SK6262000A3 - Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors - Google Patents

Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors Download PDF

Info

Publication number: SK6262000A3
Authority: SK; Slovakia
Prior art keywords: group; alkyl; independently selected; consisting essentially; carbon atoms
Prior art date: 1997-11-04

Application number

SK626-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Anthony Marfat

Original Assignee

Pfizer Prod Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-11-04

Filing date

1998-10-09

Publication date

2002-03-05

1998-10-09 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2002-03-05 Publication of SK6262000A3 publication Critical patent/SK6262000A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 197
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 title claims abstract description 38
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title claims abstract description 22
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title description 11
239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 11
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 119
239000001257 hydrogen Substances 0.000 claims abstract description 118
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 106
125000001424 substituent group Chemical group 0.000 claims abstract description 83
201000010099 disease Diseases 0.000 claims abstract description 37
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
239000000126 substance Substances 0.000 claims abstract description 22
206010040070 Septic Shock Diseases 0.000 claims abstract description 19
208000006673 asthma Diseases 0.000 claims abstract description 14
208000027866 inflammatory disease Diseases 0.000 claims abstract description 13
206010006451 bronchitis Diseases 0.000 claims abstract description 12
208000023504 respiratory system disease Diseases 0.000 claims abstract description 11
230000001225 therapeutic effect Effects 0.000 claims abstract description 11
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 9
208000011231 Crohn disease Diseases 0.000 claims abstract description 9
208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 9
206010003246 arthritis Diseases 0.000 claims abstract description 9
201000004681 Psoriasis Diseases 0.000 claims abstract description 7
206010014561 Emphysema Diseases 0.000 claims abstract description 6
206010014824 Endotoxic shock Diseases 0.000 claims abstract description 6
206010044248 Toxic shock syndrome Diseases 0.000 claims abstract description 6
231100000650 Toxic shock syndrome Toxicity 0.000 claims abstract description 6
239000003112 inhibitor Substances 0.000 claims abstract description 6
208000018937 joint inflammation Diseases 0.000 claims abstract description 6
206010006458 Bronchitis chronic Diseases 0.000 claims abstract description 5
208000035473 Communicable disease Diseases 0.000 claims abstract description 5
108010044467 Isoenzymes Proteins 0.000 claims abstract description 5
206010063837 Reperfusion injury Diseases 0.000 claims abstract description 5
208000007451 chronic bronchitis Diseases 0.000 claims abstract description 5
208000026278 immune system disease Diseases 0.000 claims abstract description 4
201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 4
-1 2-oxo-pyridyl Chemical group 0.000 claims description 259
125000004432 carbon atom Chemical group C* 0.000 claims description 172
125000000217 alkyl group Chemical group 0.000 claims description 121
239000000460 chlorine Substances 0.000 claims description 64
229910052801 chlorine Inorganic materials 0.000 claims description 61
125000003118 aryl group Chemical group 0.000 claims description 58
238000000034 method Methods 0.000 claims description 53
230000036961 partial effect Effects 0.000 claims description 53
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 50
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
229910052731 fluorine Inorganic materials 0.000 claims description 47
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 45
239000011737 fluorine Substances 0.000 claims description 45
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 44
229910052794 bromium Inorganic materials 0.000 claims description 44
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 41
229910005965 SO 2 Inorganic materials 0.000 claims description 39
125000004093 cyano group Chemical group *C#N 0.000 claims description 39
229910052799 carbon Inorganic materials 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
125000000623 heterocyclic group Chemical group 0.000 claims description 32
125000000335 thiazolyl group Chemical group 0.000 claims description 32
125000002883 imidazolyl group Chemical group 0.000 claims description 31
125000003226 pyrazolyl group Chemical group 0.000 claims description 30
125000004076 pyridyl group Chemical group 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 27
125000001425 triazolyl group Chemical group 0.000 claims description 26
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
125000002971 oxazolyl group Chemical group 0.000 claims description 23
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
125000004429 atom Chemical group 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
239000013543 active substance Substances 0.000 claims description 20
125000003831 tetrazolyl group Chemical group 0.000 claims description 20
238000011282 treatment Methods 0.000 claims description 20
125000003545 alkoxy group Chemical group 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 19
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
125000001153 fluoro group Chemical group F* 0.000 claims description 18
229910052717 sulfur Inorganic materials 0.000 claims description 18
125000001113 thiadiazolyl group Chemical group 0.000 claims description 18
125000001984 thiazolidinyl group Chemical group 0.000 claims description 18
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
125000003342 alkenyl group Chemical group 0.000 claims description 17
125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
150000003254 radicals Chemical class 0.000 claims description 16
125000000842 isoxazolyl group Chemical group 0.000 claims description 15
125000001544 thienyl group Chemical group 0.000 claims description 15
150000001721 carbon Chemical group 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
125000002632 imidazolidinyl group Chemical group 0.000 claims description 14
125000001715 oxadiazolyl group Chemical group 0.000 claims description 14
125000002757 morpholinyl group Chemical group 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims description 12
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims description 12
125000002541 furyl group Chemical group 0.000 claims description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
125000000160 oxazolidinyl group Chemical group 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 11
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 11
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 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
125000005936 piperidyl group Chemical group 0.000 claims description 11
125000000168 pyrrolyl group Chemical group 0.000 claims description 11
MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims description 10
206010001513 AIDS related complex Diseases 0.000 claims description 10
206010040047 Sepsis Diseases 0.000 claims description 10
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 10
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
125000004193 piperazinyl group Chemical group 0.000 claims description 10
206010006895 Cachexia Diseases 0.000 claims description 9
125000001931 aliphatic group Chemical group 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
125000001589 carboacyl group Chemical group 0.000 claims description 9
208000015181 infectious disease Diseases 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 claims description 8
241000282414 Homo sapiens Species 0.000 claims description 8
241000725303 Human immunodeficiency virus Species 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
230000005764 inhibitory process Effects 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
201000008482 osteoarthritis Diseases 0.000 claims description 8
230000002265 prevention Effects 0.000 claims description 8
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 7
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 7
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 7
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
230000036303 septic shock Effects 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
206010039085 Rhinitis allergic Diseases 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
201000010105 allergic rhinitis Diseases 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
125000005605 benzo group Chemical group 0.000 claims description 6
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 5
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 claims description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
GQJHRXMJKSJWLV-UHFFFAOYSA-N 6-bromo-3-ethyl-1-(4-fluorophenyl)indazole Chemical compound C12=CC(Br)=CC=C2C(CC)=NN1C1=CC=C(F)C=C1 GQJHRXMJKSJWLV-UHFFFAOYSA-N 0.000 claims description 5
206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
208000035143 Bacterial infection Diseases 0.000 claims description 5
208000006386 Bone Resorption Diseases 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
206010009900 Colitis ulcerative Diseases 0.000 claims description 5
206010017533 Fungal infection Diseases 0.000 claims description 5
208000000112 Myalgia Diseases 0.000 claims description 5
208000031888 Mycoses Diseases 0.000 claims description 5
206010037660 Pyrexia Diseases 0.000 claims description 5
201000010001 Silicosis Diseases 0.000 claims description 5
201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
208000036142 Viral infection Diseases 0.000 claims description 5
230000001580 bacterial effect Effects 0.000 claims description 5
208000022362 bacterial infectious disease Diseases 0.000 claims description 5
230000024279 bone resorption Effects 0.000 claims description 5
125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
ZIGCXRTXHFIYQO-UHFFFAOYSA-N ethyl 4-cyano-4-[3-ethyl-1-(4-fluorophenyl)indazol-6-yl]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OCC)CCC1(C#N)C1=CC=C(C(CC)=NN2C=3C=CC(F)=CC=3)C2=C1 ZIGCXRTXHFIYQO-UHFFFAOYSA-N 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
206010022000 influenza Diseases 0.000 claims description 5
208000011379 keloid formation Diseases 0.000 claims description 5
208000032839 leukemia Diseases 0.000 claims description 5
201000006417 multiple sclerosis Diseases 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
230000006433 tumor necrosis factor production Effects 0.000 claims description 5
230000003612 virological effect Effects 0.000 claims description 5
125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 4
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 4
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 4
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 4
SODQFLRLAOALCF-UHFFFAOYSA-N 1lambda3-bromacyclohexa-1,3,5-triene Chemical compound Br1=CC=CC=C1 SODQFLRLAOALCF-UHFFFAOYSA-N 0.000 claims description 4
125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
201000004624 Dermatitis Diseases 0.000 claims description 4
206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 4
206010061218 Inflammation 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
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 4
VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
UVCLSOSCOBDAOJ-UHFFFAOYSA-N ethyl 4-[3-ethyl-1-(4-fluorophenyl)indazol-6-yl]-4-hydroxycyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OCC)CCC1(O)C1=CC=C(C(CC)=NN2C=3C=CC(F)=CC=3)C2=C1 UVCLSOSCOBDAOJ-UHFFFAOYSA-N 0.000 claims description 4
208000024908 graft versus host disease Diseases 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
230000002458 infectious effect Effects 0.000 claims description 4
230000004054 inflammatory process Effects 0.000 claims description 4
125000000466 oxiranyl group Chemical group 0.000 claims description 4
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 4
231100000241 scar Toxicity 0.000 claims description 4
230000009772 tissue formation Effects 0.000 claims description 4
125000004306 triazinyl group Chemical group 0.000 claims description 4
125000004191 (C1-C6) alkoxy 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
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 3
UKVJLLRHTQPKJR-UHFFFAOYSA-N 4-[3-ethyl-1-(4-fluorophenyl)indazol-6-yl]cyclohex-3-ene-1-carboxylic acid Chemical compound C12=CC(C=3CCC(CC=3)C(O)=O)=CC=C2C(CC)=NN1C1=CC=C(F)C=C1 UKVJLLRHTQPKJR-UHFFFAOYSA-N 0.000 claims description 3
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 3
125000004450 alkenylene group Chemical group 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
150000005840 aryl radicals Chemical class 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
YFQVGIOCBQEVGB-UHFFFAOYSA-N ethyl 4-cyano-4-(1-cyclohexyl-3-ethylindazol-6-yl)cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OCC)CCC1(C#N)C1=CC=C(C(CC)=NN2C3CCCCC3)C2=C1 YFQVGIOCBQEVGB-UHFFFAOYSA-N 0.000 claims description 3
208000033065 inborn errors of immunity Diseases 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
210000001503 joint Anatomy 0.000 claims description 3
230000003211 malignant effect Effects 0.000 claims description 3
230000005741 malignant process Effects 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims description 3
125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 3
208000028529 primary immunodeficiency disease Diseases 0.000 claims description 3
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
125000003072 pyrazolidinyl group Chemical group 0.000 claims description 3
125000002098 pyridazinyl group Chemical group 0.000 claims description 3
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 2
125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 2
HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 claims description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 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
CEXQWAAGPPNOQF-UHFFFAOYSA-N 2-phenoxyethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOC1=CC=CC=C1 CEXQWAAGPPNOQF-UHFFFAOYSA-N 0.000 claims description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
UDNCRNODTXAZJD-UHFFFAOYSA-N 4-(1-cyclohexyl-3-ethylindazol-6-yl)-4-hydroxycyclohexane-1-carboxylic acid Chemical compound C12=CC(C3(O)CCC(CC3)C(O)=O)=CC=C2C(CC)=NN1C1CCCCC1 UDNCRNODTXAZJD-UHFFFAOYSA-N 0.000 claims description 2
125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 claims description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
206010063094 Cerebral malaria Diseases 0.000 claims description 2
206010012434 Dermatitis allergic Diseases 0.000 claims description 2
201000005569 Gout Diseases 0.000 claims description 2
206010019617 Henoch-Schonlein purpura Diseases 0.000 claims description 2
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208000010668 atopic eczema Diseases 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical group BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000005879 dioxolanyl group Chemical group 0.000 claims description 2
201000006549 dyspepsia Diseases 0.000 claims description 2
PNNVKHPICCNMIV-UHFFFAOYSA-N ethyl 4-[3-ethyl-1-(4-fluorophenyl)indazol-6-yl]cyclohex-3-ene-1-carboxylate Chemical compound C1C(C(=O)OCC)CCC(C=2C=C3N(C=4C=CC(F)=CC=4)N=C(CC)C3=CC=2)=C1 PNNVKHPICCNMIV-UHFFFAOYSA-N 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
208000024798 heartburn Diseases 0.000 claims description 2
208000015446 immunoglobulin a vasculitis Diseases 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
210000004072 lung Anatomy 0.000 claims description 2
206010025135 lupus erythematosus Diseases 0.000 claims description 2
201000008383 nephritis Diseases 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 2
208000024981 pyrosis Diseases 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
230000009885 systemic effect Effects 0.000 claims description 2
KRXAVBPUAIKSFF-UHFFFAOYSA-N 3,4-dihydrodithiine Chemical compound C1CC=CSS1 KRXAVBPUAIKSFF-UHFFFAOYSA-N 0.000 claims 1
206010018634 Gouty Arthritis Diseases 0.000 claims 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
150000001408 amides Chemical class 0.000 claims 1
201000005008 bacterial sepsis Diseases 0.000 claims 1
125000003518 norbornenyl group Chemical class C12(C=CC(CC1)C2)* 0.000 claims 1
230000000414 obstructive effect Effects 0.000 claims 1
OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 claims 1
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150000003512 tertiary amines Chemical class 0.000 description 1
238000002560 therapeutic procedure Methods 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
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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
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
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Classifications

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- 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
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Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Immunology (AREA)
Diabetes (AREA)
Dermatology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Oncology (AREA)
Cardiology (AREA)
Rheumatology (AREA)
Transplantation (AREA)
Pain & Pain Management (AREA)
Communicable Diseases (AREA)
Obesity (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Urology & Nephrology (AREA)
Otolaryngology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK626-2000A 1997-11-04 1998-10-09 Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors SK6262000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US6416097P	1997-11-04	1997-11-04
PCT/IB1998/001579 WO1999023076A1 (en)	1997-11-04	1998-10-09	Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors

Publications (1)

Publication Number	Publication Date
SK6262000A3 true SK6262000A3 (en)	2002-03-05

Family

ID=22053970

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK626-2000A SK6262000A3 (en)	1997-11-04	1998-10-09	Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors

Country Status (34)

Country	Link
US (2)	US6716978B2 (is)
EP (1)	EP1040100A1 (is)
JP (1)	JP2001521925A (is)
KR (1)	KR20010031783A (is)
CN (1)	CN1281441A (is)
AP (1)	AP1122A (is)
AR (1)	AR016413A1 (is)
AU (1)	AU754184B2 (is)
BG (1)	BG104391A (is)
BR (1)	BR9813938A (is)
CA (1)	CA2309175A1 (is)
CZ (1)	CZ20001623A3 (is)
DZ (1)	DZ2639A1 (is)
EA (1)	EA200000385A1 (is)
HN (1)	HN1998000172A (is)
HR (1)	HRP20000262A2 (is)
HU (1)	HUP0100330A3 (is)
ID (1)	ID24942A (is)
IL (1)	IL135714A0 (is)
IS (1)	IS5452A (is)
MA (1)	MA26562A1 (is)
NO (1)	NO20002127L (is)
NZ (1)	NZ503995A (is)
OA (1)	OA11353A (is)
PA (1)	PA8462601A1 (is)
PE (1)	PE131099A1 (is)
PL (1)	PL340799A1 (is)
SK (1)	SK6262000A3 (is)
TN (1)	TNSN98199A1 (is)
TR (1)	TR200001256T2 (is)
UY (1)	UY25232A1 (is)
WO (1)	WO1999023076A1 (is)
YU (1)	YU25400A (is)
ZA (1)	ZA9810042B (is)

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PT2124944E (pt)	2007-03-14	2012-05-17	Ranbaxy Lab Ltd	Derivados de pirazolo[3,4-b]piridina como inibidores de fosfodiesterase
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1998
- 1998-10-09 TR TR2000/01256T patent/TR200001256T2/xx unknown
- 1998-10-09 ID IDW20000820A patent/ID24942A/id unknown
- 1998-10-09 CN CN98811981A patent/CN1281441A/zh active Pending
- 1998-10-09 AU AU92777/98A patent/AU754184B2/en not_active Ceased
- 1998-10-09 US US09/381,446 patent/US6716978B2/en not_active Expired - Fee Related
- 1998-10-09 CZ CZ20001623A patent/CZ20001623A3/cs unknown
- 1998-10-09 YU YU25400A patent/YU25400A/sh unknown
- 1998-10-09 WO PCT/IB1998/001579 patent/WO1999023076A1/en not_active Ceased
- 1998-10-09 SK SK626-2000A patent/SK6262000A3/sk unknown
- 1998-10-09 PL PL98340799A patent/PL340799A1/xx not_active Application Discontinuation
- 1998-10-09 BR BR9813938-0A patent/BR9813938A/pt not_active Application Discontinuation
- 1998-10-09 HR HR20000262A patent/HRP20000262A2/xx not_active Application Discontinuation
- 1998-10-09 CA CA002309175A patent/CA2309175A1/en not_active Abandoned
- 1998-10-09 KR KR1020007004849A patent/KR20010031783A/ko not_active Abandoned
- 1998-10-09 EP EP98945473A patent/EP1040100A1/en not_active Withdrawn
- 1998-10-09 IL IL13571498A patent/IL135714A0/xx unknown
- 1998-10-09 JP JP2000518951A patent/JP2001521925A/ja not_active Ceased
- 1998-10-09 EA EA200000385A patent/EA200000385A1/ru unknown
- 1998-10-09 NZ NZ503995A patent/NZ503995A/xx unknown
- 1998-10-09 HU HU0100330A patent/HUP0100330A3/hu unknown
- 1998-10-30 PA PA19988462601A patent/PA8462601A1/es unknown
- 1998-11-02 AP APAP/P/1998/001376A patent/AP1122A/en active
- 1998-11-03 ZA ZA9810042A patent/ZA9810042B/xx unknown
- 1998-11-03 DZ DZ980249A patent/DZ2639A1/xx active
- 1998-11-03 TN TNTNSN98199A patent/TNSN98199A1/fr unknown
- 1998-11-03 MA MA25331A patent/MA26562A1/fr unknown
- 1998-11-03 PE PE1998001040A patent/PE131099A1/es not_active Application Discontinuation
- 1998-11-03 AR ARP980105533A patent/AR016413A1/es not_active Application Discontinuation
- 1998-11-04 UY UY25232A patent/UY25232A1/es not_active Application Discontinuation
- 1998-11-04 HN HN1998000172A patent/HN1998000172A/es unknown
2000
- 2000-04-14 IS IS5452A patent/IS5452A/is unknown
- 2000-04-26 NO NO20002127A patent/NO20002127L/no unknown
- 2000-04-28 BG BG104391A patent/BG104391A/xx unknown
- 2000-04-28 OA OA1200000126A patent/OA11353A/en unknown
2002
- 2002-12-12 US US10/317,779 patent/US20030158189A1/en not_active Abandoned

Also Published As

Publication number	Publication date
PA8462601A1 (es)	2000-05-24
PL340799A1 (en)	2001-02-26
HUP0100330A3 (en)	2002-03-28
AU9277798A (en)	1999-05-24
HRP20000262A2 (en)	2000-10-31
AU754184B2 (en)	2002-11-07
EA200000385A1 (ru)	2000-10-30
US6716978B2 (en)	2004-04-06
AP9801376A0 (en)	1998-12-31
AR016413A1 (es)	2001-07-04
AP1122A (en)	2002-11-29
IL135714A0 (en)	2001-05-20
IS5452A (is)	2000-04-14
NZ503995A (en)	2003-02-28
TR200001256T2 (tr)	2000-11-21
US20030158189A1 (en)	2003-08-21
WO1999023076A1 (en)	1999-05-14
PE131099A1 (es)	1999-12-17
ZA9810042B (en)	2000-05-03
HN1998000172A (es)	1999-01-08
OA11353A (en)	2003-12-19
UY25232A1 (es)	2000-12-29
DZ2639A1 (fr)	2003-03-08
HUP0100330A2 (hu)	2002-02-28
EP1040100A1 (en)	2000-10-04
BR9813938A (pt)	2000-09-26
JP2001521925A (ja)	2001-11-13
CA2309175A1 (en)	1999-05-14
CZ20001623A3 (cs)	2001-08-15
CN1281441A (zh)	2001-01-24
TNSN98199A1 (fr)	2005-03-15
KR20010031783A (ko)	2001-04-16
BG104391A (en)	2000-12-29
US20020058687A1 (en)	2002-05-16
NO20002127L (no)	2000-07-03
MA26562A1 (fr)	2004-12-20
NO20002127D0 (no)	2000-04-26
ID24942A (id)	2000-08-31
YU25400A (sh)	2003-07-07

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