JP2005526123A5 - - Google Patents
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- JP2005526123A5 JP2005526123A5 JP2004503006A JP2004503006A JP2005526123A5 JP 2005526123 A5 JP2005526123 A5 JP 2005526123A5 JP 2004503006 A JP2004503006 A JP 2004503006A JP 2004503006 A JP2004503006 A JP 2004503006A JP 2005526123 A5 JP2005526123 A5 JP 2005526123A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- chloro
- quinazoline
- fluorophenyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
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- -1 tetrahydrofuran-3-yl group Chemical group 0.000 claims 59
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 16
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 14
- 239000008194 pharmaceutical composition Substances 0.000 claims 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 11
- 102000001301 EGF receptor Human genes 0.000 claims 9
- 108060006698 EGF receptor Proteins 0.000 claims 9
- 229940044551 receptor antagonist Drugs 0.000 claims 9
- 239000002464 receptor antagonist Substances 0.000 claims 9
- 239000013543 active substance Substances 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- 229940079593 drug Drugs 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 4
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims 4
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 239000002474 gonadorelin antagonist Substances 0.000 claims 4
- 239000003149 muscarinic antagonist Substances 0.000 claims 4
- 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 4
- 230000002265 prevention Effects 0.000 claims 4
- 229960002613 tamsulosin Drugs 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- ULXXDDBFHOBEHA-INIZCTEOSA-N N-[4-(3-chloro-4-fluoroanilino)-7-[[(3S)-3-oxolanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-butenamide Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-INIZCTEOSA-N 0.000 claims 3
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 claims 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 3
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 3
- 229910052731 fluorine Inorganic materials 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 3
- UIJGHCUIUFFXJL-KRWDZBQOSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[[(2s)-oxolan-2-yl]methoxy]quinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OC[C@H]3OCCC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 UIJGHCUIUFFXJL-KRWDZBQOSA-N 0.000 claims 3
- UBUIJVSWEKUFRP-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclopentyloxyquinazolin-6-yl]-4-[cyclopropyl(methyl)amino]but-2-enamide Chemical compound C1CC1N(C)CC=CC(=O)NC(C(=CC1=NC=N2)OC3CCCC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 UBUIJVSWEKUFRP-UHFFFAOYSA-N 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
- XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 2
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 claims 2
- VMGWGDPZHXPFTC-HYBUGGRVSA-N Izonsteride Chemical compound CN([C@@H]1CCC2=C3)C(=O)CC[C@]1(C)C2=CC=C3SC(S1)=NC2=C1C=CC=C2CC VMGWGDPZHXPFTC-HYBUGGRVSA-N 0.000 claims 2
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 claims 2
- 102100024028 Progonadoliberin-1 Human genes 0.000 claims 2
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 claims 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 229960005395 cetuximab Drugs 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 claims 2
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims 2
- 229960004039 finasteride Drugs 0.000 claims 2
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 claims 2
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- ARFWPHOPKFABNZ-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(diethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(CC)CC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ARFWPHOPKFABNZ-UHFFFAOYSA-N 0.000 claims 2
- BHEXDWNZKZGCJR-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 BHEXDWNZKZGCJR-UHFFFAOYSA-N 0.000 claims 2
- PQTDSJWQNYBZMA-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-morpholin-4-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCOCC1 PQTDSJWQNYBZMA-UHFFFAOYSA-N 0.000 claims 2
- ULXXDDBFHOBEHA-MRXNPFEDSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[(3r)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(O[C@H]3COCC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-MRXNPFEDSA-N 0.000 claims 2
- UIJGHCUIUFFXJL-QGZVFWFLSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[[(2r)-oxolan-2-yl]methoxy]quinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OC[C@@H]3OCCC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 UIJGHCUIUFFXJL-QGZVFWFLSA-N 0.000 claims 2
- GWFMAFOGZMQEDM-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclopentyloxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OC3CCCC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 GWFMAFOGZMQEDM-UHFFFAOYSA-N 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 229960001972 panitumumab Drugs 0.000 claims 2
- WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 claims 2
- 229960001693 terazosin Drugs 0.000 claims 2
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 claims 2
- 229960004045 tolterodine Drugs 0.000 claims 2
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 claims 2
- 229960000575 trastuzumab Drugs 0.000 claims 2
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 claims 2
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims 1
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims 1
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- FJNRJBQUOQLUNQ-CYBMUJFWSA-N 2-[3-[[(3r)-2,3-dihydro-1,4-benzodioxin-3-yl]methylamino]propyl]pyridazin-3-one Chemical compound O=C1C=CC=NN1CCCNC[C@H]1OC2=CC=CC=C2OC1 FJNRJBQUOQLUNQ-CYBMUJFWSA-N 0.000 claims 1
- JXZZEXZZKAWDSP-UHFFFAOYSA-N 3-(2-(4-Benzamidopiperid-1-yl)ethyl)indole Chemical compound C1CN(CCC=2C3=CC=CC=C3NC=2)CCC1NC(=O)C1=CC=CC=C1 JXZZEXZZKAWDSP-UHFFFAOYSA-N 0.000 claims 1
- 102000001779 3-oxo-5-alpha-steroid 4-dehydrogenase Human genes 0.000 claims 1
- 108010029908 3-oxo-5-alpha-steroid 4-dehydrogenase Proteins 0.000 claims 1
- KULGXJSSBLEZRX-UHFFFAOYSA-N 4-[bis(2-methoxyethyl)amino]-n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(CCOC)CCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 KULGXJSSBLEZRX-UHFFFAOYSA-N 0.000 claims 1
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 claims 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 claims 1
- 229940082496 Adrenoreceptor antagonist Drugs 0.000 claims 1
- 229940122878 Alpha 1 adrenoreceptor antagonist Drugs 0.000 claims 1
- 102400000932 Gonadoliberin-1 Human genes 0.000 claims 1
- 108010069236 Goserelin Proteins 0.000 claims 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims 1
- 101500026183 Homo sapiens Gonadoliberin-1 Proteins 0.000 claims 1
- 229940123934 Reductase inhibitor Drugs 0.000 claims 1
- 229960004607 alfuzosin Drugs 0.000 claims 1
- WNMJYKCGWZFFKR-UHFFFAOYSA-N alfuzosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(C)CCCNC(=O)C1CCCO1 WNMJYKCGWZFFKR-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 claims 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 claims 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 108700008462 cetrorelix Proteins 0.000 claims 1
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 claims 1
- 229960003230 cetrorelix Drugs 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims 1
- 229960002677 darifenacin Drugs 0.000 claims 1
- HXGBXQDTNZMWGS-RUZDIDTESA-N darifenacin Chemical compound C=1C=CC=CC=1C([C@H]1CN(CCC=2C=C3CCOC3=CC=2)CC1)(C(=O)N)C1=CC=CC=C1 HXGBXQDTNZMWGS-RUZDIDTESA-N 0.000 claims 1
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 229960001389 doxazosin Drugs 0.000 claims 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims 1
- 229960001442 gonadorelin Drugs 0.000 claims 1
- 229960002913 goserelin Drugs 0.000 claims 1
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 1
- 229960002056 indoramin Drugs 0.000 claims 1
- 229950004319 izonsteride Drugs 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- FFXFCSQUTLDLAR-VWLOTQADSA-N methyl (4s)-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-3-[3-(4-pyridin-2-ylpiperidin-1-yl)propylcarbamoyl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1([C@H](C(=C(NC1=O)COC)C(=O)OC)C=1C=C(F)C(F)=CC=1)C(=O)NCCCN(CC1)CCC1C1=CC=CC=N1 FFXFCSQUTLDLAR-VWLOTQADSA-N 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- KMAPIHHPUBUULD-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[2-methoxyethyl(methyl)amino]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)CCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 KMAPIHHPUBUULD-UHFFFAOYSA-N 0.000 claims 1
- IMBFFWDWIAWOLR-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclopentyloxyquinazolin-6-yl]-4-[2-methoxyethyl(methyl)amino]but-2-enamide Chemical compound N1=CN=C2C=C(OC3CCCC3)C(NC(=O)C=CCN(C)CCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 IMBFFWDWIAWOLR-UHFFFAOYSA-N 0.000 claims 1
- ZLLOIFNEEWYATC-XMUHMHRVSA-N osaterone Chemical compound C1=C(Cl)C2=CC(=O)OC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 ZLLOIFNEEWYATC-XMUHMHRVSA-N 0.000 claims 1
- 229950006466 osaterone Drugs 0.000 claims 1
- 229960001289 prazosin Drugs 0.000 claims 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 claims 1
- 201000004240 prostatic hypertrophy Diseases 0.000 claims 1
- 229960004953 silodosin Drugs 0.000 claims 1
- PNCPYILNMDWPEY-QGZVFWFLSA-N silodosin Chemical compound N([C@@H](CC=1C=C(C=2N(CCCO)CCC=2C=1)C(N)=O)C)CCOC1=CC=CC=C1OCC(F)(F)F PNCPYILNMDWPEY-QGZVFWFLSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 229960003604 testosterone Drugs 0.000 claims 1
- 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10221018A DE10221018A1 (de) | 2002-05-11 | 2002-05-11 | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| PCT/EP2003/004606 WO2003094921A2 (de) | 2002-05-11 | 2003-05-02 | Verwendung von hemmern der egfr-vermittelten signaltransduktion zur behandlung von gutartiger prostatahyperplasie (bph)/prostatahypertrophie |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005526123A JP2005526123A (ja) | 2005-09-02 |
| JP2005526123A5 true JP2005526123A5 (enExample) | 2006-06-22 |
| JP4630659B2 JP4630659B2 (ja) | 2011-02-09 |
Family
ID=29285302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| Country | Link |
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| US (1) | US8431585B2 (enExample) |
| EP (1) | EP1505981B1 (enExample) |
| JP (1) | JP4630659B2 (enExample) |
| AR (1) | AR039987A1 (enExample) |
| AU (1) | AU2003233223A1 (enExample) |
| CA (1) | CA2483590C (enExample) |
| DE (1) | DE10221018A1 (enExample) |
| PE (1) | PE20040400A1 (enExample) |
| TW (1) | TW200407147A (enExample) |
| UY (1) | UY27800A1 (enExample) |
| WO (1) | WO2003094921A2 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2375259C (en) | 1999-06-21 | 2009-04-28 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| US20050043233A1 (en) * | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| ATE395346T1 (de) | 2003-09-16 | 2008-05-15 | Astrazeneca Ab | Chinazolinderivate als tyrosinkinaseinhibitoren |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| SI1746999T1 (sl) * | 2004-05-06 | 2012-01-31 | Warner Lambert Co | 4-fenilamino-kinazolin-6-il-amidi |
| PL1948180T3 (pl) * | 2005-11-11 | 2013-09-30 | Boehringer Ingelheim Int | Terapia skojarzona raka polegająca na podawaniu inhibitorów EGFR/HER2 |
| CA2833852C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| JP5241513B2 (ja) | 2006-01-26 | 2013-07-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
| US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| UY31867A (es) | 2008-06-06 | 2010-01-29 | Boehringer Ingelheim Int | Nuevas formulaciones farmacéuticas sólidas que comprenden bibw 2992 |
| CN102264745B (zh) | 2008-11-10 | 2015-07-22 | 财团法人卫生研究院 | 作为酪胺酸激酶抑制剂的稠合双环及多环嘧啶化合物 |
| EP2451445B1 (en) | 2009-07-06 | 2019-04-03 | Boehringer Ingelheim International GmbH | Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
| US8828391B2 (en) | 2011-05-17 | 2014-09-09 | Boehringer Ingelheim International Gmbh | Method for EGFR directed combination treatment of non-small cell lung cancer |
| WO2014180271A1 (zh) * | 2013-05-10 | 2014-11-13 | 苏州明锐医药科技有限公司 | 阿法替尼及其中间体的制备方法 |
| CN103254183B (zh) * | 2013-05-10 | 2015-11-11 | 苏州明锐医药科技有限公司 | 阿法替尼的制备方法 |
| PH12018502667A1 (en) * | 2013-10-23 | 2022-11-14 | Gemvax And Kael Co Ltd | Composition for treating and preventing benign prostatic hyperplasia |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| KR20180086187A (ko) | 2015-10-05 | 2018-07-30 | 더 트러스티이스 오브 콜롬비아 유니버시티 인 더 시티 오브 뉴욕 | 자가포식 유동의 활성체 및 포스포리파제 d 및 타우를 포함하는 단백질 응집물의 클리어런스 및 단백질질환의 치료 |
| CN105669658B (zh) * | 2016-04-05 | 2018-06-29 | 北京民康百草医药科技有限公司 | 一种阿法替尼的精制方法 |
| CN107488172B (zh) * | 2016-06-10 | 2020-06-12 | 山东新时代药业有限公司 | 一种阿法替尼的制备方法 |
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| JP4146514B2 (ja) | 1995-07-06 | 2008-09-10 | ノバルティス アクチエンゲゼルシャフト | ピロロピリミジン類およびその製造方法 |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| IL120302A0 (en) * | 1996-03-27 | 1997-06-10 | Pfizer | Use of alpha1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia |
| ES2174250T5 (es) | 1996-04-12 | 2010-04-21 | Warner-Lambert Company Llc | Inhibidores irreversibles de tirosina quinasas. |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
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| TW200813014A (en) | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
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| US20040044014A1 (en) | 2002-04-19 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| US20030225079A1 (en) | 2002-05-11 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| DE10326186A1 (de) | 2003-06-06 | 2004-12-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| US20060058311A1 (en) | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| CA2833852C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| PL1948180T3 (pl) | 2005-11-11 | 2013-09-30 | Boehringer Ingelheim Int | Terapia skojarzona raka polegająca na podawaniu inhibitorów EGFR/HER2 |
| JP5241513B2 (ja) | 2006-01-26 | 2013-07-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
| US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| UY31867A (es) | 2008-06-06 | 2010-01-29 | Boehringer Ingelheim Int | Nuevas formulaciones farmacéuticas sólidas que comprenden bibw 2992 |
| CN102227434B (zh) * | 2008-09-30 | 2015-02-18 | 马林克罗特有限公司 | 选择性胺化酮吗啡喃的方法 |
| JP2012515184A (ja) | 2009-01-14 | 2012-07-05 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 大腸がんの治療方法 |
| EP2451445B1 (en) | 2009-07-06 | 2019-04-03 | Boehringer Ingelheim International GmbH | Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
| US20130012465A1 (en) | 2009-12-07 | 2013-01-10 | Boehringer Ingelheim International Gmbh | Bibw 2992 for use in the treatment of triple negative breast cancer |
-
2002
- 2002-05-11 DE DE10221018A patent/DE10221018A1/de not_active Withdrawn
-
2003
- 2003-05-02 JP JP2004503006A patent/JP4630659B2/ja not_active Expired - Fee Related
- 2003-05-02 AU AU2003233223A patent/AU2003233223A1/en not_active Abandoned
- 2003-05-02 WO PCT/EP2003/004606 patent/WO2003094921A2/de not_active Ceased
- 2003-05-02 EP EP03727422A patent/EP1505981B1/de not_active Expired - Lifetime
- 2003-05-02 CA CA2483590A patent/CA2483590C/en not_active Expired - Fee Related
- 2003-05-06 TW TW092112331A patent/TW200407147A/zh unknown
- 2003-05-09 AR ARP030101622A patent/AR039987A1/es not_active Application Discontinuation
- 2003-05-09 PE PE2003000451A patent/PE20040400A1/es not_active Application Discontinuation
- 2003-05-09 UY UY27800A patent/UY27800A1/es not_active Application Discontinuation
-
2010
- 2010-02-17 US US12/706,819 patent/US8431585B2/en not_active Expired - Lifetime
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