OA10458A - Tricyclic 5,6-dihydro-9h-pyrazolo Ä3,4-cÜ-1,2,4-triazolo Ä4,3-alphaÜpyridines - Google Patents

Tricyclic 5,6-dihydro-9h-pyrazolo Ä3,4-cÜ-1,2,4-triazolo Ä4,3-alphaÜpyridines Download PDF

Info

Publication number: OA10458A
Authority: OA; OAPI
Prior art keywords: alkyl; dihydro; ethyl; triazolo; pyridine
Prior art date: 1995-06-06

Application number

OA60834A

Other languages

English (en)

Inventor

Allen Jacob Duplantier

Kelvin Cooper

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-06-06

Filing date

1996-06-06

Publication date

2002-03-27

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

2002-03-27 Publication of OA10458A publication Critical patent/OA10458A/en

Links

150000001875 compounds Chemical class 0.000 claims abstract description 54
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 24
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 24
108060008682 Tumor Necrosis Factor Proteins 0.000 claims abstract description 21
102000003390 tumor necrosis factor Human genes 0.000 claims abstract description 21
201000010099 disease Diseases 0.000 claims abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
150000003839 salts Chemical class 0.000 claims abstract description 9
206010006895 Cachexia Diseases 0.000 claims abstract description 6
208000030507 AIDS Diseases 0.000 claims abstract description 5
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 5
201000004681 Psoriasis Diseases 0.000 claims abstract description 5
206010040047 Sepsis Diseases 0.000 claims abstract description 5
206010003246 arthritis Diseases 0.000 claims abstract description 5
208000006673 asthma Diseases 0.000 claims abstract description 5
206010006451 bronchitis Diseases 0.000 claims abstract description 5
230000000694 effects Effects 0.000 claims abstract description 5
238000011282 treatment Methods 0.000 claims abstract description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 51
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 26
-1 (C^C^alkoxy Chemical group 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
201000004624 Dermatitis Diseases 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
239000005864 Sulphur Substances 0.000 claims description 4
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
206010020751 Hypersensitivity Diseases 0.000 claims description 3
230000007815 allergy Effects 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
206010039083 rhinitis Diseases 0.000 claims description 3
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
125000006833 (C1-C5) alkylene group Chemical group 0.000 claims 1
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
230000035939 shock Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 abstract description 9
206010040070 Septic Shock Diseases 0.000 abstract description 5
208000027866 inflammatory disease Diseases 0.000 abstract description 5
230000036303 septic shock Effects 0.000 abstract description 5
230000002401 inhibitory effect Effects 0.000 abstract description 2
206010012434 Dermatitis allergic Diseases 0.000 abstract 1
206010039085 Rhinitis allergic Diseases 0.000 abstract 1
201000010105 allergic rhinitis Diseases 0.000 abstract 1
201000008937 atopic dermatitis Diseases 0.000 abstract 1
208000010668 atopic eczema Diseases 0.000 abstract 1
238000006243 chemical reaction Methods 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 20
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
230000002829 reductive effect Effects 0.000 description 12
238000010992 reflux Methods 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
238000000034 method Methods 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
229940093499 ethyl acetate Drugs 0.000 description 10
235000019439 ethyl acetate Nutrition 0.000 description 10
230000005764 inhibitory process Effects 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
239000000010 aprotic solvent Substances 0.000 description 8
239000003880 polar aprotic solvent Substances 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 6
239000007787 solid Substances 0.000 description 6
210000003979 eosinophil Anatomy 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
239000012267 brine Substances 0.000 description 4
239000003586 protic polar solvent Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
238000003556 assay Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
SWACGCLWAODPJN-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-7-methylsulfanyl-4,5-dihydropyrazolo[3,4-c]pyridine Chemical compound C1CN=C(SC)C2=C1C(CC)=NN2C1CCCC1 SWACGCLWAODPJN-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
239000002253 acid Substances 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000002158 endotoxin Substances 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
239000010410 layer Substances 0.000 description 2
229920006008 lipopolysaccharide Polymers 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
210000005259 peripheral blood Anatomy 0.000 description 2
239000011886 peripheral blood Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
239000013641 positive control Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 1
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
QJLZPHIDOKBEGS-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-5,6-dihydro-4h-pyrazolo[3,4-c]pyridin-7-one Chemical compound C1CNC(=O)C2=C1C(CC)=NN2C1CCCC1 QJLZPHIDOKBEGS-UHFFFAOYSA-N 0.000 description 1
STPXIOFWKOIYHX-UHFFFAOYSA-N 1-methylcyclohexane-1-carbonyl chloride Chemical compound ClC(=O)C1(C)CCCCC1 STPXIOFWKOIYHX-UHFFFAOYSA-N 0.000 description 1
KNYHISBJRQVMAZ-UHFFFAOYSA-N 1h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C=NNC2=C1 KNYHISBJRQVMAZ-UHFFFAOYSA-N 0.000 description 1
XONUSAAXQLCRGJ-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-pyrazolo[3,4-c]pyridine Chemical compound N1=CCC2CNNC2=C1 XONUSAAXQLCRGJ-UHFFFAOYSA-N 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
DNGJVDGPCGXBFF-UHFFFAOYSA-N 4-methyl-n-(methyldiazenyl)aniline Chemical compound CN=NNC1=CC=C(C)C=C1 DNGJVDGPCGXBFF-UHFFFAOYSA-N 0.000 description 1
IBGCVRBLTWWXLM-UHFFFAOYSA-N 5-methoxy-1-(3-methoxyphenyl)-4-propanoyl-2,3-dihydropyridin-6-one Chemical compound C1CC(C(=O)CC)=C(OC)C(=O)N1C1=CC=CC(OC)=C1 IBGCVRBLTWWXLM-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
BAIYDCLETZLHLQ-UHFFFAOYSA-N C1CN2C=NN=C2C2=C1C=NN2 Chemical compound C1CN2C=NN=C2C2=C1C=NN2 BAIYDCLETZLHLQ-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
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 1
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Classifications

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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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OA60834A 1995-06-06 1996-06-06 Tricyclic 5,6-dihydro-9h-pyrazolo Ä3,4-cÜ-1,2,4-triazolo Ä4,3-alphaÜpyridines OA10458A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CA002223624A CA2223624C (en)	1995-06-06	1995-06-06	Tricyclic 5,6-dihydro-9h-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-.alpha.]pyridines
PCT/IB1995/000429 WO1996039408A1 (en)	1995-06-06	1995-06-06	TRICYCLIC 5,6-DIHYDRO-9H-PYRAZOLO[3,4-c]-1,2,4-TRIAZOLO[4,3-α]PYRIDINES
HU9601541A HUP9601541A3 (en)	1995-06-06	1996-06-05	Tricyclic 5,6-dihydro-9h-pyrazolo[3,4-c]-1,2,4-triazolol[4,3-a]-pyridines and pharmaceutical compositions containing them

Publications (1)

Publication Number	Publication Date
OA10458A true OA10458A (en)	2002-03-27

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ID=89994031

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Application Number	Title	Priority Date	Filing Date
OA60834A OA10458A (en)	1995-06-06	1996-06-06	Tricyclic 5,6-dihydro-9h-pyrazolo Ä3,4-cÜ-1,2,4-triazolo Ä4,3-alphaÜpyridines

Country Status (43)

Country	Link
US (1)	US6004974A (zh)
EP (1)	EP0837860B1 (zh)
JP (1)	JP3107827B2 (zh)
KR (2)	KR100191972B1 (zh)
CN (1)	CN1061044C (zh)
AP (1)	AP609A (zh)
AR (1)	AR002745A1 (zh)
AT (1)	ATE214700T1 (zh)
AU (1)	AU694871B2 (zh)
BG (1)	BG62568B1 (zh)
BR (1)	BR9602627A (zh)
CA (1)	CA2223624C (zh)
CO (1)	CO4700460A1 (zh)
CZ (1)	CZ287251B6 (zh)
DE (1)	DE69525978T2 (zh)
DK (1)	DK0837860T3 (zh)
DZ (1)	DZ2044A1 (zh)
ES (1)	ES2172583T3 (zh)
FI (1)	FI114097B (zh)
HR (1)	HRP960268B1 (zh)
HU (1)	HUP9601541A3 (zh)
IL (1)	IL118485A (zh)
IS (1)	IS1913B (zh)
LV (1)	LV11620B (zh)
MA (1)	MA23893A1 (zh)
MX (1)	MX9709897A (zh)
MY (1)	MY116527A (zh)
NO (1)	NO306256B1 (zh)
NZ (1)	NZ286734A (zh)
OA (1)	OA10458A (zh)
PL (1)	PL184195B1 (zh)
PT (1)	PT837860E (zh)
RO (1)	RO115881B1 (zh)
RU (1)	RU2161158C2 (zh)
SA (1)	SA96170065B1 (zh)
SG (1)	SG54341A1 (zh)
SI (1)	SI9600186A (zh)
SK (1)	SK282167B6 (zh)
TN (1)	TNSN96083A1 (zh)
TR (1)	TR199600482A1 (zh)
TW (1)	TW460469B (zh)
WO (1)	WO1996039408A1 (zh)
YU (1)	YU49346B (zh)

Families Citing this family (18)

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Publication number	Priority date	Publication date	Assignee	Title
FR2792938B1 (fr) *	1999-04-28	2001-07-06	Warner Lambert Co	NOUVELLES 1-AMINO TRIAZOLO [4,3-a] QUINAZOLINE-5-ONES INHIBITRICES DE PHOSPHODIESTERASES IV
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1995
- 1995-06-06 CA CA002223624A patent/CA2223624C/en not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
IL118485A (en)	2000-02-17
IS4350A (is)	1996-12-07
CA2223624C (en)	2001-02-20
EP0837860A1 (en)	1998-04-29
CZ162696A3 (en)	1997-01-15
PL314459A1 (en)	1996-12-09
HUP9601541A2 (en)	1997-02-28
DK0837860T3 (da)	2002-05-27
KR970003440A (ko)	1997-01-28
JP3107827B2 (ja)	2000-11-13
WO1996039408A1 (en)	1996-12-12
DE69525978D1 (de)	2002-04-25
TNSN96083A1 (fr)	2005-03-15
NO306256B1 (no)	1999-10-11
CZ287251B6 (en)	2000-10-11
HU9601541D0 (en)	1996-07-29
HUP9601541A3 (en)	1997-05-28
NZ286734A (en)	1998-02-26
CN1142499A (zh)	1997-02-12
KR100191972B1 (ko)	1999-06-15
MA23893A1 (fr)	1996-12-31
LV11620A (lv)	1996-12-20
RU2161158C2 (ru)	2000-12-27
RO115881B1 (ro)	2000-07-28
AU694871B2 (en)	1998-07-30
JPH10510242A (ja)	1998-10-06
YU49346B (sh)	2005-07-19
US6004974A (en)	1999-12-21
LV11620B (en)	1997-04-20
FI114097B (fi)	2004-08-13
TR199600482A1 (tr)	1997-03-21
SK71896A3 (en)	1997-05-07
IL118485A0 (en)	1996-09-12
BG62568B1 (bg)	2000-02-29
CO4700460A1 (es)	1998-12-29
HRP960268A2 (en)	1997-08-31
TW460469B (en)	2001-10-21
SG54341A1 (en)	1998-11-16
SK282167B6 (sk)	2001-11-06
PT837860E (pt)	2002-07-31
SA96170065B1 (ar)	2005-12-21
MY116527A (en)	2004-02-28
AP9600806A0 (en)	1996-07-31
AP609A (en)	1997-09-03
ES2172583T3 (es)	2002-10-01
DE69525978T2 (de)	2002-12-19
BG100640A (bg)	1997-03-31
NO962320D0 (no)	1996-06-05
SI9600186A (en)	1997-04-30
EP0837860B1 (en)	2002-03-20
ATE214700T1 (de)	2002-04-15
BR9602627A (pt)	1998-09-01
FI974434L (fi)	1997-12-05
AU5477396A (en)	1996-12-19
CN1061044C (zh)	2001-01-24
NO962320L (no)	1996-12-09
YU34696A (sh)	1999-07-28
IS1913B (is)	2004-02-03
MX9709897A (es)	1998-03-31
FI974434A0 (fi)	1997-12-05
DZ2044A1 (fr)	2002-07-21
HRP960268B1 (en)	2002-12-31
CA2223624A1 (en)	1996-12-12
KR100225719B1 (en)	1999-10-15
PL184195B1 (pl)	2002-09-30
AR002745A1 (es)	1998-04-29

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