AR075036A1 - Combinaciones que comprenden metotrexato e inhibidores de dhodh - Google Patents
Combinaciones que comprenden metotrexato e inhibidores de dhodhInfo
- Publication number
- AR075036A1 AR075036A1 ARP100100123A ARP100100123A AR075036A1 AR 075036 A1 AR075036 A1 AR 075036A1 AR P100100123 A ARP100100123 A AR P100100123A AR P100100123 A ARP100100123 A AR P100100123A AR 075036 A1 AR075036 A1 AR 075036A1
- Authority
- AR
- Argentina
- Prior art keywords
- group
- alkyl
- groups
- cycloalkyl
- atom
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 6
- 108010052167 Dihydroorotate Dehydrogenase Proteins 0.000 title 1
- 102100032823 Dihydroorotate dehydrogenase (quinone), mitochondrial Human genes 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 14
- 229940083266 Dihydroorotate dehydrogenase inhibitor Drugs 0.000 abstract 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 5
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 abstract 5
- 150000001204 N-oxides Chemical class 0.000 abstract 5
- 150000003839 salts Chemical class 0.000 abstract 5
- 229910052736 halogen Inorganic materials 0.000 abstract 4
- 150000002367 halogens Chemical group 0.000 abstract 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 3
- -1 -CONR7R8 Chemical group 0.000 abstract 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 3
- 108010005716 Interferon beta-1a Proteins 0.000 abstract 3
- 108010005714 Interferon beta-1b Proteins 0.000 abstract 3
- 125000004429 atom Chemical group 0.000 abstract 3
- 125000005843 halogen group Chemical group 0.000 abstract 3
- 125000002950 monocyclic group Chemical group 0.000 abstract 3
- 125000001424 substituent group Chemical group 0.000 abstract 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 abstract 2
- 102000015617 Janus Kinases Human genes 0.000 abstract 2
- 108010024121 Janus Kinases Proteins 0.000 abstract 2
- 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 abstract 2
- 108010057466 NF-kappa B Proteins 0.000 abstract 2
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 abstract 2
- 108010022394 Threonine synthase Proteins 0.000 abstract 2
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract 2
- 102000004419 dihydrofolate reductase Human genes 0.000 abstract 2
- 201000010099 disease Diseases 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- 125000002883 imidazolyl group Chemical group 0.000 abstract 2
- 229960000485 methotrexate Drugs 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 125000001715 oxadiazolyl group Chemical group 0.000 abstract 2
- 230000001575 pathological effect Effects 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000003226 pyrazolyl group Chemical group 0.000 abstract 2
- 125000001425 triazolyl group Chemical group 0.000 abstract 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 abstract 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 abstract 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 abstract 1
- RQVKVJIRFKVPBF-VWLOTQADSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-2-yl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C([C@H](N)CNC=1N(C(C(C=2C=C3C=CC=CC3=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 RQVKVJIRFKVPBF-VWLOTQADSA-N 0.000 abstract 1
- DOKINZMPCUUVOE-UHFFFAOYSA-N 2-[[6-(2,6-difluorophenyl)pyridin-3-yl]amino]-5-methylbenzoic acid Chemical group OC(=O)C1=CC(C)=CC=C1NC1=CC=C(C=2C(=CC=CC=2F)F)N=C1 DOKINZMPCUUVOE-UHFFFAOYSA-N 0.000 abstract 1
- NZDDUWSODQICAK-UHFFFAOYSA-N 2-[[6-[3-(cyclopropylcarbamoyl)phenyl]-5-methylpyridin-3-yl]amino]-5-methylbenzoic acid Chemical group OC(=O)C1=CC(C)=CC=C1NC1=CN=C(C=2C=C(C=CC=2)C(=O)NC2CC2)C(C)=C1 NZDDUWSODQICAK-UHFFFAOYSA-N 0.000 abstract 1
- QSUSKMBNZQHHPA-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-pyridin-4-ylimidazol-2-yl]but-3-yn-1-ol Chemical compound C=1C=CC=CC=1CCCN1C(C#CCCO)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=NC=C1 QSUSKMBNZQHHPA-UHFFFAOYSA-N 0.000 abstract 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 abstract 1
- IFGWYHGYNVGVRB-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-n-[2-(dimethylamino)ethyl]-1-(2-methylpropyl)indazole-6-carboxamide Chemical compound CN(C)CCNC(=O)C=1C=C2N(CC(C)C)N=CC2=CC=1OC1=CC=C(F)C=C1F IFGWYHGYNVGVRB-UHFFFAOYSA-N 0.000 abstract 1
- SLSURDZCCVUGLR-UHFFFAOYSA-N 5-cyclopropyl-2-[[2-(2,6-difluorophenyl)pyrimidin-5-yl]amino]benzoic acid Chemical group OC(=O)C1=CC(C2CC2)=CC=C1NC(C=N1)=CN=C1C1=C(F)C=CC=C1F SLSURDZCCVUGLR-UHFFFAOYSA-N 0.000 abstract 1
- BQLVBLBIXTYOHY-UHFFFAOYSA-N 5-methyl-2-[[6-[3-(trifluoromethyl)phenyl]pyridin-3-yl]amino]benzoic acid Chemical group OC(=O)C1=CC(C)=CC=C1NC1=CC=C(C=2C=C(C=CC=2)C(F)(F)F)N=C1 BQLVBLBIXTYOHY-UHFFFAOYSA-N 0.000 abstract 1
- 125000005330 8 membered heterocyclic group Chemical group 0.000 abstract 1
- 102000055025 Adenosine deaminases Human genes 0.000 abstract 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 abstract 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 abstract 1
- PCLITLDOTJTVDJ-UHFFFAOYSA-N Chlormethiazole Chemical compound CC=1N=CSC=1CCCl PCLITLDOTJTVDJ-UHFFFAOYSA-N 0.000 abstract 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 abstract 1
- 229930105110 Cyclosporin A Natural products 0.000 abstract 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 abstract 1
- 108010036949 Cyclosporine Proteins 0.000 abstract 1
- 108010008165 Etanercept Proteins 0.000 abstract 1
- 108010072051 Glatiramer Acetate Proteins 0.000 abstract 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 abstract 1
- ANMATWQYLIFGOK-UHFFFAOYSA-N Iguratimod Chemical compound CS(=O)(=O)NC1=CC=2OC=C(NC=O)C(=O)C=2C=C1OC1=CC=CC=C1 ANMATWQYLIFGOK-UHFFFAOYSA-N 0.000 abstract 1
- 108010050904 Interferons Proteins 0.000 abstract 1
- 102000014150 Interferons Human genes 0.000 abstract 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 abstract 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 abstract 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 abstract 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 abstract 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 abstract 1
- 229940124647 MEK inhibitor Drugs 0.000 abstract 1
- 229910003827 NRaRb Inorganic materials 0.000 abstract 1
- 239000012826 P38 inhibitor Substances 0.000 abstract 1
- 108010027220 PEGylated soluble tumor necrosis factor receptor I Proteins 0.000 abstract 1
- 201000004681 Psoriasis Diseases 0.000 abstract 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 abstract 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 abstract 1
- 101710110363 Putative adenosine/adenine deaminase Proteins 0.000 abstract 1
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 abstract 1
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 abstract 1
- 108700042805 TRU-015 Proteins 0.000 abstract 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 abstract 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 abstract 1
- 230000004913 activation Effects 0.000 abstract 1
- 229960002964 adalimumab Drugs 0.000 abstract 1
- 229960003896 aminopterin Drugs 0.000 abstract 1
- 229960004238 anakinra Drugs 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 229940003504 avonex Drugs 0.000 abstract 1
- 229940021459 betaseron Drugs 0.000 abstract 1
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- 229940046731 calcineurin inhibitors Drugs 0.000 abstract 1
- 125000002837 carbocyclic group Chemical group 0.000 abstract 1
- 229960003115 certolizumab pegol Drugs 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 229960002436 cladribine Drugs 0.000 abstract 1
- 229960004414 clomethiazole Drugs 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- MVCOAUNKQVWQHZ-UHFFFAOYSA-N doramapimod Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 MVCOAUNKQVWQHZ-UHFFFAOYSA-N 0.000 abstract 1
- 229950005521 doramapimod Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229960000403 etanercept Drugs 0.000 abstract 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 abstract 1
- 229960000556 fingolimod Drugs 0.000 abstract 1
- 239000001530 fumaric acid Substances 0.000 abstract 1
- 229960003776 glatiramer acetate Drugs 0.000 abstract 1
- 229960001743 golimumab Drugs 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 229950003909 iguratimod Drugs 0.000 abstract 1
- 239000002955 immunomodulating agent Substances 0.000 abstract 1
- 229940121354 immunomodulator Drugs 0.000 abstract 1
- 229960004461 interferon beta-1a Drugs 0.000 abstract 1
- 229960003161 interferon beta-1b Drugs 0.000 abstract 1
- 229940047124 interferons Drugs 0.000 abstract 1
- 229960004577 laquinimod Drugs 0.000 abstract 1
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 abstract 1
- 229950007278 lenercept Drugs 0.000 abstract 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract 1
- 201000006417 multiple sclerosis Diseases 0.000 abstract 1
- 231100000499 nonhepatotoxic Toxicity 0.000 abstract 1
- 229950005751 ocrelizumab Drugs 0.000 abstract 1
- 229960002450 ofatumumab Drugs 0.000 abstract 1
- 229950010444 onercept Drugs 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 229950000867 pegsunercept Drugs 0.000 abstract 1
- 229940038850 rebif Drugs 0.000 abstract 1
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
- 239000002464 receptor antagonist Substances 0.000 abstract 1
- 229940044551 receptor antagonist Drugs 0.000 abstract 1
- 108010003189 recombinant human tumor necrosis factor-binding protein-1 Proteins 0.000 abstract 1
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract 1
- 229960004641 rituximab Drugs 0.000 abstract 1
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 abstract 1
- 201000000306 sarcoidosis Diseases 0.000 abstract 1
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
- VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 abstract 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 abstract 1
- 229960001940 sulfasalazine Drugs 0.000 abstract 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 abstract 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 abstract 1
- 229960001967 tacrolimus Drugs 0.000 abstract 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 abstract 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 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 abstract 1
- 229960005289 voclosporin Drugs 0.000 abstract 1
- 108010057559 voclosporin Proteins 0.000 abstract 1
- BICRTLVBTLFLRD-PTWUADNWSA-N voclosporin Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C=C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O BICRTLVBTLFLRD-PTWUADNWSA-N 0.000 abstract 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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
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- 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
-
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- 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]
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- A61P35/00—Antineoplastic agents
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Abstract
La presente proporciona una combinacion que comprende (a) metotrexato y (b) un inhibidor de DHODH no hepatotoxico de formula (1) donde R1 se selecciona del grupo que consiste en átomos de H, halogeno, alquilo C1-4, cicloalquilo C3-4, -CF3 y -OCF3; R2 se selecciona del grupo que consiste en átomos de H, halogeno y grupos alquilo C1-4, R3 se selecciona del grupo que consiste en grupos -COOR5, -CONHR5, tetrazolilo, -SO2NHR5 y -CONHSO2R5, donde R5 se selecciona del grupo que consiste en un átomo de H y grupos alquilo C1-4 lineales o ramificados; R4 se selecciona del grupo que consiste en un átomo de H y un grupo alquilo C1-4; R9 se selecciona del grupo que consiste en un átomo de H y un grupo fenilo; G1 representa un grupo seleccionado de N y CR6 donde R6 se selecciona del grupo que consiste en átomos de H, halogeno, alquilo C1-4, cicloalquilo C3-4, alcoxi C1-4, -CF3, -OCF3, heteroarilo C5-7 monocíclico que contiene N, grupos heterociclilo C3-7 monocíclicos que contienen N y grupos arilo C6-10 estando estos grupos arilo C6-10 opcionalmente sustituido con uno o más sustituyentes seleccionados de átomos de halogeno y grupos alquilo C1-4; G2 representa un grupo seleccionado de un átomo de H, un grupo hidroxi, halogeno, cicloalquilo C3-4, alcoxi C1-4 y -NRaRb, donde Ra representa un grupo alquilo C1-4 y Rb se selecciona de un grupo que consiste en grupo alquilo C1-4 y grupo alcoxi C1-4-alquilo C1-4, o Ra y Rb junto con el átomo de N al que están unidos forman un anillo heterocíclico saturado de 6 a 8 miembros que contiene opcionalmente un átomo de O como heteroátomo adicional; un anillo heteroaromático de 5 a 10 miembros, monocíclico o bicíclico, que contiene uno o más átomos de N que está opcionalmente sustituido con uno o más sustituyentes seleccionados de átomos de halogeno, alquilo C1-4, alcoxi C1-4, cicloalquilo C3-4, cicloalcoxi C3-4, -CF3, -OCF3, y -CONR7R8, donde R7 y R8 se seleccionan, independientemente, de átomo de H, grupos alquilo C1-4 lineales o ramificados, cicloalquilo C3-7, o R7 y R8 junto con el N al que están unidos forman un grupo de formula (2) donde n es un numero entero de 0 a 3; y un grupo fenilo que está opcionalmente sustituido con uno o más sustituyentes seleccionados de átomos de halogeno, grupos alquilo C1-4, hidroxilo, alcoxi C1-4, cicloalquilo C3-4, cicloalcoxi C3-4, ciano, -CF3, -OCF3, -CONR7R8, oxadiazolilo, triazolilo, pirazolilo e imidazolilo, estando los grupos oxadiazolilo, triazolilo, pirazolilo e imidazolilo opcionalmente sustituidos con grupos alquilo C1-4 o cicloalquilo C3-7 y donde R7 y R8 se seleccionan, independientemente, de átomo de H, grupos alquilo C1-4 lineales o ramificados, cicloalquilo C3-7, o R7 y R8 junto con el N al que están unidos forman un grupo de formula (2) donde n es un numero entero de 0 a 3; o, cuando G1 representa CR6, G2 junto con R6 forma un grupo carbocíclico C5-10 no aromático o un grupo arilo C6-10, y sus sales y N-oxidos farmacéuticamente aceptables. Reivindicacion 20: Una combinacion segun la reivindicacion 1 donde el inhibidor de DHODH es acido 5-metil-2-(6-(3-(trifluorometil)fenil)piridin-3-ilamino)benzoico o una sal o N-oxido farmacéuticamente aceptable del mismo. Reivindicacion 21: Una combinacion segun la reivindicacion 1 donde el inhibidor de DHODH es ácido 5-ciclopropil-2-(2-(2,6-difluorofenil)pirimidin-5-ilamino)benzoico a una sal o N-oxido farmacéuticamente aceptable del mismo. Reivindicacion 22: Una combinacion segun la reivindicacion 1 donde el inhibidor de DHODH es ácido 2-(6-(2,6-difluorofenil)piridin-3-ilamino)-5-metilbenzoico o una sal o N-oxido farmacéuticamente aceptable del mismo. Reivindicacion 23: Una combinacion segun la reivindicacion 1 donde el inhibidor de DHODH es ácido 2-(6-(3-(ciclopropilcarbamoil)fenil)-5-metilpiridin-3-ilamino)-5-metilbenzoico o una sal o N-oxido farmacéuticamente aceptable del mismo. Reivindicacion 25: Una combinacion segun una cualquiera de las reivindicaciones precedentes, que comprende además (c) otro compuesto seleccionado de: (i) anticuerpos monoclonales anti-TNF-alfa tales corno lnfliximab, Certolizumab pegol, Golimumab, Adalimumab y AME-527 de Applied Molecular Evolution; (ii) antagonistas de TNF-alfa tales como Etanercept, Lenercept, Onercept y Pegsunercept; (iii) inhibidores de calcineurina (PP-2B) / inhibidores de la expresion de INS tales como ciclosporina A, Tacrolimus y ISA-247 de lsotechnika; (iv) antagonistas del receptor IL-1 tales como Anakinra y AMG-719 de Amgen; (v) anticuerpos monoclonales anti-CD20 tales corno Rituximab, Ofatumumab, Ocrelizumab y TRU-015 de Trubion Pharmaceuticals; (vi) inhibidores de p38 tales como AMG-548 (de Amgen), ARRY-797 (de Array Biopharma), edisilato de clormetiazol, Doramapimod, PS-540446 (de BMS), SB-203580, SB-242235, SB-235699, SB-261832, SB-681323, SB-856553 (todos de GlaxoSmithKline), KC-706 (de Kemia), LEO-1606, LEO-15520 (todos de Leo), SC-80036, SD-06 (todos de Pfizer), RWJ-67657 (de R. W. Johnson), RO-3201195, RO-4402257 (todos de Roche), AVE-9940 (de Aventis), SCIO-323, SCIO-469 (todos de Scios), TA-5493 (de Tanabe Seiyaku), y VX-745 y VX-702 (todos de Vertex); (vii) Inhibidores de la activacion de NF-kappaB (NFKB) tales corno Sulfasalazina e Iguratimod; (viii) otro inhibidor de dihidrofolato reductasa (DHFR) tal como Aminopterina y CH-1504 de Chelsea; (ix) Inhibidores de Janus quinasa (JAK), tales como CP-690, 550 de Pfizer y INCB-18424, de Incyte; (x) Inhibidor de MEK, tal corno ARRY-162 de Array; (xi) agonistas de los receptores de 1-fosfato de esfingosina, tales como fingolimod (Novartis); (xii) interferones que comprenden Interferon beta 1a tal como Avonex de Biogen Idec, CinnoVex de CinnaGen y Rebif de EMD Serono, e interferon beta 1b tal como Betaferon de Schering y Betaseron de Berlex; (xiii) inmunomoduladores tales como BG-12 (derivado de ácido fumárico) de Biogen Idec/Fumapharm AG, laquinimod (Teva y Active Biotech) o acetato de Glatiramer (Teva); y (xiv) Inhibidores de la adenosina aminohidrolasa tales como Cladribina de Merck Serono. Reivindicacion 27: Uso segun la reivindicacion 26, donde el estado patologico o enfermedad se selecciona de artritis reumatoide, artritis psoriática, espondilitis anquilosante, esclerosis multiple, granulomatosis de Wegener, lupus eritematoso sistémico, psoriasis y sarcoidosis. Reivindicacion 28: Un producto que comprende (a) metotrexato y (b) un inhibidor de DHODH como se define en una cualquiera de las reivindicaciones 1 a 23, como preparacion combinada para uso simultáneo, separado o secuencial en el tratamiento de un paciente humano o animal que padece o es susceptible de padecer un estado patologico o enfermedad de las definidas en la reivindicacion 26 o 27.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09382006A EP2210615A1 (en) | 2009-01-21 | 2009-01-21 | Combinations comprising methotrexate and DHODH inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR075036A1 true AR075036A1 (es) | 2011-03-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| ARP100100123A AR075036A1 (es) | 2009-01-21 | 2010-01-20 | Combinaciones que comprenden metotrexato e inhibidores de dhodh |
Country Status (23)
| Country | Link |
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| US (1) | US20110280831A1 (es) |
| EP (2) | EP2210615A1 (es) |
| JP (1) | JP2012515737A (es) |
| KR (1) | KR20110117658A (es) |
| CN (1) | CN102292108A (es) |
| AR (1) | AR075036A1 (es) |
| AU (1) | AU2010206334A1 (es) |
| BR (1) | BRPI1005169A2 (es) |
| CA (1) | CA2748400A1 (es) |
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| CO (1) | CO6341575A2 (es) |
| EA (1) | EA201101098A1 (es) |
| EC (1) | ECSP11011201A (es) |
| IL (1) | IL213625A0 (es) |
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| PE (1) | PE20120552A1 (es) |
| SG (2) | SG172453A1 (es) |
| TW (1) | TW201029652A (es) |
| UA (1) | UA104449C2 (es) |
| UY (1) | UY32380A (es) |
| WO (1) | WO2010083975A1 (es) |
| ZA (1) | ZA201104259B (es) |
Families Citing this family (20)
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| ES2319596B1 (es) | 2006-12-22 | 2010-02-08 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
| UY31272A1 (es) | 2007-08-10 | 2009-01-30 | Almirall Lab | Nuevos derivados de ácido azabifenilaminobenzoico |
| EP2135610A1 (en) | 2008-06-20 | 2009-12-23 | Laboratorios Almirall, S.A. | Combination comprising DHODH inhibitors and methotrexate |
| EP2239256A1 (en) | 2009-03-13 | 2010-10-13 | Almirall, S.A. | Sodium salt of 5-cyclopropyl-2-{[2-(2,6-difluorophenyl)pyrimidin-5-yl]amino}benzoic acid as DHODH inhibitor |
| EP2314577A1 (en) | 2009-10-16 | 2011-04-27 | Almirall, S.A. | Process for manufacturing 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4-yl)amino]nicotinic acid |
| EP2444086A1 (en) * | 2010-10-22 | 2012-04-25 | Almirall, S.A. | Combinations comprising DHODH inhibitors and COX inhibitors |
| EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
| EP2672963A4 (en) | 2011-02-08 | 2015-06-24 | Childrens Medical Center | METHOD FOR THE TREATMENT OF MELANOMA |
| EP2518071A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Imidazopyridine derivatives as PI3K inhibitors |
| EP2518070A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Pyrrolotriazinone derivatives as PI3K inhibitors |
| EP2526945A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | New CRTH2 Antagonists |
| EP2548863A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
| EP2548876A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists |
| EP2752190B1 (en) * | 2011-08-30 | 2021-03-03 | Toyama Chemical Co., Ltd. | Method for improving therapy for autoimmune diseases such as rheumatoid arthritis |
| WO2014060431A1 (en) | 2012-10-16 | 2014-04-24 | Almirall, S.A. | Pyrrolotriazinone derivatives as pi3k inhibitors |
| AR094797A1 (es) | 2013-02-15 | 2015-08-26 | Almirall Sa | Derivados de pirrolotriazina como inhibidores de pi3k |
| GB201809102D0 (en) | 2018-06-04 | 2018-07-18 | Univ Oxford Innovation Ltd | Compounds |
| EP3858361B1 (en) | 2018-09-28 | 2025-10-08 | FUJIFILM Corporation | Antitumor agent containing cytarabine, antitumor effect enhancer used in combination with cytarabine, antitumor kit, and antitumor agent used in combination with cytarabine |
| EP4037770A1 (en) * | 2019-10-04 | 2022-08-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Novel pyridin-2(1h)one derivatives, their preparation and their use for the treatment of pain |
| CN116056766A (zh) * | 2020-07-30 | 2023-05-02 | 富士胶片株式会社 | 含氮杂环化合物或其盐、其利用以及其中间体 |
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| US4226869A (en) * | 1979-02-02 | 1980-10-07 | American Cyanamid Company | Method of stimulating the immune response with halogenated 10-(ω-dialkylaminopolymethyleneamino)-2-methoxypyrido[3,2-b]quinolines |
| BR9608997A (pt) | 1995-06-21 | 1999-06-29 | Asta Medica Ag | Cartucho para pó farmacêutico com dispositivo de medição integrado e intalador para medicamentos em pó |
| DE10129703A1 (de) | 2001-06-22 | 2003-01-02 | Sofotec Gmbh & Co Kg | Zerstäubungssystem für eine Pulvermischung und Verfahren für Trockenpulverinhalatoren |
| DE10202940A1 (de) | 2002-01-24 | 2003-07-31 | Sofotec Gmbh & Co Kg | Patrone für einen Pulverinhalator |
| TW200714289A (en) * | 2005-02-28 | 2007-04-16 | Genentech Inc | Treatment of bone disorders |
| AR055395A1 (es) * | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| WO2008058288A2 (en) * | 2006-11-09 | 2008-05-15 | Proprius Pharmaceuticals, Inc. | Sustained release methotrexate formulations and methods of use thereof |
| UY31272A1 (es) * | 2007-08-10 | 2009-01-30 | Almirall Lab | Nuevos derivados de ácido azabifenilaminobenzoico |
| EP2135610A1 (en) * | 2008-06-20 | 2009-12-23 | Laboratorios Almirall, S.A. | Combination comprising DHODH inhibitors and methotrexate |
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| CL2011001760A1 (es) | 2012-03-09 |
| TW201029652A (en) | 2010-08-16 |
| CO6341575A2 (es) | 2011-11-21 |
| UA104449C2 (uk) | 2014-02-10 |
| CN102292108A (zh) | 2011-12-21 |
| EP2389197B1 (en) | 2014-06-18 |
| UY32380A (es) | 2010-02-26 |
| SG196826A1 (en) | 2014-02-13 |
| CA2748400A1 (en) | 2010-07-29 |
| WO2010083975A1 (en) | 2010-07-29 |
| EP2389197A1 (en) | 2011-11-30 |
| BRPI1005169A2 (pt) | 2019-09-24 |
| US20110280831A1 (en) | 2011-11-17 |
| IL213625A0 (en) | 2011-07-31 |
| PE20120552A1 (es) | 2012-05-21 |
| ZA201104259B (en) | 2012-02-29 |
| EP2210615A1 (en) | 2010-07-28 |
| JP2012515737A (ja) | 2012-07-12 |
| EA201101098A1 (ru) | 2012-01-30 |
| ECSP11011201A (es) | 2011-08-31 |
| AU2010206334A1 (en) | 2011-07-07 |
| NZ593413A (en) | 2013-12-20 |
| MX2011007446A (es) | 2011-08-03 |
| SG172453A1 (en) | 2011-07-28 |
| KR20110117658A (ko) | 2011-10-27 |
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