ES2259769T3 - Nuevas composiciones de medicamentos a base de nuevos anticolinergicos e inhibidores de egfr-quinasa. - Google Patents
Nuevas composiciones de medicamentos a base de nuevos anticolinergicos e inhibidores de egfr-quinasa.Info
- Publication number
- ES2259769T3 ES2259769T3 ES03762525T ES03762525T ES2259769T3 ES 2259769 T3 ES2259769 T3 ES 2259769T3 ES 03762525 T ES03762525 T ES 03762525T ES 03762525 T ES03762525 T ES 03762525T ES 2259769 T3 ES2259769 T3 ES 2259769T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- oxo
- quinazoline
- chloro
- buten
- 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.)
- Expired - Lifetime
Links
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- 239000003814 drug Substances 0.000 title claims abstract description 39
- 239000003112 inhibitor Substances 0.000 title description 12
- -1 salt 2,2-diphenylpropionate ester Chemical class 0.000 claims abstract description 74
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 11
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 11
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims abstract description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 8
- 150000001450 anions Chemical class 0.000 claims abstract description 8
- 229940043355 kinase inhibitor Drugs 0.000 claims abstract description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims abstract description 8
- 239000000812 cholinergic antagonist Substances 0.000 claims abstract description 7
- 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 claims abstract description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000004677 hydrates Chemical class 0.000 claims abstract description 5
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- 239000012453 solvate Substances 0.000 claims abstract description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims abstract description 3
- 229910002651 NO3 Inorganic materials 0.000 claims abstract description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims abstract description 3
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- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 3
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- 239000010452 phosphate Substances 0.000 claims abstract description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims abstract description 3
- 229940095064 tartrate Drugs 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
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- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 239000000725 suspension Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 12
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- 150000007513 acids Chemical class 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 8
- ODRFRBOBDWUQES-UHFFFAOYSA-N ethyl 3-[[4-[[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]amino]-4-oxobut-2-enyl]-(2-ethoxy-2-oxoethyl)amino]propanoate Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(CCC(=O)OCC)CC(=O)OCC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ODRFRBOBDWUQES-UHFFFAOYSA-N 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- QLVAINZHTQIWQM-QHCPKHFHSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[2-[4-[(2s)-5-oxooxolane-2-carbonyl]piperazin-1-yl]ethoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCN3CCN(CC3)C(=O)[C@H]3OC(=O)CC3)=C(NC(=O)C=C)C=C12 QLVAINZHTQIWQM-QHCPKHFHSA-N 0.000 claims description 6
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- 230000000414 obstructive effect Effects 0.000 claims description 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 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 description 5
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 5
- MPIZUARKKMOKKZ-MRXNPFEDSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[4-[(2r)-2-methyl-6-oxomorpholin-4-yl]butoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1C(=O)O[C@H](C)CN1CCCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1NC(=O)C=C MPIZUARKKMOKKZ-MRXNPFEDSA-N 0.000 claims description 5
- MPIZUARKKMOKKZ-INIZCTEOSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[4-[(2s)-2-methyl-6-oxomorpholin-4-yl]butoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1C(=O)O[C@@H](C)CN1CCCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1NC(=O)C=C MPIZUARKKMOKKZ-INIZCTEOSA-N 0.000 claims description 5
- YTKFKKLZSIVJMX-ZDUSSCGKSA-N (6s)-4-[2-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxyethyl]-6-methylmorpholin-2-one Chemical compound C=12C=C(OCCN3CC(=O)O[C@@H](C)C3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 YTKFKKLZSIVJMX-ZDUSSCGKSA-N 0.000 claims description 4
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 claims description 4
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- 230000002757 inflammatory effect Effects 0.000 claims description 4
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims description 4
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- 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 description 4
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| DE10230751A DE10230751A1 (de) | 2002-07-09 | 2002-07-09 | Neue Arzneimittelkompositionen auf der Basis neuer Anticholinergika und EGFR-Kinase-Hemmern |
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| ATE520772T1 (de) | 2000-10-31 | 2011-09-15 | Eisai Inc | Nucleinsäure kodierend für cyp1b1 und methoden zur verwendung |
| US7056916B2 (en) | 2002-11-15 | 2006-06-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments for the treatment of chronic obstructive pulmonary disease |
| EA013157B1 (ru) * | 2004-04-22 | 2010-02-26 | Бёрингер Ингельхайм Интернациональ Гмбх | Содержащие бензоксазины лекарственные комбинации для лечения заболеваний дыхательных путей |
| US7220742B2 (en) | 2004-05-14 | 2007-05-22 | Boehringer Ingelheim International Gmbh | Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments |
| WO2006094924A2 (en) * | 2005-03-09 | 2006-09-14 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and pde 5-inhibitors |
| CN101208316B (zh) | 2005-08-15 | 2012-05-09 | 贝林格尔·英格海姆国际有限公司 | 制备β-模拟物的方法 |
| EP2301923B1 (en) | 2006-03-31 | 2016-06-08 | Novartis AG | Pyridine derivatives as dgat inhibitors |
| US8507502B2 (en) | 2008-11-10 | 2013-08-13 | National Health Research Institutes | Fused bicyclic and tricyclic pyrimidine compounds as tyrosine kinase inhibitors |
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| US2927925A (en) * | 1960-03-08 | Scopine and sgopoline esters of alpha | ||
| US4570630A (en) | 1983-08-03 | 1986-02-18 | Miles Laboratories, Inc. | Medicament inhalation device |
| AT396872B (de) | 1985-07-30 | 1993-12-27 | Glaxo Group Ltd | Gerät zur verabreichung von medikamenten in pulverform |
| SG45171A1 (en) | 1990-03-21 | 1998-01-16 | Boehringer Ingelheim Int | Atomising devices and methods |
| IL107120A (en) | 1992-09-29 | 1997-09-30 | Boehringer Ingelheim Int | Atomising nozzle and filter and spray generating device |
| DE4318455A1 (de) | 1993-06-03 | 1994-12-08 | Boehringer Ingelheim Kg | Kapselhalterung |
| DE19536903C2 (de) | 1995-10-04 | 1998-09-10 | Boehringer Ingelheim Int | Vorrichtung zum Haltern eines fluidischen Bauteils |
| DE19536902A1 (de) | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Int | Vorrichtung zur Hochdruckerzeugung in einem Fluid in Miniaturausführung |
| DE19545226C1 (de) | 1995-12-05 | 1997-06-19 | Boehringer Ingelheim Int | Sperrspannwerk für einen federbetätigten Abtrieb |
| TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| DE19921693A1 (de) * | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
| WO2000078735A1 (de) * | 1999-06-21 | 2000-12-28 | Boehringer Ingelheim Pharma Kg | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US20020082270A1 (en) * | 2000-08-26 | 2002-06-27 | Frank Himmelsbach | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| DE10050994A1 (de) | 2000-10-14 | 2002-04-18 | Boehringer Ingelheim Pharma | Neue als Arneimittel einsetzbare Anticholinergika sowie Verfahren zu deren Herstellung |
| DE10206505A1 (de) * | 2002-02-16 | 2003-08-28 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und EGFR-Kinase-Hemmern |
| DE10203753A1 (de) * | 2002-01-31 | 2003-08-14 | Boehringer Ingelheim Pharma | Neue Xanthencarbonsäureester, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel |
-
2002
- 2002-07-09 DE DE10230751A patent/DE10230751A1/de not_active Withdrawn
-
2003
- 2003-06-26 DE DE50302675T patent/DE50302675D1/de not_active Expired - Lifetime
- 2003-06-26 AT AT03762525T patent/ATE320269T1/de active
- 2003-06-26 RU RU2005103397/04A patent/RU2317828C2/ru not_active IP Right Cessation
- 2003-06-26 AU AU2003242771A patent/AU2003242771B2/en not_active Ceased
- 2003-06-26 BR BR0312507-6A patent/BR0312507A/pt not_active IP Right Cessation
- 2003-06-26 PL PL03374022A patent/PL374022A1/xx not_active Application Discontinuation
- 2003-06-26 NZ NZ538096A patent/NZ538096A/en not_active IP Right Cessation
- 2003-06-26 CA CA002492037A patent/CA2492037A1/en not_active Abandoned
- 2003-06-26 CN CN038161370A patent/CN1665539A/zh active Pending
- 2003-06-26 MX MXPA05000163A patent/MXPA05000163A/es active IP Right Grant
- 2003-06-26 ES ES03762525T patent/ES2259769T3/es not_active Expired - Lifetime
- 2003-06-26 WO PCT/EP2003/006788 patent/WO2004004775A1/de not_active Ceased
- 2003-06-26 JP JP2004518591A patent/JP2005537250A/ja active Pending
- 2003-06-26 EP EP03762525A patent/EP1521595B1/de not_active Expired - Lifetime
- 2003-06-26 EP EP05109909A patent/EP1658860A1/de not_active Withdrawn
- 2003-12-23 TW TW092136571A patent/TW200520757A/zh unknown
-
2004
- 2004-11-30 ZA ZA200409676A patent/ZA200409676B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1665539A (zh) | 2005-09-07 |
| EP1521595A1 (de) | 2005-04-13 |
| BR0312507A (pt) | 2005-04-12 |
| DE50302675D1 (de) | 2006-05-11 |
| EP1658860A1 (de) | 2006-05-24 |
| ATE320269T1 (de) | 2006-04-15 |
| JP2005537250A (ja) | 2005-12-08 |
| WO2004004775A1 (de) | 2004-01-15 |
| DE10230751A1 (de) | 2004-01-22 |
| AU2003242771A1 (en) | 2004-01-23 |
| CA2492037A1 (en) | 2004-01-15 |
| ZA200409676B (en) | 2006-05-31 |
| NZ538096A (en) | 2007-04-27 |
| RU2317828C2 (ru) | 2008-02-27 |
| RU2005103397A (ru) | 2006-03-20 |
| TW200520757A (en) | 2005-07-01 |
| PL374022A1 (en) | 2005-09-19 |
| AU2003242771B2 (en) | 2009-07-30 |
| MXPA05000163A (es) | 2005-04-08 |
| EP1521595B1 (de) | 2006-03-15 |
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