JP2004526789A - 新規フタラジノン - Google Patents
新規フタラジノン Download PDFInfo
- Publication number
- JP2004526789A JP2004526789A JP2002583433A JP2002583433A JP2004526789A JP 2004526789 A JP2004526789 A JP 2004526789A JP 2002583433 A JP2002583433 A JP 2002583433A JP 2002583433 A JP2002583433 A JP 2002583433A JP 2004526789 A JP2004526789 A JP 2004526789A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- alkyl
- tetrahydro
- alkoxy
- piperidin
- 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.)
- Withdrawn
Links
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- -1 N-methylpiperidyl Chemical group 0.000 claims description 231
- 150000001875 compounds Chemical class 0.000 claims description 100
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 65
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 44
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical group C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 30
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 239000000460 chlorine Chemical group 0.000 claims description 17
- 229910052801 chlorine Chemical group 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000002883 imidazolyl group Chemical group 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 239000005711 Benzoic acid Substances 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 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 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 5
- WKLKSQPDIITJAK-SJORKVTESA-N C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 WKLKSQPDIITJAK-SJORKVTESA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 4
- MAQRYDHZOWQDGA-CVEARBPZSA-N (4ar,8as)-2-(1,3-benzothiazol-6-yl)-4-(3-chloro-4-methoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=C3SC=NC3=CC=2)C(=O)[C@@H]2[C@H]1CC=CC2 MAQRYDHZOWQDGA-CVEARBPZSA-N 0.000 claims description 3
- OUKXFRRIGMEYDR-MSOLQXFVSA-N (4ar,8as)-4-(3-chloro-4-ethoxyphenyl)-2-phenyl-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OCC)=CC=C1C1=NN(C=2C=CC=CC=2)C(=O)[C@@H]2[C@H]1CC=CC2 OUKXFRRIGMEYDR-MSOLQXFVSA-N 0.000 claims description 3
- PNFAJRGVWRHMSV-MSOLQXFVSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-(1-oxo-3h-2-benzofuran-5-yl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=C3COC(=O)C3=CC=2)C(=O)[C@@H]2[C@H]1CC=CC2 PNFAJRGVWRHMSV-MSOLQXFVSA-N 0.000 claims description 3
- LMKVPAUGSCDEIT-KGLIPLIRSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-(3-thiophen-2-yl-1,2,4-thiadiazol-5-yl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1=NC(C=2SC=CC=2)=NS1 LMKVPAUGSCDEIT-KGLIPLIRSA-N 0.000 claims description 3
- GWKHQPXIWZEUAG-MSOLQXFVSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[1-(2-oxoimidazolidine-1-carbonyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(C(=O)N2C(NCC2)=O)CC1 GWKHQPXIWZEUAG-MSOLQXFVSA-N 0.000 claims description 3
- RVNXAYVDPLDECT-PKTZIBPZSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[1-(4-methylphenyl)sulfonylpiperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 RVNXAYVDPLDECT-PKTZIBPZSA-N 0.000 claims description 3
- DTRSYKTUTDYBBR-UXHICEINSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[1-(morpholine-4-carbonyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(C(=O)N2CCOCC2)CC1 DTRSYKTUTDYBBR-UXHICEINSA-N 0.000 claims description 3
- SLXNCDDRQHKYPZ-CABCVRRESA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[6-methyl-3-(trifluoromethyl)pyridin-2-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C(=CC=C(C)N=2)C(F)(F)F)C(=O)[C@@H]2[C@H]1CC=CC2 SLXNCDDRQHKYPZ-CABCVRRESA-N 0.000 claims description 3
- HZXQJGPDTRZCNX-CVEARBPZSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-cyclopentyl-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCCC1 HZXQJGPDTRZCNX-CVEARBPZSA-N 0.000 claims description 3
- QFAHXLIVMRUENH-SJORKVTESA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-phenyl-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=CC=CC=2)C(=O)[C@@H]2[C@H]1CC=CC2 QFAHXLIVMRUENH-SJORKVTESA-N 0.000 claims description 3
- OPOCKICASWPPML-CVEARBPZSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-quinoxalin-2-yl-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2N=C3C=CC=CC3=NC=2)C(=O)[C@@H]2[C@H]1CC=CC2 OPOCKICASWPPML-CVEARBPZSA-N 0.000 claims description 3
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- HCNFONHPDDMXQF-SJORKVTESA-N C1=C(Br)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 Chemical compound C1=C(Br)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 HCNFONHPDDMXQF-SJORKVTESA-N 0.000 claims description 3
- SSIOKPPSQIDXIM-RTWAWAEBSA-N C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1CCCCOC1=CC=C(C(O)=O)C=C1 Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1CCCCOC1=CC=C(C(O)=O)C=C1 SSIOKPPSQIDXIM-RTWAWAEBSA-N 0.000 claims description 3
- SUVSLGXXBRXKFE-SJORKVTESA-N C1=C(F)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 Chemical compound C1=C(F)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(O)=O)C(=O)[C@@H]2[C@H]1CC=CC2 SUVSLGXXBRXKFE-SJORKVTESA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 3
- UWFNLSOFRPEBAG-SJORKVTESA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-(1h-indazol-5-yl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=C3C=NNC3=CC=2)C(=O)[C@@H]2[C@H]1CC=CC2 UWFNLSOFRPEBAG-SJORKVTESA-N 0.000 claims description 2
- CKKOYCZNJZPSKC-MSOLQXFVSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-(4-imidazol-1-ylbutyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1CCCCN1C=NC=C1 CKKOYCZNJZPSKC-MSOLQXFVSA-N 0.000 claims description 2
- OVMYZTUABUPBOL-YADHBBJMSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[1-(pyridin-4-ylmethyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(CC=2C=CN=CC=2)CC1 OVMYZTUABUPBOL-YADHBBJMSA-N 0.000 claims description 2
- KWSCKNOZSGEPOE-RPBOFIJWSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-[4-[4-[2-(dimethylamino)ethyl]piperazine-1-carbonyl]phenyl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NN(C=2C=CC(=CC=2)C(=O)N2CCN(CCN(C)C)CC2)C(=O)[C@@H]2[C@H]1CC=CC2 KWSCKNOZSGEPOE-RPBOFIJWSA-N 0.000 claims description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 claims description 2
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 8
- ZGBRFHWLOXQCMR-MSOLQXFVSA-N (4ar,8as)-4-(3-chloro-4-methoxyphenyl)-2-cycloheptyl-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(Cl)C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCCCCC1 ZGBRFHWLOXQCMR-MSOLQXFVSA-N 0.000 claims 1
- BUYUFJZVMVFQLQ-UHFFFAOYSA-N 4-[2-(5,5,8,8-tetramethyl-6,7-dihydroquinoxalin-2-yl)ethynyl]benzoic acid Chemical compound CC1(C=2N=CC(=NC=2C(CC1)(C)C)C#CC1=CC=C(C(=O)O)C=C1)C BUYUFJZVMVFQLQ-UHFFFAOYSA-N 0.000 claims 1
- 230000003796 beauty Effects 0.000 claims 1
- 239000012876 carrier material Substances 0.000 claims 1
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 35
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000000203 mixture Substances 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 13
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 13
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 12
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 12
- 229940095074 cyclic amp Drugs 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical group FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 8
- 101100407335 Dictyostelium discoideum pde7 gene Proteins 0.000 description 8
- 210000001744 T-lymphocyte Anatomy 0.000 description 8
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 7
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| EP01110228 | 2001-04-25 | ||
| PCT/EP2002/004438 WO2002085906A2 (en) | 2001-04-25 | 2002-04-23 | Phthalazinones derivatives useful as pde4/7 inhibitors |
Publications (2)
| Publication Number | Publication Date |
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| JP2004526789A true JP2004526789A (ja) | 2004-09-02 |
| JP2004526789A5 JP2004526789A5 (https=) | 2005-12-22 |
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| JP (1) | JP2004526789A (https=) |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006500370A (ja) * | 2002-08-10 | 2006-01-05 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４阻害剤としての、ピロリジンジオンにより置換されたピペリジン−フタラゾン |
| WO2006115221A1 (ja) * | 2005-04-21 | 2006-11-02 | Nippon Shinyaku Co., Ltd. | フタラジノン誘導体及びその医薬 |
| JP2014517021A (ja) * | 2011-06-17 | 2014-07-17 | タケダ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のフタラジノン−ピロロピリミジンカルボキサミド誘導体 |
Families Citing this family (22)
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| EE05386B1 (et) | 2001-02-15 | 2011-02-15 | ALTANA�Pharma�AG | Ftalasinoon-piperidinoderivaadid,ÁnendeÁkasutamineÁjaÁravim |
| CZ20033205A3 (en) * | 2001-04-25 | 2004-03-17 | Altana Pharma Ag | Piperazino-derivatives and their use as pde4 inhibitor |
| AU2003255376A1 (en) * | 2002-08-10 | 2004-03-11 | Altana Pharma Ag | Piperidine-derivatives as pde4 inhibitors |
| WO2004018450A1 (en) * | 2002-08-10 | 2004-03-04 | Altana Pharma Ag | Piperidine-n-oxide-derivatives |
| WO2004018451A1 (en) * | 2002-08-10 | 2004-03-04 | Altana Pharma Ag | Pyridazinone-derivatives as pde4 inhibitors |
| WO2005075437A1 (en) * | 2004-02-04 | 2005-08-18 | Altana Pharma Ag | Pyridazinone derivatives and their use as pde4 inhibitors |
| EP1716133B1 (en) * | 2004-02-04 | 2008-03-26 | Nycomed GmbH | 2-(piperidin-4-yl)-4,5-dihydro-2h-pyridazin-3-one derivatives as pde4 inhibitors |
| KR20070042164A (ko) * | 2004-07-05 | 2007-04-20 | 아스텔라스세이야쿠 가부시키가이샤 | 피라졸로피리딘 유도체 |
| ES2308916B1 (es) | 2007-03-22 | 2009-10-29 | Consejo Superior De Investigaciones Cientificas | Compuesto inhibidor dual de las enzimas pde7 y/o pde4, composiciones farmaceuticas y sus aplicaciones. |
| US8637528B2 (en) | 2007-03-27 | 2014-01-28 | Omeros Corporation | Use of PDE7 inhibitors for the treatment of movement disorders |
| WO2008119057A2 (en) * | 2007-03-27 | 2008-10-02 | Omeros Corporation | The use of pde7 inhibitors for the treatment of movement disorders |
| CA2686909C (en) | 2007-05-16 | 2016-07-05 | Nycomed Gmbh | Pyrazolone derivatives as pde4 inhibitors |
| AR074318A1 (es) | 2008-11-14 | 2011-01-05 | Nycomed Gmbh | Derivados heterociclicos de pirazolona, composiciones farmaceuticas que los contienen y uso de los mismos para el tratamiento de enfermedades de las vias respiratorias. |
| US8653098B2 (en) | 2008-11-20 | 2014-02-18 | Genentech, Inc. | Pyrazolopyridine PI3K inhibitor compounds and methods of use |
| NZ628054A (en) | 2010-11-08 | 2016-03-31 | Omeros Corp | Treatment of addiction and impulse-control disorders using pde7 inhibitors |
| US9220715B2 (en) | 2010-11-08 | 2015-12-29 | Omeros Corporation | Treatment of addiction and impulse-control disorders using PDE7 inhibitors |
| LT2672957T (lt) | 2011-02-07 | 2017-02-10 | Scipharm Sarl | Naujoji kompozicija, skirta cistinės fibrozės gydymui |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| CN102964340B (zh) * | 2012-12-12 | 2015-10-07 | 中国药科大学 | 一类治疗阿尔茨海默病的选择性多巴胺d1受体激动剂 |
| MX365950B (es) | 2013-03-13 | 2019-06-19 | Flatley Discovery Lab Llc | Compuestos de piridazinona y metodos para el tratamiento de la fibrosis quistica. |
| CN112876460B (zh) * | 2021-02-05 | 2022-05-31 | 山西大学 | 7-二乙胺基-3-乙酰基香豆素衍生物及其合成方法和应用 |
| IL318817A (en) | 2022-08-18 | 2025-04-01 | Mitodicure Gmbh | Use of a therapeutic agent with PHOSPHODIESTERASE-7 inhibitory activity for the treatment and prevention of diseases associated with chronic fatigue, exhaustion and/or exercise intolerance |
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| US5716954A (en) | 1991-10-09 | 1998-02-10 | Syntex U.S.A. Inc. | Benzopyridazinone and pyridopyridazinone compounds |
| HUT66969A (en) * | 1991-10-09 | 1995-01-30 | Syntex Inc | Benzo- and pyrido-pyridazinone- and pyridazin-thion derivatives, pharmaceutical compositions containing the same and process for the production of thereof |
| AU673569B2 (en) * | 1992-12-02 | 1996-11-14 | Pfizer Inc. | Catechol diethers as selective PDE-IV inhibitors |
| DE19533975A1 (de) | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| TR199901653T2 (xx) * | 1997-01-15 | 1999-10-21 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Fitalazinonlar. |
| WO1999031071A1 (en) * | 1997-12-15 | 1999-06-24 | Byk Gulden Lomberg Chemische Fabrik Gmbh | New phthalazinones |
| ATE258930T1 (de) | 1997-12-15 | 2004-02-15 | Altana Pharma Ag | Dihydrobenzifurane |
| EP0934933A1 (en) | 1998-02-06 | 1999-08-11 | Byk Gulden Lomberg Chemische Fabrik GmbH | Phthalazinones |
| JP2002506856A (ja) * | 1998-03-14 | 2002-03-05 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | フタラジノンｐｄｅｉｉｉ／ｉｖ阻害剤 |
| AU7654200A (en) | 1999-09-14 | 2001-04-17 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone derivatives as pd3/4 inhibitors |
| IL148807A0 (en) | 1999-10-25 | 2002-09-12 | Byk Gulden Lomberg Chem Fab | Tetrahydrothiopyran derivatives and pharmaceutical compositions containing the same |
| DE60036558D1 (de) | 1999-10-25 | 2007-11-08 | Nycomed Gmbh | Phthalazinon-derivate als pde 4 hemmer |
| NZ522882A (en) | 2000-06-05 | 2004-07-30 | Altana Pharma Bv | Pyridazinone compounds effective as beta-2-adrenoreceptor agonists as well as PDE4-inhibitors |
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2002
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- 2002-04-23 IL IL15790802A patent/IL157908A0/xx unknown
- 2002-04-23 SK SK1434-2003A patent/SK14342003A3/sk not_active Application Discontinuation
- 2002-04-23 HU HU0303998A patent/HUP0303998A3/hu unknown
- 2002-04-23 CN CNA028087429A patent/CN1503792A/zh active Pending
- 2002-04-23 CA CA002445233A patent/CA2445233A1/en not_active Abandoned
- 2002-04-23 EA EA200301100A patent/EA200301100A1/ru unknown
- 2002-04-23 PL PL02363312A patent/PL363312A1/xx not_active Application Discontinuation
- 2002-04-23 EE EEP200300514A patent/EE200300514A/xx unknown
- 2002-04-23 CZ CZ20033206A patent/CZ299347B6/cs not_active IP Right Cessation
- 2002-04-23 HR HR20030868A patent/HRP20030868A2/xx not_active Application Discontinuation
- 2002-04-23 MX MXPA03009583A patent/MXPA03009583A/es unknown
- 2002-04-23 EP EP02747291A patent/EP1385848A2/en not_active Withdrawn
- 2002-04-23 KR KR10-2003-7013937A patent/KR20040008162A/ko not_active Withdrawn
- 2002-04-23 WO PCT/EP2002/004438 patent/WO2002085906A2/en not_active Ceased
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- 2002-04-23 AU AU2002317733A patent/AU2002317733B2/en not_active Ceased
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- 2002-04-23 JP JP2002583433A patent/JP2004526789A/ja not_active Withdrawn
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- 2003-10-27 BG BG108294A patent/BG108294A/bg unknown
- 2003-11-17 ZA ZA200308930A patent/ZA200308930B/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006500370A (ja) * | 2002-08-10 | 2006-01-05 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４阻害剤としての、ピロリジンジオンにより置換されたピペリジン−フタラゾン |
| WO2006115221A1 (ja) * | 2005-04-21 | 2006-11-02 | Nippon Shinyaku Co., Ltd. | フタラジノン誘導体及びその医薬 |
| JP2014517021A (ja) * | 2011-06-17 | 2014-07-17 | タケダ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のフタラジノン−ピロロピリミジンカルボキサミド誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| HRP20030868A2 (en) | 2005-08-31 |
| US20040127707A1 (en) | 2004-07-01 |
| EP1385848A2 (en) | 2004-02-04 |
| KR20040008162A (ko) | 2004-01-28 |
| ZA200308930B (en) | 2004-06-09 |
| WO2002085906A3 (en) | 2002-12-19 |
| NO20034773D0 (no) | 2003-10-24 |
| EA200301100A1 (ru) | 2004-06-24 |
| HUP0303998A3 (en) | 2007-03-28 |
| WO2002085906A2 (en) | 2002-10-31 |
| CA2445233A1 (en) | 2002-10-31 |
| CZ20033206A3 (cs) | 2004-02-18 |
| NO20034773L (no) | 2003-12-10 |
| EE200300514A (et) | 2004-02-16 |
| NZ529221A (en) | 2005-04-29 |
| MXPA03009583A (es) | 2004-02-12 |
| SK14342003A3 (sk) | 2004-05-04 |
| PL363312A1 (en) | 2004-11-15 |
| CN1503792A (zh) | 2004-06-09 |
| IL157908A0 (en) | 2004-03-28 |
| CZ299347B6 (cs) | 2008-06-25 |
| BR0209149A (pt) | 2004-07-13 |
| BG108294A (bg) | 2004-09-30 |
| US7186710B2 (en) | 2007-03-06 |
| AU2002317733B2 (en) | 2007-12-13 |
| HUP0303998A2 (hu) | 2004-05-28 |
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