JP2010511013A5 - - Google Patents

Info

Publication number

JP2010511013A5

JP2010511013A5 JP2009538704A JP2009538704A JP2010511013A5 JP 2010511013 A5 JP2010511013 A5 JP 2010511013A5 JP 2009538704 A JP2009538704 A JP 2009538704A JP 2009538704 A JP2009538704 A JP 2009538704A JP 2010511013 A5 JP2010511013 A5 JP 2010511013A5

Authority

JP

Japan

Prior art keywords

compound

alkyl

formula

inhibitor

heteroaryl

Prior art date

2007-11-28

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

Links

• Espacenet
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• 150000001875 compounds Chemical class 0.000 claims 39
• 239000003112 inhibitor Substances 0.000 claims 8
• 125000001072 heteroaryl group Chemical group 0.000 claims 7
• 125000000217 alkyl group Chemical group 0.000 claims 6
• 125000003118 aryl group Chemical group 0.000 claims 6
• 201000010099 disease Diseases 0.000 claims 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
• 229910052739 hydrogen Inorganic materials 0.000 claims 6
• 239000008194 pharmaceutical composition Substances 0.000 claims 6
• 239000001257 hydrogen Substances 0.000 claims 5
• 206010019375 Helicobacter infections Diseases 0.000 claims 4
• 206010028980 Neoplasm Diseases 0.000 claims 4
• 239000003814 drug Substances 0.000 claims 4
• 230000001771 impaired effect Effects 0.000 claims 4
• 238000000034 method Methods 0.000 claims 4
• -1 pyridin-3-ylmethyl Chemical group 0.000 claims 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 4
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
• 125000003342 alkenyl group Chemical group 0.000 claims 3
• 239000003795 chemical substances by application Substances 0.000 claims 3
• 230000002757 inflammatory effect Effects 0.000 claims 3
• 201000006417 multiple sclerosis Diseases 0.000 claims 3
• 238000002360 preparation method Methods 0.000 claims 3
• 150000003839 salts Chemical class 0.000 claims 3
• 239000012453 solvate Substances 0.000 claims 3
• 230000001225 therapeutic effect Effects 0.000 claims 3
• 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
• 208000023697 ABri amyloidosis Diseases 0.000 claims 2
• 208000017227 ADan amyloidosis Diseases 0.000 claims 2
• 102000012440 Acetylcholinesterase Human genes 0.000 claims 2
• 108010022752 Acetylcholinesterase Proteins 0.000 claims 2
• 208000024827 Alzheimer disease Diseases 0.000 claims 2
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims 2
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims 2
• 201000001320 Atherosclerosis Diseases 0.000 claims 2
• 208000012639 Balance disease Diseases 0.000 claims 2
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims 2
• 206010009944 Colon cancer Diseases 0.000 claims 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
• 201000010374 Down Syndrome Diseases 0.000 claims 2
• 206010061825 Duodenal neoplasm Diseases 0.000 claims 2
• 208000030814 Eating disease Diseases 0.000 claims 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims 2
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 2
• 208000023105 Huntington disease Diseases 0.000 claims 2
• 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 claims 2
• 201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 claims 2
• 208000027747 Kennedy disease Diseases 0.000 claims 2
• 206010027476 Metastases Diseases 0.000 claims 2
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims 2
• 206010033645 Pancreatitis Diseases 0.000 claims 2
• 201000004681 Psoriasis Diseases 0.000 claims 2
• 206010037779 Radiculopathy Diseases 0.000 claims 2
• 206010054184 Small intestine carcinoma Diseases 0.000 claims 2
• 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
• 230000024932 T cell mediated immunity Effects 0.000 claims 2
• 206010044688 Trisomy 21 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
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims 2
• 201000008629 Zollinger-Ellison syndrome Diseases 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
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
• 230000033228 biological regulation Effects 0.000 claims 2
• 230000015572 biosynthetic process Effects 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 125000004452 carbocyclyl group Chemical group 0.000 claims 2
• 238000006243 chemical reaction Methods 0.000 claims 2
• 230000001684 chronic effect Effects 0.000 claims 2
• 230000003210 demyelinating effect Effects 0.000 claims 2
• 235000014632 disordered eating Nutrition 0.000 claims 2
• 201000000312 duodenum cancer Diseases 0.000 claims 2
• 230000008482 dysregulation Effects 0.000 claims 2
• 230000037149 energy metabolism Effects 0.000 claims 2
• 206010017758 gastric cancer Diseases 0.000 claims 2
• 201000000052 gastrinoma Diseases 0.000 claims 2
• 230000013632 homeostatic process Effects 0.000 claims 2
• 230000003054 hormonal effect Effects 0.000 claims 2
• 230000028996 humoral immune response Effects 0.000 claims 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• 208000000509 infertility Diseases 0.000 claims 2
• 230000036512 infertility Effects 0.000 claims 2
• 231100000535 infertility Toxicity 0.000 claims 2
• 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims 2
• 230000003211 malignant effect Effects 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 201000001441 melanoma Diseases 0.000 claims 2
• 230000009401 metastasis Effects 0.000 claims 2
• 230000005012 migration Effects 0.000 claims 2
• 238000013508 migration Methods 0.000 claims 2
• 208000006473 polyradiculopathy Diseases 0.000 claims 2
• 208000037803 restenosis Diseases 0.000 claims 2
• 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
• 201000000980 schizophrenia Diseases 0.000 claims 2
• 208000020685 sleep-wake disease Diseases 0.000 claims 2
• 201000011549 stomach cancer Diseases 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
• DQEZONNIYRJOSN-UHFFFAOYSA-N 5-(3h-benzimidazol-5-yl)-3h-1,3,4-oxadiazole-2-thione Chemical compound O1C(=S)NN=C1C1=CC=C(N=CN2)C2=C1 DQEZONNIYRJOSN-UHFFFAOYSA-N 0.000 claims 1
• 102000009091 Amyloidogenic Proteins Human genes 0.000 claims 1
• 108010048112 Amyloidogenic Proteins Proteins 0.000 claims 1
• 206010003840 Autonomic nervous system imbalance Diseases 0.000 claims 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
• 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 claims 1
• 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 claims 1
• 229940094664 Cysteine protease inhibitor Drugs 0.000 claims 1
• 102000004190 Enzymes Human genes 0.000 claims 1
• 108090000790 Enzymes Proteins 0.000 claims 1
• 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 1
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims 1
• 206010061218 Inflammation 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
• 229940123313 MCP-1 antagonist Drugs 0.000 claims 1
• 229940082332 Muscarinic M1 receptor antagonist Drugs 0.000 claims 1
• 108010008881 NBI 5788 Proteins 0.000 claims 1
• 229940099433 NMDA receptor antagonist Drugs 0.000 claims 1
• 229930012538 Paclitaxel Natural products 0.000 claims 1
• 102100031674 Protein-L-isoaspartate(D-aspartate) O-methyltransferase Human genes 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
• 208000025865 Ulcer Diseases 0.000 claims 1
• 229960002916 adapalene Drugs 0.000 claims 1
• 229960000548 alemtuzumab Drugs 0.000 claims 1
• 125000003545 alkoxy group Chemical group 0.000 claims 1
• 125000000304 alkynyl 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
• 239000000939 antiparkinson agent Substances 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
• 210000000467 autonomic pathway Anatomy 0.000 claims 1
• 239000002439 beta secretase inhibitor Substances 0.000 claims 1
• 125000002619 bicyclic group Chemical group 0.000 claims 1
• 210000001124 body fluid Anatomy 0.000 claims 1
• 239000010839 body fluid Substances 0.000 claims 1
• 208000035269 cancer or benign tumor Diseases 0.000 claims 1
• 229910052799 carbon Inorganic materials 0.000 claims 1
• 239000000969 carrier Substances 0.000 claims 1
• 239000003153 chemical reaction reagent Substances 0.000 claims 1
• 208000010877 cognitive disease Diseases 0.000 claims 1
• 230000008021 deposition Effects 0.000 claims 1
• 239000003085 diluting agent Substances 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 230000004064 dysfunction Effects 0.000 claims 1
• 210000003038 endothelium Anatomy 0.000 claims 1
• 239000003623 enhancer Substances 0.000 claims 1
• 239000002792 enkephalinase inhibitor Substances 0.000 claims 1
• 229940088598 enzyme Drugs 0.000 claims 1
• 239000002532 enzyme inhibitor Substances 0.000 claims 1
• 229940125532 enzyme inhibitor Drugs 0.000 claims 1
• 239000012530 fluid Substances 0.000 claims 1
• 239000003540 gamma secretase inhibitor Substances 0.000 claims 1
• 229910052736 halogen Inorganic materials 0.000 claims 1
• 150000002367 halogens Chemical class 0.000 claims 1
• 125000000623 heterocyclic group Chemical group 0.000 claims 1
• 239000003395 histamine H3 receptor antagonist Substances 0.000 claims 1
• 239000002955 immunomodulating agent Substances 0.000 claims 1
• 229940121354 immunomodulator Drugs 0.000 claims 1
• 230000002584 immunomodulator Effects 0.000 claims 1
• 229960003444 immunosuppressant agent Drugs 0.000 claims 1
• 230000001861 immunosuppressant effect Effects 0.000 claims 1
• 239000003018 immunosuppressive agent Substances 0.000 claims 1
• 230000004054 inflammatory process Effects 0.000 claims 1
• 108700027921 interferon tau Proteins 0.000 claims 1
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims 1
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
• 208000027061 mild cognitive impairment Diseases 0.000 claims 1
• 239000000234 muscarinic M1 receptor antagonist Substances 0.000 claims 1
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims 1
• 229960005027 natalizumab Drugs 0.000 claims 1
• 230000009826 neoplastic cell growth Effects 0.000 claims 1
• 239000004090 neuroprotective agent Substances 0.000 claims 1
• 229960001592 paclitaxel Drugs 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• 238000006798 ring closing metathesis reaction Methods 0.000 claims 1
• 230000001568 sexual effect Effects 0.000 claims 1
• 241000894007 species Species 0.000 claims 1
• 238000003786 synthesis reaction Methods 0.000 claims 1
• 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
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
• 108010018276 trimethylguanosine synthase Proteins 0.000 claims 1
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 claims 1
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• 229920002554 vinyl polymer Polymers 0.000 claims 1