KR20060122877A - 제약 조합물 - Google Patents
제약 조합물 Download PDFInfo
- Publication number
- KR20060122877A KR20060122877A KR1020067010547A KR20067010547A KR20060122877A KR 20060122877 A KR20060122877 A KR 20060122877A KR 1020067010547 A KR1020067010547 A KR 1020067010547A KR 20067010547 A KR20067010547 A KR 20067010547A KR 20060122877 A KR20060122877 A KR 20060122877A
- Authority
- KR
- South Korea
- Prior art keywords
- arthritis
- rheumatoid arthritis
- mtor inhibitor
- combination
- activity against
- 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.)
- Withdrawn
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 40
- 229940124302 mTOR inhibitor Drugs 0.000 claims abstract description 38
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims abstract description 38
- 206010003246 arthritis Diseases 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 208000035475 disorder Diseases 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 206010037660 Pyrexia Diseases 0.000 claims description 7
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 7
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 6
- 210000002950 fibroblast Anatomy 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 230000035755 proliferation Effects 0.000 claims description 6
- 241001111421 Pannus Species 0.000 claims description 5
- 210000002540 macrophage Anatomy 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical group C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 22
- 229960002930 sirolimus Drugs 0.000 description 20
- 239000004480 active ingredient Substances 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 17
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 16
- 229940126062 Compound A Drugs 0.000 description 10
- 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 10
- 239000002552 dosage form Substances 0.000 description 8
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 229960000485 methotrexate Drugs 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 210000002683 foot Anatomy 0.000 description 5
- 208000004454 Hyperalgesia Diseases 0.000 description 4
- 208000035154 Hyperesthesia Diseases 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000001503 joint Anatomy 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 210000002437 synoviocyte Anatomy 0.000 description 4
- -1 3-hydroxy-2- (hydroxymethyl) -2-methyl-propanoyl Chemical group 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 3
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 108010008165 Etanercept Proteins 0.000 description 3
- 206010023203 Joint destruction Diseases 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 2
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229950004398 broxuridine Drugs 0.000 description 2
- 229960000590 celecoxib Drugs 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 229960000403 etanercept Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 229960000598 infliximab Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229960000994 lumiracoxib Drugs 0.000 description 2
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- SZXUTTGMFUSMCE-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)pyridine Chemical class C1=CNC(C=2N=CC=CC=2)=N1 SZXUTTGMFUSMCE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- JBNWDYGOTHQHOZ-UHFFFAOYSA-N 2-[5-[4-[(4-fluorophenyl)methyl]piperidine-1-carbonyl]-6-methoxy-1-methylindol-3-yl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC=2N(C)C=C(C(=O)C(=O)N(C)C)C=2C=C1C(=O)N(CC1)CCC1CC1=CC=C(F)C=C1 JBNWDYGOTHQHOZ-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical class NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- PTBDIHRZYDMNKB-UHFFFAOYSA-M 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate Chemical compound OCC(C)(CO)C([O-])=O PTBDIHRZYDMNKB-UHFFFAOYSA-M 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- 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 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 238000011672 OFA rat Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 230000003072 anti-pyrogenic effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 1
- 229950009183 ibufenac Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960002595 ibuproxam Drugs 0.000 description 1
- BYPIURIATSUHDW-UHFFFAOYSA-N ibuproxam Chemical compound CC(C)CC1=CC=C(C(C)C(=O)NO)C=C1 BYPIURIATSUHDW-UHFFFAOYSA-N 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 229940054136 kineret Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XXRSWDBWKFKQEB-UHFFFAOYSA-N n-(4,6-dimethylpyridin-2-yl)furan-2-carboxamide Chemical compound CC1=CC(C)=NC(NC(=O)C=2OC=CC=2)=C1 XXRSWDBWKFKQEB-UHFFFAOYSA-N 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- QFMKPDZCOKCBAQ-NFCVMBANSA-N sar943-nxa Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)CC1 QFMKPDZCOKCBAQ-NFCVMBANSA-N 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- ZMELOYOKMZBMRB-DLBZAZTESA-N talmapimod Chemical compound C([C@@H](C)N(C[C@@H]1C)C(=O)C=2C(=CC=3N(C)C=C(C=3C=2)C(=O)C(=O)N(C)C)Cl)N1CC1=CC=C(F)C=C1 ZMELOYOKMZBMRB-DLBZAZTESA-N 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 229940087652 vioxx Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0327840.5A GB0327840D0 (en) | 2003-12-01 | 2003-12-01 | Organic compounds |
| GB0327840.5 | 2003-12-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060122877A true KR20060122877A (ko) | 2006-11-30 |
Family
ID=29798110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020067010547A Withdrawn KR20060122877A (ko) | 2003-12-01 | 2004-11-30 | 제약 조합물 |
Country Status (11)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1478648B1 (en) | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| WO2006053754A1 (en) * | 2004-11-19 | 2006-05-26 | Novartis Ag | COMBINATIONS OF ANTI-ATHEROSCLEROTIC PEPTIDES AND AN mTOR INHIBITING AGENT AND THEIR METHODS OF USE |
| AU2006315512B2 (en) * | 2005-11-14 | 2012-11-01 | Ariad Pharmaceuticals, Inc. | Administration of an mTOR inhibitor to treat patients with cancer |
| EP1880723A1 (en) * | 2006-07-14 | 2008-01-23 | Novartis AG | Combination of mTOR inhibitor and antifolate compound |
| JP2009523149A (ja) * | 2006-01-12 | 2009-06-18 | ノバルティス アクチエンゲゼルシャフト | ｍＴＯＲ阻害剤および抗葉酸化合物の組み合わせ |
| KR20140016439A (ko) * | 2006-02-02 | 2014-02-07 | 노파르티스 아게 | 결절성 경화증의 치료 |
| US20090023768A1 (en) * | 2006-02-24 | 2009-01-22 | Novartis Ag | Rapamycin derivatives for treating neuroblastoma |
| CA2669415A1 (en) | 2006-11-14 | 2008-05-22 | Ariad Pharmaceuticals, Inc. | Solid dosage form comprising ap23573 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9221220D0 (en) * | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| US5258389A (en) * | 1992-11-09 | 1993-11-02 | Merck & Co., Inc. | O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives |
| DE69624921T2 (de) * | 1995-06-09 | 2003-09-11 | Novartis Ag, Basel | Rapamycinderivate |
| GB0123025D0 (en) * | 2001-09-25 | 2001-11-14 | Eirx Therapeutics Ltd | Apoptosis |
| JP2005514411A (ja) * | 2002-01-10 | 2005-05-19 | ノバルティス アクチエンゲゼルシャフト | ラパマイシンおよびその誘導体を含む血管疾患の予防および処置用薬剤送達システム |
| EP1478648B1 (en) * | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| WO2003106622A2 (en) * | 2002-05-30 | 2003-12-24 | The Children's Hospital Of Philadelphia | Methods for treatment of acute lymphocytic leukemia |
| TW200902047A (en) * | 2003-02-14 | 2009-01-16 | Combinatorx Inc | Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines |
-
2003
- 2003-12-01 GB GBGB0327840.5A patent/GB0327840D0/en not_active Ceased
-
2004
- 2004-11-30 KR KR1020067010547A patent/KR20060122877A/ko not_active Withdrawn
- 2004-11-30 US US10/581,069 patent/US20070117833A1/en not_active Abandoned
- 2004-11-30 CN CNA2004800355130A patent/CN1886157A/zh active Pending
- 2004-11-30 JP JP2006541869A patent/JP2007512381A/ja active Pending
- 2004-11-30 RU RU2006123312/15A patent/RU2006123312A/ru not_active Application Discontinuation
- 2004-11-30 BR BRPI0417146-2A patent/BRPI0417146A/pt not_active IP Right Cessation
- 2004-11-30 AU AU2004294282A patent/AU2004294282B2/en not_active Expired - Fee Related
- 2004-11-30 WO PCT/EP2004/013587 patent/WO2005053661A2/en not_active Ceased
- 2004-11-30 CA CA002546738A patent/CA2546738A1/en not_active Abandoned
- 2004-11-30 EP EP04803369A patent/EP1819361A2/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| GB0327840D0 (en) | 2003-12-31 |
| AU2004294282B2 (en) | 2009-05-07 |
| BRPI0417146A (pt) | 2007-03-06 |
| CN1886157A (zh) | 2006-12-27 |
| EP1819361A2 (en) | 2007-08-22 |
| RU2006123312A (ru) | 2008-01-20 |
| WO2005053661A3 (en) | 2005-12-29 |
| US20070117833A1 (en) | 2007-05-24 |
| JP2007512381A (ja) | 2007-05-17 |
| CA2546738A1 (en) | 2005-06-16 |
| AU2004294282A1 (en) | 2005-06-16 |
| WO2005053661A2 (en) | 2005-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tanaka et al. | In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis | |
| US8361467B2 (en) | Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints | |
| JP5902141B2 (ja) | 脂質キナーゼおよびｍＴＯＲのデュアル阻害剤としてのイミダゾキノリン | |
| US8986696B2 (en) | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints | |
| Tanaka et al. | JAK inhibitor tofacitinib for treating rheumatoid arthritis: from basic to clinical | |
| US20090162351A1 (en) | Transdiscal administration of inhibitors of p38 MAP kinase | |
| Hosoya et al. | Cell cycle regulation therapy combined with cytokine blockade enhances antiarthritic effects without increasing immune suppression | |
| JP2020105181A (ja) | 同種抗体により駆動される慢性移植片対宿主病を処置及び予防する方法 | |
| EP1631266B1 (en) | A method of treating degenerative disc disease | |
| AU2008265974B2 (en) | Use of TACI-Ig fusion protein such as atacicept for the manufacture of a medicament for treating Lupus Erythematosus | |
| CN1545419A (zh) | 诸如雷帕霉素和吉西他滨或氟尿嘧淀的抗肿瘤联合 | |
| EP1589960A1 (en) | Treatment of obesity and associated conditions with tgf-beta inhibitors | |
| JOOSTEN et al. | ANTICYTOKINE TREATMENT OF ESTABLISHED TYPE II COLLAGEN-INDUCED ARTHRITIS IN DBA/1 MICE: A Comparative Study using Anti-TNFα, Anti-IL-αa/β, and IL-1Ra | |
| JP2020203908A (ja) | 疼痛の治療のためのｖａｐ−１阻害剤 | |
| CN109069467A (zh) | 肌生成抑制蛋白拮抗剂的用途、含有它们的组合及其用途 | |
| Guo et al. | Inflammatory cytokines in midbrain periaqueductal gray contribute to diabetic induced pain hypersensitivity through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway | |
| AU2004294282B2 (en) | Pharmaceutical combinations | |
| KR101461767B1 (ko) | 만성 활성 ｂ-세포-수용체 신호전달이 있는 ｂ-세포 림프종의 치료를 위한 ｐｋｃ 억제제 | |
| KR102849806B1 (ko) | 항-OSMRß 항체 전달에 의한 피부 질환 또는 장애 치료 | |
| US20100273750A1 (en) | Serotonin receptor antagonists for treating arthritis | |
| MXPA06006220A (en) | Pharmaceutical combinations | |
| Tanaka et al. | Cytokine-mediated signals as targets for treatment of rheumatoid arthritis: a JAK inhibitor in vitro and in vivo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20060530 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |