SK148298A3 - Substituted indazole derivatives and their use as inhibitors phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) - Google Patents
Substituted indazole derivatives and their use as inhibitors phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) Download PDFInfo
- Publication number
- SK148298A3 SK148298A3 SK1482-98A SK148298A SK148298A3 SK 148298 A3 SK148298 A3 SK 148298A3 SK 148298 A SK148298 A SK 148298A SK 148298 A3 SK148298 A3 SK 148298A3
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- SK
- Slovakia
- Prior art keywords
- alkyl
- formula
- carbon atoms
- ethyl
- alkenyl
- Prior art date
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- 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
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 16
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 9
- 239000003112 inhibitor Substances 0.000 title description 2
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 43
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 241000124008 Mammalia Species 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000004432 carbon atom Chemical group C* 0.000 claims description 52
- -1 C 2 -C 3 alkenyl Chemical group 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000001544 thienyl group Chemical group 0.000 claims description 24
- 150000002473 indoazoles Chemical class 0.000 claims description 19
- 150000003254 radicals Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 229910005965 SO 2 Inorganic materials 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 125000001425 triazolyl group Chemical group 0.000 claims description 13
- 206010040070 Septic Shock Diseases 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 208000030507 AIDS Diseases 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 206010001513 AIDS related complex Diseases 0.000 claims description 6
- 206010006895 Cachexia Diseases 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 206010040047 Sepsis Diseases 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 230000036303 septic shock Effects 0.000 claims description 5
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 claims description 4
- IXFMUXXUQOUUPE-UHFFFAOYSA-N 1-(1-cyclopentyl-3-ethylindazol-6-yl)-4-oxocyclohexane-1-carbonitrile Chemical compound C12=CC(C3(CCC(=O)CC3)C#N)=CC=C2C(CC)=NN1C1CCCC1 IXFMUXXUQOUUPE-UHFFFAOYSA-N 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 206010006451 bronchitis Diseases 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- UFEHHWAXLUKWBV-UHFFFAOYSA-N 1-(1-cyclohexyl-3-ethylindazol-6-yl)-4-oxocyclohexane-1-carbonitrile Chemical compound C12=CC(C3(CCC(=O)CC3)C#N)=CC=C2C(CC)=NN1C1CCCCC1 UFEHHWAXLUKWBV-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
- 206010014824 Endotoxic shock Diseases 0.000 claims description 3
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 3
- 201000005569 Gout 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
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 201000010001 Silicosis 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
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 230000024279 bone resorption Effects 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 230000005741 malignant process Effects 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 201000008383 nephritis Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000036573 scar formation Effects 0.000 claims description 3
- 230000009885 systemic effect Effects 0.000 claims description 3
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 2
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 claims description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
- BNSRVFGXRITOQK-UHFFFAOYSA-N 2-(1,2-dichloroethyl)-4-methyl-1,3-dioxolane Chemical compound CC1COC(C(Cl)CCl)O1 BNSRVFGXRITOQK-UHFFFAOYSA-N 0.000 claims description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000027950 fever generation Effects 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 230000010410 reperfusion Effects 0.000 claims 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 208000000112 Myalgia Diseases 0.000 claims 2
- 206010035664 Pneumonia Diseases 0.000 claims 2
- 201000005008 bacterial sepsis Diseases 0.000 claims 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 2
- 125000004450 alkenylene group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000004149 thio group Chemical group *S* 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 19
- 238000002360 preparation method Methods 0.000 abstract description 11
- 230000005764 inhibitory process Effects 0.000 abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000000203 mixture Substances 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 238000004458 analytical method Methods 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 16
- 239000003480 eluent Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- 229910052801 chlorine Inorganic materials 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 13
- 239000012267 brine Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- 238000010992 reflux Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000003880 polar aprotic solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
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- 210000004027 cell Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 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 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
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- 239000007858 starting material Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
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- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
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- 239000004533 oil dispersion Substances 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
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- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- ZOYIRSVTXOTVSM-UHFFFAOYSA-N dipentylborane Chemical compound CCCCCBCCCCC ZOYIRSVTXOTVSM-UHFFFAOYSA-N 0.000 description 1
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- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
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- VGGFOBULOWCQJG-UHFFFAOYSA-N methyl 5-cyano-5-(1-cyclohexyl-3-ethylindazol-6-yl)-2-oxocyclohexane-1-carboxylate Chemical compound C12=CC(C3(CC(C(=O)CC3)C(=O)OC)C#N)=CC=C2C(CC)=NN1C1CCCCC1 VGGFOBULOWCQJG-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-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
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
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- 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
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- 125000004043 oxo group Chemical group O=* 0.000 description 1
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- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- 125000006239 protecting group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 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
- 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
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- 238000013207 serial dilution Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
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- 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
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
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- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- WMXCDAVJEZZYLT-UHFFFAOYSA-N tert-butylthiol Chemical compound CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-M thien-2-ylacetate Chemical compound [O-]C(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-M 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- 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
- C07D409/08—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 linked by a carbon chain containing alicyclic rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1686196P | 1996-05-03 | 1996-05-03 | |
| PCT/IB1997/000323 WO1997042174A1 (en) | 1996-05-03 | 1997-04-01 | Substituted indazole derivatives and their use as inhibitors phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK148298A3 true SK148298A3 (en) | 2000-02-14 |
Family
ID=21779401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1482-98A SK148298A3 (en) | 1996-05-03 | 1997-04-01 | Substituted indazole derivatives and their use as inhibitors phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf) |
Country Status (41)
| Country | Link |
|---|---|
| US (2) | US6211222B1 (is) |
| EP (1) | EP0912521B1 (is) |
| JP (1) | JP3148254B2 (is) |
| KR (1) | KR100339935B1 (is) |
| CN (2) | CN1112359C (is) |
| AP (4) | AP2001002304A0 (is) |
| AR (1) | AR006906A1 (is) |
| AT (1) | ATE292626T1 (is) |
| AU (1) | AU725576B2 (is) |
| BG (1) | BG64211B1 (is) |
| BR (1) | BR9709051A (is) |
| CA (2) | CA2389918A1 (is) |
| CO (1) | CO4650038A1 (is) |
| CZ (1) | CZ292825B6 (is) |
| DE (1) | DE69732966T2 (is) |
| DZ (1) | DZ2217A1 (is) |
| EA (1) | EA002272B1 (is) |
| ES (1) | ES2238079T3 (is) |
| GT (1) | GT199700043A (is) |
| HN (1) | HN1997000046A (is) |
| HR (1) | HRP970227B1 (is) |
| HU (1) | HUP9902459A3 (is) |
| ID (1) | ID16856A (is) |
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| NO (1) | NO312959B1 (is) |
| NZ (1) | NZ332240A (is) |
| OA (1) | OA10904A (is) |
| PE (1) | PE64598A1 (is) |
| PL (1) | PL329836A1 (is) |
| SK (1) | SK148298A3 (is) |
| TN (1) | TNSN97070A1 (is) |
| TR (1) | TR199802202T2 (is) |
| TW (1) | TW449585B (is) |
| UA (1) | UA65536C2 (is) |
| UY (1) | UY24532A1 (is) |
| WO (1) | WO1997042174A1 (is) |
| YU (1) | YU16397A (is) |
| ZA (1) | ZA973804B (is) |
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| CA2258728C (en) | 1996-06-19 | 2011-09-27 | Rhone Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| PT983249E (pt) | 1997-05-08 | 2002-08-30 | Pfizer Prod Inc | Procesos e intermediarios para a preparacao de derivados de indazole substituidos |
| EA200000385A1 (ru) * | 1997-11-04 | 2000-10-30 | Пфайзер Продактс Инк. | Терапевтически активные соединения на основе индазольной биоизостерической замены катехина в ингибиторах фосфодиэстеразы типа vi (pde4) |
| EA200000488A1 (ru) * | 1997-11-04 | 2000-10-30 | Пфайзер Продактс Инк. | Замена катехина на биоизостеру индазола в терапевтически активных соединениях |
| IL126745A (en) | 1997-11-04 | 2003-09-17 | Pfizer Prod Inc | Methods of preparing 4-cyano-4- (substituted indazole) cyclohexanecarboxylic acids useful as pde4 inhibitors |
| IL132407A0 (en) | 1998-10-21 | 2001-03-19 | Pfizer Prod Inc | Method for treating congestive heart failure |
| 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 |
| US6303782B1 (en) * | 1999-04-20 | 2001-10-16 | Pfizer Inc | Process for preparing benzylnitriles |
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| US6362213B1 (en) | 1999-12-23 | 2002-03-26 | Icos Corporation | Cyclic AMP-specific phosphodiesterase inhibitors |
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| US7211594B2 (en) * | 2000-07-31 | 2007-05-01 | Signal Pharmaceuticals, Llc | Indazole compounds and compositions thereof as JNK inhibitors and for the treatment of diseases associated therewith |
| US6953774B2 (en) | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| WO2003051344A1 (en) | 2001-12-14 | 2003-06-26 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation_using a non-polypeptide camp level modulator |
| US20040034084A1 (en) * | 2002-05-24 | 2004-02-19 | Celgene Corporation | Methods for using JNK inhibitors for treating or preventing disease-related wasting |
| US7196082B2 (en) * | 2002-11-08 | 2007-03-27 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| US20050019366A1 (en) * | 2002-12-31 | 2005-01-27 | Zeldis Jerome B. | Drug-coated stents and methods of use therefor |
| DE10318610A1 (de) | 2003-04-24 | 2004-11-11 | Elbion Ag | 7-Azaindole und deren Verwendung als Therapeutika |
| US7601847B2 (en) | 2004-10-26 | 2009-10-13 | Wyeth | Preparation and purification of 4-(indazol-3-yl)phenols |
| US20070004777A1 (en) * | 2005-03-23 | 2007-01-04 | Bhagwat Shripad S | Methods for treating or preventing acute myelogenous leukemia |
| EP1928437A2 (en) | 2005-08-26 | 2008-06-11 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| JP2009512711A (ja) | 2005-10-21 | 2009-03-26 | ブレインセルス，インコーポレイティド | Ｐｄｅ阻害による神経新生の調節 |
| WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| US8277809B2 (en) * | 2006-04-21 | 2012-10-02 | Centocor, Inc. | CXCL13 antagonists and their use for the treatment of inflammatory diseases |
| WO2007134136A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2804603A1 (en) | 2012-01-10 | 2014-11-26 | President and Fellows of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| KR20200104291A (ko) | 2017-11-06 | 2020-09-03 | 랩트 테라퓨틱스, 인크. | 항암제 |
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| AP2001002304A0 (en) * | 1996-05-03 | 2001-12-31 | Pfizer | Substituted indazole derivatives and related compounds |
| PT983249E (pt) * | 1997-05-08 | 2002-08-30 | Pfizer Prod Inc | Procesos e intermediarios para a preparacao de derivados de indazole substituidos |
-
1996
- 1996-05-03 AP AP2001002304A patent/AP2001002304A0/xx unknown
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1997
- 1997-01-04 UA UA98105434A patent/UA65536C2/uk unknown
- 1997-04-01 SK SK1482-98A patent/SK148298A3/sk unknown
- 1997-04-01 AU AU19373/97A patent/AU725576B2/en not_active Ceased
- 1997-04-01 CA CA002389918A patent/CA2389918A1/en not_active Abandoned
- 1997-04-01 CN CN97194356A patent/CN1112359C/zh not_active Expired - Fee Related
- 1997-04-01 DE DE69732966T patent/DE69732966T2/de not_active Expired - Fee Related
- 1997-04-01 ES ES97907247T patent/ES2238079T3/es not_active Expired - Lifetime
- 1997-04-01 AT AT97907247T patent/ATE292626T1/de not_active IP Right Cessation
- 1997-04-01 BR BR9709051A patent/BR9709051A/pt active Search and Examination
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- 1997-04-01 JP JP53967097A patent/JP3148254B2/ja not_active Expired - Fee Related
- 1997-04-01 WO PCT/IB1997/000323 patent/WO1997042174A1/en not_active Ceased
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- 1997-04-01 KR KR1019980708867A patent/KR100339935B1/ko not_active Expired - Fee Related
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- 1997-04-01 EA EA199800882A patent/EA002272B1/ru not_active IP Right Cessation
- 1997-04-01 PL PL97329836A patent/PL329836A1/xx unknown
- 1997-04-01 TW TW086104176A patent/TW449585B/zh active
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- 1997-04-04 HN HN1997000046A patent/HN1997000046A/es unknown
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- 1997-04-28 UY UY24532A patent/UY24532A1/es not_active IP Right Cessation
- 1997-04-29 AR ARP970101769A patent/AR006906A1/es not_active Application Discontinuation
- 1997-04-29 YU YU16397A patent/YU16397A/sh unknown
- 1997-04-30 TN TNTNSN97070A patent/TNSN97070A1/fr unknown
- 1997-04-30 DZ DZ970064A patent/DZ2217A1/fr active
- 1997-04-30 MA MA24577A patent/MA24158A1/fr unknown
- 1997-04-30 AP APAP/P/1997/000975A patent/AP1146A/en active
- 1997-04-30 PE PE1997000330A patent/PE64598A1/es not_active Application Discontinuation
- 1997-05-02 ZA ZA973804A patent/ZA973804B/xx unknown
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- 1997-05-02 HR HR970227A patent/HRP970227B1/xx not_active IP Right Cessation
- 1997-05-02 MY MYPI97001923A patent/MY132499A/en unknown
- 1997-05-05 CO CO97023872A patent/CO4650038A1/es unknown
- 1997-11-04 US US08/963,904 patent/US6211222B1/en not_active Expired - Fee Related
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1998
- 1998-10-16 IS IS4871A patent/IS4871A/is unknown
- 1998-10-23 OA OA9800201A patent/OA10904A/en unknown
- 1998-11-02 NO NO19985095A patent/NO312959B1/no not_active IP Right Cessation
- 1998-11-23 BG BG102946A patent/BG64211B1/bg unknown
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1999
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2002
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