OA10985A - Indazole derivatives and their use as inhibitors of phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) - Google Patents

Indazole derivatives and their use as inhibitors of phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) Download PDF

Info

Publication number: OA10985A
Authority: OA; OAPI
Prior art keywords: compound; alkyl; mmol; add; equiv
Prior art date: 1996-09-04

Application number

OA9900046A

Other languages

English (en)

Inventor

Anthony Marfat

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.)

1996-09-04

Filing date

1999-03-01

Publication date

2001-11-01

1999-03-01 Application filed by Pfizer filed Critical Pfizer

2001-11-01 Publication of OA10985A publication Critical patent/OA10985A/en

Links

108060008682 Tumor Necrosis Factor Proteins 0.000 title claims abstract description 21
102000003390 tumor necrosis factor Human genes 0.000 title claims abstract description 21
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 14
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 14
238000004519 manufacturing process Methods 0.000 title claims abstract description 11
239000003112 inhibitor Substances 0.000 title description 3
125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 215
238000000034 method Methods 0.000 claims abstract description 68
241000124008 Mammalia Species 0.000 claims abstract description 10
230000005764 inhibitory process Effects 0.000 claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
239000002253 acid Substances 0.000 claims description 51
229910052799 carbon Inorganic materials 0.000 claims description 51
125000000217 alkyl group Chemical group 0.000 claims description 49
-1 pyrimidinyi Chemical group 0.000 claims description 37
125000005843 halogen group Chemical group 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 21
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 17
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
201000010099 disease Diseases 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000003342 alkenyl group Chemical group 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 8
206010040070 Septic Shock Diseases 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
206010040047 Sepsis Diseases 0.000 claims description 6
150000001408 amides Chemical class 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
208000015181 infectious disease Diseases 0.000 claims description 6
230000001684 chronic effect Effects 0.000 claims description 5
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
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208000006673 asthma Diseases 0.000 claims description 4
206010006451 bronchitis Diseases 0.000 claims description 4
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
206010006895 Cachexia Diseases 0.000 claims description 3
208000011231 Crohn disease Diseases 0.000 claims description 3
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 3
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
201000004810 Vascular dementia Diseases 0.000 claims description 3
230000002917 arthritic effect Effects 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
230000001363 autoimmune Effects 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
208000018937 joint inflammation Diseases 0.000 claims description 3
201000004792 malaria Diseases 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
231100000241 scar Toxicity 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
230000009772 tissue formation Effects 0.000 claims description 3
206010012289 Dementia Diseases 0.000 claims description 2
206010037549 Purpura Diseases 0.000 claims description 2
241001672981 Purpura Species 0.000 claims description 2
208000025865 Ulcer Diseases 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
210000000988 bone and bone Anatomy 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
201000008383 nephritis Diseases 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 7
206010037660 Pyrexia Diseases 0.000 claims 2
125000002947 alkylene group Chemical group 0.000 claims 2
206010025135 lupus erythematosus Diseases 0.000 claims 2
230000009885 systemic effect Effects 0.000 claims 2
206010001513 AIDS related complex Diseases 0.000 claims 1
201000005569 Gout Diseases 0.000 claims 1
206010018634 Gouty Arthritis Diseases 0.000 claims 1
102100039334 HAUS augmin-like complex subunit 1 Human genes 0.000 claims 1
101001035831 Homo sapiens HAUS augmin-like complex subunit 1 Proteins 0.000 claims 1
101000702560 Homo sapiens Probable global transcription activator SNF2L1 Proteins 0.000 claims 1
101000702544 Homo sapiens SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 Proteins 0.000 claims 1
102000044753 ISWI Human genes 0.000 claims 1
208000027418 Wounds and injury Diseases 0.000 claims 1
125000004450 alkenylene group Chemical group 0.000 claims 1
125000001589 carboacyl group Chemical group 0.000 claims 1
230000006378 damage Effects 0.000 claims 1
208000024908 graft versus host disease Diseases 0.000 claims 1
208000014674 injury Diseases 0.000 claims 1
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206010039073 rheumatoid arthritis Diseases 0.000 claims 1
125000003107 substituted aryl group Chemical group 0.000 claims 1
125000001113 thiadiazolyl group Chemical group 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 6
238000002360 preparation method Methods 0.000 abstract description 3
239000000543 intermediate Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 107
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
239000000243 solution Substances 0.000 description 57
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235000019439 ethyl acetate Nutrition 0.000 description 36
239000002585 base Substances 0.000 description 35
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 32
238000005481 NMR spectroscopy Methods 0.000 description 32
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
239000007858 starting material Substances 0.000 description 27
238000003756 stirring Methods 0.000 description 27
238000001035 drying Methods 0.000 description 26
239000007787 solid Substances 0.000 description 24
239000000499 gel Substances 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
238000001914 filtration Methods 0.000 description 19
150000002148 esters Chemical class 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
238000010992 reflux Methods 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
239000000706 filtrate Substances 0.000 description 15
239000000843 powder Substances 0.000 description 14
239000000284 extract Substances 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
229910001868 water Inorganic materials 0.000 description 12
239000013078 crystal Substances 0.000 description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
238000010189 synthetic method Methods 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical class C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 7
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
239000004533 oil dispersion Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000007832 Na2SO4 Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000006260 foam Substances 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000010410 layer Substances 0.000 description 5
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
239000000047 product Substances 0.000 description 5
125000004076 pyridyl group Chemical group 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
235000017550 sodium carbonate Nutrition 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
208000030507 AIDS Diseases 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
239000000010 aprotic solvent Substances 0.000 description 4
238000003556 assay Methods 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
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SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
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235000010288 sodium nitrite Nutrition 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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239000012954 diazonium Substances 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 3
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
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KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 description 2
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206010020751 Hypersensitivity Diseases 0.000 description 2
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OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
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239000012280 lithium aluminium hydride Substances 0.000 description 2
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238000006396 nitration reaction Methods 0.000 description 2
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NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
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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 1
FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
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Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
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OA9900046A 1996-09-04 1999-03-01 Indazole derivatives and their use as inhibitors of phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) OA10985A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US2544696P	1996-09-04	1996-09-04

Publications (1)

Publication Number	Publication Date
OA10985A true OA10985A (en)	2001-11-01

Family

ID=21826124

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900046A OA10985A (en)	1996-09-04	1999-03-01	Indazole derivatives and their use as inhibitors of phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf)

Country Status (35)

Country	Link
US (1)	US6262040B1 (id)
EP (1)	EP0931075A1 (id)
JP (2)	JP3554337B2 (id)
KR (1)	KR100338610B1 (id)
CN (1)	CN1234031A (id)
AP (1)	AP795A (id)
AR (1)	AR008162A1 (id)
AU (1)	AU724549B2 (id)
BG (1)	BG64447B1 (id)
BR (1)	BR9712005A (id)
CA (1)	CA2264798A1 (id)
CO (1)	CO4600636A1 (id)
DZ (1)	DZ2303A1 (id)
EA (1)	EA002113B1 (id)
GT (1)	GT199700102A (id)
HN (1)	HN1997000126A (id)
HR (1)	HRP970478B1 (id)
HU (1)	HUP9903248A3 (id)
ID (1)	ID18157A (id)
IL (1)	IL128642A0 (id)
IS (1)	IS4979A (id)
MA (1)	MA26439A1 (id)
NO (1)	NO991048L (id)
NZ (1)	NZ334213A (id)
OA (1)	OA10985A (id)
PA (1)	PA8437301A1 (id)
PE (1)	PE107998A1 (id)
PL (1)	PL332187A1 (id)
SK (1)	SK27299A3 (id)
TN (1)	TNSN97148A1 (id)
TR (1)	TR199900481T2 (id)
TW (1)	TW402595B (id)
WO (1)	WO1998009961A1 (id)
YU (1)	YU11299A (id)
ZA (1)	ZA977903B (id)

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1997
- 1997-08-25 KR KR1019997001779A patent/KR100338610B1/ko not_active Expired - Fee Related
- 1997-08-25 TR TR1999/00481T patent/TR199900481T2/xx unknown
- 1997-08-25 SK SK272-99A patent/SK27299A3/sk unknown
- 1997-08-25 IL IL12864297A patent/IL128642A0/xx unknown
- 1997-08-25 CN CN97199022A patent/CN1234031A/zh active Pending
- 1997-08-25 CA CA002264798A patent/CA2264798A1/en not_active Abandoned
- 1997-08-25 EP EP97934678A patent/EP0931075A1/en not_active Withdrawn
- 1997-08-25 WO PCT/IB1997/001023 patent/WO1998009961A1/en not_active Ceased
- 1997-08-25 HU HU9903248A patent/HUP9903248A3/hu unknown
- 1997-08-25 US US09/254,346 patent/US6262040B1/en not_active Expired - Fee Related
- 1997-08-25 PL PL97332187A patent/PL332187A1/xx unknown
- 1997-08-25 NZ NZ334213A patent/NZ334213A/xx unknown
- 1997-08-25 YU YU11299A patent/YU11299A/sh unknown
- 1997-08-25 AU AU37813/97A patent/AU724549B2/en not_active Ceased
- 1997-08-25 EA EA199900183A patent/EA002113B1/ru not_active IP Right Cessation
- 1997-08-25 BR BR9712005A patent/BR9712005A/pt not_active Application Discontinuation
- 1997-08-25 JP JP51240998A patent/JP3554337B2/ja not_active Expired - Fee Related
- 1997-08-29 HN HN1997000126A patent/HN1997000126A/es unknown
- 1997-09-01 TW TW086112518A patent/TW402595B/zh not_active IP Right Cessation
- 1997-09-02 PE PE1997000777A patent/PE107998A1/es not_active Application Discontinuation
- 1997-09-02 AR ARP970104001A patent/AR008162A1/es unknown
- 1997-09-03 MA MA24783A patent/MA26439A1/fr unknown
- 1997-09-03 DZ DZ970153A patent/DZ2303A1/xx active
- 1997-09-03 ID IDP973065A patent/ID18157A/id unknown
- 1997-09-03 PA PA19978437301A patent/PA8437301A1/es unknown
- 1997-09-03 GT GT199700102A patent/GT199700102A/es unknown
- 1997-09-03 TN TNTNSN97148A patent/TNSN97148A1/fr unknown
- 1997-09-03 ZA ZA977903A patent/ZA977903B/xx unknown
- 1997-09-04 AP APAP/P/1997/001080A patent/AP795A/en active
- 1997-09-04 CO CO97051473A patent/CO4600636A1/es unknown
- 1997-09-04 HR HR970478A patent/HRP970478B1/xx not_active IP Right Cessation
1999
- 1999-02-16 IS IS4979A patent/IS4979A/is unknown
- 1999-02-22 BG BG103195A patent/BG64447B1/bg unknown
- 1999-03-01 OA OA9900046A patent/OA10985A/en unknown
- 1999-03-03 NO NO991048A patent/NO991048L/no unknown
2004
- 2004-03-23 JP JP2004083812A patent/JP2004217668A/ja active Pending

Also Published As

Publication number	Publication date
AP795A (en)	1999-12-28
CO4600636A1 (es)	1998-05-08
AU724549B2 (en)	2000-09-28
BR9712005A (pt)	1999-08-24
NZ334213A (en)	2000-08-25
SK27299A3 (en)	2000-10-09
CN1234031A (zh)	1999-11-03
JP2004217668A (ja)	2004-08-05
HUP9903248A3 (en)	2000-07-28
NO991048L (no)	1999-05-03
WO1998009961A1 (en)	1998-03-12
ID18157A (id)	1998-03-05
AU3781397A (en)	1998-03-26
ZA977903B (en)	1999-03-03
IS4979A (is)	1999-02-16
EP0931075A1 (en)	1999-07-28
IL128642A0 (en)	2000-01-31
US6262040B1 (en)	2001-07-17
EA199900183A1 (ru)	1999-08-26
YU11299A (sh)	2001-07-10
HN1997000126A (es)	1997-12-26
PL332187A1 (en)	1999-08-30
KR100338610B1 (ko)	2002-05-27
NO991048D0 (no)	1999-03-03
PA8437301A1 (es)	1999-12-27
HRP970478A2 (en)	1998-08-31
AP9701080A0 (en)	1997-10-31
JP3554337B2 (ja)	2004-08-18
TNSN97148A1 (fr)	2005-03-15
MA26439A1 (fr)	2004-12-20
KR20000068421A (ko)	2000-11-25
BG103195A (en)	1999-09-30
EA002113B1 (ru)	2001-12-24
AR008162A1 (es)	1999-12-09
GT199700102A (es)	1999-02-25
DZ2303A1 (fr)	2002-12-28
HUP9903248A2 (hu)	2000-04-28
TR199900481T2 (xx)	1999-06-21
HRP970478B1 (en)	2002-10-31
CA2264798A1 (en)	1998-03-12
PE107998A1 (es)	1999-01-30
TW402595B (en)	2000-08-21
BG64447B1 (en)	2005-02-28
JP2000502724A (ja)	2000-03-07

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