SK27299A3 - 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: SK27299A3
Authority: SK; Slovakia
Prior art keywords: alkyl; indazole; ethyl; formula; phenyl
Prior art date: 1996-09-04

Application number

SK272-99A

Other languages

English (en)

Slovak (sk)

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

1997-08-25

Publication date

2000-10-09

1997-08-25 Application filed by Pfizer filed Critical Pfizer

2000-10-09 Publication of SK27299A3 publication Critical patent/SK27299A3/sk

Links

102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 20
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 20
108060008682 Tumor Necrosis Factor Proteins 0.000 title claims abstract description 17
102000003390 tumor necrosis factor Human genes 0.000 title claims abstract description 17
238000004519 manufacturing process Methods 0.000 title claims abstract description 7
125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 3
239000003112 inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 218
150000003839 salts Chemical class 0.000 claims abstract description 42
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
241000124008 Mammalia Species 0.000 claims abstract description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 83
229910052739 hydrogen Inorganic materials 0.000 claims description 62
-1 phenyl radicals Chemical class 0.000 claims description 61
125000003118 aryl group Chemical group 0.000 claims description 60
239000001257 hydrogen Substances 0.000 claims description 59
125000004432 carbon atom Chemical group C* 0.000 claims description 53
125000000217 alkyl group Chemical group 0.000 claims description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 31
150000002367 halogens Chemical group 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
150000002431 hydrogen Chemical class 0.000 claims description 21
125000004076 pyridyl group Chemical group 0.000 claims description 20
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000004093 cyano group Chemical group *C#N 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
229910005965 SO 2 Inorganic materials 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
125000000623 heterocyclic group Chemical group 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
206010040070 Septic Shock Diseases 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
208000030507 AIDS Diseases 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
150000002473 indoazoles Chemical class 0.000 claims description 8
150000003254 radicals Chemical group 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
230000001684 chronic effect Effects 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
125000003831 tetrazolyl group Chemical group 0.000 claims description 7
125000000335 thiazolyl group Chemical group 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000001425 triazolyl group Chemical group 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
125000006545 (C1-C9) alkyl group Chemical group 0.000 claims description 6
206010001513 AIDS related complex Diseases 0.000 claims description 6
206010006895 Cachexia Diseases 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
208000015181 infectious disease Diseases 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
101100495912 Arabidopsis thaliana CHR12 gene Proteins 0.000 claims description 5
208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 5
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125000003342 alkenyl group Chemical group 0.000 claims description 5
201000008383 nephritis Diseases 0.000 claims description 5
125000002971 oxazolyl group Chemical group 0.000 claims description 5
125000003226 pyrazolyl group Chemical group 0.000 claims description 5
125000002098 pyridazinyl group Chemical group 0.000 claims description 5
125000005493 quinolyl group Chemical group 0.000 claims description 5
230000010410 reperfusion Effects 0.000 claims description 5
230000036303 septic shock Effects 0.000 claims description 5
RGJGUBIRNFMTKP-UHFFFAOYSA-N 1-cyclopentyl-n-(3,5-dichloropyridin-4-yl)-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CN=CC=3Cl)Cl)=CC=C2C(CC)=NN1C1CCCC1 RGJGUBIRNFMTKP-UHFFFAOYSA-N 0.000 claims description 4
VQXPUWAIJHXSON-UHFFFAOYSA-N 2-amino-N-phenylmethoxypropanamide Chemical compound CC(N)C(=O)NOCC1=CC=CC=C1 VQXPUWAIJHXSON-UHFFFAOYSA-N 0.000 claims description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
206010018364 Glomerulonephritis Diseases 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
206010039085 Rhinitis allergic Diseases 0.000 claims description 4
102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims description 4
201000010105 allergic rhinitis Diseases 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
206010006451 bronchitis Diseases 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
201000010064 diabetes insipidus Diseases 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 3
QMNCCUDDXOUFBD-UHFFFAOYSA-N 1-cyclobutyl-n-(3,5-dichloropyridin-4-yl)-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CN=CC=3Cl)Cl)=CC=C2C(CC)=NN1C1CCC1 QMNCCUDDXOUFBD-UHFFFAOYSA-N 0.000 claims description 3
UTNQGCAXMWZVHF-UHFFFAOYSA-N 1-cyclohexyl-n-(3,5-dichloropyridin-4-yl)-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CN=CC=3Cl)Cl)=CC=C2C(CC)=NN1C1CCCCC1 UTNQGCAXMWZVHF-UHFFFAOYSA-N 0.000 claims description 3
CDNUDVJNYLASKG-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-6-phenylindazole Chemical compound C12=CC(C=3C=CC=CC=3)=CC=C2C(CC)=NN1C1CCCC1 CDNUDVJNYLASKG-UHFFFAOYSA-N 0.000 claims description 3
AIRORULAFCDFBP-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-n-(2-methylsulfanylethyl)indazole-6-carboxamide Chemical compound C12=CC(C(=O)NCCSC)=CC=C2C(CC)=NN1C1CCCC1 AIRORULAFCDFBP-UHFFFAOYSA-N 0.000 claims description 3
USBYMDFDMFTLDN-LLVKDONJSA-N 1-cyclopentyl-3-ethyl-n-[(2r)-1-(hydroxyamino)-1-oxopropan-2-yl]indazole-6-carboxamide Chemical compound C12=CC(C(=O)N[C@H](C)C(=O)NO)=CC=C2C(CC)=NN1C1CCCC1 USBYMDFDMFTLDN-LLVKDONJSA-N 0.000 claims description 3
BOZIUZKHHXMJPH-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-n-[2-(hydroxyamino)-2-oxoethyl]-n-methylindazole-6-carboxamide Chemical compound C12=CC(C(=O)N(C)CC(=O)NO)=CC=C2C(CC)=NN1C1CCCC1 BOZIUZKHHXMJPH-UHFFFAOYSA-N 0.000 claims description 3
QCRZIHACFORZTO-UHFFFAOYSA-N 1-cyclopentyl-n-(2,6-dichlorophenyl)-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CC=CC=3Cl)Cl)=CC=C2C(CC)=NN1C1CCCC1 QCRZIHACFORZTO-UHFFFAOYSA-N 0.000 claims description 3
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
208000006386 Bone Resorption Diseases 0.000 claims description 3
206010063094 Cerebral malaria Diseases 0.000 claims description 3
206010009900 Colitis ulcerative Diseases 0.000 claims description 3
201000004624 Dermatitis Diseases 0.000 claims description 3
206010014824 Endotoxic shock Diseases 0.000 claims description 3
201000005569 Gout Diseases 0.000 claims description 3
206010018634 Gouty Arthritis Diseases 0.000 claims description 3
206010019617 Henoch-Schonlein purpura Diseases 0.000 claims description 3
208000031814 IgA Vasculitis Diseases 0.000 claims description 3
206010061218 Inflammation Diseases 0.000 claims description 3
208000000112 Myalgia Diseases 0.000 claims description 3
206010037660 Pyrexia 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
201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
230000002917 arthritic effect Effects 0.000 claims description 3
230000024279 bone resorption Effects 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
208000015446 immunoglobulin a vasculitis Diseases 0.000 claims description 3
208000027866 inflammatory disease Diseases 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
208000011379 keloid formation Diseases 0.000 claims description 3
208000032839 leukemia Diseases 0.000 claims description 3
230000005741 malignant process Effects 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
ANGKMQZJDSXIBF-UHFFFAOYSA-N n-(3,5-dichloropyridin-4-yl)-3-ethyl-1-(4-fluorophenyl)indazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CN=CC=3Cl)Cl)=CC=C2C(CC)=NN1C1=CC=C(F)C=C1 ANGKMQZJDSXIBF-UHFFFAOYSA-N 0.000 claims description 3
ZNXUMZCAXJXCGI-UHFFFAOYSA-N n-(3,5-dichloropyridin-4-yl)-3-ethyl-1-propan-2-ylindazole-6-carboxamide Chemical compound C=1C=C2C(CC)=NN(C(C)C)C2=CC=1C(=O)NC1=C(Cl)C=NC=C1Cl ZNXUMZCAXJXCGI-UHFFFAOYSA-N 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 2
PXBZAGRZLQQNGA-UHFFFAOYSA-N 1-(cyclopropylmethyl)-n-(3,5-dichloropyridin-4-yl)-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C(=CN=CC=3Cl)Cl)=CC=C2C(CC)=NN1CC1CC1 PXBZAGRZLQQNGA-UHFFFAOYSA-N 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
208000011231 Crohn disease Diseases 0.000 claims description 2
206010035664 Pneumonia Diseases 0.000 claims description 2
201000010001 Silicosis Diseases 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000004450 alkenylene group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000005956 isoquinolyl group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
125000005936 piperidyl group Chemical group 0.000 claims description 2
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000003107 substituted aryl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
201000005008 bacterial sepsis Diseases 0.000 claims 2
231100000241 scar Toxicity 0.000 claims 2
201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
230000009772 tissue formation Effects 0.000 claims 2
HTMGQIXFZMZZKD-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline Chemical compound N1=CC=C2CCCCC2=C1 HTMGQIXFZMZZKD-UHFFFAOYSA-N 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
230000002685 pulmonary effect Effects 0.000 claims 1
238000000034 method Methods 0.000 abstract description 87
238000002360 preparation method Methods 0.000 abstract description 19
230000005764 inhibitory process Effects 0.000 abstract description 7
239000000543 intermediate Substances 0.000 abstract description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 210
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
239000000243 solution Substances 0.000 description 81
239000000203 mixture Substances 0.000 description 79
239000011541 reaction mixture Substances 0.000 description 75
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
239000007787 solid Substances 0.000 description 65
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
238000004458 analytical method Methods 0.000 description 45
239000007858 starting material Substances 0.000 description 41
238000005481 NMR spectroscopy Methods 0.000 description 38
239000000706 filtrate Substances 0.000 description 37
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
239000002585 base Substances 0.000 description 35
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
239000003921 oil Substances 0.000 description 32
235000019198 oils Nutrition 0.000 description 32
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
239000000460 chlorine Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000000741 silica gel Substances 0.000 description 27
229910002027 silica gel Inorganic materials 0.000 description 27
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
229910052938 sodium sulfate Inorganic materials 0.000 description 26
235000011152 sodium sulphate Nutrition 0.000 description 26
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
239000012267 brine Substances 0.000 description 19
239000003480 eluent Substances 0.000 description 19
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
229910052801 chlorine Inorganic materials 0.000 description 18
239000000843 powder Substances 0.000 description 18
238000010992 reflux Methods 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000000284 extract Substances 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
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239000002253 acid Substances 0.000 description 14
QUKDARNAEGBEOY-UHFFFAOYSA-N 1-cyclopentyl-3-ethylindazole-6-carboxylic acid Chemical compound C12=CC(C(O)=O)=CC=C2C(CC)=NN1C1CCCC1 QUKDARNAEGBEOY-UHFFFAOYSA-N 0.000 description 13
238000003756 stirring Methods 0.000 description 13
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230000008018 melting Effects 0.000 description 10
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LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
239000007788 liquid Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
CSQGAIUWKCKTHI-UHFFFAOYSA-N methyl 3-ethyl-2h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(CC)=NNC2=C1 CSQGAIUWKCKTHI-UHFFFAOYSA-N 0.000 description 8
239000004533 oil dispersion Substances 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
229920006395 saturated elastomer Polymers 0.000 description 8
NWNSMAXWOXQTNY-UHFFFAOYSA-N 3-ethyl-2h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(CC)=NNC2=C1 NWNSMAXWOXQTNY-UHFFFAOYSA-N 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
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BZXZYBJLFJKTGY-UHFFFAOYSA-N methyl 3-ethyl-1-propan-2-ylindazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(CC)=NN(C(C)C)C2=C1 BZXZYBJLFJKTGY-UHFFFAOYSA-N 0.000 description 1
ISAARQWRSVBGIR-UHFFFAOYSA-N methyl 4-[(1-cyclopentyl-3-ethylindazole-6-carbonyl)amino]benzoate Chemical compound C12=CC(C(=O)NC=3C=CC(=CC=3)C(=O)OC)=CC=C2C(CC)=NN1C1CCCC1 ISAARQWRSVBGIR-UHFFFAOYSA-N 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
210000005087 mononuclear cell Anatomy 0.000 description 1
UQITYHFQHOJCPG-UHFFFAOYSA-N n-(3-chlorophenyl)-1-cyclopentyl-3-ethylindazole-6-carboxamide Chemical compound C12=CC(C(=O)NC=3C=C(Cl)C=CC=3)=CC=C2C(CC)=NN1C1CCCC1 UQITYHFQHOJCPG-UHFFFAOYSA-N 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
229960000988 nystatin Drugs 0.000 description 1
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
229950005741 rolipram Drugs 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
238000003118 sandwich ELISA Methods 0.000 description 1
230000036573 scar formation Effects 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000012414 tert-butyl nitrite Substances 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
CVNKFOIOZXAFBO-UHFFFAOYSA-J tin(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Sn+4] CVNKFOIOZXAFBO-UHFFFAOYSA-J 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000002747 voluntary effect Effects 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/06—Antipsoriatics
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Diabetes (AREA)
Immunology (AREA)
Hematology (AREA)
Dermatology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Virology (AREA)
Obesity (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Oncology (AREA)
Endocrinology (AREA)
Biomedical Technology (AREA)
Molecular Biology (AREA)
Neurosurgery (AREA)
Orthopedic Medicine & Surgery (AREA)
Emergency Medicine (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK272-99A 1996-09-04 1997-08-25 Indazole derivatives and their use as inhibitors of phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) SK27299A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2544696P	1996-09-04	1996-09-04
PCT/IB1997/001023 WO1998009961A1 (fr)	1996-09-04	1997-08-25	Derives d'indazole et leur utilisation en tant qu'inhibiteurs de phosphodiesterase (pde) de type iv et de la production du facteur de necrose des tumeurs (tnf)

Publications (1)

Publication Number	Publication Date
SK27299A3 true SK27299A3 (en)	2000-10-09

Family

ID=21826124

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK272-99A SK27299A3 (en)	1996-09-04	1997-08-25	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 (fr)
EP (1)	EP0931075A1 (fr)
JP (2)	JP3554337B2 (fr)
KR (1)	KR100338610B1 (fr)
CN (1)	CN1234031A (fr)
AP (1)	AP795A (fr)
AR (1)	AR008162A1 (fr)
AU (1)	AU724549B2 (fr)
BG (1)	BG64447B1 (fr)
BR (1)	BR9712005A (fr)
CA (1)	CA2264798A1 (fr)
CO (1)	CO4600636A1 (fr)
DZ (1)	DZ2303A1 (fr)
EA (1)	EA002113B1 (fr)
GT (1)	GT199700102A (fr)
HN (1)	HN1997000126A (fr)
HR (1)	HRP970478B1 (fr)
HU (1)	HUP9903248A3 (fr)
ID (1)	ID18157A (fr)
IL (1)	IL128642A0 (fr)
IS (1)	IS4979A (fr)
MA (1)	MA26439A1 (fr)
NO (1)	NO991048L (fr)
NZ (1)	NZ334213A (fr)
OA (1)	OA10985A (fr)
PA (1)	PA8437301A1 (fr)
PE (1)	PE107998A1 (fr)
PL (1)	PL332187A1 (fr)
SK (1)	SK27299A3 (fr)
TN (1)	TNSN97148A1 (fr)
TR (1)	TR199900481T2 (fr)
TW (1)	TW402595B (fr)
WO (1)	WO1998009961A1 (fr)
YU (1)	YU11299A (fr)
ZA (1)	ZA977903B (fr)

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4373497B2 (ja)	1996-06-19	2009-11-25	ローン−プーラン・ロレ・リミテツド	置換されたアザビシクロ化合物、ならびにｔｎｆおよびサイクリックａｍｐホスホジエステラーゼ産生の阻害剤としてのそれらの使用
TR200001256T2 (tr) *	1997-11-04	2000-11-21	Pfizer Products Inc.	Terapötik olarak aktif bileşimler.
PL340753A1 (en) *	1997-11-04	2001-02-26	Pfizer Prod Inc	Substitution of indazolic bioisoster for cathechol in therapeutically active compounds
JP2000198734A (ja) *	1998-12-30	2000-07-18	Pfizer Inc	胃運動性減弱および関連疾患の治療のための運動性増強薬
US6191300B1 (en)	1999-04-16	2001-02-20	Eastman Chemical Company	Process for the preparation of cyclopropylacetonitrile
UA71971C2 (en)	1999-06-04	2005-01-17	Agoron Pharmaceuticals Inc	Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases
US7141581B2 (en)	1999-07-02	2006-11-28	Agouron Pharmaceuticals, Inc.	Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
PE20010306A1 (es) *	1999-07-02	2001-03-29	Agouron Pharma	Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa
TWI262914B (en)	1999-07-02	2006-10-01	Agouron Pharma	Compounds and pharmaceutical compositions for inhibiting protein kinases
CA2715683A1 (fr)	1999-08-21	2001-03-01	Nycomed Gmbh	Combinaison synergiste
WO2001047915A1 (fr) *	1999-12-23	2001-07-05	Icos Corporation	Inhibiteurs de phosphodiesterase specifique d'amp cyclique
US6362213B1 (en)	1999-12-23	2002-03-26	Icos Corporation	Cyclic AMP-specific phosphodiesterase inhibitors
US7217722B2 (en)	2000-02-01	2007-05-15	Kirin Beer Kabushiki Kaisha	Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same
BR0110302A (pt)	2000-04-18	2003-01-14	Agouron Pharma	Compostos de pirazol para inibição de proteìnas cinase, sal e pró-droga farmaceuticamente aceitável, metabólito farmaceuticamente ativo ou sal farmaceuticamente aceitável de metabólito, composição farmacêutica, método de tratamento de condição doentia em mamìferos mediada pela atividade de proteìna cinase, método de modulação ou inibição da atividade de um receptor de proteìna cinase
US7153871B2 (en) *	2001-01-22	2006-12-26	Memory Pharmaceuticals Corporation	Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs
US7205320B2 (en)	2001-01-22	2007-04-17	Memory Pharmaceuticals Corp.	Phosphodiesterase 4 inhibitors
WO2002094320A1 (fr) *	2001-05-23	2002-11-28	Tanabe Seiyaku Co., Ltd.	Compositions therapeutiques permettant de reparer la chondropathie
WO2002094321A1 (fr) *	2001-05-23	2002-11-28	Tanabe Seiyaku Co., Ltd.	Compositions favorisant la guérison d'une fracture osseuse
TWI221838B (en)	2001-08-09	2004-10-11	Tanabe Seiyaku Co	Pyrazinoisoquinoline compound or naphthalene compound
PE20030701A1 (es)	2001-12-20	2003-08-21	Schering Corp	Compuestos para el tratamiento de trastornos inflamatorios
MY140561A (en)	2002-02-20	2009-12-31	Nycomed Gmbh	Dosage form containing pde 4 inhibitor as active ingredient
WO2003087333A2 (fr) *	2002-04-12	2003-10-23	Celgene Corporation	Modulation de differenciation de cellule souche et de cellule progenitrice, analyses et utilisations associees
WO2003102151A2 (fr) *	2002-05-30	2003-12-11	Celgene Corporation	Procedes d'utilisation d'inhibiteurs de jnk ou de mkk en vue de moduler la differenciation cellulaire et de traiter des troubles myeloproliferatifs et des syndromes myelodysplasiques
RU2354648C2 (ru) *	2002-07-19	2009-05-10	Мемори Фармасьютиклз Корпорейшн	Соединения 6-амино-1н-индазола и 4-аминобензофурана в качестве ингибиторов фосфодиэстеразы 4
CA2492907A1 (fr)	2002-07-19	2004-01-29	Memory Pharmaceuticals Corporation	Inhibiteurs de phosphodiesterase 4 comprenant des analogues de diphenylamine et d'aniline n-substitues
EP1569908B1 (fr) *	2002-11-19	2010-09-15	Memory Pharmaceuticals Corporation	Pyridines N-Oxyde comme iNHIBITEURS DE LA PHOSPHODIESTERASE 4
US7109337B2 (en)	2002-12-20	2006-09-19	Pfizer Inc	Pyrimidine derivatives for the treatment of abnormal cell growth
EA013248B1 (ru)	2002-12-20	2010-04-30	Пфайзер Продактс Инк.	Производные пиримидина для лечения патологического роста клеток
US7135575B2 (en)	2003-03-03	2006-11-14	Array Biopharma, Inc.	P38 inhibitors and methods of use thereof
EA200501548A1 (ru)	2003-04-01	2006-02-24	Апплайд Резеч Системз Арс Холдинг Н.В.	Ингибиторы фосфодиэстераз при бесплодии
US7297709B2 (en) *	2003-05-22	2007-11-20	Abbott Laboratories	Indazole, benzisoxazole, and benzisothiazole kinase inhibitors
US20090048255A1 (en) *	2003-07-21	2009-02-19	Schumacher Richard A	Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs
JP2005089457A (ja)	2003-09-03	2005-04-07	Yung Shin Pharmaceutical Industry Co Ltd	骨成長を促進するまたは骨吸収を阻害するための薬剤組成物
MY141255A (en) *	2003-12-11	2010-03-31	Memory Pharm Corp	Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs
JP2007523938A (ja)	2004-02-27	2007-08-23	エフ．ホフマン−ラ　ロシュ　アーゲー	ピラゾールの縮合誘導体
CN1922150A (zh)	2004-02-27	2007-02-28	霍夫曼-拉罗奇有限公司	吲唑衍生物以及含有它们的药物组合物
KR100844864B1 (ko)	2004-02-27	2008-07-09	에프. 호프만-라 로슈 아게	헤테로아릴-융합 피라졸로 유도체
MXPA06011658A (es)	2004-05-14	2006-12-14	Pfizer Prod Inc	Derivados de pirimidina para el tratamiento del crecimiento celular anormal.
WO2005111016A1 (fr)	2004-05-14	2005-11-24	Pfizer Products Inc.	Derives de pyrimidine pour le traitement d'une croissance cellulaire anormale
WO2005111022A1 (fr)	2004-05-14	2005-11-24	Pfizer Products Inc.	Derives pyrimidiques pour le traitement de la croissance de cellules anormales
JP2008505969A (ja) *	2004-07-12	2008-02-28	メルク　エンド　カムパニー　インコーポレーテッド	ヒストン脱アセチル化酵素の阻害剤
US7601847B2 (en)	2004-10-26	2009-10-13	Wyeth	Preparation and purification of 4-(indazol-3-yl)phenols
TW200621237A (en)	2004-11-01	2006-07-01	Wyeth Corp	[(1-h-indazol-3-yl)methyl]phenols and (hydroxyphenyl)(1h-indazol-3-yl)methanones
WO2006129158A2 (fr) *	2005-05-30	2006-12-07	Ranbaxy Laboratories Limited	Inhibiteurs de la phosphodiesterase de type iv
KR101011956B1 (ko)	2005-08-25	2011-01-31	에프. 호프만-라 로슈 아게	Ｐ３８ｍαｐ 키나아제 저해제 및 이의 사용 방법
EP1928866A1 (fr)	2005-09-05	2008-06-11	Ranbaxy Laboratories Limited	Indazoles substitues utilises en tant qu'inhibiteurs de phosphodiesterase de type-iv
US7915286B2 (en)	2005-09-16	2011-03-29	Ranbaxy Laboratories Limited	Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors
AU2007210073B2 (en)	2006-01-31	2011-10-06	Array Biopharma Inc.	Kinase inhibitors and methods of use thereof
US20100056791A1 (en) *	2006-09-01	2010-03-04	Yasushi Kohno	Pyrazolopyridine carboxamide derivative and phosphodiesterase (pde) inhibitor containing the same
EP2091329A4 (fr) *	2006-12-05	2011-02-23	Univ Nat Chiao Tung	Composés d'indazole
PT2124944E (pt)	2007-03-14	2012-05-17	Ranbaxy Lab Ltd	Derivados de pirazolo[3,4-b]piridina como inibidores de fosfodiesterase
WO2010003084A2 (fr) *	2008-07-02	2010-01-07	Memory Pharmaceuticals Corporation	Inhibiteurs de la phosphodiestérase 4
ES2660892T3 (es) *	2009-03-23	2018-03-26	Merck Sharp & Dohme Corp.	Antagonistas del receptor P2X3 para el tratamiento del dolor
JP2013525370A (ja) *	2010-04-22	2013-06-20	ヤンセンファーマシューティカエヌ．ベー．	ケトヘキソキナーゼ阻害剤として有用なインダゾール化合物
EP3323820B1 (fr)	2011-02-28	2023-05-10	Epizyme, Inc.	Composés hétéroaryles bicycliques substitués condensés en 6,5
WO2015166370A1 (fr)	2014-04-28	2015-11-05	Pfizer Inc.	Composés hétéroaromatiques et leur utilisation en tant que ligands de la dopamine d1
KR20190078646A (ko) *	2016-11-18	2019-07-04	머크 샤프 앤드 돔 코포레이션	디아실글리세리드 o-아실트랜스퍼라제 2의 억제제로서 유용한 인다졸 유도체
CN114450274A (zh)	2019-07-11	2022-05-06	伊斯凯普生物公司	作为lrrk2抑制剂的吲唑及氮杂吲唑
GB201910608D0 (en) *	2019-07-24	2019-09-04	Enterprise Therapeutics Ltd	Compounds
CN112694474B (zh) *	2019-10-23	2022-03-18	四川大学	吲唑类衍生物及其制备方法和用途
US20240279828A1 (en) *	2021-05-31	2024-08-22	Genscript Usa Inc.	Electrografted films for dna synthesis
TWI907890B (zh) *	2022-12-14	2025-12-11	國立成功大學	化合物及其合成方法與應用
CN116003325B (zh) *	2023-01-09	2025-04-25	南方医科大学	吲唑类化合物或其药学上可接受的盐及其制备方法和应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE531433A (fr) *	1953-06-17
US4665397A (en)	1983-11-01	1987-05-12	Universal Photonics, Inc.	Apparatus and method for a universal electronic locking system
GB8524157D0 (en) *	1984-10-19	1985-11-06	Ici America Inc	Heterocyclic amides
JPH061350B2 (ja) *	1985-07-26	1994-01-05	コニカ株式会社	ハロゲン化銀写真感光材料
JPS6250751A (ja) *	1985-08-29	1987-03-05	Konishiroku Photo Ind Co Ltd	ハロゲン化銀写真感光材料
GB8609175D0 (en) *	1986-04-15	1986-05-21	Ici America Inc	Heterocyclic carboxamides
EP0381422B1 (fr) *	1989-02-02	1996-10-23	Yamanouchi Pharmaceutical Co. Ltd.	Dérivés de tétrahydrobenzimidazole
ES2102367T3 (es)	1990-05-18	1997-08-01	Hoechst Ag	Amidas de acidos isoxazol-4-carboxilicos y amidas de acidos hidroxialquiliden-cianoaceticos, medicamentos que contienen estos compuestos y su utilizacion.
US5444038A (en) *	1992-03-09	1995-08-22	Zeneca Limited	Arylindazoles and their use as herbicides
AU695301B2 (en) *	1993-07-06	1998-08-13	Pfizer Inc.	Bicyclic tetrahydro pyrazolopyridines
GB9401460D0 (en) *	1994-01-26	1994-03-23	Rhone Poulenc Rorer Ltd	Compositions of matter
JPH09510191A (ja)	1994-02-17	1997-10-14	アメリカン・ホーム・プロダクツ・コーポレイション	ホスホジエステラーゼ阻害薬としての置換ビフェニル誘導体
WO1995027692A1 (fr)	1994-04-08	1995-10-19	Smithkline Beecham Corporation	Inhibiteurs du facteur de necrose tumorale a substitution biphenyle
JPH08143525A (ja) *	1994-11-21	1996-06-04	Banyu Pharmaceut Co Ltd	ヒドロキシ安息香酸アミド誘導体を有効成分とする骨疾患の予防・治療剤
EA002274B1 (ru) *	1996-06-25	2002-02-28	Пфайзер Инк.	Призводные замещенного индазола и их применение в качестве ингибиторов фосфодиэстеразы (фдэ) типа iv и фактора некроза опухоли (фно)
ATE211740T1 (de) *	1996-06-27	2002-01-15	Pfizer	Substituierte indazolderivate

1997
- 1997-08-25 PL PL97332187A patent/PL332187A1/xx unknown
- 1997-08-25 WO PCT/IB1997/001023 patent/WO1998009961A1/fr not_active Ceased
- 1997-08-25 BR BR9712005A patent/BR9712005A/pt not_active Application Discontinuation
- 1997-08-25 HU HU9903248A patent/HUP9903248A3/hu unknown
- 1997-08-25 JP JP51240998A patent/JP3554337B2/ja not_active Expired - Fee Related
- 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 TR TR1999/00481T patent/TR199900481T2/xx unknown
- 1997-08-25 NZ NZ334213A patent/NZ334213A/xx unknown
- 1997-08-25 KR KR1019997001779A patent/KR100338610B1/ko not_active Expired - Fee Related
- 1997-08-25 US US09/254,346 patent/US6262040B1/en not_active Expired - Fee Related
- 1997-08-25 CA CA002264798A patent/CA2264798A1/fr not_active Abandoned
- 1997-08-25 YU YU11299A patent/YU11299A/sh unknown
- 1997-08-25 CN CN97199022A patent/CN1234031A/zh active Pending
- 1997-08-25 SK SK272-99A patent/SK27299A3/sk unknown
- 1997-08-25 EP EP97934678A patent/EP0931075A1/fr not_active Withdrawn
- 1997-08-25 IL IL12864297A patent/IL128642A0/xx unknown
- 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 AR ARP970104001A patent/AR008162A1/es unknown
- 1997-09-02 PE PE1997000777A patent/PE107998A1/es not_active Application Discontinuation
- 1997-09-03 PA PA19978437301A patent/PA8437301A1/es unknown
- 1997-09-03 ZA ZA977903A patent/ZA977903B/xx unknown
- 1997-09-03 DZ DZ970153A patent/DZ2303A1/fr active
- 1997-09-03 GT GT199700102A patent/GT199700102A/es unknown
- 1997-09-03 TN TNTNSN97148A patent/TNSN97148A1/fr unknown
- 1997-09-03 MA MA24783A patent/MA26439A1/fr unknown
- 1997-09-03 ID IDP973065A patent/ID18157A/id unknown
- 1997-09-04 AP APAP/P/1997/001080A patent/AP795A/en active
- 1997-09-04 HR HR970478A patent/HRP970478B1/xx not_active IP Right Cessation
- 1997-09-04 CO CO97051473A patent/CO4600636A1/es unknown
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
ZA977903B (en)	1999-03-03
EA002113B1 (ru)	2001-12-24
OA10985A (en)	2001-11-01
HN1997000126A (es)	1997-12-26
JP2000502724A (ja)	2000-03-07
HRP970478A2 (en)	1998-08-31
AU3781397A (en)	1998-03-26
PE107998A1 (es)	1999-01-30
TW402595B (en)	2000-08-21
KR20000068421A (ko)	2000-11-25
AR008162A1 (es)	1999-12-09
MA26439A1 (fr)	2004-12-20
HUP9903248A2 (hu)	2000-04-28
AU724549B2 (en)	2000-09-28
NO991048L (no)	1999-05-03
AP795A (en)	1999-12-28
PA8437301A1 (es)	1999-12-27
US6262040B1 (en)	2001-07-17
DZ2303A1 (fr)	2002-12-28
GT199700102A (es)	1999-02-25
YU11299A (sh)	2001-07-10
BR9712005A (pt)	1999-08-24
BG64447B1 (en)	2005-02-28
IS4979A (is)	1999-02-16
TR199900481T2 (xx)	1999-06-21
HUP9903248A3 (en)	2000-07-28
NO991048D0 (no)	1999-03-03
HRP970478B1 (en)	2002-10-31
EP0931075A1 (fr)	1999-07-28
IL128642A0 (en)	2000-01-31
WO1998009961A1 (fr)	1998-03-12
BG103195A (en)	1999-09-30
ID18157A (id)	1998-03-05
JP2004217668A (ja)	2004-08-05
EA199900183A1 (ru)	1999-08-26
NZ334213A (en)	2000-08-25
PL332187A1 (en)	1999-08-30
JP3554337B2 (ja)	2004-08-18
AP9701080A0 (en)	1997-10-31
TNSN97148A1 (fr)	2005-03-15
CO4600636A1 (es)	1998-05-08
CN1234031A (zh)	1999-11-03
CA2264798A1 (fr)	1998-03-12
KR100338610B1 (ko)	2002-05-27

Publication	Publication Date	Title
US6262040B1 (en)	2001-07-17	Indazole derivatives and their use as inhibitors of phosphodiesterase (PDE) type IV and the production of tumor necrosis factor (TNF)
AP1025A (en)	2001-11-19	The invention relates to compounds of the formula
EP0672031B1 (fr)	2003-03-12	Diethers de pyrocatechine utilises comme inhibiteurs selectifs de la pde iv
US6127398A (en)	2000-10-03	Substituted indazole derivatives and related compounds
US5958953A (en)	1999-09-28	Substituted indazole derivatives
CZ71099A3 (cs)	2000-03-15	Deriváty indazolu, farmaceutické kompozice na jejich bázi, meziprodukty a způsob léčení chorob
US20140303186A1 (en)	2014-10-09	Nitrogen-containing fused ring compounds as crth2 antagonists