYCNOOAHGFHL-UHFFFAOYSA-N 8-azahypoxanthine Chemical compound O=C1N=CN=C2NNN=C12 OEEYCNOOAHGFHL-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
108010076278 Adenosine kinase Proteins 0.000 description 1
102100032534 Adenosine kinase Human genes 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
208000009849 Female Genital Neoplasms Diseases 0.000 description 1
208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
102400000921 Gastrin Human genes 0.000 description 1
108010052343 Gastrins Proteins 0.000 description 1
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
244000025272 Persea americana Species 0.000 description 1
235000008673 Persea americana Nutrition 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
230000010799 Receptor Interactions Effects 0.000 description 1
101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
208000015634 Rectal Neoplasms Diseases 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
238000003436 Schotten-Baumann reaction Methods 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
239000000642 acaricide Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000000033 alkoxyamino group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
238000007098 aminolysis reaction Methods 0.000 description 1
230000002491 angiogenic effect Effects 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
238000011394 anticancer treatment Methods 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
230000008901 benefit Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
230000002252 carbamoylating effect Effects 0.000 description 1
230000021235 carbamoylation Effects 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000010307 cell transformation Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
210000000448 cultured tumor cell Anatomy 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
238000006900 dealkylation reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000000417 fungicide Substances 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000000762 glandular Effects 0.000 description 1
230000002518 glial effect Effects 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
230000009422 growth inhibiting effect Effects 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
201000003911 head and neck carcinoma Diseases 0.000 description 1
208000014829 head and neck neoplasm Diseases 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
125000005027 hydroxyaryl group Chemical group 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
230000002267 hypothalamic effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000006698 induction Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000002917 insecticide Substances 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
150000002505 iron Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
DLLZUNNKHQPKTL-UHFFFAOYSA-N n-(1h-indol-5-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C2NC=CC2=CC=1NC1=NC=NC2=C1C=CN2 DLLZUNNKHQPKTL-UHFFFAOYSA-N 0.000 description 1
XWMKFKWJQLAMCB-UHFFFAOYSA-N n-(3-chlorophenyl)-2h-triazolo[4,5-d]pyrimidin-7-amine Chemical compound ClC1=CC=CC(NC=2C3=NNN=C3N=CN=2)=C1 XWMKFKWJQLAMCB-UHFFFAOYSA-N 0.000 description 1
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 description 1
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 description 1
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 description 1
HGTHTZHDDWHETJ-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-(2-morpholin-4-ylethyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C#CC1=CC=CC(NC=2C=3C=CN(CCN4CCOCC4)C=3N=CN=2)=C1 HGTHTZHDDWHETJ-UHFFFAOYSA-N 0.000 description 1
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 description 1
XBMUTDGAFSUQOT-UHFFFAOYSA-N n-(3-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.CC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 XBMUTDGAFSUQOT-UHFFFAOYSA-N 0.000 description 1
AVPRSHDQDKHRBJ-UHFFFAOYSA-N n-(3-methylphenyl)pyrimidin-4-amine Chemical compound CC1=CC=CC(NC=2N=CN=CC=2)=C1 AVPRSHDQDKHRBJ-UHFFFAOYSA-N 0.000 description 1
ZPCDCFLMNLYSGD-UHFFFAOYSA-N n-(6-chloro-5-fluoro-2,3-dihydroindol-1-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C=C(Cl)C(F)=CC=2CCN1NC1=NC=NC2=C1C=CN2 ZPCDCFLMNLYSGD-UHFFFAOYSA-N 0.000 description 1
YMPAUSSHJRQSED-UHFFFAOYSA-N n-(6-iodo-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(NN3CCC4=CC=C(C=C43)I)=NC=NC2=C1 YMPAUSSHJRQSED-UHFFFAOYSA-N 0.000 description 1
AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical class N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
238000011580 nude mouse model Methods 0.000 description 1
239000002674 ointment Substances 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-M periodate Chemical compound [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
ICFMKXPAKFZZAW-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=C=N[CH]1 ICFMKXPAKFZZAW-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 description 1
150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
229920005604 random copolymer Polymers 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
201000001275 rectum cancer Diseases 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
230000011664 signaling Effects 0.000 description 1
230000007781 signaling event Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229960001407 sodium bicarbonate Drugs 0.000 description 1
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
239000012089 stop solution Substances 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000013076 thyroid tumor Diseases 0.000 description 1
238000004448 titration Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Dermatology (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

OA60838A 1995-06-07 1996-06-07 Heterocyclic ring-fused pyrimidine derivatives OA10460A (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
OA10460A true OA10460A (en)	2002-03-28

Family

ID=89994036

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60838A OA10460A (en)	1995-06-07	1996-06-07	Heterocyclic ring-fused pyrimidine derivatives

Country Status (32)

Country	Link
EP (1)	EP0831829B1 (xx)
JP (1)	JP3290666B2 (xx)
CN (1)	CN1141298A (xx)
AP (1)	AP637A (xx)
AR (1)	AR002746A1 (xx)
AT (1)	ATE247469T1 (xx)
AU (1)	AU5479196A (xx)
BR (1)	BR9602695A (xx)
CA (1)	CA2223081C (xx)
CO (1)	CO4440628A1 (xx)
CZ (1)	CZ164196A3 (xx)
DE (1)	DE69531558T2 (xx)
DK (1)	DK0831829T3 (xx)
ES (1)	ES2203642T3 (xx)
FI (1)	FI974443A0 (xx)
HR (1)	HRP960269A2 (xx)
HU (1)	HUP9601559A3 (xx)
IL (1)	IL118487A0 (xx)
MA (1)	MA26409A1 (xx)
MX (1)	MX9709867A (xx)
NO (1)	NO962386L (xx)
NZ (1)	NZ286755A (xx)
OA (1)	OA10460A (xx)
PL (1)	PL314641A1 (xx)
PT (1)	PT831829E (xx)
RU (1)	RU2136683C1 (xx)
SG (1)	SG45483A1 (xx)
SI (1)	SI9600184A (xx)
SK (1)	SK72996A3 (xx)
TR (1)	TR199600474A2 (xx)
WO (1)	WO1996040142A1 (xx)
ZA (1)	ZA964725B (xx)

Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE59500788D1 (de) *	1994-05-03	1997-11-20	Ciba Geigy Ag	Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
TW321649B (xx) *	1994-11-12	1997-12-01	Zeneca Ltd
GB9424233D0 (en) *	1994-11-30	1995-01-18	Zeneca Ltd	Quinazoline derivatives
CA2214086C (en) *	1995-04-03	2008-07-29	Novartis Ag	Pyrazole derivatives and processes for the preparation thereof
GB9508535D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivative
GB9508538D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
GB9508565D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quiazoline derivative
JPH11507329A (ja) *	1995-04-27	1999-06-29	ゼネカリミテッド	キナゾリン誘導体
GB9508537D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
SI9620103A (sl) *	1995-07-06	1998-10-31	Novartis Ag	Pirolopirimidini in postopki za njihovo pripravo
GB9624482D0 (en) *	1995-12-18	1997-01-15	Zeneca Phaema S A	Chemical compounds
AU1441497A (en) *	1996-01-23	1997-08-20	Novartis Ag	Pyrrolopyrimidines and processes for their preparation
DE69720965T2 (de)	1996-02-13	2004-02-05	Astrazeneca Ab	Chinazolinderivate und deren verwendung als vegf hemmer
GB9603097D0 (en) *	1996-02-14	1996-04-10	Zeneca Ltd	Quinazoline compounds
GB9603095D0 (en)	1996-02-14	1996-04-10	Zeneca Ltd	Quinazoline derivatives
NZ331191A (en)	1996-03-05	2000-03-27	Zeneca Ltd	4-anilinoquinazoline derivatives and pharmaceutical compositions thereof
EA001595B1 (ru)	1996-04-12	2001-06-25	Варнер-Ламберт Компани	Необратимые ингибиторы тирозинкиназ
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
WO1998023613A1 (en)	1996-11-27	1998-06-04	Pfizer Inc.	Fused bicyclic pyrimidine derivatives
US6245769B1 (en)	1997-09-02	2001-06-12	Dupont Pharmaceuticals Company	Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone(CRH) antagonists, useful for treating CNS and stress-related disorders
EP1028964A1 (en) *	1997-11-11	2000-08-23	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
EP1067123B1 (en)	1998-03-31	2011-01-19	Kyowa Hakko Kirin Co., Ltd.	Nitrogenous heterocyclic compounds
PA8474101A1 (es) *	1998-06-19	2000-09-29	Pfizer Prod Inc	Compuestos de pirrolo [2,3-d] pirimidina
SK286640B6 (sk) *	1998-06-19	2009-03-05	Pfizer Products Inc.	Pyrol [2,3-d] pyrimidínová zlúčenina, jej použitie na výrobu liečiva, farmaceutická kompozícia s jej obsahom, použitie jej kombinácie s ďalšími činidlami a súpravy s jej obsahom na výrobu liečiva
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
UA71945C2 (en) *	1999-01-27	2005-01-17	Pfizer Prod Inc	Substituted bicyclic derivatives being used 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
US6933299B1 (en)	1999-07-09	2005-08-23	Smithkline Beecham Corporation	Anilinoquinazolines as protein tyrosine kinase inhibitors
JP2003504363A (ja)	1999-07-09	2003-02-04	グラクソグループリミテッド	プロテインチロシンキナーゼ阻害剤としてのアニリノキナゾリン類
US6432979B1 (en)	1999-08-12	2002-08-13	American Cyanamid Company	Method of treating or inhibiting colonic polyps and colorectal cancer
US7169778B2 (en) *	1999-09-15	2007-01-30	Warner-Lambert Company	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
KR100881105B1 (ko)	1999-11-05	2009-02-02	아스트라제네카 아베	Ｖｅｇｆ 억제제로서의 퀴나졸린 유도체
JP2001142235A (ja)	1999-11-17	2001-05-25	Fuji Denki Gazo Device Kk	電子写真用感光体
DE60037345T2 (de)	1999-12-10	2008-11-13	Pfizer Products Inc., Groton	Pyrrolo(2,3-d)pyrimidin-Verbindungen
BR0111377A (pt)	2000-06-06	2003-06-03	Pfizer Prod Inc	Derivados de tiofeno úteis como agentes anticancerìgenos
ATE423120T1 (de)	2000-06-26	2009-03-15	Pfizer Prod Inc	Pyrroloä2,3-düpyrimidin verbindungen als immunosuppressive wirkstoffe
JP2004509876A (ja)	2000-09-20	2004-04-02	メルク　パテント　ゲゼルシャフト　ミット　ベシュレンクテル　ハフトング	４−アミノ−キナゾリン
AU9598601A (en)	2000-10-20	2002-04-29	Eisai Co Ltd	Nitrogenous aromatic ring compounds
ES2263743T3 (es) *	2001-04-13	2006-12-16	Pfizer Products Inc.	Derivados de 4-aminopiridopirimidina sustituidos con un grupo biciclico.
TWI238824B (en) *	2001-05-14	2005-09-01	Novartis Ag	4-amino-5-phenyl-7-cyclobutyl-pyrrolo[2,3-d]pyrimidine derivatives
US7301023B2 (en)	2001-05-31	2007-11-27	Pfizer Inc.	Chiral salt resolution
WO2003000194A2 (en)	2001-06-21	2003-01-03	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
JP4505228B2 (ja) *	2002-01-10	2010-07-21	バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト	Ｒｈｏ−キナーゼ阻害剤
HUP0500200A2 (hu)	2002-01-17	2005-07-28	Neurogen Corporation	Szubsztituált kinazolin-4-ilamin analógok, mint kapszaicin modulátorok és ezeket tartalmazó gyógyszerkészítmények
EP1470121B1 (en)	2002-01-23	2012-07-11	Bayer HealthCare LLC	Pyrimidine derivatives as rho-kinase inhibitors
MXPA04007196A (es)	2002-01-23	2005-06-08	Bayer Pharmaceuticals Corp	Inhibidores de rho-quinasa.
JP2003238561A (ja)	2002-02-13	2003-08-27	Fuji Denki Gazo Device Kk	キノメタン化合物
AU2003206068A1 (en)	2002-03-01	2003-09-16	Pfizer Inc.	Indolyl-urea derivatives of thienopyridines useful as anti-angiogenic agents
ES2314224T3 (es) *	2002-03-07	2009-03-16	F. Hoffmann-La Roche Ag	Inhibidores pirimidina y piridina biciclicos de p38 quinasa.
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
JP2006516571A (ja)	2003-01-17	2006-07-06	スレッシュオールドファーマシューティカルズ，インコーポレイテッド	良性前立腺増殖症の処置
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
BR122019010200B8 (pt)	2003-05-22	2021-07-27	Nerviano Medical Science S R L	compostos de pirazol-quinazolina, seus sais, produtos ou kits e composições farmacêuticas
MXPA06001758A (es) *	2003-08-15	2006-08-11	Irm Llc	Anilino purinas sustituidas en la posicion 6 utiles como inhibidores de rtk.
US7338957B2 (en) *	2003-08-28	2008-03-04	Irm Llc	Compounds and compositions as protein kinase inhibitors
ES2314444T3 (es)	2003-08-29	2009-03-16	Pfizer Inc.	Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos.
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
AU2004309166B2 (en)	2003-12-23	2008-02-21	Pfizer Inc.	Novel quinoline derivatives
JPWO2005095419A1 (ja) *	2004-04-01	2008-02-21	武田薬品工業株式会社	チアゾロピリミジン誘導体
JP4842929B2 (ja)	2004-05-27	2011-12-21	ファイザー・プロダクツ・インク	癌治療に有用なピロロピリミジン誘導体
ZA200610669B (en) *	2004-06-02	2008-06-25	Takeda Pharmaceutical	Fused heterocyclic compound
CA2569016C (en) *	2004-06-02	2012-11-27	Takeda Pharmaceutical Company Limited	Fused heterocyclic compound
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
ATE428421T1 (de)	2004-09-17	2009-05-15	Eisai R&D Man Co Ltd	Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften
ATE501148T1 (de) *	2004-12-14	2011-03-15	Astrazeneca Ab	Pyrazolopyrimidinverbindungen als antitumormittel
KR20070104641A (ko) *	2005-02-03	2007-10-26	버텍스 파마슈티칼스 인코포레이티드	단백질 키나제의 억제제로 유용한 피롤로피리미딘
WO2006091450A1 (en)	2005-02-18	2006-08-31	Lexicon Genetics Incorporated	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
ES2314933T3 (es) *	2005-06-17	2009-03-16	Janssen Pharmaceutica Nv	Compuestos de naftiridina.
JP4989476B2 (ja)	2005-08-02	2012-08-01	エーザイ・アール・アンド・ディー・マネジメント株式会社	血管新生阻害物質の効果を検定する方法
WO2007081517A2 (en) *	2005-12-21	2007-07-19	Abbott Laboratories	Anti-viral compounds
RU2441010C2 (ru) *	2005-12-21	2012-01-27	Эбботт Лэборетриз	Противовирусные соединения
EP1979349B1 (en)	2005-12-21	2010-07-28	Abbott Laboratories	Anti-viral compounds
US7910595B2 (en) *	2005-12-21	2011-03-22	Abbott Laboratories	Anti-viral compounds
CA2644910C (en) *	2006-03-31	2014-01-28	Abbott Laboratories	Indazole compounds
WO2007114926A2 (en) *	2006-04-04	2007-10-11	The Regents Of The University Of California	Kinase antagonists
CN104706637A (zh)	2006-05-18	2015-06-17	卫材R&D管理有限公司	针对甲状腺癌的抗肿瘤剂
EP1889847A1 (en) *	2006-07-10	2008-02-20	DeveloGen Aktiengesellschaft	Pyrrolopyrimidines for pharmaceutical compositions
WO2008026748A1 (en)	2006-08-28	2008-03-06	Eisai R & D Management Co., Ltd.	Antitumor agent for undifferentiated gastric cancer
US20100004238A1 (en) *	2006-12-12	2010-01-07	Takeda Pharmaceutical Company Limited	Fused heterocyclic compound
US8236950B2 (en)	2006-12-20	2012-08-07	Abbott Laboratories	Anti-viral compounds
CA2676796C (en)	2007-01-29	2016-02-23	Eisai R & D Management Co., Ltd.	Composition for treatment of undifferentiated gastric cancer
US8952035B2 (en)	2007-11-09	2015-02-10	Eisai R&D Management Co., Ltd.	Combination of anti-angiogenic substance and anti-tumor platinum complex
EP2253633A4 (en)	2008-03-12	2012-02-29	Takeda Pharmaceutical	CONDENSED HETEROCYCLIC COMPOUND
CA2729045A1 (en) *	2008-07-31	2010-02-04	Philippe Bergeron	Pyrimidine compounds, compositions and methods of use
KR101335843B1 (ko)	2008-08-20	2013-12-02	조에티스 엘엘씨	피롤로[2,3-ｄ]피리미딘 화합물
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
NZ779754A (en)	2009-01-16	2023-04-28	Exelixis Inc	Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer
DE102009005193A1 (de) *	2009-01-20	2010-07-22	Merck Patent Gmbh	Neue heterocyclische Verbindungen als MetAP-2 Inhibitoren
EP2398797B1 (en) *	2009-02-17	2013-11-06	Boehringer Ingelheim International GmbH	Pyrimido[5,4-d]pyrimidine derivatives for the inhibition of tyrosine kinases
UA108618C2 (uk)	2009-08-07	2015-05-25		Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку
MY162940A (en)	2009-08-19	2017-07-31	Eisai R&D Man Co Ltd	Quinoline derivative-containing pharmaceutical composition
EP2499143B1 (en)	2009-11-12	2016-03-16	F.Hoffmann-La Roche Ag	N7-substituted purine and pyrazolopyrimidine compounds, compositions and methods of use
JP5579864B2 (ja)	2009-11-12	2014-08-27	エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト	Ｎ−９−置換プリン化合物、組成物及び使用の方法
MX2012009074A (es) *	2010-02-05	2012-08-23	Pfizer	Compuestos de urea pirrolo [2, 3-d] pirimidina como inhibidores de janus quinasa.
CN102958523B (zh)	2010-06-25	2014-11-19	卫材R&D管理有限公司	使用具有激酶抑制作用的组合的抗肿瘤剂
EA201300283A1 (ru) *	2010-08-27	2013-08-30	Мерк Патент Гмбх	Производные фуропиридина
US8541576B2 (en)	2010-12-17	2013-09-24	Nerviano Medical Sciences Srl	Substituted pyrazolo-quinazoline derivatives as kinase inhibitors
WO2012122058A2 (en)	2011-03-04	2012-09-13	Newgen Therapeutics, Inc.	Alkyne substituted quinazoline compound and methods of use
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
CA2863717C (en) *	2012-02-21	2021-09-28	Lars Burgdorf	Furopyridine derivatives
WO2014048869A1 (en)	2012-09-26	2014-04-03	Bayer Pharma Aktiengesellschaft	Substituted indazol-pyrrolopyrimidines useful in the treatment of hyperproliferative diseases
US20150218173A1 (en)	2012-09-26	2015-08-06	Bayer Pharma Aktiengesellschaft	Substituted indazol-pyrrolopyrimidines useful in the treatment of hyperfoliferative disorders
KR20150098605A (ko)	2012-12-21	2015-08-28	에자이 알앤드디 매니지먼트 가부시키가이샤	퀴놀린 유도체의 비정질 형태 및 그의 제조방법
CA2899662A1 (en) *	2013-02-01	2014-08-07	Bayer Pharma Aktiengesellschaft	Substituted pyrazolopyrimidinylamino-indazoles
WO2014145576A2 (en)	2013-03-15	2014-09-18	Northwestern University	Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer
NZ714049A (en)	2013-05-14	2020-05-29	Eisai R&D Man Co Ltd	Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds
CR20170077A (es)	2014-08-04	2017-06-26	Nuevolution As	Derivados de heterociclilo opcionalmente condensados de pirimidina útiles para el tratamiento de enfermedades inflamatorias, metabólicas, oncológicas y autoinmunitarias
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
LT3263106T (lt)	2015-02-25	2024-01-10	Eisai R&D Management Co., Ltd.	Chinolino darinių kartumo sumažinimo būdas
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
MX373231B (es)	2015-06-16	2020-05-08	Eisai R&D Man Co Ltd	Agente anticancerigeno.
US12220398B2 (en)	2015-08-20	2025-02-11	Eisai R&D Management Co., Ltd.	Tumor therapeutic agent
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
US12303505B2 (en)	2017-02-08	2025-05-20	Eisai R&D Management Co., Ltd.	Tumor-treating pharmaceutical composition
RU2019134940A (ru)	2017-05-16	2021-06-16	Эйсай Ар Энд Ди Менеджмент Ко., Лтд.	Лечение гепатоцеллюлярной карциномы
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
UY38994A (es)	2019-12-20	2021-07-30	Nuevolution As	Compuestos activos frente a receptores nucleares
MX2022007265A (es)	2019-12-20	2022-09-09	Nuevolution As	Compuestos activos frente a receptores nucleares.
AU2021245397A1 (en)	2020-03-31	2022-10-20	Nuevolution A/S	Compounds active towards nuclear receptors
WO2021198956A1 (en)	2020-03-31	2021-10-07	Nuevolution A/S	Compounds active towards nuclear receptors
TW202309022A (zh)	2021-04-13	2023-03-01	美商努法倫特公司	用於治療具egfr突變之癌症之胺基取代雜環

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
IE60433B1 (en) *	1986-08-26	1994-07-13	Warner Lambert Co	Novel 9-deazaguanines
NO169490C (no) *	1988-03-24	1992-07-01	Takeda Chemical Industries Ltd	Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrrolopyrimidinderivater
CA2067221C (en) *	1989-10-11	1997-04-15	Yasuji Sakuma	Fused pyrimidine derivative, process for preparation of same and pharmaceutical preparation comprising same as active ingredient
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
KR19990067704A (ko) *	1992-12-17	1999-08-25	디. 제이. 우드, 스피겔 알렌 제이	부신피질자극호르몬 유리인자 길항제로서의 피롤로피리미딘을함유하는 약학 조성물
AU6855594A (en) *	1993-06-30	1995-01-24	Biocryst Pharmaceuticals, Inc.	9-deazahypoxanthines as pnp inhibitors

1995
- 1995-06-07 JP JP50039097A patent/JP3290666B2/ja not_active Expired - Fee Related
- 1995-06-07 SK SK729-96A patent/SK72996A3/sk unknown
- 1995-06-07 ES ES95924027T patent/ES2203642T3/es not_active Expired - Lifetime
- 1995-06-07 FI FI974443A patent/FI974443A0/fi unknown
- 1995-06-07 WO PCT/US1995/007881 patent/WO1996040142A1/en not_active Ceased
- 1995-06-07 PT PT95924027T patent/PT831829E/pt 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 MX MX9709867A patent/MX9709867A/es not_active IP Right Cessation
- 1995-06-07 AT AT95924027T patent/ATE247469T1/de not_active IP Right Cessation
- 1995-06-07 CA CA002223081A patent/CA2223081C/en not_active Expired - Fee Related
- 1995-06-07 DK DK95924027T patent/DK0831829T3/da active
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 PL PL96314641A patent/PL314641A1/xx unknown
- 1996-06-05 CN CN96108101A patent/CN1141298A/zh active Pending
- 1996-06-05 SG SG1996009982A patent/SG45483A1/en unknown
- 1996-06-06 NO NO962386A patent/NO962386L/no unknown
- 1996-06-06 CZ CZ961641A patent/CZ164196A3/cs unknown
- 1996-06-06 ZA ZA9604725A patent/ZA964725B/xx unknown
- 1996-06-06 SI SI9600184A patent/SI9600184A/sl unknown
- 1996-06-06 AU AU54791/96A patent/AU5479196A/en not_active Abandoned
- 1996-06-06 HU HU9601559A patent/HUP9601559A3/hu unknown
- 1996-06-06 HR HR95/007,881A patent/HRP960269A2/hr not_active Application Discontinuation
- 1996-06-06 NZ NZ286755A patent/NZ286755A/en unknown
- 1996-06-06 TR TR96/00474A patent/TR199600474A2/xx unknown
- 1996-06-07 BR BR9602695A patent/BR9602695A/pt active Search and Examination
- 1996-06-07 CO CO96029731A patent/CO4440628A1/es unknown
- 1996-06-07 OA OA60838A patent/OA10460A/en unknown
- 1996-06-07 RU RU96111016A patent/RU2136683C1/ru active

Also Published As

Publication number	Publication date
AP637A (en)	1998-04-08
ZA964725B (en)	1997-12-08
SI9600184A (en)	1997-04-30
NO962386D0 (no)	1996-06-06
TR199600474A2 (tr)	1996-12-21
JP3290666B2 (ja)	2002-06-10
PL314641A1 (en)	1996-12-09
WO1996040142A1 (en)	1996-12-19
BR9602695A (pt)	1998-10-06
AR002746A1 (es)	1998-04-29
CO4440628A1 (es)	1997-05-07
JPH10508875A (ja)	1998-09-02
HRP960269A2 (en)	1997-08-31
HUP9601559A2 (en)	1997-02-28
DK0831829T3 (da)	2003-12-15
FI974443L (fi)	1997-12-05
EP0831829A1 (en)	1998-04-01
RU2136683C1 (ru)	1999-09-10
CA2223081A1 (en)	1996-12-19
PT831829E (pt)	2003-12-31
NO962386L (no)	1996-12-09
EP0831829A4 (en)	1998-11-25
MA26409A1 (fr)	2004-12-20
MX9709867A (es)	1998-03-31
ES2203642T3 (es)	2004-04-16
AP9600805A0 (en)	1996-07-31
AU5479196A (en)	1996-12-19
HUP9601559A3 (en)	1997-07-28
ATE247469T1 (de)	2003-09-15
FI974443A7 (fi)	1997-12-05
IL118487A0 (en)	1996-09-12
HU9601559D0 (en)	1996-08-28
DE69531558T2 (de)	2004-03-18
SK72996A3 (en)	1997-04-09
DE69531558D1 (de)	2003-09-25
FI974443A0 (fi)	1997-12-05
SG45483A1 (en)	1998-01-16
CZ164196A3 (en)	1996-12-11
EP0831829B1 (en)	2003-08-20
CA2223081C (en)	2001-03-06
CN1141298A (zh)	1997-01-29
NZ286755A (en)	1998-03-25

Publication	Publication Date	Title
OA10460A (en)	2002-03-28	Heterocyclic ring-fused pyrimidine derivatives
US6395733B1 (en)	2002-05-28	Heterocyclic ring-fused pyrimidine derivatives
US6413971B1 (en)	2002-07-02	Fused bicyclic pyrimidine derivatives
RU2694252C2 (ru)	2019-07-10	Производные 4-(замещенного фениламино)хиназолина или их фармацевтически приемлемые соли, способ ингибирования рецепторной тирозинкиназы и фармацевтическая композиция
AU2004293026B2 (en)	2012-01-19	AKT protein kinase inhibitors
JP3370340B2 (ja)	2003-01-27	チロシンキナーゼの不可逆的阻害剤
US6596726B1 (en)	2003-07-22	Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
CN102014627B (zh)	2014-10-29	作为极光激酶抑制剂的稠合双环嘧啶化合物
US5679683A (en)	1997-10-21	Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
JPH0753556A (ja)	1995-02-28	三環式誘導体、その製造方法及び温血動物において抗癌作用を発生させるために使用する薬剤学的組成物
US3980645A (en)	1976-09-14	Fused quinazolinones and a process for production thereof
Zaher	2010	Synthesis of some new thiophene and thiopyrimidine compounds of expected anticancer activity and studying the augmenting effect of gamma radiation
HK1151694B (en)	2015-07-31	Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
PL167014B1 (pl)	1995-07-31	Sposób wytwarzania nowych pochodnych azolu