LV11620B - Tricyclic 5,6-dihydro-9h-pyrazolo£3,4-c|-1,2,4-triazolo£4,3-a|pyridines - Google Patents

Tricyclic 5,6-dihydro-9h-pyrazolo£3,4-c|-1,2,4-triazolo£4,3-a|pyridines Download PDF

Info

Publication number: LV11620B
Authority: LV; Latvia
Prior art keywords: alkyl; pyridine; pyrazolo; ethyl; dihydro
Prior art date: 1995-06-06

Application number

LVP-96-174A

Other languages

English (en)

Latvian (lv)

Other versions

LV11620A (lv

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

1996-06-04

Publication date

1997-04-20

1996-06-04 Application filed by Pfizer filed Critical Pfizer

1996-12-20 Publication of LV11620A publication Critical patent/LV11620A/xx

1997-04-20 Publication of LV11620B publication Critical patent/LV11620B/en

Links

150000003222 pyridines Chemical class 0.000 title 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 74
150000001875 compounds Chemical class 0.000 claims description 64
125000000217 alkyl group Chemical group 0.000 claims description 51
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 38
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 30
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 28
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 28
-1 1-methylcyclohex-1-yl Chemical group 0.000 claims description 24
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 22
102000003390 tumor necrosis factor Human genes 0.000 claims description 22
238000004519 manufacturing process Methods 0.000 claims description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
230000005764 inhibitory process Effects 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
150000002431 hydrogen Chemical class 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
208000027866 inflammatory disease Diseases 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
208000030507 AIDS Diseases 0.000 claims description 7
201000004681 Psoriasis Diseases 0.000 claims description 7
206010040070 Septic Shock Diseases 0.000 claims description 7
206010003246 arthritis Diseases 0.000 claims description 7
208000006673 asthma Diseases 0.000 claims description 7
208000010668 atopic eczema Diseases 0.000 claims description 7
206010006451 bronchitis Diseases 0.000 claims description 7
230000036303 septic shock Effects 0.000 claims description 7
206010006895 Cachexia Diseases 0.000 claims description 6
206010012434 Dermatitis allergic Diseases 0.000 claims description 6
206010039085 Rhinitis allergic Diseases 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
201000010105 allergic rhinitis Diseases 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
201000008937 atopic dermatitis Diseases 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
238000011321 prophylaxis Methods 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
125000001424 substituent group Chemical group 0.000 claims description 3
PISKBBMPBXMWMB-UHFFFAOYSA-N CCC1=NN(C=2C=CC(F)=CC=2)C2=C1CCN1C2=NN=C1C1(C)CCCCC1 Chemical compound CCC1=NN(C=2C=CC(F)=CC=2)C2=C1CCN1C2=NN=C1C1(C)CCCCC1 PISKBBMPBXMWMB-UHFFFAOYSA-N 0.000 claims description 2
DHCOPPHTVOXDKU-UHFFFAOYSA-N Tofimilast Chemical compound C1CN2C(C=3SC=CC=3)=NN=C2C2=C1C(CC)=NN2C1CCCC1 DHCOPPHTVOXDKU-UHFFFAOYSA-N 0.000 claims description 2
CEMQXLVYSIOKKQ-UHFFFAOYSA-N chembl218653 Chemical compound C1CN(C(=NN=2)C=3C(=CC=CC=3)Cl)C=2C2=C1C(CC)=NN2C1CCCC1 CEMQXLVYSIOKKQ-UHFFFAOYSA-N 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
229910005965 SO 2 Inorganic materials 0.000 claims 2
206010049590 Upper respiratory tract inflammation Diseases 0.000 claims 2
230000015572 biosynthetic process Effects 0.000 claims 2
230000001684 chronic effect Effects 0.000 claims 2
229910052717 sulfur Inorganic materials 0.000 claims 2
239000011593 sulfur Chemical group 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
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
201000004624 Dermatitis Diseases 0.000 claims 1
206010061218 Inflammation Diseases 0.000 claims 1
125000000304 alkynyl group Chemical group 0.000 claims 1
230000000172 allergic effect Effects 0.000 claims 1
229910052799 carbon Inorganic materials 0.000 claims 1
PHIVEUQACADDGU-UHFFFAOYSA-N chembl218103 Chemical compound C1CN(C(=NN=2)C(C)(C)C)C=2C2=C1C(CC)=NN2C1CCCC1 PHIVEUQACADDGU-UHFFFAOYSA-N 0.000 claims 1
ZMFFNWKGXSCXBM-UHFFFAOYSA-N chembl218641 Chemical compound C1CN(C(=NN=2)C=3C=CN=CC=3)C=2C2=C1C(CC)=NN2C1CCCC1 ZMFFNWKGXSCXBM-UHFFFAOYSA-N 0.000 claims 1
OTBUQMMSFVAASQ-UHFFFAOYSA-N chembl374995 Chemical compound C1CN2C(C3CCCC3)=NN=C2C2=C1C(CC)=NN2C1CCCC1 OTBUQMMSFVAASQ-UHFFFAOYSA-N 0.000 claims 1
AJOWVHDRHWCPEK-UHFFFAOYSA-N chembl376440 Chemical compound C1CN2C(C3=CSC=C3)=NN=C2C2=C1C(CC)=NN2C1CCCC1 AJOWVHDRHWCPEK-UHFFFAOYSA-N 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
230000004054 inflammatory process Effects 0.000 claims 1
230000033764 rhythmic process Effects 0.000 claims 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 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
238000002360 preparation method Methods 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
239000000203 mixture Substances 0.000 description 17
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
150000003839 salts Chemical class 0.000 description 12
239000000010 aprotic solvent Substances 0.000 description 10
238000000034 method Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
239000003880 polar aprotic solvent Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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
239000003480 eluent Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
230000000694 effects Effects 0.000 description 5
210000003979 eosinophil Anatomy 0.000 description 5
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 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
239000005864 Sulphur Substances 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
125000004104 aryloxy group Chemical group 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000004587 chromatography analysis Methods 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
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
206010040047 Sepsis Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000002252 acyl group Chemical group 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
125000006526 (C1-C2) alkyl group Chemical group 0.000 description 2
125000006701 (C1-C7) alkyl group Chemical group 0.000 description 2
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
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 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
125000004399 C1-C4 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
241000124008 Mammalia Species 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
238000005481 NMR spectroscopy Methods 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 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
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000010949 copper Substances 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
238000000099 in vitro assay Methods 0.000 description 2
230000004968 inflammatory condition 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
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
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
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
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
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
125000004169 (C1-C6) 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
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
VLJHFRUUVXVJPY-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-6-(4-methoxyphenyl)-4,5-dihydropyrazolo[3,4-c]pyridin-7-one Chemical compound C1CN(C=2C=CC(OC)=CC=2)C(=O)C2=C1C(CC)=NN2C1CCCC1 VLJHFRUUVXVJPY-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
238000005160 1H NMR spectroscopy Methods 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
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
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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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- 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
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- A—HUMAN NECESSITIES
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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
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Bioinformatics & Cheminformatics (AREA)
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Communicable Diseases (AREA)
Virology (AREA)
Dermatology (AREA)
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Pain & Pain Management (AREA)
Molecular Biology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Tropical Medicine & Parasitology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

LVP-96-174A 1995-06-06 1996-06-04 Tricyclic 5,6-dihydro-9h-pyrazolo£3,4-c|-1,2,4-triazolo£4,3-a|pyridines LV11620B (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CA002223624A CA2223624C (fr)	1995-06-06	1995-06-06	5,6-dihydro-9h-pyrazolo[3,4-c]-1,2-4-triazolo[4,3-.alpha.]pyridines tricycliques
PCT/IB1995/000429 WO1996039408A1 (fr)	1995-06-06	1995-06-06	5,6-DIHYDRO-9H-PYRAZOLO[3,4-c]-1,2-4-TRIAZOLO[4,3-α]PYRIDINES TRICYCLIQUES
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
LV11620A LV11620A (lv)	1996-12-20
LV11620B true LV11620B (en)	1997-04-20

Family

ID=89994031

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LVP-96-174A LV11620B (en)	1995-06-06	1996-06-04	Tricyclic 5,6-dihydro-9h-pyrazolo£3,4-c\|-1,2,4-triazolo£4,3-a\|pyridines

Country Status (43)

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

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EP1380585B1 (fr) *	1999-04-30	2004-11-10	Pfizer Products Inc.	Pyrazolopyridinone comme intermédiaire
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
EP1212089B1 (fr)	1999-08-21	2006-03-22	ALTANA Pharma AG	Combinaison synergetique de roflumilast et salmeterol
CA2402384A1 (fr) *	2000-03-16	2001-09-20	Inflazyme Pharmaceuticals Ltd.	Inhibiteurs benzyles de pde4
BR0209992A (pt) *	2001-05-25	2004-04-06	Pfizer	Inibidor de pde4 e um agente anticolinérgico em combinação para o tratamento de doenças obstrutivas das vias respiratórias
WO2002096423A2 (fr) *	2001-05-25	2002-12-05	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Combinaison d'un inhibiteur de pde4 et de tiotropium ou d'un derive de ce dernier destinee au traitement des maladies obstructives des voies aeriennes et d'autres maladies inflammatoires
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
MXPA05010373A (es)	2003-04-01	2005-12-05	Applied Research Systems	Inhibidores de fosfodiesterasas en infertilidad.
WO2006075748A1 (fr) *	2005-01-17	2006-07-20	Santen Pharmaceutical Co., Ltd.	Agent therapeutique pour maladie conjonctivale allergique
US8008317B2 (en) *	2005-06-10	2011-08-30	Merck Sharp & Dohme Corp.	Inhibitors of akt activtiy
RU2008119323A (ru)	2005-10-19	2009-11-27	Рэнбакси Лабораториз Лимитед (In)	Фармацевтические композиции мускаринового рецептора
EP2359826B1 (fr)	2006-07-05	2013-10-30	Takeda GmbH	Combinaison d'un inhibiteur de la HMG-CoA reductase rosuvastatine avec un inhibiteur de la phosphodiesterase 4, tel que roflumilast, roflumilast-N-oxyde, pour le traitement de maladies pulmonaires inflammatoires
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
ES2527363T3 (es) *	2009-12-04	2015-01-22	Nerviano Medical Sciences S.R.L.	Derivados de triciclopirazol
WO2013084182A1 (fr)	2011-12-08	2013-06-13	Glenmark Pharmaceuticals S.A.	Composition pharmaceutique comprenant un inhibiteur de l'enzyme pde4 et un agent analgésique

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1995
- 1995-06-06 JP JP08511176A patent/JP3107827B2/ja not_active Expired - Fee Related
- 1995-06-06 DE DE69525978T patent/DE69525978T2/de not_active Expired - Fee Related
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- 1995-06-06 DK DK95918707T patent/DK0837860T3/da active
- 1995-06-06 EP EP95918707A patent/EP0837860B1/fr not_active Expired - Lifetime
- 1995-06-06 PT PT95918707T patent/PT837860E/pt unknown
- 1995-06-06 US US08/973,590 patent/US6004974A/en not_active Expired - Fee Related
- 1995-06-06 SK SK718-96A patent/SK282167B6/sk unknown
- 1995-06-06 WO PCT/IB1995/000429 patent/WO1996039408A1/fr not_active Ceased
- 1995-06-06 AT AT95918707T patent/ATE214700T1/de not_active IP Right Cessation
- 1995-06-06 CA CA002223624A patent/CA2223624C/fr not_active Expired - Fee Related
- 1995-06-06 ES ES95918707T patent/ES2172583T3/es not_active Expired - Lifetime
1996
- 1996-05-02 TW TW085105271A patent/TW460469B/zh not_active IP Right Cessation
- 1996-05-06 AP APAP/P/1996/000806A patent/AP609A/en active
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- 1996-06-05 DZ DZ960088A patent/DZ2044A1/fr active
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- 1996-06-05 RU RU96111027/04A patent/RU2161158C2/ru not_active IP Right Cessation
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1997
- 1997-12-05 FI FI974434A patent/FI114097B/fi active
1998
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Also Published As

Publication number	Publication date
WO1996039408A1 (fr)	1996-12-12
CZ287251B6 (en)	2000-10-11
CA2223624A1 (fr)	1996-12-12
SG54341A1 (en)	1998-11-16
JP3107827B2 (ja)	2000-11-13
MX9709897A (es)	1998-03-31
SK282167B6 (sk)	2001-11-06
DE69525978D1 (de)	2002-04-25
SK71896A3 (en)	1997-05-07
ES2172583T3 (es)	2002-10-01
IL118485A (en)	2000-02-17
AU5477396A (en)	1996-12-19
SI9600186A (en)	1997-04-30
AU694871B2 (en)	1998-07-30
RO115881B1 (ro)	2000-07-28
MY116527A (en)	2004-02-28
NO306256B1 (no)	1999-10-11
CN1142499A (zh)	1997-02-12
HRP960268A2 (en)	1997-08-31
IL118485A0 (en)	1996-09-12
FI114097B (fi)	2004-08-13
DZ2044A1 (fr)	2002-07-21
BG100640A (bg)	1997-03-31
RU2161158C2 (ru)	2000-12-27
EP0837860B1 (fr)	2002-03-20
IS4350A (is)	1996-12-07
ATE214700T1 (de)	2002-04-15
FI974434L (fi)	1997-12-05
YU34696A (sh)	1999-07-28
PL184195B1 (pl)	2002-09-30
NO962320D0 (no)	1996-06-05
NZ286734A (en)	1998-02-26
IS1913B (is)	2004-02-03
US6004974A (en)	1999-12-21
YU49346B (sh)	2005-07-19
KR970003440A (ko)	1997-01-28
CO4700460A1 (es)	1998-12-29
CZ162696A3 (en)	1997-01-15
AP9600806A0 (en)	1996-07-31
OA10458A (en)	2002-03-27
JPH10510242A (ja)	1998-10-06
MA23893A1 (fr)	1996-12-31
PT837860E (pt)	2002-07-31
SA96170065B1 (ar)	2005-12-21
PL314459A1 (en)	1996-12-09
FI974434A0 (fi)	1997-12-05
DK0837860T3 (da)	2002-05-27
KR100191972B1 (ko)	1999-06-15
TNSN96083A1 (fr)	2005-03-15
TR199600482A1 (tr)	1997-03-21
AP609A (en)	1997-09-03
EP0837860A1 (fr)	1998-04-29
AR002745A1 (es)	1998-04-29
NO962320L (no)	1996-12-09
KR100225719B1 (en)	1999-10-15
DE69525978T2 (de)	2002-12-19
HU9601541D0 (en)	1996-07-29
LV11620A (lv)	1996-12-20
CA2223624C (fr)	2001-02-20
TW460469B (en)	2001-10-21
BR9602627A (pt)	1998-09-01
HRP960268B1 (en)	2002-12-31
BG62568B1 (bg)	2000-02-29
CN1061044C (zh)	2001-01-24
HUP9601541A3 (en)	1997-05-28
HUP9601541A2 (en)	1997-02-28

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EP4531843A1 (fr)	2025-04-09	Inhibiteurs de pad4 hétérocycliques
MXPA98004050A (en)	1999-02-24	Derivatives of pirido (2,3-d) pyrimidine and pharmaceutical compositions of mis
CZ367499A3 (cs)	2000-02-16	Sloučeniny