JP2016020375A - アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 - Google Patents
アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 Download PDFInfo
- Publication number
- JP2016020375A JP2016020375A JP2015189993A JP2015189993A JP2016020375A JP 2016020375 A JP2016020375 A JP 2016020375A JP 2015189993 A JP2015189993 A JP 2015189993A JP 2015189993 A JP2015189993 A JP 2015189993A JP 2016020375 A JP2016020375 A JP 2016020375A
- Authority
- JP
- Japan
- Prior art keywords
- treatment
- methyl
- pharmaceutically acceptable
- carbonic anhydrase
- acceptable salt
- 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.)
- Ceased
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 31
- 108010029485 Protein Isoforms Proteins 0.000 title claims abstract description 27
- 102000001708 Protein Isoforms Human genes 0.000 title claims abstract description 27
- 230000001404 mediated effect Effects 0.000 title claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims abstract description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 208000035475 disorder Diseases 0.000 claims abstract description 23
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 13
- 206010020772 Hypertension Diseases 0.000 claims abstract description 13
- 206010019233 Headaches Diseases 0.000 claims abstract description 12
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 claims abstract description 12
- 208000008445 altitude sickness Diseases 0.000 claims abstract description 12
- 206010015037 epilepsy Diseases 0.000 claims abstract description 12
- 231100000869 headache Toxicity 0.000 claims abstract description 12
- 208000008589 Obesity Diseases 0.000 claims abstract description 11
- 235000020824 obesity Nutrition 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- -1 4-methylpiperazin-1-ylmethyl Chemical group 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 13
- 201000001119 neuropathy Diseases 0.000 claims description 9
- 230000007823 neuropathy Effects 0.000 claims description 9
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 150000004682 monohydrates Chemical class 0.000 claims description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 208000012902 Nervous system disease Diseases 0.000 abstract 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 28
- 229960002411 imatinib Drugs 0.000 description 25
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 25
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 24
- 229960001346 nilotinib Drugs 0.000 description 23
- 108090000209 Carbonic anhydrases Proteins 0.000 description 14
- 102000003846 Carbonic anhydrases Human genes 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 9
- 108010044467 Isoenzymes Proteins 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 5
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 5
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108700012439 CA9 Proteins 0.000 description 3
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 3
- 229960000571 acetazolamide Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000001146 hypoxic effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 102100033040 Carbonic anhydrase 12 Human genes 0.000 description 2
- 101710094325 Carbonic anhydrase 12 Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017886 Gastroduodenal ulcer Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound 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
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 229960003685 imatinib mesylate Drugs 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- YCBPQSYLYYBPDW-UHFFFAOYSA-N 4-methyl-n-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide;hydrate;hydrochloride Chemical compound O.Cl.C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 YCBPQSYLYYBPDW-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000984236 Homo sapiens Carbonic anhydrase 1 Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940069905 tasigna Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
- 229960002911 zonisamide Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
(1)(a)イマチニブまたはその医薬上許容される塩、および(b)本明細書に記載の障害の1つの治療に適している少なくとも1つのさらなる化合物を含む組み合わせ、
(2)(a)ニロチニブまたはその医薬上許容される塩、および(b)本明細書に記載の障害の1つの治療に適している少なくとも1つのさらなる化合物を含む組み合わせ、
(3)(a)イマチニブまたはその医薬上許容される塩、および(b)ニロチニブまたはその医薬上許容される塩を含む組み合わせ、ならびに
(4)(a)イマチニブまたはその医薬上許容される塩、(b)ニロチニブまたはその医薬上許容される塩、および(c)本明細書に記載の障害の1つの治療に適している少なくとも1つのさらなる化合物を含む組み合わせ。
Khalifah, R. G., J. Biol. Chem. 1971, 246, 2561に記載の方法に従ってCA触媒CO2水和反応活性をアッセイするために、Applied Photophysics(Oxford、UK)ストップトフロー装置を使用した。簡単に説明すれば、フェノールレッド(0.2mMの濃度)を指示薬として使用し、CA触媒CO2水和反応に従って、557nmの最大吸光度で、緩衝液として10mM Hepes(pH7.5)を用い、0.1M Na2SO4(イオン強度を一定に保持するため)を用いて行う。CO2濃度は、運動パラメーターおよび阻害定数の決定のために1.7〜17mMの範囲である。各阻害剤について、初速度を決定するために反応の最初の5〜10%の少なくとも6つのトレースを使用する。同様に無触媒率を決定し、観察された全体の率から差し引く。5〜10%(v/v)のDMSO(これらの濃度では阻害しない)を含む蒸留脱イオン水を用いて阻害剤の貯蔵液(10mM)を調製し、その後、蒸留脱イオン水により0.1nMまでの希釈を行う。E−I複合体を形成させるために、阻害剤の溶液および酵素の溶液をアッセイ前に室温で15分間一緒にプレインキュベートする。阻害定数は、PRISM3を使用して非線形最小二乗法によって得られ、少なくとも3つの異なる測定からの平均を表す。CAアイソザイムは、以下の文献によって以前に報告されたように得られる組換え体である:(a)Pastorekova, S. et al, J. Enz. Inhib. Med. Chem. 2004, 19, 199;(b)Supuran, C.T., Scozzafava, A. Bioorg. Med. Chem. 2007, 15, 4336;(c)Nishimori, I. et al, Bioorg. Med. Chem. 2007, 15, 7229;(d)Vullo, D. et al, Bioorg. Med. Chem. Lett. 2005, 15, 971;(e)Nishimori, I. et al, Bioorg. Med. Chem. Lett. 2005, 15, 3828;(f)Vullo, D. et al, Bioorg. Med. Chem. Lett. 2005, 15, 963。
Claims (6)
- 眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症から選択されるα−炭酸脱水酵素アイソフォームによって媒介される障害の処置のための、4−(4−メチルピペラジン−1−イルメチル)−N−[4−メチル−3−(4−ピリジン−3−イル)ピリミジン−2−イルアミノ)フェニル]−ベンズアミドもしくはその医薬上許容される塩、または4−メチル−3−[[4−(3−ピリジニル)−2−ピリミジニル]アミノ]−N−[5−(4−メチル−1H−イミダゾール−1−イル)−3−(トリフルオロメチル)フェニル]ベンズアミドもしくはその医薬上許容される塩。
- 眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症から選択されるα−炭酸脱水酵素アイソフォームによって媒介される障害の処置のための、4−(4−メチルピペラジン−1−イルメチル)−N−[4−メチル−3−(4−ピリジン−3−イル)ピリミジン−2−イルアミノ)フェニル]−ベンズアミドまたはその医薬上許容される塩である、請求項1記載の化合物。
- 眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症から選択されるα−炭酸脱水酵素アイソフォームによって媒介される障害の処置のための、メシル酸塩の形態の、請求項2記載の化合物。
- 眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症から選択されるα−炭酸脱水酵素アイソフォームによって媒介される障害の処置のための、4−メチル−3−[[4−(3−ピリジニル)−2−ピリミジニル]アミノ]−N−[5−(4−メチル−1H−イミダゾール−1−イル)−3−(トリフルオロメチル)フェニル]ベンズアミドまたはその医薬上許容される塩である、請求項1記載の化合物。
- 眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症から選択されるα−炭酸脱水酵素アイソフォームによって媒介される障害の処置のための、塩酸塩・一水和物の形態の、請求項4記載の化合物。
- (a)4−(4−メチルピペラジン−1−イルメチル)−N−[4−メチル−3−(4−ピリジン−3−イル)ピリミジン−2−イルアミノ)フェニル]−ベンズアミドもしくはその医薬上許容される塩、または(b)4−メチル−3−[[4−(3−ピリジニル)−2−ピリミジニル]アミノ]−N−[5−(4−メチル−1H−イミダゾール−1−イル)−3−(トリフルオロメチル)フェニル]ベンズアミドもしくはその医薬上許容される塩、および(c)眼圧亢進症(緑内障)、てんかん、レノックス・ガストー症候群、高山病、頭痛、神経障害および肥満症の処置に適している少なくとも1つのさらなる化合物を含む組み合わせ。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09161720.9 | 2009-06-02 | ||
EP09161720 | 2009-06-02 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012513590A Division JP2012528824A (ja) | 2009-06-02 | 2010-06-01 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017146753A Division JP2017203037A (ja) | 2009-06-02 | 2017-07-28 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016020375A true JP2016020375A (ja) | 2016-02-04 |
JP2016020375A5 JP2016020375A5 (ja) | 2016-06-02 |
Family
ID=40902237
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012513590A Withdrawn JP2012528824A (ja) | 2009-06-02 | 2010-06-01 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
JP2015189993A Ceased JP2016020375A (ja) | 2009-06-02 | 2015-09-28 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
JP2017146753A Withdrawn JP2017203037A (ja) | 2009-06-02 | 2017-07-28 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012513590A Withdrawn JP2012528824A (ja) | 2009-06-02 | 2010-06-01 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017146753A Withdrawn JP2017203037A (ja) | 2009-06-02 | 2017-07-28 | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 |
Country Status (5)
Country | Link |
---|---|
US (1) | US9623025B2 (ja) |
EP (1) | EP2437745B1 (ja) |
JP (3) | JP2012528824A (ja) |
TW (2) | TW201102068A (ja) |
WO (2) | WO2010139678A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101386697B1 (ko) * | 2012-06-18 | 2014-04-18 | 아주대학교산학협력단 | 이매티닙 또는 이의 약학적으로 허용되는 염을 유효성분으로 포함하는 혈관 투과성 관련 질환의 치료 또는 예방용 조성물 |
KR101778004B1 (ko) * | 2015-06-22 | 2017-09-15 | (주) 에빅스젠 | 이마티닙을 유효성분으로 포함하는 안구 건조 질환 예방 및 치료용 약학 조성물 |
CA3063524A1 (en) | 2017-05-19 | 2018-11-22 | Trudell Medical International | Positive expiratory pressure device |
USD903097S1 (en) | 2018-05-18 | 2020-11-24 | Trudell Medical International | Mask |
USD874064S1 (en) | 2018-05-18 | 2020-01-28 | Trudell Medical International | Mask |
TWI770624B (zh) | 2018-06-15 | 2022-07-11 | 漢達生技醫藥股份有限公司 | 尼洛替尼十二烷基硫酸鹽在製備用於治療慢性骨髓性白血病之劑型的用途 |
USD893806S1 (en) | 2018-11-09 | 2020-08-18 | Trudell Medical Internationl | Mask and shroud |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017146753A (ja) * | 2016-02-17 | 2017-08-24 | セイコーエプソン株式会社 | 位置検出装置、及び、そのコントラスト調整方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
TW225528B (ja) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
US5798380A (en) * | 1996-02-21 | 1998-08-25 | Wisconsin Alumni Research Foundation | Cytoskeletal active agents for glaucoma therapy |
CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
CA2477111A1 (en) * | 2002-02-27 | 2003-09-04 | Ab Science | Use of tyrosine kinase inhibitors for treating cns disorders |
GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
BRPI0510485A (pt) * | 2004-04-30 | 2007-11-13 | Allergan Inc | implantes inibidores de tirosina cinase intravìtreos biodegradáveis |
DE602006012313D1 (de) * | 2005-06-03 | 2010-04-01 | Novartis Ag | Kombination aus pyrimidylaminobenzamid-verbindungen und imatinib zur behandlung oder verhinderung proliferativer erkrankungen |
GT200600316A (es) | 2005-07-20 | 2007-04-02 | Sales de 4-metilo-n-(3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo)-3-(4-piridina-3-ilo-pirimidina-2-iloamino)- benzamida. | |
GT200600315A (es) | 2005-07-20 | 2007-03-19 | Formas cristalinas de 4-metilo-n-[3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo]-3-(4-pyridina-3-ilo-pirimidina-2-iloamino)-benzamida | |
EP2139921A2 (en) * | 2007-04-17 | 2010-01-06 | Imclone LLC | PDGFRbeta-SPECIFIC INHIBITORS |
PE20090368A1 (es) * | 2007-06-19 | 2009-04-28 | Boehringer Ingelheim Int | Anticuerpos anti-igf |
-
2010
- 2010-05-31 TW TW099117452A patent/TW201102068A/zh unknown
- 2010-06-01 WO PCT/EP2010/057598 patent/WO2010139678A1/en active Application Filing
- 2010-06-01 WO PCT/US2010/036836 patent/WO2010141427A1/en active Application Filing
- 2010-06-01 EP EP10722356.2A patent/EP2437745B1/en not_active Not-in-force
- 2010-06-01 US US13/375,946 patent/US9623025B2/en not_active Expired - Fee Related
- 2010-06-01 JP JP2012513590A patent/JP2012528824A/ja not_active Withdrawn
- 2010-06-01 TW TW099117619A patent/TWI565466B/zh not_active IP Right Cessation
-
2015
- 2015-09-28 JP JP2015189993A patent/JP2016020375A/ja not_active Ceased
-
2017
- 2017-07-28 JP JP2017146753A patent/JP2017203037A/ja not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017146753A (ja) * | 2016-02-17 | 2017-08-24 | セイコーエプソン株式会社 | 位置検出装置、及び、そのコントラスト調整方法 |
Non-Patent Citations (3)
Title |
---|
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, JPN6016028280, July 2009 (2009-07-01), pages 4102 - 4106 * |
HEMATOL.ONCOL.CLIN.N.AM., vol. 23(1), JPN6015020219, February 2009 (2009-02-01), pages 109 - 114 * |
LEUKEMIA RESEARCH, vol. 32, JPN6015020218, 2008, pages 1022 - 1025 * |
Also Published As
Publication number | Publication date |
---|---|
EP2437745B1 (en) | 2017-08-23 |
WO2010141427A1 (en) | 2010-12-09 |
WO2010139678A1 (en) | 2010-12-09 |
JP2012528824A (ja) | 2012-11-15 |
US9623025B2 (en) | 2017-04-18 |
TW201102069A (en) | 2011-01-16 |
JP2017203037A (ja) | 2017-11-16 |
EP2437745A1 (en) | 2012-04-11 |
US20120088776A1 (en) | 2012-04-12 |
TW201102068A (en) | 2011-01-16 |
TWI565466B (zh) | 2017-01-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2017203037A (ja) | アルファ−炭酸脱水酵素アイソフォームにより媒介される哺乳動物の障害の処置 | |
US20150202203A1 (en) | Method of Treating Gastrointestinal Stromal Tumors | |
US8703787B2 (en) | Methods of using ALK inhibitors | |
TWI839690B (zh) | 治療黑色素瘤的藥物組合的用途 | |
TW201332550A (zh) | 治療胃腸道基質瘤之方法 | |
WO2013063003A1 (en) | Method of treating gastrointestinal stromal tumors | |
JP2018515544A (ja) | Egfr変異癌を治療する方法 | |
JP2014040446A (ja) | Egfr依存性疾患またはegfrファミリーメンバーを標的とする薬剤に対して耐性を獲得した疾患を治療するためのピリミジン誘導体の使用 | |
JP2014526524A (ja) | キナーゼ阻害剤としてのピリジン化合物 | |
US20210179591A1 (en) | New compounds for use as a therapeutically active substance and in particular for use in the treatment of tumors | |
JP2023502252A (ja) | 虚血再灌流傷害および/または肺傷害を処置するための化合物、組成物および方法 | |
Lee et al. | TAK733 attenuates adrenergic receptor-mediated cardiomyocyte hypertrophy via inhibiting Erk Thr188 phosphorylation | |
TWI554502B (zh) | 受體型激酶調節劑及治療多囊性腎疾病的方法 | |
CA2712087A1 (en) | Method of optimizing the treatment of proliferative diseases mediated by the tyrosine kinase receptor kit with imatinib | |
NZ622155B2 (en) | Method of treating gastrointestinal stromal tumors | |
TW201332551A (zh) | 治療胃腸道基質瘤之方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151028 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160328 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160726 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161020 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20170328 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170728 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20170908 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A132 Effective date: 20171003 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171005 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171031 |
|
A045 | Written measure of dismissal of application [lapsed due to lack of payment] |
Free format text: JAPANESE INTERMEDIATE CODE: A045 Effective date: 20180227 |