BG62568B1 - Трициклени5,6-дихидро-9н-пиразоло[3,4-c]-1,2,4-триазоло[4,3-a] пиридини - Google Patents

Трициклени5,6-дихидро-9н-пиразоло[3,4-c]-1,2,4-триазоло[4,3-a] пиридини Download PDF

Info

Publication number: BG62568B1
Authority: BG; Bulgaria
Prior art keywords: alkyl; pyridine; ethyl; dihydro; compound
Prior art date: 1995-06-06

Application number

BG100640A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG100640A (bg

Inventor

Allen J. Duplantier

Kelvin Cooper

Original Assignee

Pfizer Inc.

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

1996-06-05

Publication date

2000-02-29

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

1997-03-31 Publication of BG100640A publication Critical patent/BG100640A/bg

2000-02-29 Publication of BG62568B1 publication Critical patent/BG62568B1/bg

Links

150000003222 pyridines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 73
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 29
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 29
238000004519 manufacturing process Methods 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 13
208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
206010040070 Septic Shock Diseases 0.000 claims abstract description 8
230000036303 septic shock Effects 0.000 claims abstract description 8
238000011282 treatment Methods 0.000 claims abstract description 7
208000030507 AIDS Diseases 0.000 claims abstract description 6
206010012434 Dermatitis allergic Diseases 0.000 claims abstract description 6
201000004681 Psoriasis Diseases 0.000 claims abstract description 6
206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 6
206010040047 Sepsis Diseases 0.000 claims abstract description 6
201000010105 allergic rhinitis Diseases 0.000 claims abstract description 6
206010003246 arthritis Diseases 0.000 claims abstract description 6
208000006673 asthma Diseases 0.000 claims abstract description 6
201000008937 atopic dermatitis Diseases 0.000 claims abstract description 6
208000010668 atopic eczema Diseases 0.000 claims abstract description 6
206010006451 bronchitis Diseases 0.000 claims abstract description 6
230000001684 chronic effect Effects 0.000 claims abstract description 6
230000000414 obstructive effect Effects 0.000 claims abstract description 6
206010006895 Cachexia Diseases 0.000 claims abstract description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 27
-1 1-methylcyclohex-1-yl Chemical group 0.000 claims description 22
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 21
239000001257 hydrogen Substances 0.000 claims description 21
102000003390 tumor necrosis factor Human genes 0.000 claims description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
238000000034 method Methods 0.000 claims description 15
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
230000005764 inhibitory process Effects 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
229910005965 SO 2 Inorganic materials 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
150000002431 hydrogen Chemical class 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
FABWMAMCDJJROT-UHFFFAOYSA-N 3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,10-pentaene Chemical compound C1=CN2C=NN=C2C2=C1C=NN2 FABWMAMCDJJROT-UHFFFAOYSA-N 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 3
DHCOPPHTVOXDKU-UHFFFAOYSA-N Tofimilast Chemical compound C1CN2C(C=3SC=CC=3)=NN=C2C2=C1C(CC)=NN2C1CCCC1 DHCOPPHTVOXDKU-UHFFFAOYSA-N 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 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 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
230000003110 anti-inflammatory effect Effects 0.000 claims description 2
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 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
WHTVLUBBPXQFPV-UHFFFAOYSA-N chembl439000 Chemical compound C1CN(C(=NN=2)C=3C=CC=CC=3)C=2C2=C1C(CC)=NN2C1CCCC1 WHTVLUBBPXQFPV-UHFFFAOYSA-N 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000005843 halogen 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
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
125000004648 C2-C8 alkenyl group Chemical group 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
125000000000 cycloalkoxy group Chemical group 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 3
239000003112 inhibitor Substances 0.000 abstract description 2
210000002345 respiratory system Anatomy 0.000 abstract description 2
238000006243 chemical reaction Methods 0.000 description 38
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 23
239000000203 mixture Substances 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
238000002360 preparation method Methods 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
239000000010 aprotic solvent Substances 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
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
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
239000007787 solid Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000003880 polar aprotic solvent Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000002904 solvent Substances 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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 6
238000005481 NMR spectroscopy Methods 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
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 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
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 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
241000282412 Homo Species 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
239000013543 active substance Substances 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
238000000921 elemental analysis Methods 0.000 description 4
239000000284 extract 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
BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 3
BAIYDCLETZLHLQ-UHFFFAOYSA-N C1CN2C=NN=C2C2=C1C=NN2 Chemical class C1CN2C=NN=C2C2=C1C=NN2 BAIYDCLETZLHLQ-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000003039 volatile agent Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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 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
FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-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
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 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
125000002252 acyl group Chemical group 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
238000009835 boiling Methods 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012043 crude product 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
238000002474 experimental method Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
238000012417 linear regression Methods 0.000 description 2
229920006008 lipopolysaccharide Polymers 0.000 description 2
238000001819 mass spectrum Methods 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
238000007911 parenteral administration Methods 0.000 description 2
210000005259 peripheral blood Anatomy 0.000 description 2
239000011886 peripheral blood Substances 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
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
238000010186 staining Methods 0.000 description 2
150000003571 thiolactams Chemical class 0.000 description 2
238000005406 washing Methods 0.000 description 2
125000000229 (C1-C4)alkoxy 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
IDJCCRRYIMWLSQ-UHFFFAOYSA-N 1-(4-methoxyphenyl)pyrrolidin-2-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)CCC1 IDJCCRRYIMWLSQ-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
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
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
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Classifications

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- 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
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- 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
- A61P37/04—Immunostimulants
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
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)

BG100640A 1995-06-06 1996-06-05 Трициклени5,6-дихидро-9н-пиразоло[3,4-c]-1,2,4-триазоло[4,3-a] пиридини BG62568B1 (bg)

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
BG100640A BG100640A (bg)	1997-03-31
BG62568B1 true BG62568B1 (bg)	2000-02-29

Family

ID=89994031

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG100640A BG62568B1 (bg)	1995-06-06	1996-06-05	Трициклени5,6-дихидро-9н-пиразоло[3,4-c]-1,2,4-триазоло[4,3-a] пиридини

Country Status (43)

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

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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 (en) *	1999-04-30	2004-11-10	Pfizer Products Inc.	Pyrazolopyridinone as intermediate
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

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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
CN1048015C (zh) *	1993-07-06	2000-01-05	美国辉瑞有限公司	双环四氢吡唑并吡啶类化合物
CA2143143A1 (en) *	1994-03-08	1995-09-09	Toshihiko Tanaka	3-phenylpyrrolidine derivatives

1995
- 1995-06-06 MX MX9709897A patent/MX9709897A/es unknown
- 1995-06-06 SK SK718-96A patent/SK282167B6/sk unknown
- 1995-06-06 ES ES95918707T patent/ES2172583T3/es not_active Expired - Lifetime
- 1995-06-06 US US08/973,590 patent/US6004974A/en not_active Expired - Fee Related
- 1995-06-06 DK DK95918707T patent/DK0837860T3/da active
- 1995-06-06 EP EP95918707A patent/EP0837860B1/en not_active Expired - Lifetime
- 1995-06-06 CA CA002223624A patent/CA2223624C/en not_active Expired - Fee Related
- 1995-06-06 PT PT95918707T patent/PT837860E/pt unknown
- 1995-06-06 AT AT95918707T patent/ATE214700T1/de not_active IP Right Cessation
- 1995-06-06 DE DE69525978T patent/DE69525978T2/de not_active Expired - Fee Related
- 1995-06-06 JP JP08511176A patent/JP3107827B2/ja not_active Expired - Fee Related
- 1995-06-06 WO PCT/IB1995/000429 patent/WO1996039408A1/en not_active Ceased
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
- 1996-05-20 AR ARP960102626A patent/AR002745A1/es unknown
- 1996-05-27 PL PL96314459A patent/PL184195B1/pl not_active IP Right Cessation
- 1996-05-30 IL IL11848596A patent/IL118485A/xx not_active IP Right Cessation
- 1996-06-03 IS IS4350A patent/IS1913B/is unknown
- 1996-06-04 LV LVP-96-174A patent/LV11620B/en unknown
- 1996-06-04 SA SA96170065A patent/SA96170065B1/ar unknown
- 1996-06-04 BR BR9602627A patent/BR9602627A/pt active Search and Examination
- 1996-06-05 HU HU9601541A patent/HUP9601541A3/hu unknown
- 1996-06-05 TN TNTNSN96083A patent/TNSN96083A1/fr unknown
- 1996-06-05 AU AU54773/96A patent/AU694871B2/en not_active Ceased
- 1996-06-05 DZ DZ960088A patent/DZ2044A1/fr active
- 1996-06-05 YU YU34696A patent/YU49346B/sh unknown
- 1996-06-05 KR KR1019960020169A patent/KR100191972B1/ko not_active Expired - Fee Related
- 1996-06-05 BG BG100640A patent/BG62568B1/bg unknown
- 1996-06-05 SG SG1996009983A patent/SG54341A1/en unknown
- 1996-06-05 MA MA24263A patent/MA23893A1/fr unknown
- 1996-06-05 NO NO962320A patent/NO306256B1/no unknown
- 1996-06-05 RU RU96111027/04A patent/RU2161158C2/ru not_active IP Right Cessation
- 1996-06-05 CZ CZ19961626A patent/CZ287251B6/cs not_active IP Right Cessation
- 1996-06-05 NZ NZ286734A patent/NZ286734A/en unknown
- 1996-06-05 MY MYPI96002201A patent/MY116527A/en unknown
- 1996-06-06 TR TR96/00482A patent/TR199600482A1/xx unknown
- 1996-06-06 SI SI9600186A patent/SI9600186A/sl not_active IP Right Cessation
- 1996-06-06 OA OA60834A patent/OA10458A/en unknown
- 1996-06-06 RO RO96-01157A patent/RO115881B1/ro unknown
- 1996-06-06 CN CN96107630A patent/CN1061044C/zh not_active Expired - Fee Related
- 1996-06-06 CO CO96029521A patent/CO4700460A1/es unknown
- 1996-06-06 HR HR960268A patent/HRP960268B1/xx not_active IP Right Cessation
1997
- 1997-12-05 FI FI974434A patent/FI114097B/fi active
1998
- 1998-10-24 KR KR1019980044720A patent/KR100225719B1/ko not_active Expired - Fee Related

Also Published As

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
IS1913B (is)	2004-02-03
FI114097B (fi)	2004-08-13
IL118485A (en)	2000-02-17
DE69525978T2 (de)	2002-12-19
EP0837860B1 (en)	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 (en)	1998-04-29
DK0837860T3 (da)	2002-05-27
AP9600806A0 (en)	1996-07-31
DE69525978D1 (de)	2002-04-25
WO1996039408A1 (en)	1996-12-12
AP609A (en)	1997-09-03
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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