IL130659A - Pathalazinone compounds, drugs containing them and their use - Google Patents

Pathalazinone compounds, drugs containing them and their use

Info

Publication number: IL130659A
Authority: IL; Israel
Prior art keywords: alkyl; alkoxy; halogen; phenyl; hydroxyl
Prior art date: 1997-01-15

Application number

IL13065998A

Other languages

English (en)

Hebrew (he)

Other versions

IL130659A0 (en

Original Assignee

Byk Gulden Lomberg Chem Fab

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.)

1997-01-15

Filing date

1998-01-12

Publication date

2002-07-25

1998-01-12 Application filed by Byk Gulden Lomberg Chem Fab filed Critical Byk Gulden Lomberg Chem Fab

2000-06-01 Publication of IL130659A0 publication Critical patent/IL130659A0/xx

2002-07-25 Publication of IL130659A publication Critical patent/IL130659A/en

Links

239000003814 drug Substances 0.000 title claims description 14
IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical class C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 title description 2
-1 N-methylpiperidyl Chemical group 0.000 claims abstract description 198
150000001875 compounds Chemical class 0.000 claims abstract description 188
229910052736 halogen Inorganic materials 0.000 claims abstract description 87
150000002367 halogens Chemical class 0.000 claims abstract description 86
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 72
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 70
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 47
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 45
239000001257 hydrogen Substances 0.000 claims abstract description 41
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 40
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 35
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims abstract description 33
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 32
229910052731 fluorine Inorganic materials 0.000 claims abstract description 31
239000011737 fluorine Substances 0.000 claims abstract description 31
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 22
125000004076 pyridyl group Chemical group 0.000 claims abstract description 22
125000001624 naphthyl group Chemical group 0.000 claims abstract description 21
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 18
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims abstract description 16
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims abstract description 15
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 14
125000002883 imidazolyl group Chemical group 0.000 claims abstract description 12
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 11
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 11
125000002971 oxazolyl group Chemical group 0.000 claims abstract description 11
125000004193 piperazinyl group Chemical group 0.000 claims abstract description 11
125000000335 thiazolyl group Chemical group 0.000 claims abstract description 11
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 abstract description 10
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims abstract description 8
125000005956 isoquinolyl group Chemical group 0.000 claims abstract description 8
125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 8
125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 8
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 8
125000005493 quinolyl group Chemical group 0.000 claims abstract description 8
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims abstract description 8
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 7
125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 7
125000002541 furyl group Chemical group 0.000 claims abstract description 5
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 claims abstract description 5
125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 5
125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 5
125000001544 thienyl group Chemical group 0.000 claims abstract description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
238000011282 treatment Methods 0.000 claims description 14
150000002431 hydrogen Chemical group 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000005936 piperidyl group Chemical group 0.000 claims description 10
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 9
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 8
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 8
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 7
125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 5
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000012876 carrier material Substances 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
125000005592 polycycloalkyl group Polymers 0.000 abstract description 2
125000000217 alkyl group Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 238
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
238000004587 chromatography analysis Methods 0.000 description 58
239000000203 mixture Substances 0.000 description 48
229960004132 diethyl ether Drugs 0.000 description 47
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
229940125904 compound 1 Drugs 0.000 description 43
239000000243 solution Substances 0.000 description 40
239000003208 petroleum Substances 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
239000002904 solvent Substances 0.000 description 31
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
229910052943 magnesium sulfate Inorganic materials 0.000 description 24
235000019341 magnesium sulphate Nutrition 0.000 description 23
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 23
239000002253 acid Substances 0.000 description 22
239000007858 starting material Substances 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
238000000034 method Methods 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 18
238000001704 evaporation Methods 0.000 description 17
239000012044 organic layer Substances 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
229940126214 compound 3 Drugs 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
150000003254 radicals Chemical class 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
229910000104 sodium hydride Inorganic materials 0.000 description 11
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 10
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 10
229910052740 iodine Inorganic materials 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000002425 crystallisation Methods 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 8
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
208000035475 disorder Diseases 0.000 description 8
239000000725 suspension Substances 0.000 description 8
XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 7
GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 7
239000005711 Benzoic acid Substances 0.000 description 7
229940126062 Compound A Drugs 0.000 description 7
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 7
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 7
235000010233 benzoic acid Nutrition 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 7
OITNBJHJJGMFBN-UHFFFAOYSA-N 4-(chloromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CCl)C=C1 OITNBJHJJGMFBN-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
LOXORFRCPXUORP-UHFFFAOYSA-N bromo-Cycloheptane Chemical compound BrC1CCCCCC1 LOXORFRCPXUORP-UHFFFAOYSA-N 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
150000004715 keto acids Chemical class 0.000 description 6
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 6
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 6
208000006673 asthma Diseases 0.000 description 5
208000010668 atopic eczema Diseases 0.000 description 5
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 5
229940073608 benzyl chloride Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
239000003921 oil Substances 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 5
239000002571 phosphodiesterase inhibitor Substances 0.000 description 5
238000011321 prophylaxis Methods 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
101100296719 Caenorhabditis elegans pde-4 gene Proteins 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
230000000172 allergic effect Effects 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 4
230000000694 effects Effects 0.000 description 4
230000002757 inflammatory effect Effects 0.000 description 4
229940067157 phenylhydrazine Drugs 0.000 description 4
230000008569 process Effects 0.000 description 4
238000000746 purification Methods 0.000 description 4
208000017520 skin disease Diseases 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 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 description 4
229940086542 triethylamine Drugs 0.000 description 4
102000003390 tumor necrosis factor Human genes 0.000 description 4
KMOUUZVZFBCRAM-OLQVQODUSA-N (3as,7ar)-3a,4,7,7a-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1C=CC[C@@H]2C(=O)OC(=O)[C@@H]21 KMOUUZVZFBCRAM-OLQVQODUSA-N 0.000 description 3
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 3
SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 3
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 3
NVRVNSHHLPQGCU-UHFFFAOYSA-N 6-bromohexanoic acid Chemical compound OC(=O)CCCCCBr NVRVNSHHLPQGCU-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
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
206010040070 Septic Shock Diseases 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
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- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (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)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Plural Heterocyclic Compounds (AREA)
Compositions Of Macromolecular Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Lubricants (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)

IL13065998A 1997-01-15 1998-01-12 Pathalazinone compounds, drugs containing them and their use IL130659A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97100488		1997-01-15
PCT/EP1998/000124 WO1998031674A1 (fr)	1997-01-15	1998-01-12	Phthalazinones

Publications (2)

Publication Number	Publication Date
IL130659A0 IL130659A0 (en)	2000-06-01
IL130659A true IL130659A (en)	2002-07-25

Family

ID=8226366

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL13065998A IL130659A (en)	1997-01-15	1998-01-12	Pathalazinone compounds, drugs containing them and their use

Country Status (26)

Country	Link
US (1)	US6103718A (fr)
EP (1)	EP0971901B1 (fr)
JP (1)	JP2001508078A (fr)
KR (1)	KR20000070150A (fr)
CN (1)	CN1127487C (fr)
AT (1)	ATE233247T1 (fr)
AU (1)	AU735934B2 (fr)
BR (1)	BR9806752A (fr)
CA (1)	CA2276455C (fr)
CY (1)	CY2446B1 (fr)
CZ (1)	CZ293815B6 (fr)
DE (1)	DE69811645T2 (fr)
DK (1)	DK0971901T3 (fr)
EA (1)	EA002764B1 (fr)
EE (1)	EE03968B1 (fr)
ES (1)	ES2193508T3 (fr)
HU (1)	HUP0001541A3 (fr)
IL (1)	IL130659A (fr)
NO (1)	NO313137B1 (fr)
NZ (1)	NZ336573A (fr)
PL (1)	PL189418B1 (fr)
PT (1)	PT971901E (fr)
SI (1)	SI0971901T1 (fr)
SK (1)	SK283270B6 (fr)
TR (1)	TR199901653T2 (fr)
WO (1)	WO1998031674A1 (fr)

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CA2715683A1 (fr)	1999-08-21	2001-03-01	Nycomed Gmbh	Combinaison synergiste
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HUP0203487A2 (hu)	1999-10-25	2003-02-28	Byk Gulden Lomberg Chemische Fabrik Gmbh	Tetrahidrotiopirán-ftalazinon-származékok, mint PDE4-inhibitorok és ezeket tartalmazó gyógyszerkészítmények
WO2001030766A1 (fr) *	1999-10-25	2001-05-03	Byk Gulden Lomberg Chemische Fabrik Gmbh	Derives de phthalazinone, utilises comme inhibiteurs de pde4
NZ522882A (en)	2000-06-05	2004-07-30	Altana Pharma Bv	Pyridazinone compounds effective as beta-2-adrenoreceptor agonists as well as PDE4-inhibitors
US7868015B2 (en) *	2000-08-10	2011-01-11	Cold Spring Harbor Laboratory	Phosphodiesesterase 4 inhibitors for the treatment of a cognitive deficit
US20040224316A1 (en) *	2000-08-10	2004-11-11	Tully Timothy P.	Augmented cognitive training
CZ20032491A3 (cs) *	2001-02-15	2004-01-14	Altana Pharma Ag	Ftalazinonpiperidinové deriváty
EP1385848A2 (fr) *	2001-04-25	2004-02-04	ALTANA Pharma AG	Phtalazinones
BR0209076A (pt) *	2001-04-25	2004-08-10	Altana Pharma Ag	Derivados de piperazino e seu uso como inibidor de pde4
AU2003211381B9 (en)	2002-02-19	2009-07-30	Ono Pharmaceutical Co., Ltd.	Fused pyridazine derivative compounds and drugs containing the compounds as the active ingredient
WO2004018449A1 (fr) *	2002-08-10	2004-03-04	Altana Pharma Ag	Derives de piperidine utilises comme inhibiteurs de la phospodiesterase-4 (pde4)
EP1556369A1 (fr) *	2002-08-10	2005-07-27	ALTANA Pharma AG	Derives de pyridazinone utilises comme inhibiteurs de pde4
BR0313330A (pt)	2002-08-10	2005-06-14	Altana Pharma Ag	Piperidina-ftalazonas substituìdas com pirrolidinadiona como inibidores de pde4
US20060166995A1 (en) *	2002-08-10	2006-07-27	Altana Pharma Ag	Piperidine-n-oxide-derivatives
US7153824B2 (en)	2003-04-01	2006-12-26	Applied Research Systems Ars Holding N.V.	Inhibitors of phosphodiesterases in infertility
WO2004098633A1 (fr) *	2003-05-12	2004-11-18	Altana Pharma Ag	Composition comprenant un inhibiteur de la pde-4 et un antagoniste du tnf-alpha
EP1661894A4 (fr)	2003-07-14	2007-02-28	Ube Industries	Procede de production de 4-aminotetrahydropyranes et de sels de ces derniers presentant des acides, intermediaires pour ledit procede et procede de production de ces derniers
US20080227790A1 (en) *	2004-02-04	2008-09-18	Altana Pharma Ag	Pyridazinone Derivatives and their Use as Pde4 Inhibitors
DE602005005638T2 (de) *	2004-02-04	2009-05-14	Nycomed Gmbh	2-(piperidin-4-yl)-4,5-dihydro-2h-pyridazin-3-on-derivate als pde4-inhibitoren
BRPI0607533A2 (pt) *	2005-04-21	2009-09-15	Nippon Shinyaku Co Ltd	derivado de ftalazinona, composição farmacêutica, inibidor de fosfodiesterase do tipo 4,supressor da produção de tnf-alfa, agente preventivo ou terapêutico, preparado externo, bem como uso do referido derivado
EP2275095A3 (fr)	2005-08-26	2011-08-17	Braincells, Inc.	Neurogenese par modulation des recepteurs muscariniques
EP2258358A3 (fr)	2005-08-26	2011-09-07	Braincells, Inc.	Neurogenèse avec un inhibiteur de l'acetylcholinestérase
EP1940389A2 (fr)	2005-10-21	2008-07-09	Braincells, Inc.	Modulation de la neurogenese par inhibition de la pde
AU2006308889A1 (en)	2005-10-31	2007-05-10	Braincells, Inc.	GABA receptor mediated modulation of neurogenesis
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
JP2009536667A (ja)	2006-05-09	2009-10-15	ブレインセルス，インコーポレイティド	５ｈｔ受容体介在性の神経新生
EP2382975A3 (fr)	2006-05-09	2012-02-29	Braincells, Inc.	Neurogénèse par modulation d'angiotensine
AU2007292848A1 (en)	2006-09-08	2008-03-13	Braincells, Inc.	Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en)	2006-09-19	2010-07-22	Braincells, Inc.	Modulation of neurogenesis by ppar agents
ES2427442T3 (es) *	2007-05-16	2013-10-30	Takeda Gmbh	Derivados de pirazolona como inhibidores de PDE4
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.
WO2010099217A1 (fr)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation de neurogenèse à l'aide de combinaisons de d-cyclosérine
US20140112945A1 (en) *	2011-06-17	2014-04-24	Takeda Gmbh	Novel phthalazinone-pyrrolopyrimidinecarboxamide derivatives
WO2013106547A1 (fr)	2012-01-10	2013-07-18	President And Fellows Of Harvard College	Composés promoteurs de réplication des cellules bêta et leurs procédés d'utilisation
EP2968323A4 (fr)	2013-03-13	2016-12-14	Flatley Discovery Lab	Composés de pyridazinone et procédés pour le traitement de fibrose kystique
US20150050626A1 (en) *	2013-03-15	2015-02-19	Dart Neuroscience, Llc	Systems, Methods, and Software for Improving Cognitive and Motor Abilities

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1998
- 1998-01-12 BR BR9806752-4A patent/BR9806752A/pt active Search and Examination
- 1998-01-12 IL IL13065998A patent/IL130659A/en not_active IP Right Cessation
- 1998-01-12 SK SK951-99A patent/SK283270B6/sk unknown
- 1998-01-12 AT AT98901959T patent/ATE233247T1/de not_active IP Right Cessation
- 1998-01-12 CN CN98803169A patent/CN1127487C/zh not_active Expired - Fee Related
- 1998-01-12 JP JP53363598A patent/JP2001508078A/ja not_active Ceased
- 1998-01-12 HU HU0001541A patent/HUP0001541A3/hu unknown
- 1998-01-12 PT PT98901959T patent/PT971901E/pt unknown
- 1998-01-12 US US09/341,135 patent/US6103718A/en not_active Expired - Fee Related
- 1998-01-12 AU AU58629/98A patent/AU735934B2/en not_active Ceased
- 1998-01-12 EE EEP199900274A patent/EE03968B1/xx not_active IP Right Cessation
- 1998-01-12 CZ CZ19992533A patent/CZ293815B6/cs not_active IP Right Cessation
- 1998-01-12 DE DE69811645T patent/DE69811645T2/de not_active Expired - Fee Related
- 1998-01-12 KR KR1019997006376A patent/KR20000070150A/ko not_active Ceased
- 1998-01-12 DK DK98901959T patent/DK0971901T3/da active
- 1998-01-12 PL PL98334561A patent/PL189418B1/pl not_active IP Right Cessation
- 1998-01-12 ES ES98901959T patent/ES2193508T3/es not_active Expired - Lifetime
- 1998-01-12 EP EP98901959A patent/EP0971901B1/fr not_active Expired - Lifetime
- 1998-01-12 WO PCT/EP1998/000124 patent/WO1998031674A1/fr not_active Ceased
- 1998-01-12 EA EA199900620A patent/EA002764B1/ru not_active IP Right Cessation
- 1998-01-12 SI SI9830396T patent/SI0971901T1/xx unknown
- 1998-01-12 NZ NZ336573A patent/NZ336573A/xx unknown
- 1998-01-12 CA CA002276455A patent/CA2276455C/fr not_active Expired - Fee Related
- 1998-01-12 TR TR1999/01653T patent/TR199901653T2/xx unknown
1999
- 1999-07-02 NO NO19993301A patent/NO313137B1/no unknown
2004
- 2004-08-11 CY CY0400064A patent/CY2446B1/xx unknown

Also Published As

Publication number	Publication date
NO313137B1 (no)	2002-08-19
EA199900620A1 (ru)	2000-04-24
NO993301D0 (no)	1999-07-02
EP0971901A1 (fr)	2000-01-19
DE69811645T2 (de)	2003-12-04
US6103718A (en)	2000-08-15
JP2001508078A (ja)	2001-06-19
AU5862998A (en)	1998-08-07
EA002764B1 (ru)	2002-08-29
PL334561A1 (en)	2000-03-13
CN1249749A (zh)	2000-04-05
EE9900274A (et)	2000-02-15
NZ336573A (en)	2000-10-27
SI0971901T1 (en)	2003-10-31
SK95199A3 (en)	1999-12-10
PT971901E (pt)	2003-07-31
PL189418B1 (pl)	2005-08-31
BR9806752A (pt)	2000-03-14
SK283270B6 (sk)	2003-04-01
CN1127487C (zh)	2003-11-12
CY2446B1 (en)	2004-11-12
EP0971901B1 (fr)	2003-02-26
HUP0001541A2 (hu)	2001-05-28
HUP0001541A3 (en)	2001-11-28
CA2276455C (fr)	2006-10-31
ES2193508T3 (es)	2003-11-01
CZ293815B6 (cs)	2004-08-18
WO1998031674A1 (fr)	1998-07-23
EE03968B1 (et)	2003-02-17
TR199901653T2 (xx)	1999-10-21
IL130659A0 (en)	2000-06-01
CA2276455A1 (fr)	1998-07-23
NO993301L (no)	1999-09-10
HK1024692A1 (en)	2000-10-20
DE69811645D1 (de)	2003-04-03
DK0971901T3 (da)	2003-06-10
AU735934B2 (en)	2001-07-19
KR20000070150A (ko)	2000-11-25
CZ253399A3 (cs)	2000-05-17
ATE233247T1 (de)	2003-03-15

Legal Events

Date	Code	Title
2003-01-12	FF	Patent granted
2003-03-12	KB	Patent renewed
2004-02-19	KB	Patent renewed
2008-02-10	KB	Patent renewed
2012-10-31	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
CA2276455C (fr)	2006-10-31	Phthalazinones
US6410551B1 (en)	2002-06-25	Tetrazole derivatives
US20060116518A1 (en)	2006-06-01	Novel phenanthridines
HUP0003311A2 (en)	2001-03-28	Substituted 6-phenylphenanthridine derivatives, pocess for producing them and pharmaceutical compositions containing them
US6380196B1 (en)	2002-04-30	Dihydrobenzofurans
CA2445233A1 (fr)	2002-10-31	Phtalazinones
CA2334979A1 (fr)	1999-12-16	Benzamides avec des substituants tetrahydrofuranyloxy utilises comme inhibiteurs de la phosphodiesterase 4
WO1999031071A1 (fr)	1999-06-24	Nouveaux phtalazinones
EP0934933A1 (fr)	1999-08-11	Phtalazinones
CA2554797C (fr)	2012-09-04	Derives de 2-(piperidin-4-yl)-4,5-dihydro-2h-pyridazin-3-one inhibiteurs de pde4
HK1024692B (en)	2003-06-20	Phthalazinones
EP1720854A1 (fr)	2006-11-15	Dérivés de phthalazinone comme inhibiteurs de pde4
MXPA99006580A (en)	2000-01-21	Phthalazinones
US20080227790A1 (en)	2008-09-18	Pyridazinone Derivatives and their Use as Pde4 Inhibitors