AP609A - Tricyclic 5,6-dihydro-9H-pyrazolo[3,4c]-1,2,4-triazolo[4,3-A]pyridines. - Google Patents

Tricyclic 5,6-dihydro-9H-pyrazolo[3,4c]-1,2,4-triazolo[4,3-A]pyridines. Download PDF

Info

Publication number: AP609A
Authority: AP; ARIPO
Prior art keywords: alkyl; pyrazolo; ethyl; dihydro; pyridine
Prior art date: 1995-06-06

Application number

APAP/P/1996/000806A

Other languages

English (en)

Other versions

AP9600806A0 (en

Inventor

Allen Jacob Duplantier

Kevin 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

1996-05-06

Publication date

1997-09-03

1996-05-06 Application filed by Pfizer filed Critical Pfizer

1996-07-31 Publication of AP9600806A0 publication Critical patent/AP9600806A0/xx

1997-09-03 Application granted granted Critical

1997-09-03 Publication of AP609A publication Critical patent/AP609A/en

Links

150000003222 pyridines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 63
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 32
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 32
108060008682 Tumor Necrosis Factor Proteins 0.000 claims abstract description 25
102000003390 tumor necrosis factor Human genes 0.000 claims abstract description 25
238000004519 manufacturing process Methods 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 14
201000010099 disease Diseases 0.000 claims abstract description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
208000027866 inflammatory disease Diseases 0.000 claims abstract description 9
206010006895 Cachexia Diseases 0.000 claims abstract description 8
206010040070 Septic Shock Diseases 0.000 claims abstract description 8
230000036303 septic shock Effects 0.000 claims abstract description 8
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 7
206010012434 Dermatitis allergic Diseases 0.000 claims abstract description 7
201000004681 Psoriasis Diseases 0.000 claims abstract description 7
206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 7
201000010105 allergic rhinitis Diseases 0.000 claims abstract description 7
206010003246 arthritis Diseases 0.000 claims abstract description 7
208000006673 asthma Diseases 0.000 claims abstract description 7
201000008937 atopic dermatitis Diseases 0.000 claims abstract description 7
208000010668 atopic eczema Diseases 0.000 claims abstract description 7
206010006451 bronchitis Diseases 0.000 claims abstract description 7
230000000694 effects Effects 0.000 claims abstract description 7
206010040047 Sepsis Diseases 0.000 claims abstract description 6
238000011282 treatment Methods 0.000 claims abstract description 6
230000002401 inhibitory effect Effects 0.000 claims abstract description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 61
125000000217 alkyl group Chemical group 0.000 claims description 40
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 31
-1 (C2CJalkenyl Chemical group 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 21
238000000034 method Methods 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
230000005764 inhibitory process Effects 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
229910052684 Cerium Inorganic materials 0.000 claims description 7
208000030507 AIDS Diseases 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
150000002431 hydrogen Chemical group 0.000 claims description 5
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
125000002252 acyl group Chemical group 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
229910052799 carbon Inorganic materials 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 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
239000003937 drug carrier Substances 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
229920006395 saturated elastomer Polymers 0.000 claims description 3
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000002947 alkylene 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
230000004968 inflammatory condition Effects 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
CZSOESDMMFWTJY-UHFFFAOYSA-N 12-cyclopentyl-10-ethyl-5-(2-iodophenyl)-3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,10-tetraene Chemical compound C1CN(C(=NN=2)C=3C(=CC=CC=3)I)C=2C2=C1C(CC)=NN2C1CCCC1 CZSOESDMMFWTJY-UHFFFAOYSA-N 0.000 claims 1
229910014585 C2-Ce Inorganic materials 0.000 claims 1
230000003110 anti-inflammatory effect Effects 0.000 claims 1
238000006243 chemical reaction Methods 0.000 description 37
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
238000002360 preparation method Methods 0.000 description 19
239000000203 mixture Substances 0.000 description 16
239000000243 solution Substances 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
230000002829 reductive effect Effects 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 13
238000010992 reflux Methods 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
210000004027 cell Anatomy 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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000000010 aprotic solvent Substances 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
239000003880 polar aprotic solvent Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000007787 solid Substances 0.000 description 8
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
239000003480 eluent Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
210000003979 eosinophil Anatomy 0.000 description 5
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 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
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 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000000463 material Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
239000003586 protic polar solvent Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
241000282412 Homo Species 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 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
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 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 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
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
125000000882 C2-C6 alkenyl group Chemical group 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
239000012981 Hank's balanced salt solution Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
210000005091 airway smooth muscle Anatomy 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
229910002092 carbon dioxide Inorganic materials 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
239000002158 endotoxin Substances 0.000 description 2
238000010438 heat treatment Methods 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
238000012417 linear regression Methods 0.000 description 2
229920006008 lipopolysaccharide Polymers 0.000 description 2
210000000440 neutrophil Anatomy 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
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
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000002904 solvent Substances 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
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
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
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 1
STPXIOFWKOIYHX-UHFFFAOYSA-N 1-methylcyclohexane-1-carbonyl chloride Chemical compound ClC(=O)C1(C)CCCCC1 STPXIOFWKOIYHX-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
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
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-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
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
AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
108010001478 Bacitracin Proteins 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
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 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
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
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Health & Medical Sciences (AREA)
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Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Oncology (AREA)
Pulmonology (AREA)
Communicable Diseases (AREA)
Virology (AREA)
Rheumatology (AREA)
Dermatology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

APAP/P/1996/000806A 1995-06-06 1996-05-06 Tricyclic 5,6-dihydro-9H-pyrazolo[3,4c]-1,2,4-triazolo[4,3-A]pyridines. AP609A (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 (2)

Publication Number	Publication Date
AP9600806A0 AP9600806A0 (en)	1996-07-31
AP609A true AP609A (en)	1997-09-03

Family

ID=89994031

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1996/000806A AP609A (en)	1995-06-06	1996-05-06	Tricyclic 5,6-dihydro-9H-pyrazolo[3,4c]-1,2,4-triazolo[4,3-A]pyridines.

Country Status (43)

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

Families Citing this family (18)

* Cited by examiner, † Cited by third party
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
US6326495B2 (en) *	1999-04-30	2001-12-04	Pfizer Inc.	Process for preparing 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacenes and intermediates useful therein
EP1380585B1 (de) *	1999-04-30	2004-11-10	Pfizer Products Inc.	Pyrazolopyridinon als Zwischenprodukt
PL200923B1 (pl)	1999-08-21	2009-02-27	Nycomed Gmbh	Lek zawierający inhibitor PDE w połączeniu z agonistą receptoraß₂ -adrenergicznego oraz zastosowanie połączenia roflumilastu i salmeterolu
CA2402384A1 (en) *	2000-03-16	2001-09-20	Inflazyme Pharmaceuticals Ltd.	Benzylated pde4 inhibitors
PA8546001A1 (es) *	2001-05-25	2003-12-30	Pfizer	Un inhibidor de pde4 y un agente anticolinergico en combinacion para tratar enfermedades obstructivas de vias respiratorias
WO2002096423A2 (en) *	2001-05-25	2002-12-05	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Combination of a pde4 inhibitor and tiotropium or derivate thereof for treating obstructive airways
GB0122031D0 (en) *	2001-09-12	2001-10-31	Pfizer Ltd	Use of pde4 inhibitors in a dry powder inhaler
GB0129395D0 (en) *	2001-12-07	2002-01-30	Pfizer Ltd	Pharmaceutical combination
US20050107420A1 (en) *	2002-05-23	2005-05-19	Boehringe Ingelheim Pharma Gmbh & Co. Kg	Combination of a PDE4 inhibitor and tiotropium or derivative thereof for treating obstructive airways and other inflammatory diseases
JP2006522151A (ja)	2003-04-01	2006-09-28	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	不妊症におけるホスホジエステラーゼ阻害剤
WO2006075748A1 (ja) *	2005-01-17	2006-07-20	Santen Pharmaceutical Co., Ltd.	アレルギー性結膜疾患治療剤
WO2006135627A2 (en) *	2005-06-10	2006-12-21	Merck & Co., Inc.	Inhibitors of akt activity
WO2007045979A1 (en)	2005-10-19	2007-04-26	Ranbaxy Laboratories Limited	Pharmaceutical compositions of muscarinic receptor antagonists
PT2359826E (pt)	2006-07-05	2014-01-20	Takeda Gmbh	Combinação de um inibidor da hmg-coa redutase rosuvastatina e um inibidor da fosfodiesterase 4, tais como roflumilaste, óxido de n-roflumilaste, para o tratamento de doenças pulmonares inflamatórias
JP5579724B2 (ja) *	2008-10-17	2014-08-27	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	ホスファチジルイノシトール−３−キナーゼ（ｐｉ−３キナーゼ）阻害剤としてのテトラ−アザ−複素環
WO2011067145A1 (en)	2009-12-04	2011-06-09	Nerviano Medical Sciences S.R.L.	Tricyclopyrazole derivatives
WO2013084182A1 (en)	2011-12-08	2013-06-13	Glenmark Pharmaceuticals S.A.	Pharmaceutical composition that includes a pde4 enzyme inhibitor and an analgesic agent

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1995001980A1 (en) *	1993-07-06	1995-01-19	Pfizer Inc.	Bicyclic tetrahydro pyrazolopyridines

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3697532A (en) *	1970-08-12	1972-10-10	Squibb & Sons Inc	5-methyldipyrazolo {8 3,4-b;3{40 ,4{40 -d{9 {0 pyridin-3(2h)-ones
SU1048746A1 (ru) *	1982-01-29	1987-12-30	Институт физико-органической химии и углехимии АН УССР	Гидробромид 8-адамантил-1,з-диметилимидазо 4,5-с имидазо 1,2-а пиридин-2-она,обладающий спазмолитическим действием
FR2579208B1 (fr) *	1985-03-22	1987-05-07	Sanofi Sa	Nouveaux derives de le 5-h pyrido (3', 4' : 4,5) pyrrolo (3,2-c) pyridine, leur procede de preparation et leur activite antitumorale
US4940715A (en) *	1988-05-17	1990-07-10	Kissei Pharmaceutical Co., Ltd.	5H-pyrazolo[4,3-A] quinolizin-5-one compounds exhibiting therapeutic activities
CA2030056C (en) *	1989-11-17	1995-10-17	Karl D. Hargrave	5,11-dihydro-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepines and their use in the prevention or treatment of hiv infection
CA2143143A1 (en) *	1994-03-08	1995-09-09	Toshihiko Tanaka	3-phenylpyrrolidine derivatives

1995
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- 1995-06-06 ES ES95918707T patent/ES2172583T3/es not_active Expired - Lifetime
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- 1995-06-06 DK DK95918707T patent/DK0837860T3/da active
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- 1995-06-06 CA CA002223624A patent/CA2223624C/en not_active Expired - Fee Related
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1996
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- 1996-06-05 AU AU54773/96A patent/AU694871B2/en not_active Ceased
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1997
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1998
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Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1995001980A1 (en) *	1993-07-06	1995-01-19	Pfizer Inc.	Bicyclic tetrahydro pyrazolopyridines

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Publication number	Publication date
MA23893A1 (fr)	1996-12-31
HRP960268A2 (en)	1997-08-31
AU5477396A (en)	1996-12-19
LV11620B (en)	1997-04-20
TR199600482A1 (tr)	1997-03-21
CA2223624C (en)	2001-02-20
BG62568B1 (bg)	2000-02-29
IS1913B (is)	2004-02-03
FI114097B (fi)	2004-08-13
IL118485A (en)	2000-02-17
DE69525978T2 (de)	2002-12-19
EP0837860B1 (de)	2002-03-20
IS4350A (is)	1996-12-07
CO4700460A1 (es)	1998-12-29
RO115881B1 (ro)	2000-07-28
FI974434A0 (fi)	1997-12-05
HRP960268B1 (en)	2002-12-31
YU34696A (sh)	1999-07-28
SK282167B6 (sk)	2001-11-06
BG100640A (bg)	1997-03-31
KR100191972B1 (ko)	1999-06-15
HU9601541D0 (en)	1996-07-29
KR100225719B1 (en)	1999-10-15
CZ287251B6 (en)	2000-10-11
CA2223624A1 (en)	1996-12-12
TW460469B (en)	2001-10-21
EP0837860A1 (de)	1998-04-29
DK0837860T3 (da)	2002-05-27
AP9600806A0 (en)	1996-07-31
DE69525978D1 (de)	2002-04-25
WO1996039408A1 (en)	1996-12-12
NO962320D0 (no)	1996-06-05
DZ2044A1 (fr)	2002-07-21
MY116527A (en)	2004-02-28
MX9709897A (es)	1998-03-31
HUP9601541A3 (en)	1997-05-28
RU2161158C2 (ru)	2000-12-27
PL184195B1 (pl)	2002-09-30
YU49346B (sh)	2005-07-19
JP3107827B2 (ja)	2000-11-13
FI974434L (fi)	1997-12-05
NO962320L (no)	1996-12-09
PT837860E (pt)	2002-07-31
SA96170065B1 (ar)	2005-12-21
LV11620A (lv)	1996-12-20
CN1061044C (zh)	2001-01-24
US6004974A (en)	1999-12-21
TNSN96083A1 (fr)	2005-03-15
IL118485A0 (en)	1996-09-12
SK71896A3 (en)	1997-05-07
JPH10510242A (ja)	1998-10-06
AR002745A1 (es)	1998-04-29
BR9602627A (pt)	1998-09-01
SI9600186A (en)	1997-04-30
ES2172583T3 (es)	2002-10-01
SG54341A1 (en)	1998-11-16
PL314459A1 (en)	1996-12-09
OA10458A (en)	2002-03-27
KR970003440A (ko)	1997-01-28
AU694871B2 (en)	1998-07-30
NO306256B1 (no)	1999-10-11
HUP9601541A2 (en)	1997-02-28
CN1142499A (zh)	1997-02-12
ATE214700T1 (de)	2002-04-15
NZ286734A (en)	1998-02-26
CZ162696A3 (en)	1997-01-15

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