ES2972295T3 - Sales de 2-(tert-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida - Google Patents
Sales de 2-(tert-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida Download PDFInfo
- Publication number
- ES2972295T3 ES2972295T3 ES20158407T ES20158407T ES2972295T3 ES 2972295 T3 ES2972295 T3 ES 2972295T3 ES 20158407 T ES20158407 T ES 20158407T ES 20158407 T ES20158407 T ES 20158407T ES 2972295 T3 ES2972295 T3 ES 2972295T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- salt
- approximately
- weight
- twenty
- 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.)
- Active
Links
- QBBRJRLJWXRSHQ-CKYFFXLPSA-N 2-(tert-butylamino)-4-[[(1r,3r,4r)-3-hydroxy-4-methylcyclohexyl]amino]pyrimidine-5-carboxamide Chemical class C1[C@@H](O)[C@H](C)CC[C@H]1NC1=NC(NC(C)(C)C)=NC=C1C(N)=O QBBRJRLJWXRSHQ-CKYFFXLPSA-N 0.000 title abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 126
- 238000000034 method Methods 0.000 claims abstract description 102
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 75
- 150000003895 L-lactate salts Chemical class 0.000 claims abstract description 68
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims abstract 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 group 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 abstract 2
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 237
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 119
- 239000000203 mixture Substances 0.000 claims description 104
- 208000035475 disorder Diseases 0.000 claims description 70
- 201000010099 disease Diseases 0.000 claims description 49
- 230000003176 fibrotic effect Effects 0.000 claims description 27
- 230000002440 hepatic effect Effects 0.000 claims description 23
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 16
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 206010025135 lupus erythematosus Diseases 0.000 claims description 12
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 10
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 206010063209 Chronic allograft nephropathy Diseases 0.000 claims description 8
- 201000001200 Crouzon syndrome-acanthosis nigricans syndrome Diseases 0.000 claims description 8
- 206010039710 Scleroderma Diseases 0.000 claims description 8
- 230000009885 systemic effect Effects 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- 208000034189 Sclerosis Diseases 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 abstract description 131
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 abstract description 47
- 150000003890 succinate salts Chemical class 0.000 abstract description 42
- 150000001860 citric acid derivatives Chemical class 0.000 abstract description 17
- ORZMSMCZBZARKY-UHFFFAOYSA-N 1,3,2$l^{6}-benzodioxathiole 2,2-dioxide Chemical class C1=CC=C2OS(=O)(=O)OC2=C1 ORZMSMCZBZARKY-UHFFFAOYSA-N 0.000 abstract description 3
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 abstract 1
- 208000037765 diseases and disorders Diseases 0.000 abstract 1
- 229940125904 compound 1 Drugs 0.000 description 392
- 238000000634 powder X-ray diffraction Methods 0.000 description 192
- 229940126062 Compound A Drugs 0.000 description 186
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 186
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 186
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 183
- 150000003840 hydrochlorides Chemical class 0.000 description 154
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 136
- 239000003826 tablet Substances 0.000 description 131
- 238000011282 treatment Methods 0.000 description 122
- 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 107
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
- 235000019359 magnesium stearate Nutrition 0.000 description 91
- 239000007787 solid Substances 0.000 description 91
- 239000011248 coating agent Substances 0.000 description 82
- 238000000576 coating method Methods 0.000 description 82
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 79
- 239000000243 solution Substances 0.000 description 76
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 69
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- 229930195725 Mannitol Natural products 0.000 description 65
- 239000000594 mannitol Substances 0.000 description 65
- 235000010355 mannitol Nutrition 0.000 description 65
- 239000000523 sample Substances 0.000 description 65
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 63
- 239000012458 free base Substances 0.000 description 61
- 239000002552 dosage form Substances 0.000 description 60
- 238000001704 evaporation Methods 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 238000002441 X-ray diffraction Methods 0.000 description 56
- 239000003085 diluting agent Substances 0.000 description 54
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 53
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 53
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 53
- 238000009472 formulation Methods 0.000 description 52
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 52
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 48
- 239000001768 carboxy methyl cellulose Substances 0.000 description 48
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 48
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 48
- 239000000546 pharmaceutical excipient Substances 0.000 description 46
- 150000001875 compounds Chemical class 0.000 description 43
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 42
- 238000012360 testing method Methods 0.000 description 41
- 235000019886 MethocelTM Nutrition 0.000 description 40
- 239000007884 disintegrant Substances 0.000 description 40
- 238000005259 measurement Methods 0.000 description 40
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 38
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 38
- 239000008108 microcrystalline cellulose Substances 0.000 description 38
- 229940016286 microcrystalline cellulose Drugs 0.000 description 38
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 229920003084 Avicel® PH-102 Polymers 0.000 description 36
- 239000004094 surface-active agent Substances 0.000 description 36
- 238000002411 thermogravimetry Methods 0.000 description 34
- 235000010980 cellulose Nutrition 0.000 description 33
- 229920002678 cellulose Polymers 0.000 description 33
- 239000001913 cellulose Substances 0.000 description 33
- 239000008279 sol Substances 0.000 description 33
- 238000001237 Raman spectrum Methods 0.000 description 32
- 239000000314 lubricant Substances 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 30
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 30
- 239000000463 material Substances 0.000 description 28
- -1 phospho Chemical class 0.000 description 28
- 238000001757 thermogravimetry curve Methods 0.000 description 28
- 239000003814 drug Substances 0.000 description 27
- 230000000694 effects Effects 0.000 description 27
- 239000000843 powder Substances 0.000 description 27
- 239000007858 starting material Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 25
- 239000011230 binding agent Substances 0.000 description 23
- 210000004369 blood Anatomy 0.000 description 23
- 239000008280 blood Substances 0.000 description 23
- 230000003203 everyday effect Effects 0.000 description 23
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 22
- 238000001574 biopsy Methods 0.000 description 22
- 238000010438 heat treatment Methods 0.000 description 22
- 230000000291 postprandial effect Effects 0.000 description 22
- 210000003491 skin Anatomy 0.000 description 22
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 21
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 20
- 102100023132 Transcription factor Jun Human genes 0.000 description 20
- 239000003937 drug carrier Substances 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- 229920002785 Croscarmellose sodium Polymers 0.000 description 18
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 18
- 229960001681 croscarmellose sodium Drugs 0.000 description 18
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 18
- 238000012216 screening Methods 0.000 description 18
- 238000000113 differential scanning calorimetry Methods 0.000 description 17
- 235000013305 food Nutrition 0.000 description 17
- 238000002156 mixing Methods 0.000 description 17
- 230000036470 plasma concentration Effects 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 208000016261 weight loss Diseases 0.000 description 17
- 230000004580 weight loss Effects 0.000 description 17
- 238000003364 immunohistochemistry Methods 0.000 description 16
- 230000003285 pharmacodynamic effect Effects 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- 210000002784 stomach Anatomy 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 239000002775 capsule Substances 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 208000005069 pulmonary fibrosis Diseases 0.000 description 14
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 14
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 14
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 13
- 230000037396 body weight Effects 0.000 description 13
- 229940116298 l- malic acid Drugs 0.000 description 13
- 235000011090 malic acid Nutrition 0.000 description 13
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 13
- 230000037361 pathway Effects 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 108010082126 Alanine transaminase Proteins 0.000 description 12
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 12
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 12
- 230000007423 decrease Effects 0.000 description 12
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 12
- 235000012054 meals Nutrition 0.000 description 12
- 230000003287 optical effect Effects 0.000 description 12
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 11
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 238000005469 granulation Methods 0.000 description 10
- 230000003179 granulation Effects 0.000 description 10
- 230000002265 prevention Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 231100000240 steatosis hepatitis Toxicity 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 238000007906 compression Methods 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 229940098779 methanesulfonic acid Drugs 0.000 description 9
- 201000004071 non-specific interstitial pneumonia Diseases 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 206010052779 Transplant rejections Diseases 0.000 description 8
- 208000036142 Viral infection Diseases 0.000 description 8
- 239000003925 fat Substances 0.000 description 8
- 229940057948 magnesium stearate Drugs 0.000 description 8
- 229960001855 mannitol Drugs 0.000 description 8
- 238000007390 skin biopsy Methods 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 230000009385 viral infection Effects 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 201000009594 Systemic Scleroderma Diseases 0.000 description 7
- 206010042953 Systemic sclerosis Diseases 0.000 description 7
- 210000001217 buttock Anatomy 0.000 description 7
- 208000019425 cirrhosis of liver Diseases 0.000 description 7
- 238000000354 decomposition reaction Methods 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 208000004930 Fatty Liver Diseases 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 6
- 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 6
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 6
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 6
- 206010028813 Nausea Diseases 0.000 description 6
- 235000021152 breakfast Nutrition 0.000 description 6
- 230000006835 compression Effects 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000001530 fumaric acid Substances 0.000 description 6
- 208000006454 hepatitis Diseases 0.000 description 6
- 231100000283 hepatitis Toxicity 0.000 description 6
- 230000000155 isotopic effect Effects 0.000 description 6
- 239000004816 latex Substances 0.000 description 6
- 229920000126 latex Polymers 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000002483 medication Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000008693 nausea Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 239000002910 solid waste Substances 0.000 description 6
- 238000007619 statistical method Methods 0.000 description 6
- 239000001384 succinic acid Substances 0.000 description 6
- 235000011149 sulphuric acid Nutrition 0.000 description 6
- 230000004584 weight gain Effects 0.000 description 6
- 235000019786 weight gain Nutrition 0.000 description 6
- 206010019708 Hepatic steatosis Diseases 0.000 description 5
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 5
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 102000001253 Protein Kinase Human genes 0.000 description 5
- 238000001069 Raman spectroscopy Methods 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000007882 cirrhosis Effects 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 238000002591 computed tomography Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 208000010706 fatty liver disease Diseases 0.000 description 5
- 230000009246 food effect Effects 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940116871 l-lactate Drugs 0.000 description 5
- 229960005489 paracetamol Drugs 0.000 description 5
- 108060006633 protein kinase Proteins 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000002336 sorption--desorption measurement Methods 0.000 description 5
- 230000007863 steatosis Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 4
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 4
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 4
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 230000003466 anti-cipated effect Effects 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229940000406 drug candidate Drugs 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 239000007888 film coating Substances 0.000 description 4
- 238000009501 film coating Methods 0.000 description 4
- 208000002672 hepatitis B Diseases 0.000 description 4
- 231100000304 hepatotoxicity Toxicity 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 238000007449 liver function test Methods 0.000 description 4
- 230000007056 liver toxicity Effects 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000002547 new drug Substances 0.000 description 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 238000001907 polarising light microscopy Methods 0.000 description 4
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 4
- 208000010157 sclerosing cholangitis Diseases 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 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 description 3
- 101150015280 Cel gene Proteins 0.000 description 3
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 3
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 3
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 3
- 206010072268 Drug-induced liver injury Diseases 0.000 description 3
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 3
- 208000006933 Hermanski-Pudlak Syndrome Diseases 0.000 description 3
- 206010071775 Hermansky-Pudlak syndrome Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 108091054455 MAP kinase family Proteins 0.000 description 3
- 108091007780 MiR-122 Proteins 0.000 description 3
- 239000004677 Nylon Substances 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 208000002353 alcoholic hepatitis Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 239000012062 aqueous buffer Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 239000007963 capsule composition Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000006255 coating slurry Substances 0.000 description 3
- 208000018631 connective tissue disease Diseases 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000021471 food effect Nutrition 0.000 description 3
- 239000003517 fume Substances 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 230000002650 habitual effect Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 238000009802 hysterectomy Methods 0.000 description 3
- 238000010191 image analysis Methods 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 230000005906 menstruation Effects 0.000 description 3
- 108091051828 miR-122 stem-loop Proteins 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229920001778 nylon Polymers 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- 229920002635 polyurethane Polymers 0.000 description 3
- 239000004814 polyurethane Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 238000009490 roller compaction Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 235000012976 tarts Nutrition 0.000 description 3
- 238000002076 thermal analysis method Methods 0.000 description 3
- 231100000041 toxicology testing Toxicity 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 241001573498 Compacta Species 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 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 2
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- 206010039203 Road traffic accident Diseases 0.000 description 2
- 102000006463 Talin Human genes 0.000 description 2
- 108010083809 Talin Proteins 0.000 description 2
- 102000007000 Tenascin Human genes 0.000 description 2
- 108010008125 Tenascin Proteins 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 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
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000009838 combustion analysis Methods 0.000 description 2
- 238000005056 compaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000011985 exploratory data analysis Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 230000000423 heterosexual effect Effects 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 229940127554 medical product Drugs 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000004682 monohydrates Chemical group 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 229940127285 new chemical entity Drugs 0.000 description 2
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 2
- 238000000424 optical density measurement Methods 0.000 description 2
- 239000007935 oral tablet Substances 0.000 description 2
- 229940096978 oral tablet Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 238000007415 particle size distribution analysis Methods 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 238000009597 pregnancy test Methods 0.000 description 2
- 239000003909 protein kinase inhibitor Substances 0.000 description 2
- 238000007388 punch biopsy Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000009781 safety test method Methods 0.000 description 2
- 238000012772 sequence design Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 235000011888 snacks Nutrition 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000000934 spermatocidal agent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229940126703 systemic medication Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 229940126702 topical medication Drugs 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000009810 tubal ligation Methods 0.000 description 2
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 238000002562 urinalysis Methods 0.000 description 2
- 238000009528 vital sign measurement Methods 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- UUDLQDCYDSATCH-ZVGUSBNCSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;hydrate Chemical compound O.OC(=O)[C@H](O)[C@@H](O)C(O)=O UUDLQDCYDSATCH-ZVGUSBNCSA-N 0.000 description 1
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- QBWLKDFBINPHFT-UHFFFAOYSA-L 1,3,2$l^{2}-benzodioxabismin-4-one;hydrate Chemical compound O.C1=CC=C2C(=O)O[Bi]OC2=C1 QBWLKDFBINPHFT-UHFFFAOYSA-L 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- DYKCZVHJLMDZEP-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid tetrahydrate Chemical group O.O.O.O.OC(=O)C(O)C(O)C(O)=O DYKCZVHJLMDZEP-UHFFFAOYSA-N 0.000 description 1
- JIMDQTNPLVRAES-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(oxetan-3-yl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2COC2)C=CC=1 JIMDQTNPLVRAES-UHFFFAOYSA-N 0.000 description 1
- KJLPSBMDOIVXSN-UHFFFAOYSA-N 4-[4-[2-[4-(3,4-dicarboxyphenoxy)phenyl]propan-2-yl]phenoxy]phthalic acid Chemical compound C=1C=C(OC=2C=C(C(C(O)=O)=CC=2)C(O)=O)C=CC=1C(C)(C)C(C=C1)=CC=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 KJLPSBMDOIVXSN-UHFFFAOYSA-N 0.000 description 1
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 208000036641 Aspergillus infections Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 208000025962 Crush injury Diseases 0.000 description 1
- 208000000130 Cytochrome P-450 CYP3A Inducers Diseases 0.000 description 1
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010014970 Ephelides Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 241001069765 Fridericia <angiosperm> Species 0.000 description 1
- 231100001273 GLP toxicology study Toxicity 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000023329 Gun shot wound Diseases 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 description 1
- 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101001093997 Homo sapiens Solute carrier family 22 member 8 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 1
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 description 1
- 208000005168 Intussusception Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 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
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000004318 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010007127 Pulmonary Surfactant-Associated Protein D Proteins 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 102100027845 Pulmonary surfactant-associated protein D Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 108091006735 SLC22A2 Proteins 0.000 description 1
- 108091006731 SLCO1B1 Proteins 0.000 description 1
- 108091006730 SLCO1B3 Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 102100035227 Solute carrier family 22 member 8 Human genes 0.000 description 1
- 102100027233 Solute carrier organic anion transporter family member 1B1 Human genes 0.000 description 1
- 102100027239 Solute carrier organic anion transporter family member 1B3 Human genes 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000036981 active tuberculosis Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000026802 afebrile Diseases 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000007486 appendectomy Methods 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000007681 bariatric surgery Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 238000009811 bilateral tubal ligation Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 229960000782 bismuth subsalicylate Drugs 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- 238000002192 cholecystectomy Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000012669 compression test Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000003066 decision tree Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical group 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229940017733 esbriet Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000012395 formulation development Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical class O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000002117 illicit drug Substances 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 208000003243 intestinal obstruction Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000005817 liver abnormality Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940029985 mineral supplement Drugs 0.000 description 1
- 235000020786 mineral supplement Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960004378 nintedanib Drugs 0.000 description 1
- 231100000062 no-observed-adverse-effect level Toxicity 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229940015847 ofev Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960003073 pirfenidone Drugs 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940076155 protein modulator Drugs 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000009613 pulmonary function test Methods 0.000 description 1
- 238000002106 pulse oximetry Methods 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 208000036273 reactive airway disease Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 230000036555 skin type Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 235000019505 tobacco product Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000007879 vasectomy Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/02—Immunomodulators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462092537P | 2014-12-16 | 2014-12-16 | |
| US201562196044P | 2015-07-23 | 2015-07-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2972295T3 true ES2972295T3 (es) | 2024-06-12 |
Family
ID=56110500
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES20158407T Active ES2972295T3 (es) | 2014-12-16 | 2015-12-15 | Sales de 2-(tert-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida |
| ES15870856T Active ES2877642T3 (es) | 2014-12-16 | 2015-12-15 | Formulaciones de 2-(terc-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15870856T Active ES2877642T3 (es) | 2014-12-16 | 2015-12-15 | Formulaciones de 2-(terc-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US9796685B2 (enExample) |
| EP (2) | EP3233809B1 (enExample) |
| JP (2) | JP6762940B2 (enExample) |
| KR (1) | KR102606253B1 (enExample) |
| CN (2) | CN107108524A (enExample) |
| AU (2) | AU2015362728B2 (enExample) |
| BR (1) | BR112017012795A2 (enExample) |
| CA (2) | CA3210612C (enExample) |
| CL (1) | CL2017001545A1 (enExample) |
| CO (1) | CO2017006087A2 (enExample) |
| EA (1) | EA033530B1 (enExample) |
| EC (1) | ECSP17038150A (enExample) |
| ES (2) | ES2972295T3 (enExample) |
| IL (1) | IL252900B (enExample) |
| MX (2) | MX382253B (enExample) |
| NZ (1) | NZ732793A (enExample) |
| SA (1) | SA517381749B1 (enExample) |
| SG (2) | SG11201704827UA (enExample) |
| WO (1) | WO2016100310A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20240097T1 (hr) | 2011-04-22 | 2024-03-29 | Signal Pharmaceuticals, Llc | Supstituirani diaminokarboksamid i diaminokarbonitril pirimidini, njihovi pripravci i postupci liječenja s njima |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| WO2016100310A1 (en) | 2014-12-16 | 2016-06-23 | Signal Pharmaceuticals, Llc | Formulations of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methycyclohexylamino)-pyrimidine-5-carboxamide |
| EP3233808B1 (en) * | 2014-12-16 | 2021-07-14 | Signal Pharmaceuticals, LLC | Medical uses comprising methods for measurement of inhibition of c-jun n-terminal kinase in skin |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| ES2994877T3 (en) | 2015-07-24 | 2025-02-03 | Celgene Corp | Methods of synthesis of (1r,2r,5r)-5-amino-2-methylcyclohexanol hydrochloride and intermediates useful therein |
| DK3358347T3 (da) * | 2015-09-30 | 2020-11-30 | Univ Tohoku | Markør til bestemmelse af diabetisk nefropati |
| AU2019280822A1 (en) | 2018-06-06 | 2021-01-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| KR20200043618A (ko) * | 2018-10-18 | 2020-04-28 | 주식회사유한양행 | 아미노피리미딘 유도체 또는 이의 염을 포함하는 경구투여용 약학 조성물 |
| KR20210029989A (ko) | 2019-09-09 | 2021-03-17 | 김경민 | 야구경기 데이터 기록 서버 및 야구경기 기록데이터 분석방법 |
| CN112574123B (zh) * | 2019-09-30 | 2024-06-11 | 武汉朗来科技发展有限公司 | Jnk抑制剂、其药物组合物和用途 |
| TW202434251A (zh) | 2022-11-04 | 2024-09-01 | 美商必治妥美雅史谷比公司 | 治療癌症之療法 |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH549339A (de) | 1971-05-12 | 1974-05-31 | Ciba Geigy Ag | Herbizides mittel. |
| AU1507199A (en) | 1997-12-15 | 1999-07-05 | Yamanouchi Pharmaceutical Co., Ltd. | Novel pyrimidine-5-carboxamide derivatives |
| DE69933680T2 (de) | 1998-08-29 | 2007-08-23 | Astrazeneca Ab | Pyrimidine verbindungen |
| AU5107900A (en) | 1999-06-09 | 2000-12-28 | Yamanouchi Pharmaceutical Co., Ltd. | Novel heterocyclic carboxamide derivatives |
| AU5108000A (en) | 1999-06-10 | 2001-01-02 | Yamanouchi Pharmaceutical Co., Ltd. | Novel nitrogen-contaiing heterocyclic derivatives or salts thereof |
| HK1045507A1 (zh) * | 1999-08-12 | 2002-11-29 | Vertex Pharmaceuticals Incorporated | C-jun n-末端激酶(jnk)及其他蛋白质激酶的抑制物 |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
| AU2003220968A1 (en) | 2002-03-28 | 2003-10-13 | Kyowa Hakko Kogyo Co., Ltd. | Anti-inflammatory agent |
| EP1518855B1 (en) | 2002-06-28 | 2011-10-26 | Astellas Pharma Inc. | Diaminopyrimidinecarboxa mide derivative |
| BR0313059B8 (pt) | 2002-07-29 | 2021-07-27 | Rigel Pharmaceuticals | composto, e, composição farmacêutica |
| WO2004054617A1 (ja) | 2002-12-13 | 2004-07-01 | Kyowa Hakko Kogyo Co., Ltd. | 中枢疾患の予防および／または治療剤 |
| DE602004022633D1 (de) | 2003-01-30 | 2009-10-01 | Boehringer Ingelheim Pharma | 2,4-diaminopyrimidinderivate, die sich als inhibitoren von pkc-theta eignen |
| TWI378923B (en) | 2003-08-15 | 2012-12-11 | Novartis Ag | Pyrimidine derivatives |
| CN1871009A (zh) | 2003-09-24 | 2006-11-29 | 惠氏控股公司 | 作为抗癌剂的5－芳基嘧啶 |
| WO2005095382A1 (ja) | 2004-03-30 | 2005-10-13 | Kyowa Hakko Kogyo Co., Ltd. | 抗腫瘍剤 |
| WO2006014482A1 (en) | 2004-07-08 | 2006-02-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Pyrimidine derivatives useful as inhibitors of pkc-theta |
| JP2008512429A (ja) | 2004-09-10 | 2008-04-24 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロフルミラストとｓｙｋインヒビターとの組合せ物並びにその使用方法 |
| EP1796679A1 (en) | 2004-09-10 | 2007-06-20 | Altana Pharma AG | Ciclesonide and syk inhibitor combination and methods of use thereof |
| RU2410379C2 (ru) | 2004-09-30 | 2011-01-27 | Тиботек Фармасьютикалз Лтд. | 5-замещенные пиримидины, ингибирующие вич |
| JP2006124387A (ja) | 2004-09-30 | 2006-05-18 | Taisho Pharmaceut Co Ltd | 新規なキノリン、テトラヒドロキナゾリン、及びピリミジン誘導体と、これらを使用することに関連した治療方法 |
| WO2006091737A1 (en) | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Modulators of gsk-3 activity |
| CA2657260A1 (en) | 2006-07-21 | 2008-01-24 | Novartis Ag | 2, 4 -di (arylaminio) -pyrimidine-5-carboxamide compounds as jak kinases inhibitors |
| US20080139531A1 (en) | 2006-12-04 | 2008-06-12 | Alcon Manufacturing Ltd. | Use of connective tissue mast cell stabilizers to facilitate ocular surface re-epithelization and wound repair |
| AP2009005010A0 (en) | 2007-04-18 | 2009-10-31 | Pfizer Prod Inc | Sulfonyl amide derivatives for the treatment of abnormal cell growth |
| US20090036440A1 (en) | 2007-04-27 | 2009-02-05 | Astrazeneca Ab | Novel pyrimidine derivatives - 816 |
| WO2009010789A2 (en) | 2007-07-16 | 2009-01-22 | Astrazeneca Ab | Pyrimidine derivatives 934 |
| CN101903357A (zh) | 2007-07-17 | 2010-12-01 | 里格尔药品股份有限公司 | 作为pkc抑制剂的环状胺取代的嘧啶二胺 |
| JP5705720B2 (ja) | 2008-04-16 | 2015-04-22 | ポートラ ファーマシューティカルズ， インコーポレイテッド | Ｓｙｋまたはｊａｋキナーゼ阻害剤としての２，６−ジアミノ−ピリミジン−５−イル−カルボキサミド |
| KR20100132550A (ko) | 2008-04-16 | 2010-12-17 | 포톨라 파마슈티컬스, 인코포레이티드 | ｓｙｋ 또는 ＪＡＫ 키나제 억제제로서의 ２,６－디아미노-피리미딘－５－일－카르복스아미드 |
| JP2011518219A (ja) | 2008-04-22 | 2011-06-23 | ポートラ ファーマシューティカルズ， インコーポレイテッド | タンパク質キナーゼの阻害剤 |
| EP2300013B2 (en) | 2008-05-21 | 2024-11-13 | Takeda Pharmaceutical Company Limited | Phosphorous derivatives as kinase inhibitors |
| UY31929A (es) | 2008-06-25 | 2010-01-05 | Irm Llc | Compuestos y composiciones como inhibidores de cinasa |
| NZ603525A (en) | 2008-06-27 | 2015-02-27 | Celgene Avilomics Res Inc | Pyrimidine based compound and uses thereof |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| WO2010024430A1 (ja) | 2008-09-01 | 2010-03-04 | アステラス製薬株式会社 | 2,4-ジアミノピリミジン化合物 |
| CA2737738A1 (en) | 2008-09-18 | 2010-03-25 | Astellas Pharma Inc. | Heterocyclic carboxamide compounds |
| TW201016676A (en) | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| CN102272291B (zh) | 2008-10-31 | 2018-01-16 | 詹森生物科技公司 | 人胚胎干细胞向胰腺内分泌谱系的分化 |
| US8513242B2 (en) * | 2008-12-12 | 2013-08-20 | Cystic Fibrosis Foundation Therapeutics, Inc. | Pyrimidine compounds and methods of making and using same |
| EP2375899B1 (en) | 2009-01-12 | 2015-02-25 | Array Biopharma Inc. | Piperidine-containing compounds and use thereof in the treatment of diabetes |
| MX2011007499A (es) | 2009-01-13 | 2011-08-04 | Glaxo Group Ltd | Derivados de pirimidin-carboxamida como inhibidores de la cinasa syk. |
| ES2635504T3 (es) | 2009-01-21 | 2017-10-04 | Rigel Pharmaceuticals, Inc. | Derivados de N2-(3-piridilo o fenil)-N4-(4-piperidil)-2,4-pirimidinadiamina útiles en el tratamiento de enfermedades inflamatorias, toimmunitarias o proliferativas |
| US8367689B2 (en) | 2009-05-06 | 2013-02-05 | Portola Pharmaceuticals, Inc. | Inhibitors of JAK |
| JP5364159B2 (ja) | 2009-05-08 | 2013-12-11 | アステラス製薬株式会社 | ジアミノへテロ環カルボキサミド化合物 |
| CN102498110A (zh) | 2009-06-10 | 2012-06-13 | 雅培制药有限公司 | 作为激酶抑制剂的2-(lh-吡唑-4-基氨基)-嘧啶 |
| JP2012197231A (ja) | 2009-08-06 | 2012-10-18 | Oncotherapy Science Ltd | Ｔｔｋ阻害作用を有するピリジンおよびピリミジン誘導体 |
| WO2011036461A1 (en) | 2009-09-24 | 2011-03-31 | Centro Nacional De Investigaciones Oncόlogicas (Cnio) | Fused imidazo [3, 2 - d] pyrazines as pi3 kinase inhibitors |
| WO2011065800A2 (ko) | 2009-11-30 | 2011-06-03 | 주식회사 오스코텍 | 피리미딘 유도체, 이의 제조방법 및 이를 함유하는 약학적 조성물 |
| US20110130415A1 (en) | 2009-12-01 | 2011-06-02 | Rajinder Singh | Protein kinase c inhibitors and uses thereof |
| JP6035238B2 (ja) | 2010-07-21 | 2016-11-30 | ライジェル ファーマシューティカルズ， インコーポレイテッド | プロテインキナーゼｃ阻害剤およびその使用 |
| US8580805B2 (en) | 2010-08-31 | 2013-11-12 | Hubert Maehr | Pyrimidine carboxamide derivatives |
| WO2012045010A1 (en) | 2010-09-30 | 2012-04-05 | Portola Pharmaceuticals, Inc. | Combinations of 4-(3-(2h-1,2,3-triazo-2-yl) phenylamino)-2-((1r,2s)-2-aminocyclohexylamino) pyrimidine-5-carboxamide and fludarabine |
| WO2012044936A1 (en) | 2010-09-30 | 2012-04-05 | Portola Pharmaceuticals, Inc. | Combination therapy with 4-(3-(2h-1,2,3-triazol-2-yl)phenylamino)-2-((1r,2s)-2-aminocyclohexylamino)pyrimidine-5-carboxamide |
| HRP20240097T1 (hr) * | 2011-04-22 | 2024-03-29 | Signal Pharmaceuticals, Llc | Supstituirani diaminokarboksamid i diaminokarbonitril pirimidini, njihovi pripravci i postupci liječenja s njima |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| WO2016100310A1 (en) * | 2014-12-16 | 2016-06-23 | Signal Pharmaceuticals, Llc | Formulations of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methycyclohexylamino)-pyrimidine-5-carboxamide |
| EP3233808B1 (en) | 2014-12-16 | 2021-07-14 | Signal Pharmaceuticals, LLC | Medical uses comprising methods for measurement of inhibition of c-jun n-terminal kinase in skin |
-
2015
- 2015-12-15 WO PCT/US2015/065774 patent/WO2016100310A1/en not_active Ceased
- 2015-12-15 CN CN201580068532.1A patent/CN107108524A/zh active Pending
- 2015-12-15 SG SG11201704827UA patent/SG11201704827UA/en unknown
- 2015-12-15 EP EP15870856.0A patent/EP3233809B1/en active Active
- 2015-12-15 CA CA3210612A patent/CA3210612C/en active Active
- 2015-12-15 EP EP20158407.5A patent/EP3712134B1/en active Active
- 2015-12-15 SG SG10202010389TA patent/SG10202010389TA/en unknown
- 2015-12-15 ES ES20158407T patent/ES2972295T3/es active Active
- 2015-12-15 CA CA2970926A patent/CA2970926C/en active Active
- 2015-12-15 AU AU2015362728A patent/AU2015362728B2/en active Active
- 2015-12-15 BR BR112017012795-4A patent/BR112017012795A2/pt not_active Application Discontinuation
- 2015-12-15 US US14/969,750 patent/US9796685B2/en active Active
- 2015-12-15 CN CN202011351088.3A patent/CN112451502B/zh active Active
- 2015-12-15 JP JP2017532034A patent/JP6762940B2/ja active Active
- 2015-12-15 KR KR1020177016285A patent/KR102606253B1/ko active Active
- 2015-12-15 EA EA201791327A patent/EA033530B1/ru not_active IP Right Cessation
- 2015-12-15 NZ NZ732793A patent/NZ732793A/en unknown
- 2015-12-15 ES ES15870856T patent/ES2877642T3/es active Active
- 2015-12-15 MX MX2017007883A patent/MX382253B/es unknown
-
2017
- 2017-06-14 IL IL252900A patent/IL252900B/en unknown
- 2017-06-14 CL CL2017001545A patent/CL2017001545A1/es unknown
- 2017-06-15 MX MX2021005207A patent/MX2021005207A/es unknown
- 2017-06-15 SA SA517381749A patent/SA517381749B1/ar unknown
- 2017-06-19 EC ECIEPI201738150A patent/ECSP17038150A/es unknown
- 2017-06-20 CO CONC2017/0006087A patent/CO2017006087A2/es unknown
- 2017-09-18 US US15/707,047 patent/US10131639B2/en active Active
-
2018
- 2018-10-02 US US16/149,393 patent/US10590089B2/en active Active
-
2020
- 2020-05-22 JP JP2020089532A patent/JP7022172B2/ja active Active
- 2020-05-28 AU AU2020203497A patent/AU2020203497B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2020203497B2 (en) | Formulations of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methycyclohexylamino)-pyrimidine-5-carboxamide | |
| JP6483714B2 (ja) | 噴霧乾燥製剤 | |
| US10449184B2 (en) | Pharmaceutical compositions of therapeutically active compounds | |
| JP2025108571A (ja) | オメカムチブメカルビルの塩及び結晶形態 | |
| KR102841419B1 (ko) | sGC 자극제를 포함하는 고체 분산물 | |
| WO2020242935A1 (en) | Methods of treatment for cystic fibrosis | |
| TW202517269A (zh) | 治療克羅恩氏病和潰瘍性結腸炎之方法 | |
| JP2018531288A6 (ja) | ピリミジン組成物、超高純度組成物およびその塩、それを作成する方法、ならびにヒスタミンｈ４受容体（ｈ４）によって媒介される疾患および状態を治療するためにそれを用いる方法 | |
| JP2018531288A (ja) | ピリミジン組成物、超高純度組成物およびその塩、それを作成する方法、ならびにヒスタミンｈ４受容体（ｈ４）によって媒介される疾患および状態を治療するためにそれを用いる方法 | |
| CN113330007A (zh) | 尼拉帕利游离碱的晶体形式 | |
| JP7370126B2 (ja) | エルロチニブを有効成分とする医薬錠剤 | |
| BR122023016197B1 (pt) | Sal cristalino de 2-(terc-butilamino)-4-((1r,3r,4r)-3-hidroxi-4-metilciclohexilamino)-pirimidina-5-carboxamida, composição farmacêutica o compreendendo e uso dos mesmos | |
| HK40036372A (en) | Spray dry formulations | |
| CN120112284A (zh) | 阿达格拉西布固体药物组合物 | |
| TW201215597A (en) | Hydrobromide salts of a pyrazolylaminoquinazoline |