AU2003295656B2 - Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors - Google Patents
Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors Download PDFInfo
- Publication number
- AU2003295656B2 AU2003295656B2 AU2003295656A AU2003295656A AU2003295656B2 AU 2003295656 B2 AU2003295656 B2 AU 2003295656B2 AU 2003295656 A AU2003295656 A AU 2003295656A AU 2003295656 A AU2003295656 A AU 2003295656A AU 2003295656 B2 AU2003295656 B2 AU 2003295656B2
- Authority
- AU
- Australia
- Prior art keywords
- carbon atoms
- oxy
- pyridylmethyl
- phenyl
- alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 15
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 title description 4
- -1 nitroxide compounds Chemical class 0.000 claims abstract description 363
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims abstract description 115
- 230000005764 inhibitory process Effects 0.000 claims abstract description 23
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims abstract 3
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 280
- 125000000217 alkyl group Chemical group 0.000 claims description 156
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 144
- 229910052736 halogen Inorganic materials 0.000 claims description 101
- 150000002367 halogens Chemical class 0.000 claims description 101
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 91
- 125000003545 alkoxy group Chemical group 0.000 claims description 85
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 84
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 65
- 239000005711 Benzoic acid Substances 0.000 claims description 64
- 235000010233 benzoic acid Nutrition 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 125000004043 oxo group Chemical group O=* 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 43
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 39
- 125000006413 ring segment Chemical group 0.000 claims description 37
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 36
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
- 229920006395 saturated elastomer Polymers 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 22
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 16
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 16
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 16
- 206010027175 memory impairment Diseases 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 15
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 15
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 14
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 102000004190 Enzymes Human genes 0.000 claims description 13
- 108090000790 Enzymes Proteins 0.000 claims description 13
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000004434 sulfur atom Chemical group 0.000 claims description 13
- 208000023105 Huntington disease Diseases 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 201000000980 schizophrenia Diseases 0.000 claims description 10
- HFZZTHJMXZSGFP-UHFFFAOYSA-N 1-benzofuran-2-amine Chemical compound C1=CC=C2OC(N)=CC2=C1 HFZZTHJMXZSGFP-UHFFFAOYSA-N 0.000 claims description 9
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 206010012289 Dementia Diseases 0.000 claims description 8
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 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 7
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 208000010877 cognitive disease Diseases 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000003944 tolyl group Chemical group 0.000 claims description 7
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 5
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
- 208000026139 Memory disease Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 206010003694 Atrophy Diseases 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000028698 Cognitive impairment Diseases 0.000 claims description 4
- 206010019196 Head injury Diseases 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 230000000172 allergic effect Effects 0.000 claims description 4
- 230000037444 atrophy Effects 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 230000019771 cognition Effects 0.000 claims description 4
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 4
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
- 230000007423 decrease Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000007954 hypoxia Effects 0.000 claims description 4
- 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 208000020431 spinal cord injury Diseases 0.000 claims description 4
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 230000007000 age related cognitive decline Effects 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 208000026935 allergic disease Diseases 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- YUCFVHQCAFKDQG-UHFFFAOYSA-N fluoromethane Chemical group F[CH] YUCFVHQCAFKDQG-UHFFFAOYSA-N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 239000003193 general anesthetic agent Substances 0.000 claims description 3
- 208000024714 major depressive disease Diseases 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 208000025307 bipolar depression Diseases 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 208000008013 morphine dependence Diseases 0.000 claims description 2
- 230000001537 neural effect Effects 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 229940039407 aniline Drugs 0.000 claims 25
- FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 claims 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims 2
- RLXNWBVDCNYQJV-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-phenylurea Chemical compound C=1C=CC=CC=1S(=O)(=O)NC(=O)NC1=CC=CC=C1 RLXNWBVDCNYQJV-UHFFFAOYSA-N 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 230000007278 cognition impairment Effects 0.000 claims 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 1
- WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 description 39
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 30
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 30
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 25
- 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 description 20
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 20
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 8
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 8
- 229960005305 adenosine Drugs 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 101100296719 Caenorhabditis elegans pde-4 gene Proteins 0.000 description 7
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 7
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000015654 memory Effects 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 6
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 6
- 229950005741 rolipram Drugs 0.000 description 6
- 208000000044 Amnesia Diseases 0.000 description 5
- 108010044467 Isoenzymes Proteins 0.000 description 5
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 5
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 5
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000000926 neurological effect Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- 102100032187 Androgen receptor Human genes 0.000 description 4
- 201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229960004050 aminobenzoic acid Drugs 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000007787 long-term memory Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 102000007371 Ataxin-3 Human genes 0.000 description 3
- 102000007370 Ataxin2 Human genes 0.000 description 3
- 108010032951 Ataxin2 Proteins 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010063837 Reperfusion injury Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004802 cyanophenyl group Chemical group 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 125000004188 dichlorophenyl group Chemical group 0.000 description 3
- 125000001207 fluorophenyl group Chemical group 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000006984 memory degeneration Effects 0.000 description 3
- 208000023060 memory loss Diseases 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 125000006501 nitrophenyl group Chemical group 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229920000155 polyglutamine Polymers 0.000 description 3
- 108010040003 polyglutamine Proteins 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000003936 working memory Effects 0.000 description 3
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- UCJYEZKDLOGBOD-UHFFFAOYSA-N 3-(chloromethyl)-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=CC(CCl)=C1 UCJYEZKDLOGBOD-UHFFFAOYSA-N 0.000 description 2
- CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 2
- 102000009346 Adenosine receptors Human genes 0.000 description 2
- 108050000203 Adenosine receptors Proteins 0.000 description 2
- 102000004321 Atrophin-1 Human genes 0.000 description 2
- 108090000806 Atrophin-1 Proteins 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000027747 Kennedy disease Diseases 0.000 description 2
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 2
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- 238000012879 PET imaging Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 201000003622 Spinocerebellar ataxia type 2 Diseases 0.000 description 2
- 201000003620 Spinocerebellar ataxia type 6 Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229950006790 adenosine phosphate Drugs 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000003109 amnesic effect Effects 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000005266 diarylamine group Chemical class 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 231100000863 loss of memory Toxicity 0.000 description 2
- 125000006178 methyl benzyl group Chemical group 0.000 description 2
- 208000027061 mild cognitive impairment Diseases 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 108010028584 nucleotidase Proteins 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004344 phenylpropyl group Chemical group 0.000 description 2
- RRRUXBQSQLKHEL-UHFFFAOYSA-N piclamilast Chemical compound COC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OC1CCCC1 RRRUXBQSQLKHEL-UHFFFAOYSA-N 0.000 description 2
- 229950005184 piclamilast Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 2
- 201000003632 spinocerebellar ataxia type 7 Diseases 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- HJPRDDKCXVCFOH-UHFFFAOYSA-N 1,3-dibutyl-7-(2-oxopropyl)purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC(C)=O)C=N2 HJPRDDKCXVCFOH-UHFFFAOYSA-N 0.000 description 1
- DOYCWNXWPMYJQN-UHFFFAOYSA-N 1-(3-cyclopentyloxy-4-methoxyphenyl)-2h-pyridin-4-amine Chemical compound COC1=CC=C(N2C=CC(N)=CC2)C=C1OC1CCCC1 DOYCWNXWPMYJQN-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- YOCZJJNZPGJJRC-UHFFFAOYSA-N 4-(chloromethyl)-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=C(CCl)C=C1 YOCZJJNZPGJJRC-UHFFFAOYSA-N 0.000 description 1
- UTUUPXBCDMQYRR-HSZRJFAPSA-N 4-[(2r)-2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl]pyridine Chemical compound COC1=CC=C([C@H](CC=2C=CN=CC=2)C=2C=CC=CC=2)C=C1OC1CCCC1 UTUUPXBCDMQYRR-HSZRJFAPSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- UPJKSWLLCONYMW-UHFFFAOYSA-N 5'-Adenosine monophosphate Natural products COc1cc(O)c(C(=O)C)c(OC2OC(COC3OC(C)C(O)C(O)C3O)C(O)C(O)C2O)c1 UPJKSWLLCONYMW-UHFFFAOYSA-N 0.000 description 1
- 102100022464 5'-nucleotidase Human genes 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010051113 Arterial restenosis Diseases 0.000 description 1
- 102000007372 Ataxin-1 Human genes 0.000 description 1
- 108010032963 Ataxin-1 Proteins 0.000 description 1
- 102100021321 Ataxin-3 Human genes 0.000 description 1
- 108010032947 Ataxin-3 Proteins 0.000 description 1
- 102000007368 Ataxin-7 Human genes 0.000 description 1
- 108010032953 Ataxin-7 Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- 101100243082 Caenorhabditis elegans pde-1 gene Proteins 0.000 description 1
- 101100135858 Caenorhabditis elegans pde-2 gene Proteins 0.000 description 1
- 101100135867 Caenorhabditis elegans pde-3 gene Proteins 0.000 description 1
- 101100296726 Caenorhabditis elegans pde-5 gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- RVGDKGUZJCDBKG-UHFFFAOYSA-N Cl.ClCC1=CC=CC=N1.[O-][N+]1=CC=CC(CCl)=C1 Chemical compound Cl.ClCC1=CC=CC=N1.[O-][N+]1=CC=CC(CCl)=C1 RVGDKGUZJCDBKG-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010016880 Folate deficiency Diseases 0.000 description 1
- 206010017865 Gastritis erosive Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001098805 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4A Proteins 0.000 description 1
- 101000988424 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4B Proteins 0.000 description 1
- 101000988423 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4C Proteins 0.000 description 1
- 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000031814 IgA Vasculitis Diseases 0.000 description 1
- 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 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
- 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
- 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 201000009904 bacterial meningitis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102100037092 cAMP-specific 3',5'-cyclic phosphodiesterase 4A Human genes 0.000 description 1
- 102100029168 cAMP-specific 3',5'-cyclic phosphodiesterase 4B Human genes 0.000 description 1
- 102100029169 cAMP-specific 3',5'-cyclic phosphodiesterase 4C Human genes 0.000 description 1
- 102100029170 cAMP-specific 3',5'-cyclic phosphodiesterase 4D Human genes 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- VNWKTOKETHGBQD-AKLPVKDBSA-N carbane Chemical group [15CH4] VNWKTOKETHGBQD-AKLPVKDBSA-N 0.000 description 1
- VNWKTOKETHGBQD-YPZZEJLDSA-N carbane Chemical group [10CH4] VNWKTOKETHGBQD-YPZZEJLDSA-N 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229950004687 denbufylline Drugs 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- LJJVZJSGXHJIPP-UHFFFAOYSA-N ethylpentyl Chemical group [CH2+]CCC[CH]C[CH2-] LJJVZJSGXHJIPP-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 229940005494 general anesthetics Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002315 glycerophosphates Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- 229960000443 hydrochloric acid Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- WRSXUNSJGJUKHE-UHFFFAOYSA-N indazole Chemical compound C1=CC=C[C]2C=NN=C21 WRSXUNSJGJUKHE-UHFFFAOYSA-N 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 230000009681 mesenchymal cell proliferation Effects 0.000 description 1
- 230000002503 metabolic effect Effects 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
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000006384 methylpyridyl group Chemical group 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- BWZQUYCUJOYLNB-UHFFFAOYSA-N n,n-diphenyl-2h-tetrazol-5-amine Chemical compound C1=CC=CC=C1N(C=1C=CC=CC=1)C1=NNN=N1 BWZQUYCUJOYLNB-UHFFFAOYSA-N 0.000 description 1
- JJGVUQXLNNGWPZ-UHFFFAOYSA-N n-phenyl-2h-tetrazol-5-amine Chemical compound C=1C=CC=CC=1NC1=NN=NN1 JJGVUQXLNNGWPZ-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000009689 neuronal regeneration Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000012223 nuclear import Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 208000007138 otopalatodigital syndrome type 1 Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000004700 rosacea Diseases 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- LZCVVMQABORALM-UHFFFAOYSA-N spiro[2.5]octyl Chemical group [CH]1CC11CCCCC1 LZCVVMQABORALM-UHFFFAOYSA-N 0.000 description 1
- GAJDDVONBAWAGB-UHFFFAOYSA-N spiro[2.6]nonyl Chemical group [CH]1CC11CCCCCC1 GAJDDVONBAWAGB-UHFFFAOYSA-N 0.000 description 1
- LMUMMJCCZMWLEN-UHFFFAOYSA-N spiro[3.3]heptyl Chemical group [CH]1CCC11CCC1 LMUMMJCCZMWLEN-UHFFFAOYSA-N 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000001384 succinic acid Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000001806 thionaphthenyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- 201000005539 vernal conjunctivitis Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
- 229940045999 vitamin b 12 Drugs 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive 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
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42722102P | 2002-11-19 | 2002-11-19 | |
| US60/427,221 | 2002-11-19 | ||
| PCT/US2003/036986 WO2004046113A2 (en) | 2002-11-19 | 2003-11-19 | Pyridine n-oxide compounds as phosphodiesterase 4 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2003295656A1 AU2003295656A1 (en) | 2004-06-15 |
| AU2003295656A2 AU2003295656A2 (en) | 2005-06-30 |
| AU2003295656B2 true AU2003295656B2 (en) | 2010-11-11 |
Family
ID=32326501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003295656A Expired - Fee Related AU2003295656B2 (en) | 2002-11-19 | 2003-11-19 | Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US7087625B2 (enExample) |
| EP (1) | EP1569908B1 (enExample) |
| JP (1) | JP2006508987A (enExample) |
| KR (1) | KR20050075430A (enExample) |
| CN (1) | CN100513397C (enExample) |
| AT (1) | ATE481387T1 (enExample) |
| AU (1) | AU2003295656B2 (enExample) |
| BR (1) | BR0315705A (enExample) |
| CA (1) | CA2506297A1 (enExample) |
| DE (1) | DE60334243D1 (enExample) |
| MX (1) | MXPA05005345A (enExample) |
| NO (1) | NO20052976L (enExample) |
| NZ (1) | NZ540138A (enExample) |
| RU (1) | RU2356893C2 (enExample) |
| WO (1) | WO2004046113A2 (enExample) |
| ZA (1) | ZA200503995B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7153871B2 (en) * | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| US20030149052A1 (en) * | 2002-01-22 | 2003-08-07 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| ES2323688T3 (es) * | 2002-07-19 | 2009-07-23 | Memory Pharmaceuticals Corporation | Compuestos de 4-aminobenzofurano como inhibidores de fosfodiesterasa 4. |
| WO2004009552A1 (en) * | 2002-07-19 | 2004-01-29 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
| US20050282814A1 (en) * | 2002-10-03 | 2005-12-22 | Targegen, Inc. | Vasculostatic agents and methods of use thereof |
| EP1549614A4 (en) * | 2002-10-03 | 2008-04-16 | Targegen Inc | VASCULATORY AGENTS AND METHODS FOR THEIR APPLICATION |
| ES2211344B1 (es) * | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| US20090048255A1 (en) * | 2003-07-21 | 2009-02-19 | Schumacher Richard A | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
| MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
| EP2543376A1 (en) | 2004-04-08 | 2013-01-09 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| WO2006135828A2 (en) * | 2005-06-10 | 2006-12-21 | Memory Pharmaceuticals Corporation | Trisubstituted amines as phosphodiesterase 4 inhibitors |
| WO2008105386A1 (ja) * | 2007-02-27 | 2008-09-04 | National University Corporation Okayama University | アルコキシ基を有するレキシノイド化合物 |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
| JP2010523695A (ja) * | 2007-04-11 | 2010-07-15 | アルコン リサーチ， リミテッド | アレルギー性鼻炎およびアレルギー性結膜炎を処置するためのＴＮＦαのインヒビターおよび抗ヒスタミン薬の使用 |
| WO2009067607A2 (en) * | 2007-11-20 | 2009-05-28 | Memory Pharmaceuticals Corporation | Combinations of pde4 inhibitors and antipsychotics for the treatment of psychotic disorders |
| EP2070913A1 (en) * | 2007-12-14 | 2009-06-17 | CHIESI FARMACEUTICI S.p.A. | Ester derivatives as phosphodiesterase inhibitors |
| EP2110375A1 (en) * | 2008-04-14 | 2009-10-21 | CHIESI FARMACEUTICI S.p.A. | Phosphodiesterase-4 inhibitors belonging to the tertiary amine class |
| US20100029689A1 (en) * | 2008-07-02 | 2010-02-04 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| WO2010041449A1 (ja) * | 2008-10-09 | 2010-04-15 | 国立大学法人 岡山大学 | Rxr作動性物質を有効成分とする抗アレルギー剤 |
| BR112012007091A2 (pt) * | 2009-10-01 | 2016-04-19 | Alcon Res Ltd | composições de olopatadina e seus usos |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| CA2895209C (en) | 2013-03-14 | 2022-07-19 | Venkataiah Bollu | Substituted pyridine and pyrazine compounds as pde4 inhibitors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002074726A2 (en) * | 2001-01-22 | 2002-09-26 | Memory Pharmaceuticals Corporation | Aniline derivatives useful as phosphodiesterase 4 inhibitors |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9311281D0 (en) | 1993-06-01 | 1993-07-21 | Rhone Poulenc Rorer Ltd | Novel composition of matter |
| US5935978A (en) | 1991-01-28 | 1999-08-10 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| US5698711A (en) | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| US6096768A (en) | 1992-01-28 | 2000-08-01 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| EP0607373B1 (en) | 1992-06-15 | 1997-03-19 | Celltech Therapeutics Limited | Trisubstituted phenyl derivatives as selective phosphodiesterase iv inhibitors |
| JP3775684B2 (ja) | 1992-07-28 | 2006-05-17 | ローン−プーラン・ロレ・リミテツド | 脂肪族−またはヘテロ原子−含有連結基によりアリールまたはヘテロアリールに連結されたフェニル含有化合物 |
| US5679696A (en) | 1992-07-28 | 1997-10-21 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic-or heteroatom-containing linking group |
| US5814651A (en) | 1992-12-02 | 1998-09-29 | Pfizer Inc. | Catechol diethers as selective PDEIV inhibitors |
| TW263495B (enExample) | 1992-12-23 | 1995-11-21 | Celltech Ltd | |
| US5622977A (en) | 1992-12-23 | 1997-04-22 | Celltech Therapeutics Limited | Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same |
| RU2083562C1 (ru) * | 1993-02-05 | 1997-07-10 | Исихара Сангио Кайся Лтд. | Производные пиридина, способ их получения, инсектицидная композиция |
| GB9304920D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| EP0700389A1 (en) | 1993-05-27 | 1996-03-13 | Smithkline Beecham Laboratoires Pharmaceutiques | Anti-arrhythmic n-substituted 3-benzazepines or isoquinolines |
| SI0706513T1 (en) | 1993-07-02 | 2002-10-31 | Altana Pharma Ag | Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors |
| GB9315595D0 (en) | 1993-07-28 | 1993-09-08 | Res Inst Medicine Chem | New compounds |
| GB9326699D0 (en) | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| ATE260911T1 (de) | 1993-12-22 | 2004-03-15 | Celltech R&D Ltd | Trisubstituierte phenyl-derivate, verfahren zu deren herstellung und deren verwendung als phosphodiesterase (typ iv) hemmstoffe |
| GB9401460D0 (en) * | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
| AU707748B2 (en) | 1994-03-25 | 1999-07-22 | Isotechnika Inc. | Enhancement of the efficacy of drugs by deuteration |
| US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| US5786354A (en) | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| GB9412571D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412672D0 (en) | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| US5591776A (en) | 1994-06-24 | 1997-01-07 | Euro-Celtique, S.A. | Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV |
| FR2729142A1 (fr) | 1995-01-06 | 1996-07-12 | Smithkline Beecham Lab | Nouvelles amines heterocycliques, leur procede de preparation et leur utilisation en tant que medicaments et notamment en tant qu'agents anti-arythmiques |
| US5731477A (en) | 1995-01-31 | 1998-03-24 | Smithkline Beecham Corporation | Method for synthesis of aryl difluoromethyl ethers |
| IT1275433B (it) | 1995-05-19 | 1997-08-07 | Smithkline Beecham Farma | Derivati di diarildiammine |
| AU5772196A (en) | 1995-05-19 | 1996-11-29 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| FR2735777B1 (fr) | 1995-06-21 | 1997-09-12 | Sanofi Sa | Derives de 4-phenylaminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant |
| WO1997022586A1 (en) * | 1995-12-15 | 1997-06-26 | Merck Frosst Canada Inc. | Tri-aryl ethane derivatives as pde iv inhibitors |
| GB9603723D0 (en) | 1996-02-22 | 1996-04-24 | Merck & Co Inc | Diphenyl pyridyl derivatives as pde iv inhibitors |
| US5710170A (en) | 1995-12-15 | 1998-01-20 | Merck Frosst Canada, Inc. | Tri-aryl ethane derivatives as PDE IV inhibitors |
| GB9526243D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526245D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1997048697A1 (en) * | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| SK176598A3 (en) | 1996-06-25 | 2000-06-12 | Pfizer | Indazole derivatives, pharmaceutical composition on their base and methods of treatment |
| JPH1072415A (ja) | 1996-06-26 | 1998-03-17 | Nikken Chem Co Ltd | ３−アニリノ−２−シクロアルケノン誘導体 |
| CN1234031A (zh) | 1996-09-04 | 1999-11-03 | 辉瑞大药厂 | 吲唑衍生物及其作为磷酸二酯酶(pde)iv型和肿瘤坏死因子(tnf)产生的抑制剂的应用 |
| GB9622386D0 (en) | 1996-10-28 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| GB9625184D0 (en) | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1998058901A1 (en) | 1997-06-24 | 1998-12-30 | Nikken Chemicals Co., Ltd. | 3-anilino-2-cycloalkenone derivates |
| TW374919B (en) * | 1997-08-28 | 1999-11-21 | Hitachi Ltd | Synchronous memory unit |
| US5919937A (en) | 1997-10-29 | 1999-07-06 | Merck & Co., Inc. | Process for phosphodiesterase IV inhibitors |
| PT1045690E (pt) | 1997-11-25 | 2003-08-29 | Warner Lambert Co | Benzenossulfonamidas inibidoras da pde-iv e seu uso terapeutico |
| JP4754068B2 (ja) | 1997-12-24 | 2011-08-24 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | δ−オピオイドレセプターに結合する４−［アリール（ピペリジン−４−イル）］アミノベンズアミド類 |
| JP3542482B2 (ja) * | 1997-12-25 | 2004-07-14 | 日研化学株式会社 | ３−アニリノ−２−シクロアルケノン誘導体 |
| AU2529799A (en) * | 1998-02-09 | 1999-08-23 | Darwin Discovery Limited | Benzofuran-4-carboxamides and their therapeutic use |
| AU764005B2 (en) | 1999-02-25 | 2003-08-07 | Merck Frosst Canada & Co. | PDE IV inhibiting compounds, compositions and methods of treatment |
| US6180650B1 (en) | 1999-04-23 | 2001-01-30 | Merck Frosst Canada & Co. | Heterosubstituted pyridine derivatives as PDE 4 inhibitors |
| US6200993B1 (en) | 1999-05-05 | 2001-03-13 | Merck Frosst Canada & Co. | Heterosubstituted pyridine derivatives as PDE4 inhibitors |
| GB2350110A (en) | 1999-05-17 | 2000-11-22 | Bayer Ag | Pharmaceutically active benzofurans |
| WO2000071129A1 (en) | 1999-05-21 | 2000-11-30 | Bristol-Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
| JP4434362B2 (ja) | 1999-06-28 | 2010-03-17 | 興和創薬株式会社 | ホスホジエステラーゼ阻害剤 |
| DE50011851D1 (de) * | 1999-12-18 | 2006-01-19 | Wella Ag | 2-Aminoalkyl-1,4-diaminobenzol-Derivate und diese Verbindungen enthaltende Färbemittel |
| MY123585A (en) | 2000-03-23 | 2006-05-31 | Merck Canada Inc | Tri-aryl-substituted-ethane pde4 inhibitors. |
| CA2407780A1 (en) * | 2000-05-25 | 2001-11-29 | Merck Frosst Canada & Co./Merck Frosst Canada & Cie | Fluoroalkoxy-substituted benzamide dichloropyridinyl n-oxide pde4 inhibitor |
| KR100847169B1 (ko) | 2000-12-21 | 2008-07-17 | 글락소 그룹 리미티드 | 혈관형성 조절제로서의 피리미딘아민 |
| US6699890B2 (en) | 2000-12-22 | 2004-03-02 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| WO2004009552A1 (en) * | 2002-07-19 | 2004-01-29 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
-
2003
- 2003-11-19 EP EP03786857A patent/EP1569908B1/en not_active Expired - Lifetime
- 2003-11-19 CN CNB2003801036392A patent/CN100513397C/zh not_active Expired - Fee Related
- 2003-11-19 AT AT03786857T patent/ATE481387T1/de not_active IP Right Cessation
- 2003-11-19 DE DE60334243T patent/DE60334243D1/de not_active Expired - Lifetime
- 2003-11-19 MX MXPA05005345A patent/MXPA05005345A/es active IP Right Grant
- 2003-11-19 JP JP2004553941A patent/JP2006508987A/ja not_active Ceased
- 2003-11-19 RU RU2005119627/04A patent/RU2356893C2/ru not_active IP Right Cessation
- 2003-11-19 NZ NZ540138A patent/NZ540138A/en not_active IP Right Cessation
- 2003-11-19 US US10/715,819 patent/US7087625B2/en not_active Expired - Fee Related
- 2003-11-19 WO PCT/US2003/036986 patent/WO2004046113A2/en not_active Ceased
- 2003-11-19 AU AU2003295656A patent/AU2003295656B2/en not_active Expired - Fee Related
- 2003-11-19 BR BR0315705-9A patent/BR0315705A/pt not_active Application Discontinuation
- 2003-11-19 CA CA002506297A patent/CA2506297A1/en not_active Abandoned
- 2003-11-19 KR KR1020057008915A patent/KR20050075430A/ko not_active Ceased
-
2005
- 2005-05-18 ZA ZA200503995A patent/ZA200503995B/en unknown
- 2005-06-17 NO NO20052976A patent/NO20052976L/no unknown
-
2006
- 2006-03-20 US US11/378,615 patent/US7700631B2/en not_active Expired - Fee Related
-
2010
- 2010-03-16 US US12/724,750 patent/US20100173942A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002074726A2 (en) * | 2001-01-22 | 2002-09-26 | Memory Pharmaceuticals Corporation | Aniline derivatives useful as phosphodiesterase 4 inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1714081A (zh) | 2005-12-28 |
| NO20052976L (no) | 2005-08-18 |
| KR20050075430A (ko) | 2005-07-20 |
| AU2003295656A1 (en) | 2004-06-15 |
| US7087625B2 (en) | 2006-08-08 |
| US20100173942A1 (en) | 2010-07-08 |
| MXPA05005345A (es) | 2005-08-26 |
| WO2004046113A3 (en) | 2005-03-24 |
| RU2005119627A (ru) | 2006-01-27 |
| NO20052976D0 (no) | 2005-06-17 |
| EP1569908B1 (en) | 2010-09-15 |
| EP1569908A2 (en) | 2005-09-07 |
| BR0315705A (pt) | 2005-09-06 |
| CN100513397C (zh) | 2009-07-15 |
| DE60334243D1 (de) | 2010-10-28 |
| US7700631B2 (en) | 2010-04-20 |
| ZA200503995B (en) | 2006-08-30 |
| WO2004046113A2 (en) | 2004-06-03 |
| RU2356893C2 (ru) | 2009-05-27 |
| AU2003295656A2 (en) | 2005-06-30 |
| JP2006508987A (ja) | 2006-03-16 |
| ATE481387T1 (de) | 2010-10-15 |
| US20060211865A1 (en) | 2006-09-21 |
| CA2506297A1 (en) | 2004-06-03 |
| US20040152902A1 (en) | 2004-08-05 |
| NZ540138A (en) | 2008-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003295656B2 (en) | Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors | |
| EP1692109B1 (en) | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs | |
| EP1435944B1 (en) | 4(4-alkoxy-3-hydroxyphenyl)-2-pyrrolidone derivatives as pde-4 inhibitors for the treatment of neurological syndromes | |
| AU2003256616B2 (en) | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs | |
| AU2002303078B2 (en) | Aniline derivatives useful as phosphodiesterase 4 inhibitors | |
| AU2002303078A1 (en) | Aniline derivatives useful as phosphodiesterase 4 inhibitors | |
| US20100093806A1 (en) | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs | |
| AU2002335015A1 (en) | 4-(4-alkoxy-3-hydroxyphenyl)-2-pyrrolidone derivatives as pde-4 inhibitors for the treatment of neurological syndromes | |
| US7205320B2 (en) | Phosphodiesterase 4 inhibitors | |
| US7153871B2 (en) | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs | |
| NZ547469A (en) | 6-Amino-1H-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 26 MAY 2005 |
|
| MK25 | Application lapsed reg. 22.2i(2) - failure to pay acceptance fee |