NO20210693A1 - - Google Patents
Download PDFInfo
- Publication number
- NO20210693A1 NO20210693A1 NO20210693A NO20210693A NO20210693A1 NO 20210693 A1 NO20210693 A1 NO 20210693A1 NO 20210693 A NO20210693 A NO 20210693A NO 20210693 A NO20210693 A NO 20210693A NO 20210693 A1 NO20210693 A1 NO 20210693A1
- Authority
- NO
- Norway
- Prior art keywords
- straight chain
- alkyl
- compound
- group
- branched
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 128
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 97
- 239000000203 mixture Substances 0.000 claims description 85
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- 238000011282 treatment Methods 0.000 claims description 66
- 125000000304 alkynyl group Chemical group 0.000 claims description 60
- 125000003342 alkenyl group Chemical group 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- -1 sulfoxy Chemical group 0.000 claims description 52
- 125000002252 acyl group Chemical group 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 49
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 46
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 239000012453 solvate Substances 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 125000001153 fluoro group Chemical group F* 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 125000003277 amino group Chemical group 0.000 claims description 20
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 20
- 150000002500 ions Chemical class 0.000 claims description 20
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 20
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 19
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 125000001246 bromo group Chemical group Br* 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 125000002346 iodo group Chemical group I* 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000000565 sulfonamide group Chemical group 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229910018830 PO3H Inorganic materials 0.000 claims description 8
- 239000005864 Sulphur Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 96
- 108091008606 PDGF receptors Proteins 0.000 description 51
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 51
- 210000004027 cell Anatomy 0.000 description 32
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical class COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 24
- 230000004083 survival effect Effects 0.000 description 23
- 230000000694 effects Effects 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 238000009650 gentamicin protection assay Methods 0.000 description 18
- 230000005025 clonogenic survival Effects 0.000 description 16
- 230000037396 body weight Effects 0.000 description 14
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 101150062967 PHOX2A gene Proteins 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 11
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 11
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 11
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 11
- 210000002919 epithelial cell Anatomy 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 210000004072 lung Anatomy 0.000 description 11
- 231100000673 dose–response relationship Toxicity 0.000 description 10
- 230000008508 epithelial proliferation Effects 0.000 description 10
- 229960002504 capsaicin Drugs 0.000 description 9
- 235000017663 capsaicin Nutrition 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 208000029523 Interstitial Lung disease Diseases 0.000 description 8
- 230000003021 clonogenic effect Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 102100037362 Fibronectin Human genes 0.000 description 7
- 108010067306 Fibronectins Proteins 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 206010011224 Cough Diseases 0.000 description 6
- 238000001516 cell proliferation assay Methods 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 125000001624 naphthyl group Chemical group 0.000 description 6
- 229960004378 nintedanib Drugs 0.000 description 6
- 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 6
- 229960003073 pirfenidone Drugs 0.000 description 6
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 208000005069 pulmonary fibrosis Diseases 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000004761 fibrosis Effects 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 description 4
- 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 description 4
- 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 101150111293 cor-1 gene Proteins 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000007747 plating Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000037390 scarring Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000002560 therapeutic procedure 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 3
- 229960004308 acetylcysteine Drugs 0.000 description 3
- 230000009798 acute exacerbation Effects 0.000 description 3
- 230000020411 cell activation Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000004199 lung function Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 102000009016 Cholera Toxin Human genes 0.000 description 2
- 108010049048 Cholera Toxin Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000003566 TRPV1 Human genes 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 101150016206 Trpv1 gene Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- GSIBPCYHSFDLTC-UHFFFAOYSA-N n-[(4-hydroxy-3-methoxyphenyl)methyl]-7-phenylhept-6-ynamide Chemical compound C1=C(O)C(OC)=CC(CNC(=O)CCCCC#CC=2C=CC=CC=2)=C1 GSIBPCYHSFDLTC-UHFFFAOYSA-N 0.000 description 2
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002206 pro-fibrotic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000009613 pulmonary function test Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FPQLDOYYKRWPLF-UHFFFAOYSA-N CC(OC(C=CC(CNC(CCCCC#CC1=CC=CC=C1)=O)=C1)=C1OC)=O Chemical compound CC(OC(C=CC(CNC(CCCCC#CC1=CC=CC=C1)=O)=C1)=C1OC)=O FPQLDOYYKRWPLF-UHFFFAOYSA-N 0.000 description 1
- LCJMVHSJVOESMJ-UHFFFAOYSA-N CCCCCCCCCCCCCCCC(OC(C=CC(CNC(CCCCC#CC1=CC=CC=C1)=O)=C1)=C1OC)=O Chemical compound CCCCCCCCCCCCCCCC(OC(C=CC(CNC(CCCCC#CC1=CC=CC=C1)=O)=C1)=C1OC)=O LCJMVHSJVOESMJ-UHFFFAOYSA-N 0.000 description 1
- UJCNHEOMIOIOCC-WEVVVXLNSA-N COC(C=C(CNC(CCCC/C=C/C1=CC=CC=C1)=O)C=C1)=C1O Chemical compound COC(C=C(CNC(CCCC/C=C/C1=CC=CC=C1)=O)C=C1)=C1O UJCNHEOMIOIOCC-WEVVVXLNSA-N 0.000 description 1
- SFGWJVLQHWWAIF-UHFFFAOYSA-N COC(C=C(CNC(CCCCC#CC(C=C1)=CC=C1[N+]([O-])=O)=O)C=C1)=C1O Chemical compound COC(C=C(CNC(CCCCC#CC(C=C1)=CC=C1[N+]([O-])=O)=O)C=C1)=C1O SFGWJVLQHWWAIF-UHFFFAOYSA-N 0.000 description 1
- ZIYYZIVJRMMQEP-UHFFFAOYSA-N COC(C=C(CNC(CCCCC#CC1=CC=CC2=CC=CC=C12)=O)C=C1)=C1O Chemical compound COC(C=C(CNC(CCCCC#CC1=CC=CC2=CC=CC=C12)=O)C=C1)=C1O ZIYYZIVJRMMQEP-UHFFFAOYSA-N 0.000 description 1
- CQYMBMDQFFVYTF-UHFFFAOYSA-N COC(C=C(CNC(CCCCC#CC1=CC=CC=C1)=O)C=C1)=C1OC(CCC(O)=O)=O Chemical compound COC(C=C(CNC(CCCCC#CC1=CC=CC=C1)=O)C=C1)=C1OC(CCC(O)=O)=O CQYMBMDQFFVYTF-UHFFFAOYSA-N 0.000 description 1
- PQTXYANSKNBSTP-UHFFFAOYSA-N COC(C=C1)=CC=C1C#CCCCCC(NCC(C=C1)=CC(OC)=C1O)=O Chemical compound COC(C=C1)=CC=C1C#CCCCCC(NCC(C=C1)=CC(OC)=C1O)=O PQTXYANSKNBSTP-UHFFFAOYSA-N 0.000 description 1
- QXKRRKSRHPEOIE-UHFFFAOYSA-N COC(C=C1)=CC=C1C#CCCCCC(NCC(C=C1)=CC(OC)=C1OCC1=CC=CC=C1)=O Chemical compound COC(C=C1)=CC=C1C#CCCCCC(NCC(C=C1)=CC(OC)=C1OCC1=CC=CC=C1)=O QXKRRKSRHPEOIE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010009691 Clubbing Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010073303 Exposure via inhalation Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000921 acute inhalation toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 231100000244 chromosomal damage Toxicity 0.000 description 1
- 208000013116 chronic cough Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ONAHJHLNXUYDHS-UHFFFAOYSA-N n-[(4-hydroxy-3-methoxyphenyl)methyl]-7-phenylheptanamide Chemical compound C1=C(O)C(OC)=CC(CNC(=O)CCCCCCC=2C=CC=CC=2)=C1 ONAHJHLNXUYDHS-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000043 nose-only exposure Toxicity 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 238000011422 pharmacological therapy Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000005801 respiratory difficulty Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20210693A NO346587B1 (en) | 2021-06-02 | 2021-06-02 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
| US18/564,031 US20240277637A1 (en) | 2021-06-02 | 2022-06-01 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
| CN202280039778.6A CN117412742A (zh) | 2021-06-02 | 2022-06-01 | 治疗特发性肺纤维化的辣椒素衍生物 |
| JP2023574384A JP2024520650A (ja) | 2021-06-02 | 2022-06-01 | 特発性肺線維症の処置におけるカプサイシン誘導体 |
| EP22731584.3A EP4346789A1 (en) | 2021-06-02 | 2022-06-01 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
| PCT/EP2022/064876 WO2022253884A1 (en) | 2021-06-02 | 2022-06-01 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20210693A NO346587B1 (en) | 2021-06-02 | 2021-06-02 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO346587B1 NO346587B1 (en) | 2022-10-17 |
| NO20210693A1 true NO20210693A1 (enExample) | 2022-10-17 |
Family
ID=82115682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20210693A NO346587B1 (en) | 2021-06-02 | 2021-06-02 | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20240277637A1 (enExample) |
| EP (1) | EP4346789A1 (enExample) |
| JP (1) | JP2024520650A (enExample) |
| CN (1) | CN117412742A (enExample) |
| NO (1) | NO346587B1 (enExample) |
| WO (1) | WO2022253884A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO348880B1 (en) * | 2023-03-13 | 2025-06-30 | Axichem Ab | Physical performance aid |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10237423A1 (de) * | 2002-08-16 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von LCK-Inhibitoren für die Behandlung von immunologischen Erkrankungen |
| NO20034069L (no) | 2003-09-12 | 2005-03-14 | Aximed As | Fremstilling og bruk av capsaicinderivater |
| AU2012279499B2 (en) * | 2011-07-07 | 2017-05-04 | Eva MILLQVIST | Cough reducing product |
| WO2015160842A1 (en) * | 2014-04-14 | 2015-10-22 | Flex Pharma, Inc. | Methods and formulatiions of capsaicinoids and capsinoids |
| WO2017160156A1 (en) * | 2016-03-18 | 2017-09-21 | Axichem Ab | Synthetic capasaicin analogs as trpv1 agonists |
| JP7412424B2 (ja) * | 2018-09-18 | 2024-01-12 | ブリストル-マイヤーズ スクイブ カンパニー | Lpaアンタゴニストとしてのオキサビシクロ酸 |
| WO2020160225A1 (en) * | 2019-01-30 | 2020-08-06 | Ohio State Innovation Foundation | ESTROGEN RECEPTOR BETA (ERβ) AGONISTS FOR THE TREATMENT OF FIBROTIC CONDITIONS |
| WO2020191501A1 (en) * | 2019-03-27 | 2020-10-01 | Algernon Pharmaceuticals Inc. | Methods and uses of bemithyl and derivatives for treating lung disease, fatty liver disease, and kidney disorders |
| WO2020227331A1 (en) * | 2019-05-06 | 2020-11-12 | Inspira, LLC | Chemical entities, pharmaceutical formulations, and methods for treating fibrosis |
| CN114026072A (zh) * | 2019-06-25 | 2022-02-08 | 北京泰德制药股份有限公司 | 治疗特发性肺纤维化的方法 |
| NO345530B1 (en) | 2020-03-20 | 2021-03-29 | Axichem As | Synthesis of capsaicin derivatives |
-
2021
- 2021-06-02 NO NO20210693A patent/NO346587B1/en unknown
-
2022
- 2022-06-01 WO PCT/EP2022/064876 patent/WO2022253884A1/en not_active Ceased
- 2022-06-01 US US18/564,031 patent/US20240277637A1/en active Pending
- 2022-06-01 JP JP2023574384A patent/JP2024520650A/ja active Pending
- 2022-06-01 EP EP22731584.3A patent/EP4346789A1/en active Pending
- 2022-06-01 CN CN202280039778.6A patent/CN117412742A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| NO346587B1 (en) | 2022-10-17 |
| JP2024520650A (ja) | 2024-05-24 |
| US20240277637A1 (en) | 2024-08-22 |
| CN117412742A (zh) | 2024-01-16 |
| WO2022253884A1 (en) | 2022-12-08 |
| EP4346789A1 (en) | 2024-04-10 |
| WO2022253884A4 (en) | 2023-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11975005B2 (en) | Treatment of respiratory diseases | |
| US20070065366A1 (en) | Pharmaceutical formulations comprising a long-acting beta2-agonist for administration by nebulisation | |
| EP1225878B1 (en) | Rar-gamma selective retinoid agonists for the treatment of emphysema | |
| CA3176909A1 (en) | Compositions and methods for the prevention and/or treatment of mitochondrial disease, including friedreich's ataxia | |
| US20240277637A1 (en) | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis | |
| US20140024683A1 (en) | Chloride channel and chloride transporter modulators for therapy in smooth muscle diseases | |
| US20250161250A1 (en) | Compositions and methods for treatment of idiopathic pulmonary fibrosis | |
| US11534398B2 (en) | Inhaled preparation of isoglycyrrhizic acid or salt thereof, and use in preparing drugs for treating respiratory system diseases | |
| AU2005274875A1 (en) | Methods and materials for treating mental illness | |
| WO2005007191A1 (ja) | 医薬組成物 | |
| EP4623908A1 (en) | Use of (-)-epigallocatechin gallate compound | |
| JP2016504358A (ja) | オキシブチニンを投与するための方法および組成物 | |
| US7842702B2 (en) | Treatment for irritable bowel syndrome | |
| JP6935930B2 (ja) | 生薬成分を含む肺高血圧症の予防又は治療剤 | |
| WO2021209003A1 (en) | Prevention and treatment of organ injuries | |
| TW202504602A (zh) | 用於治療臟器纖維化相關疾病的藥物組合物和方法 | |
| NZ579186A (en) | A carbostyril derivative with probucol for treating chronic obstructive pulmonary disease | |
| HK40088174A (zh) | 排尿症状治疗剂 | |
| HK40088174B (zh) | 排尿症状治疗剂 | |
| CN114681476A (zh) | 一种环烯醚萜苷化合物抗特发性肺纤维化的用途 | |
| WO2004087151A1 (ja) | 医薬組成物 | |
| WO2004087149A1 (ja) | 医薬組成物 |