JP2014508184A5 - - Google Patents

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Publication number

JP2014508184A5

JP2014508184A5 JP2013558454A JP2013558454A JP2014508184A5 JP 2014508184 A5 JP2014508184 A5 JP 2014508184A5 JP 2013558454 A JP2013558454 A JP 2013558454A JP 2013558454 A JP2013558454 A JP 2013558454A JP 2014508184 A5 JP2014508184 A5 JP 2014508184A5

Authority

JP

Japan

Prior art keywords

phenyl

substituted

cycloalkyl

alkyl

heterocyclyl

Prior art date

2012-03-16

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.)

Granted

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• Espacenet
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• 125000000217 alkyl group Chemical group 0.000 claims 35
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 34
• 150000001875 compounds Chemical class 0.000 claims 21
• 125000000623 heterocyclic group Chemical group 0.000 claims 15
• 125000000753 cycloalkyl group Chemical group 0.000 claims 10
• 229910052736 halogen Inorganic materials 0.000 claims 10
• 150000002367 halogens Chemical class 0.000 claims 10
• -1 cyano, hydroxyl Chemical group 0.000 claims 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 7
• 239000003112 inhibitor Substances 0.000 claims 7
• 239000008194 pharmaceutical composition Substances 0.000 claims 6
• 125000001072 heteroaryl group Chemical group 0.000 claims 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 4
• 229910052731 fluorine Inorganic materials 0.000 claims 4
• 239000011737 fluorine Substances 0.000 claims 4
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 3
• 239000003795 chemical substances by application Substances 0.000 claims 3
• 201000010099 disease Diseases 0.000 claims 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 2
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims 2
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims 2
• 102000012440 Acetylcholinesterase Human genes 0.000 claims 2
• 108010022752 Acetylcholinesterase Proteins 0.000 claims 2
• 206010019375 Helicobacter infections Diseases 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims 2
• 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims 2
• 229940022698 acetylcholinesterase Drugs 0.000 claims 2
• LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 claims 2
• 125000003302 alkenyloxy group Chemical group 0.000 claims 2
• 125000003545 alkoxy group Chemical group 0.000 claims 2
• 125000005133 alkynyloxy group Chemical group 0.000 claims 2
• 239000003814 drug Substances 0.000 claims 2
• 229910052739 hydrogen Inorganic materials 0.000 claims 2
• 239000001257 hydrogen Substances 0.000 claims 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
• 230000001771 impaired effect Effects 0.000 claims 2
• 230000002757 inflammatory effect Effects 0.000 claims 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
• 201000006417 multiple sclerosis Diseases 0.000 claims 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
• 125000003386 piperidinyl group Chemical group 0.000 claims 2
• 150000003839 salts Chemical class 0.000 claims 2
• 239000012453 solvate Substances 0.000 claims 2
• 125000004001 thioalkyl group Chemical group 0.000 claims 2
• NITUEMISTORFON-PPFXTMJRSA-N (2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2R)-2-aminopropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@@H](C)N)C(C)C)C(C)C)C1=CC=CC=C1 NITUEMISTORFON-PPFXTMJRSA-N 0.000 claims 1
• 208000023697 ABri amyloidosis Diseases 0.000 claims 1
• 208000017227 ADan amyloidosis Diseases 0.000 claims 1
• 208000024827 Alzheimer disease Diseases 0.000 claims 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims 1
• 102000009091 Amyloidogenic Proteins Human genes 0.000 claims 1
• 108010048112 Amyloidogenic Proteins Proteins 0.000 claims 1
• 201000001320 Atherosclerosis Diseases 0.000 claims 1
• 208000012639 Balance disease Diseases 0.000 claims 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
• 201000010374 Down Syndrome Diseases 0.000 claims 1
• 206010061825 Duodenal neoplasm Diseases 0.000 claims 1
• 208000030814 Eating disease Diseases 0.000 claims 1
• 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
• 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 1
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 1
• 208000023105 Huntington disease Diseases 0.000 claims 1
• 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 claims 1
• 201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 claims 1
• 101710144961 Interferon tau-1 Proteins 0.000 claims 1
• 101710144950 Interferon tau-2 Proteins 0.000 claims 1
• 101710144962 Interferon tau-3 Proteins 0.000 claims 1
• 102000004388 Interleukin-4 Human genes 0.000 claims 1
• 108090000978 Interleukin-4 Proteins 0.000 claims 1
• 208000027747 Kennedy disease Diseases 0.000 claims 1
• 206010027476 Metastases Diseases 0.000 claims 1
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims 1
• 229940082332 Muscarinic M1 receptor antagonist Drugs 0.000 claims 1
• 108010008881 NBI 5788 Proteins 0.000 claims 1
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 claims 1
• 229930012538 Paclitaxel Natural products 0.000 claims 1
• 206010033645 Pancreatitis Diseases 0.000 claims 1
• 102100031674 Protein-L-isoaspartate(D-aspartate) O-methyltransferase Human genes 0.000 claims 1
• 201000004681 Psoriasis Diseases 0.000 claims 1
• 208000028017 Psychotic disease Diseases 0.000 claims 1
• 206010037779 Radiculopathy Diseases 0.000 claims 1
• 102100028656 Sigma non-opioid intracellular receptor 1 Human genes 0.000 claims 1
• 101710104750 Sigma non-opioid intracellular receptor 1 Proteins 0.000 claims 1
• 206010054184 Small intestine carcinoma Diseases 0.000 claims 1
• 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims 1
• 201000008629 Zollinger-Ellison syndrome Diseases 0.000 claims 1
• 229960002916 adapalene Drugs 0.000 claims 1
• 229960000548 alemtuzumab Drugs 0.000 claims 1
• 125000002877 alkyl aryl group Chemical group 0.000 claims 1
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 1
• 229940035678 anti-parkinson drug Drugs 0.000 claims 1
• 239000000935 antidepressant agent Substances 0.000 claims 1
• 229940005513 antidepressants Drugs 0.000 claims 1
• 239000000164 antipsychotic agent Substances 0.000 claims 1
• 229940005529 antipsychotics Drugs 0.000 claims 1
• 239000002249 anxiolytic agent Substances 0.000 claims 1
• 230000000949 anxiolytic effect Effects 0.000 claims 1
• 229940005530 anxiolytics Drugs 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 claims 1
• 210000000467 autonomic pathway Anatomy 0.000 claims 1
• 239000002439 beta secretase inhibitor Substances 0.000 claims 1
• 230000033228 biological regulation Effects 0.000 claims 1
• 230000015572 biosynthetic process Effects 0.000 claims 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
• 229910052794 bromium Inorganic materials 0.000 claims 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 201000011510 cancer Diseases 0.000 claims 1
• 208000035269 cancer or benign tumor Diseases 0.000 claims 1
• 239000000969 carrier Substances 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 claims 1
• 229910052801 chlorine Inorganic materials 0.000 claims 1
• 239000000460 chlorine Substances 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• 208000010877 cognitive disease Diseases 0.000 claims 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
• 230000003210 demyelinating effect Effects 0.000 claims 1
• 230000008021 deposition Effects 0.000 claims 1
• 238000010511 deprotection reaction Methods 0.000 claims 1
• 239000003085 diluting agent Substances 0.000 claims 1
• 235000014632 disordered eating Nutrition 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 201000000312 duodenum cancer Diseases 0.000 claims 1
• 230000004064 dysfunction Effects 0.000 claims 1
• 230000008482 dysregulation Effects 0.000 claims 1
• 230000037149 energy metabolism Effects 0.000 claims 1
• 239000003623 enhancer Substances 0.000 claims 1
• 239000002792 enkephalinase inhibitor Substances 0.000 claims 1
• 239000002532 enzyme inhibitor Substances 0.000 claims 1
• 229940125532 enzyme inhibitor Drugs 0.000 claims 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
• 239000012530 fluid Substances 0.000 claims 1
• 239000003540 gamma secretase inhibitor Substances 0.000 claims 1
• 206010017758 gastric cancer Diseases 0.000 claims 1
• 201000000052 gastrinoma Diseases 0.000 claims 1
• 125000001188 haloalkyl group Chemical group 0.000 claims 1
• 239000003395 histamine H3 receptor antagonist Substances 0.000 claims 1
• 230000013632 homeostatic process Effects 0.000 claims 1
• 230000003054 hormonal effect Effects 0.000 claims 1
• 230000028996 humoral immune response Effects 0.000 claims 1
• 239000002955 immunomodulating agent Substances 0.000 claims 1
• 229940121354 immunomodulator Drugs 0.000 claims 1
• 229960003444 immunosuppressant agent Drugs 0.000 claims 1
• 239000003018 immunosuppressive agent Substances 0.000 claims 1
• 208000000509 infertility Diseases 0.000 claims 1
• 230000036512 infertility Effects 0.000 claims 1
• 231100000535 infertility Toxicity 0.000 claims 1
• 108700027921 interferon tau Proteins 0.000 claims 1
• 229940028885 interleukin-4 Drugs 0.000 claims 1
• 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims 1
• 230000021633 leukocyte mediated immunity Effects 0.000 claims 1
• 230000003211 malignant effect Effects 0.000 claims 1
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims 1
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims 1
• 201000001441 melanoma Diseases 0.000 claims 1
• 230000009401 metastasis Effects 0.000 claims 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
• 230000005012 migration Effects 0.000 claims 1
• 238000013508 migration Methods 0.000 claims 1
• 208000027061 mild cognitive impairment Diseases 0.000 claims 1
• 125000002757 morpholinyl group Chemical group 0.000 claims 1
• 239000000234 muscarinic M1 receptor antagonist Substances 0.000 claims 1
• 229960005027 natalizumab Drugs 0.000 claims 1
• 230000004770 neurodegeneration Effects 0.000 claims 1
• 239000004090 neuroprotective agent Substances 0.000 claims 1
• 229910052757 nitrogen Inorganic materials 0.000 claims 1
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
• 229960001592 paclitaxel Drugs 0.000 claims 1
• 230000001717 pathogenic effect Effects 0.000 claims 1
• 125000004193 piperazinyl group Chemical group 0.000 claims 1
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• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
• 108010018276 trimethylguanosine synthase Proteins 0.000 claims 1
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 claims 1
• 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 claims 1