AR072174A1 - Combinaciones que comprenden inhibidores de dhodh (dihidroorotato deshidrogenasa) y metotrexato. uso. producto. kit. metodo. - Google Patents
Combinaciones que comprenden inhibidores de dhodh (dihidroorotato deshidrogenasa) y metotrexato. uso. producto. kit. metodo.Info
- Publication number
- AR072174A1 AR072174A1 ARP090102209A ARP090102209A AR072174A1 AR 072174 A1 AR072174 A1 AR 072174A1 AR P090102209 A ARP090102209 A AR P090102209A AR P090102209 A ARP090102209 A AR P090102209A AR 072174 A1 AR072174 A1 AR 072174A1
- Authority
- AR
- Argentina
- Prior art keywords
- groups
- substituents selected
- optionally substituted
- halogen
- hydroxy groups
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 8
- 108010052167 Dihydroorotate Dehydrogenase Proteins 0.000 title abstract 4
- 102100032823 Dihydroorotate dehydrogenase (quinone), mitochondrial Human genes 0.000 title abstract 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 14
- 125000001424 substituent group Chemical group 0.000 abstract 12
- 125000005843 halogen group Chemical group 0.000 abstract 9
- 229910052736 halogen Inorganic materials 0.000 abstract 7
- 150000002367 halogens Chemical class 0.000 abstract 7
- -1 3'-ethoxy-3,5-difluorobiphenyl-4-ylamino Chemical group 0.000 abstract 6
- 229940083266 Dihydroorotate dehydrogenase inhibitor Drugs 0.000 abstract 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 6
- 150000001204 N-oxides Chemical class 0.000 abstract 5
- 239000002253 acid Substances 0.000 abstract 5
- 150000003839 salts Chemical class 0.000 abstract 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
- 229910052739 hydrogen Inorganic materials 0.000 abstract 4
- 239000001257 hydrogen Substances 0.000 abstract 4
- 108010005714 Interferon beta-1b Proteins 0.000 abstract 3
- 201000010099 disease Diseases 0.000 abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 3
- 230000001575 pathological effect Effects 0.000 abstract 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 2
- 108010005716 Interferon beta-1a Proteins 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
- 241001465754 Metazoa Species 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
- 150000001875 compounds Chemical class 0.000 abstract 2
- 102000004419 dihydrofolate reductase Human genes 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 2
- 229960000485 methotrexate Drugs 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
- 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
- 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
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 abstract 1
- 206010019663 Hepatic failure Diseases 0.000 abstract 1
- 206010019851 Hepatotoxicity 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
- 108090000467 Interferon-beta Proteins 0.000 abstract 1
- 102000003996 Interferon-beta Human genes 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
- 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
- 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
- 229940003504 avonex Drugs 0.000 abstract 1
- 229940021459 betaseron Drugs 0.000 abstract 1
- 229940046731 calcineurin inhibitors Drugs 0.000 abstract 1
- 150000001768 cations Chemical class 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
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract 1
- 108010089007 dehydroorotate dehydrogenase Proteins 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
- 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
- 229960001743 golimumab Drugs 0.000 abstract 1
- 231100000304 hepatotoxicity Toxicity 0.000 abstract 1
- 230000007686 hepatotoxicity Effects 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
- 229960000598 infliximab Drugs 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 229960003161 interferon beta-1b Drugs 0.000 abstract 1
- 229960001388 interferon-beta Drugs 0.000 abstract 1
- 229940047124 interferons Drugs 0.000 abstract 1
- 229950007278 lenercept Drugs 0.000 abstract 1
- 231100000835 liver failure Toxicity 0.000 abstract 1
- 208000007903 liver failure Diseases 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
- 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
- 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
- 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
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- 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
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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
-
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
Una combinacion que comprende (a) metotrexato y (b) un inhibidor de DHODH (dihidroorotato deshidrogenasa) no hepatotoxico. Reivindicacion 3: Una combinacion segun la reivindicacion 1 o 2, donde el inhibidor de DHODH (b) es un compuesto de formula (1) en la que uno de los grupos G1 representa un tomo de nitrogeno o un grupo CRc y el otro representa un grupo CRc; G2 representa un tomo de nitrogeno o un grupo CRd; R1 representa un grupo seleccionado de tomos de hidrogeno, halogeno, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, y grupos cicloalquilo C3-8 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi; R2 representa un grupo seleccionado de tomos de hidrogeno, halogeno, grupos hidroxilo, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, y grupos cicloalquilo C3-8 que pueden estar opcionalmente sustituidos o con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi; Ra, Rb y Rc independientemente representan grupos seleccionados de tomos de hidrogeno, halogeno, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, y grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi; Rd representa un grupo seleccionado de tomos de hidrogeno, halogeno, grupos hidroxilo, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, y grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, y grupos cicloalcoxi C3-8 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, uno de los grupos G3 y G4 es un tomo de nitrogeno y el otro es un grupo CH, M es un tomo de hidrogeno o un cation farmaceuticamente aceptable con la condicion de que, cuando al menos uno de los grupos Ra y Rb representa un tomo de hidrogeno y G2 es un grupo CRd, entonces Rd representa un grupo seleccionado de grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi, grupos cicloalcoxi C3-8 que pueden estar opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados de tomos de halogeno y grupos hidroxi; y sus sales y N-oxidos farmaceuticamente aceptables. Reivindicacion 26: Una combinacion segun la reivindicacion 3 o 4 donde el inhibidor de DHODH es cido 2-(3'-etoxi-3,5-difluorobifenil-4-ilamino)nicot¡nico o una sal o N-oxido farmaceuticamente aceptable del mismo. Reivindicacion 27: Una combinacion segun la reivindicacion 3 o 4 donde el inhibidor de DHODH es cido 2-(3,5-difluoro-3'-metoxibifenil-4-ilamino)nicot¡nico o una sal o N-oxido farmaceuticamente aceptable del mismo. Reivindicacion 28: Una combinacion segun la reivindicacion 3 o 4 donde el inhibidor de DHODH es cido 2-(3'-ciclopropoxi-3,5-difluorobifenil-4-ilamino)nicot¡nico o una sal o N-oxido farmaceuticamente aceptable del mismo. Reivindicacion 29: Una combinacion segun la reivindicacion 3 o 4 donde el inhibidor de DHOOH es cido 2-(3,5-difluoro-3'-metoxibifenil-4-ilamino)-5-metiInicot¡nico o una sal o N-oxido farmaceuticamente aceptable del mismo. Reivindicacion 31: Una combinacion segun una cualquiera de las reivindicaciones precedentes, que comprende adem s (c) otro compuesto seleccionado de: (i) Anticuerpos monoclonales anti-TNF-alfa tales como Infliximab, 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 Isotechnika; (iv) Antagonistas del receptor IL-1 tales como Anakinra y AMG-719 de Amgen; (v) Anticuerpos monoclonales anti-CD20 tales como 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-281832, 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 como 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 como ARRY-162 de Array; (xi) Agonistas de los receptores de 1-fosfato de esfingosina, tales como fingolimod (Novartis); (xii) Interferones que comprenden Interferon beta la tal como Avonex de Biogen ldec, 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 del cido fum rico) de Biogen Idec/Fumapharm AG, (xiv) Inhibidores de la adenosina aminohidrolasa tales como Cladribina de Merck Serono. Reivindicacion 32: Uso de (a) metotrexato y (b) un inhibidor de DHODH como se define en una cualquiera de las reivindicaciones 1 a 29 para la preparacion de un medicamento para uso simult neo, separado o secuencial en el tratamiento de un estado patologico o enfermedad susceptible a mejorar por inhibicion de deshidroorotato deshidrogenasa. Reivindicacion 33: Uso segun la reivindicacion 32, donde el estado patologico o enfermedad se selecciona de artritis reumatoide, artritis psori tica, espondilitis anquilosante, esclerosis multiple, granulomatosis de Wegener, lupus eritematoso sistemico, psoriasis y sarcoidosis. Reivindicacion 49: Un inhibidor de DHODH como se ha definido en una cualquiera de las reivindicaciones 1 a 29, para uso en el tratamiento de un paciente humano o animal que padece un estado patologico o enfermedad, como se ha definido en la reivindicacion 32 o 33, donde el paciente humano o animal padece o es susceptible de padecer insuficiencia hep tica o un estado que se agravar¡a por hepatotoxicidad, como se ha definido en la reivindicacion 43 o 44.
Applications Claiming Priority (1)
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| EP08382022A EP2135610A1 (en) | 2008-06-20 | 2008-06-20 | Combination comprising DHODH inhibitors and methotrexate |
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