DE10237722A1 - Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase - Google Patents
Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase Download PDFInfo
- Publication number
- DE10237722A1 DE10237722A1 DE10237722A DE10237722A DE10237722A1 DE 10237722 A1 DE10237722 A1 DE 10237722A1 DE 10237722 A DE10237722 A DE 10237722A DE 10237722 A DE10237722 A DE 10237722A DE 10237722 A1 DE10237722 A1 DE 10237722A1
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- formula
- compound
- hydrogen
- diseases
- 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- Withdrawn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
- 102000001284 I-kappa-B kinase Human genes 0.000 title claims abstract description 16
- 108060006678 I-kappa-B kinase Proteins 0.000 title claims abstract description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 19
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims description 9
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 8
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 5
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 60
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 230000000694 effects Effects 0.000 claims abstract description 8
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
- 238000011321 prophylaxis Methods 0.000 claims abstract description 3
- -1 Heteroaryl radical Chemical class 0.000 claims description 63
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 44
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 14
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 12
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims description 11
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 10
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical compound OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 claims description 9
- YDCVQGAUCOROHB-UHFFFAOYSA-N oxadiazolidine-4,5-dione Chemical compound O=C1NNOC1=O YDCVQGAUCOROHB-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 150000003852 triazoles Chemical class 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 7
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 7
- ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical class O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 6
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 6
- IGAVZWMNOPFOCW-UHFFFAOYSA-N 2h-1,2,4-thiadiazol-5-one Chemical compound O=C1NC=NS1 IGAVZWMNOPFOCW-UHFFFAOYSA-N 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
- 201000008482 osteoarthritis Diseases 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 150000003536 tetrazoles Chemical class 0.000 claims description 6
- YSVFAMDLJASIGW-UHFFFAOYSA-N 5h-1,2,3,5-oxathiadiazole 2-oxide Chemical class O=S1NC=NO1 YSVFAMDLJASIGW-UHFFFAOYSA-N 0.000 claims description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 5
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010017533 Fungal infection Diseases 0.000 claims description 4
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 4
- 229930194542 Keto Natural products 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
- RKPNOOCIENNLRT-SANMLTNESA-N 2-[2-(methylamino)pyrimidin-4-yl]-n-[(1s)-1-(2-oxo-3h-1,3,4-oxadiazol-5-yl)-2-(n-phenylanilino)ethyl]-1h-indole-5-carboxamide Chemical compound CNC1=NC=CC(C=2NC3=CC=C(C=C3C=2)C(=O)N[C@@H](CN(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2OC(=O)NN=2)=N1 RKPNOOCIENNLRT-SANMLTNESA-N 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 3
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 3
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 208000030507 AIDS Diseases 0.000 claims description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 208000036487 Arthropathies Diseases 0.000 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- 208000027932 Collagen disease Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 201000005569 Gout Diseases 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 206010022714 Intestinal ulcer Diseases 0.000 claims description 2
- 208000012659 Joint disease Diseases 0.000 claims description 2
- 206010024229 Leprosy Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 201000009906 Meningitis Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- 208000030852 Parasitic disease Diseases 0.000 claims description 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- 206010041591 Spinal osteoarthritis Diseases 0.000 claims description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 208000026816 acute arthritis Diseases 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 230000004097 bone metabolism Effects 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 208000023819 chronic asthma Diseases 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 208000017760 chronic graft versus host disease Diseases 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 210000002808 connective tissue Anatomy 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- 238000001212 derivatisation Methods 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 230000001900 immune effect Effects 0.000 claims description 2
- 206010022000 influenza Diseases 0.000 claims description 2
- 208000028774 intestinal disease Diseases 0.000 claims description 2
- 210000003041 ligament Anatomy 0.000 claims description 2
- 201000004792 malaria Diseases 0.000 claims description 2
- 230000002503 metabolic effect Effects 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 230000002018 overexpression Effects 0.000 claims description 2
- 210000004417 patella Anatomy 0.000 claims description 2
- 208000028169 periodontal disease Diseases 0.000 claims description 2
- 230000002035 prolonged effect Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 208000005801 spondylosis Diseases 0.000 claims description 2
- 230000036262 stenosis Effects 0.000 claims description 2
- 208000037804 stenosis Diseases 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 230000009529 traumatic brain injury Effects 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 230000036269 ulceration Effects 0.000 claims description 2
- 241000701161 unidentified adenovirus Species 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- MCEPFRNVLLBMLD-UHFFFAOYSA-N 3-hydroxypyrrole-2,4-dione Chemical compound OC1C(=O)C=NC1=O MCEPFRNVLLBMLD-UHFFFAOYSA-N 0.000 claims 1
- 208000017667 Chronic Disease Diseases 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 210000002346 musculoskeletal system Anatomy 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- VGPFMJFWIPSHJO-UHFFFAOYSA-N 2-[2-(methylamino)pyrimidin-4-yl]-1h-indole-5-carboxylic acid Chemical compound CNC1=NC=CC(C=2NC3=CC=C(C=C3C=2)C(O)=O)=N1 VGPFMJFWIPSHJO-UHFFFAOYSA-N 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- JEDMTEAAGFRXDN-HNNXBMFYSA-N methyl (2s)-2-amino-3-(n-phenylanilino)propanoate Chemical compound C=1C=CC=CC=1N(C[C@H](N)C(=O)OC)C1=CC=CC=C1 JEDMTEAAGFRXDN-HNNXBMFYSA-N 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000009833 condensation Methods 0.000 description 7
- 230000005494 condensation Effects 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 6
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- HDAJRPWVPFVJBR-NRFANRHFSA-N (2s)-3-(n-phenylanilino)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)N(C=1C=CC=CC=1)C1=CC=CC=C1 HDAJRPWVPFVJBR-NRFANRHFSA-N 0.000 description 5
- OVRSIQWVIJSERH-UHFFFAOYSA-N 1-(dimethylamino)-4,4-dimethoxypent-1-en-3-one Chemical compound COC(C)(OC)C(=O)C=CN(C)C OVRSIQWVIJSERH-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- AXLOCHLTNQDFFS-BESJYZOMSA-N azastene Chemical compound C([C@H]1[C@@H]2CC[C@@]([C@]2(CC[C@@H]1[C@@]1(C)C2)C)(O)C)C=C1C(C)(C)C1=C2C=NO1 AXLOCHLTNQDFFS-BESJYZOMSA-N 0.000 description 4
- 150000001556 benzimidazoles Chemical class 0.000 description 4
- 230000037058 blood plasma level Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- RHXSYTACTOMVLJ-UHFFFAOYSA-N 1H-benzimidazole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=NC2=C1 RHXSYTACTOMVLJ-UHFFFAOYSA-N 0.000 description 2
- KFGVDCBVGNMCJC-UHFFFAOYSA-N 2-hydrazinylbenzoic acid Chemical class NNC1=CC=CC=C1C(O)=O KFGVDCBVGNMCJC-UHFFFAOYSA-N 0.000 description 2
- HDAJRPWVPFVJBR-UHFFFAOYSA-N 3-(n-phenylanilino)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)O)CN(C=1C=CC=CC=1)C1=CC=CC=C1 HDAJRPWVPFVJBR-UHFFFAOYSA-N 0.000 description 2
- HDQGBTMXRHGWRF-UHFFFAOYSA-N 4-(1,1-dimethoxyethyl)-n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC(C(C)(OC)OC)=N1 HDQGBTMXRHGWRF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 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 2
- 238000002965 ELISA Methods 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 108010001441 Phosphopeptides Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229940080469 phosphocellulose Drugs 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- LBFSHXXTLRZXST-UHFFFAOYSA-N pyridazine;pyrimidine Chemical compound C1=CC=NN=C1.C1=CN=CN=C1 LBFSHXXTLRZXST-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- GNIDSOFZAKMQAO-VIFPVBQESA-N (2s)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 GNIDSOFZAKMQAO-VIFPVBQESA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- UALBREDZRPQFER-UHFFFAOYSA-N 1,2-thiazole;1,3-thiazole Chemical compound C=1C=NSC=1.C1=CSC=N1 UALBREDZRPQFER-UHFFFAOYSA-N 0.000 description 1
- VJQCNCOGZPSOQZ-UHFFFAOYSA-N 1-Methylguanidine hydrochloride Chemical compound [Cl-].C[NH2+]C(N)=N VJQCNCOGZPSOQZ-UHFFFAOYSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- UFQBSPGKRRSATO-UHFFFAOYSA-N 3,3-dimethoxybutan-2-one Chemical compound COC(C)(OC)C(C)=O UFQBSPGKRRSATO-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- PCNFLKVWBDNNOW-UHFFFAOYSA-N 4-hydrazinylbenzoic acid Chemical compound NNC1=CC=C(C(O)=O)C=C1 PCNFLKVWBDNNOW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000052052 Casein Kinase II Human genes 0.000 description 1
- 108010010919 Casein Kinase II Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 239000003458 I kappa b kinase inhibitor Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- QKDLQFSLLCQTOH-UHFFFAOYSA-N Trichodonin Natural products C1C(O)C2C3(COC(=O)C)C(C=O)C(C)(C)CCC3OC(=O)C22C(=O)C(=C)C1C2 QKDLQFSLLCQTOH-UHFFFAOYSA-N 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- NNNDGNSOCBWTJG-UHFFFAOYSA-N aniline;benzoic acid Chemical class NC1=CC=CC=C1.OC(=O)C1=CC=CC=C1 NNNDGNSOCBWTJG-UHFFFAOYSA-N 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 102000043871 biotin binding protein Human genes 0.000 description 1
- 108700021042 biotin binding protein Proteins 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 108010073357 cyanoginosin LR Proteins 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SLPJGDQJLTYWCI-UHFFFAOYSA-N dimethyl-(4,5,6,7-tetrabromo-1h-benzoimidazol-2-yl)-amine Chemical compound BrC1=C(Br)C(Br)=C2NC(N(C)C)=NC2=C1Br SLPJGDQJLTYWCI-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- JEDMTEAAGFRXDN-UHFFFAOYSA-N methyl 2-amino-3-(n-phenylanilino)propanoate Chemical compound C=1C=CC=CC=1N(CC(N)C(=O)OC)C1=CC=CC=C1 JEDMTEAAGFRXDN-UHFFFAOYSA-N 0.000 description 1
- PMKMEVDOPSRHMN-UHFFFAOYSA-N methyl 3-(n-phenylanilino)-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)OC)CN(C=1C=CC=CC=1)C1=CC=CC=C1 PMKMEVDOPSRHMN-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- ZYZCGGRZINLQBL-GWRQVWKTSA-N microcystin-LR Chemical compound C([C@H](OC)[C@@H](C)\C=C(/C)\C=C\[C@H]1[C@@H](C(=O)N[C@H](CCC(=O)N(C)C(=C)C(=O)N[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]([C@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(O)=O)C(O)=O)C)C1=CC=CC=C1 ZYZCGGRZINLQBL-GWRQVWKTSA-N 0.000 description 1
- DIDLWIPCWUSYPF-UHFFFAOYSA-N microcystin-LR Natural products COC(Cc1ccccc1)C(C)C=C(/C)C=CC2NC(=O)C(NC(CCCNC(=N)N)C(=O)O)NC(=O)C(C)C(NC(=O)C(NC(CC(C)C)C(=O)O)NC(=O)C(C)NC(=O)C(=C)N(C)C(=O)CCC(NC(=O)C2C)C(=O)O)C(=O)O DIDLWIPCWUSYPF-UHFFFAOYSA-N 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108010005709 protein kinase C kinase Proteins 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 210000002023 somite Anatomy 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- AIDS & HIV (AREA)
- Psychiatry (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
Priority Applications (52)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10237722A DE10237722A1 (de) | 2002-08-17 | 2002-08-17 | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| UAA200502387A UA78591C2 (en) | 2002-08-17 | 2003-05-08 | INDOLE OR BENZIMIDAZOLE DERIVATIVE AS SUBSTANCES MODULATING IkB KINASE |
| JO200387A JO2764B1 (en) | 2002-08-17 | 2003-07-23 | Indole derivatives or benzimidazole derivatives to modify the enzyme AKP kinase |
| EP03793685A EP1530568B1 (de) | 2002-08-17 | 2003-08-05 | INDOL-ODER BENZIMIDAZOLDERIVATE ZUR MODULATION DER IkB-KINASE |
| PE2003000772A PE20040893A1 (es) | 2002-08-17 | 2003-08-05 | DERIVADOS DE INDOL O DERIVADOS DE BENCIMIDAZOL PARA MODULAR IkB QUINASA |
| DK03793685.3T DK1530568T3 (da) | 2002-08-17 | 2003-08-05 | Indol- eller benzimidazolderivater til modulering af ikb-kinasen |
| PL03374229A PL374229A1 (en) | 2002-08-17 | 2003-08-05 | Indole or benzimidazole derivatives for modulating ik b kinase |
| AU2003263196A AU2003263196B2 (en) | 2002-08-17 | 2003-08-05 | Indole or benzimidazole derivatives for modulating IkappaB kinase |
| SI200332173T SI2233483T1 (sl) | 2002-08-17 | 2003-08-05 | Indolni ali benzimidazolni derivati za modulacijo IkapaB-kinaze in intermediati za njihovo pripravo |
| PT03793685T PT1530568E (pt) | 2002-08-17 | 2003-08-05 | DERIVADOS DE INDOLE OU DE BENZIMIDAZOLE PARA A MODULAÇÃO DA IkappaB CINASE |
| OA1200500047A OA12908A (en) | 2002-08-17 | 2003-08-05 | Indole or benzimidazole derivatives for modulatingIKB-kinase. |
| EP10163200A EP2233483B1 (de) | 2002-08-17 | 2003-08-05 | Indol- oder Benzimidazolderivate zur Modulation der IkB-Kinase und Zwischenprodukte zu deren Herstellung |
| ES03793685T ES2358795T3 (es) | 2002-08-17 | 2003-08-05 | Derivados de indol o derivados de bencimidazol para modular la ikb quinasa. |
| DE50313372T DE50313372D1 (de) | 2002-08-17 | 2003-08-05 | INDOL-ODER BENZIMIDAZOLDERIVATE ZUR MODULATION DER IkB-KINASE |
| CNB038195437A CN1314683C (zh) | 2002-08-17 | 2003-08-05 | 用于调节IkB激酶的吲哚或苯并咪唑衍生物 |
| SI200331971T SI1530568T1 (sl) | 2002-08-17 | 2003-08-05 | Indolni ali benzimidazolni derivati za modulacijo IkapaB-kinaze |
| BRPI0313562-4A BR0313562A (pt) | 2002-08-17 | 2003-08-05 | derivados de indol ou benzimidazol para a modulação da ikb-cinase |
| YU20050104A RS51902B (sr) | 2002-08-17 | 2003-08-05 | Derivati indola ili benzimidazola za modulaciju ikb-kinaze |
| JP2004533319A JP4504812B2 (ja) | 2002-08-17 | 2003-08-05 | IκBキナーゼをモジュレートするためのインドール誘導体またはベンズイミダゾール誘導体 |
| DK10163200.8T DK2233483T3 (da) | 2002-08-17 | 2003-08-05 | Indol- eller benzimidazol-derivater til modulering af IKB-kinase og mellemprodukter til fremstilling deraf |
| NZ538296A NZ538296A (en) | 2002-08-17 | 2003-08-05 | Indole derivatives or benzimidazole derivatives for modulating IkB kinase |
| ES10163200T ES2387954T3 (es) | 2002-08-17 | 2003-08-05 | Derivados de indol o de bencimidazol para modular la IkB quinasa, y productos intermedios para su preparación |
| HRP20050042AA HRP20050042B1 (hr) | 2002-08-17 | 2003-08-05 | DERIVATI INDOLA ILI BENZIMIDAZOLA ZA MODULACIJU IkB KINAZE |
| MEP-606/08A MEP60608A (en) | 2002-08-17 | 2003-08-05 | INDOLE OR BENZIMIDAZOLE DERIVATIVES FOR MODULATING IkappaB KINASE |
| KR1020057002707A KR101162046B1 (ko) | 2002-08-17 | 2003-08-05 | IκB 키나제 조절용 인돌 또는 벤즈이미다졸 유도체 |
| HK05111392.6A HK1079509B (en) | 2002-08-17 | 2003-08-05 | INDOLE OR BENZIMIDAZOLE DERIVATIVES FOR MODULATING IκB KINASE |
| PT10163200T PT2233483E (pt) | 2002-08-17 | 2003-08-05 | Derivados de indole ou de benzimidazole para a modulação da iκb cinase e produtos intermédios para a sua preparação |
| RU2005107418/04A RU2318820C2 (ru) | 2002-08-17 | 2003-08-05 | ПРОИЗВОДНЫЕ ИНДОЛА ИЛИ БЕНЗИМИДАЗОЛА ДЛЯ МОДУЛЯЦИИ IkB-КИНАЗЫ |
| PCT/EP2003/008629 WO2004022553A1 (de) | 2002-08-17 | 2003-08-05 | INDOL-ODER BENZIMIDAZOLDERIVATE ZUR MODULATION DER IλB-KINASE |
| AT03793685T ATE493402T1 (de) | 2002-08-17 | 2003-08-05 | Indol-oder benzimidazolderivate zur modulation der ikb-kinase |
| CA2498559A CA2498559C (en) | 2002-08-17 | 2003-08-05 | Indole derivatives or benzimidazole derivatives for modulating i.kappa.b kinase |
| MXPA05001314A MXPA05001314A (es) | 2002-08-17 | 2003-08-05 | Derivados de indol o derivados de bencimidazol para modular ikb quinasa. |
| AT10163200T ATE557018T1 (de) | 2002-08-17 | 2003-08-05 | Indol- oder benzimidazolderivate zur modulation der ikb-kinase und zwischenprodukte zu deren herstellung |
| PA20038580501A PA8580501A1 (es) | 2002-08-17 | 2003-08-12 | Derivados de indol o derivados de bencimidazol para modular ikb quinasa |
| ARP030102946A AR040975A1 (es) | 2002-08-17 | 2003-08-14 | Derivados de indol o derivados de bencimidazol para modular ikb quinasa, un procedimiento para su preparacion y su uso para preparar un producto farmaceutico |
| TW092122309A TWI290552B (en) | 2002-08-17 | 2003-08-14 | Indole derivatives or benzimidazole derivatives for modulating IkB kinase |
| UY27941A UY27941A1 (es) | 2002-08-17 | 2003-08-15 | Derivados de indol o derivados de bencimidazol para modular ikb quinasa |
| SV2003001599A SV2004001599A (es) | 2002-08-17 | 2003-08-15 | Derivados de indol o de bencimidazol para modula ikb quinasa |
| MYPI20033115A MY140074A (en) | 2002-08-17 | 2003-08-15 | INDOLE DERIVATIVES OR BENZIMIDAZOLE DERIVATIVES FOR MODULATING IkB KINASE |
| HN2003000249A HN2003000249A (es) | 2002-08-17 | 2003-08-15 | Derivados de indol o derivados de bencimidazol para modular ikb quinasa |
| US10/642,970 US7285560B2 (en) | 2002-08-17 | 2003-08-18 | Indole derivatives or benzimidazole derivatives for modulating IκB kinase |
| ZA200500322A ZA200500322B (en) | 2002-08-17 | 2005-01-13 | INdole of benzimidazole derivatives for modulating kB kinase |
| CR7668A CR7668A (es) | 2002-08-17 | 2005-01-28 | Derivados del indole o benzimidazole para modular ikappab kinasa |
| IL16678505A IL166785A0 (en) | 2002-08-17 | 2005-02-09 | Indole derivatives or benzimidazole derivatives for modulating ikappab kinase |
| MA28106A MA27382A1 (fr) | 2002-08-17 | 2005-02-15 | DERIVES D'INDOLE OU DE BENZIMIDAZOLE POUR MODULER L'IkB KINASE |
| CO05013335A CO5690586A2 (es) | 2002-08-17 | 2005-02-15 | Derivados de indol o derivados de bencimidazol para modular ixb quinasa |
| TNP2005000045A TNSN05045A1 (en) | 2002-08-17 | 2005-02-16 | Indole or benzimidazole derivatives for modulating ikappab kinase |
| EC2005005612A ECSP055612A (es) | 2002-08-17 | 2005-02-17 | Derivados de indol o derivados de bencimidazol para modular IkB quinasa |
| NO20051337A NO330981B1 (no) | 2002-08-17 | 2005-03-15 | Indol- eller benzimidazolderivater for modulering av IkB-kinase, fremgangsmate for fremstilling av disse, legemiddel og anvendelse av forbindelsene |
| US11/758,978 US8778955B2 (en) | 2002-08-17 | 2007-06-06 | Indole derivatives or benzimidazole derivatives for modulating IkB kinase |
| CY20111100246T CY1111692T1 (el) | 2002-08-17 | 2011-03-02 | ΠΑΡΑΓΩΓΑ ΙΝΔΟΛΗΣ Ή ΒΕΝΖΙΜΙΔΑΖΟΛΗΣ ΓΙΑ ΤΗ ΡΥΘΜΙΣΗ ΤΗΣ ΙκΒ ΚΙΝΑΣΗΣ |
| CY20121100658T CY1112991T1 (el) | 2002-08-17 | 2012-07-24 | ΠΑΡΑΓΩΓΑ ΙΝΔΟΛΗΣ Ή ΒΕΝΖΙΜΙΔΑΖΟΛΗΣ ΓΙΑ ΤΗ ΡΥΘΜΙΣΗ ΤΗΣ ΙκΒ ΚΙΝΑΣΗΣ ΚΑΙ ΕΝΔΙΑΜΕΣΑ ΠΡΟΪΟΝΤΑ ΓΙΑ ΤΗΝ ΠΑΡΑΣΚΕΥΗ ΤΟΥΣ |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10237722A DE10237722A1 (de) | 2002-08-17 | 2002-08-17 | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10237722A1 true DE10237722A1 (de) | 2004-08-19 |
Family
ID=31968974
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10237722A Withdrawn DE10237722A1 (de) | 2002-08-17 | 2002-08-17 | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| DE50313372T Expired - Lifetime DE50313372D1 (de) | 2002-08-17 | 2003-08-05 | INDOL-ODER BENZIMIDAZOLDERIVATE ZUR MODULATION DER IkB-KINASE |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50313372T Expired - Lifetime DE50313372D1 (de) | 2002-08-17 | 2003-08-05 | INDOL-ODER BENZIMIDAZOLDERIVATE ZUR MODULATION DER IkB-KINASE |
Country Status (42)
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19951360A1 (de) * | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
| DE10237723A1 (de) * | 2002-08-17 | 2004-07-08 | Aventis Pharma Deutschland Gmbh | Verwendung von IKappaB-Kinase Inhibitoren in der Schmerztherapie |
| DE10237722A1 (de) * | 2002-08-17 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| DE602004009295T2 (de) | 2003-01-14 | 2008-07-03 | Arena Pharmaceuticals, Inc., San Diego | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| AR045047A1 (es) * | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| WO2005113544A1 (en) * | 2004-05-12 | 2005-12-01 | Aventis Pharmaceuticals Inc. | Substantially pure 2-{[2-(2-methylamino-pyrimidin-4-yl)-1h-indole-5-carbonyl]-amino}-3-(phenylpyridin-2-yl-amino)-propionic acid as an ikb kinase inhibitor |
| PE20060373A1 (es) | 2004-06-24 | 2006-04-29 | Smithkline Beecham Corp | Derivados 3-piperidinil-7-carboxamida-indazol como inhibidores de la actividad cinasa de ikk2 |
| DE102004033406A1 (de) | 2004-07-10 | 2006-02-16 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung der enantiomeren Formen von 2,3-Diaminopropionsäurederivaten |
| TW200626142A (en) | 2004-09-21 | 2006-08-01 | Glaxo Group Ltd | Chemical compounds |
| DOP2006000010A (es) * | 2005-01-10 | 2006-07-31 | Arena Pharm Inc | Procedimiento para preparar eteres aromáticos |
| AR053114A1 (es) * | 2005-01-12 | 2007-04-25 | Aventis Pharma Inc | Sal monopotasica del acido 2-{[2-(-2-metilamino-pirimidin-4-il)-1h-indol-5-carbonil]-amino}-3-(fenilpiridin-2-il-amino)-propionico,inhibidora de ikk-2 quinasa |
| US20070142417A1 (en) * | 2005-05-11 | 2007-06-21 | Aventis Pharmaceuticals Inc | Substantially Pure 2-{[2-(2-Methylamino-Pyrimidin-4-YL)-1H-Indole-5-Carbonyl]-Amino}-3-Phenylpyridin-2-YL-Amino)-Propionic Acid as an IkB Kinase Inhibitor |
| DE102005025225A1 (de) * | 2005-06-01 | 2006-12-07 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung von 2-(2-Amino-pyrimidin-4-yl)-1H-indol-5-carbonsäure-derivaten |
| US8063071B2 (en) | 2007-10-31 | 2011-11-22 | GlaxoSmithKline, LLC | Chemical compounds |
| EP1896014A4 (en) | 2005-06-30 | 2010-07-21 | Glaxosmithkline Llc | CHEMICAL COMPOUNDS |
| ES2431050T3 (es) * | 2005-08-04 | 2013-11-22 | Sirtris Pharmaceuticals, Inc. | Benzotiazoles y tiazolopiridinas como moduladores de la sirtuína |
| US7855289B2 (en) * | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8088928B2 (en) * | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8093401B2 (en) * | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US20100069387A1 (en) | 2005-09-07 | 2010-03-18 | Palmer Stephen S | IKK Inhibitors for the Treatment of Endometriosis |
| JP2009001495A (ja) * | 2005-10-13 | 2009-01-08 | Taisho Pharmaceutical Co Ltd | 2−アリール−ベンゾイミダゾール−5−カルボキサミド誘導体 |
| BRPI0715160A2 (pt) | 2006-08-08 | 2013-06-11 | Sanofi Aventis | imidazolidina-2,4-dionas substituÍdas por arilamimoaril-alquil-, processo para preparÁ-las, medicamentos compeendendo estes compostos, e seu uso |
| AR065804A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Compuesto de indol carboxamida, composicion farmaceutica que lo comprende y uso de dicho compuesto para preparar un medicamento |
| CL2008001822A1 (es) * | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| KR20090018593A (ko) * | 2007-08-17 | 2009-02-20 | 주식회사 엘지생명과학 | 세포괴사 저해제로서의 인돌 및 인다졸 화합물 |
| WO2009058348A1 (en) * | 2007-11-01 | 2009-05-07 | Sirtris Pharmaceuticals, Inc. | Amide derivatives as sirtuin modulators |
| WO2009061453A1 (en) * | 2007-11-08 | 2009-05-14 | Sirtris Pharmaceuticals, Inc. | Solubilized thiazolopyridines |
| US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| BRPI0922435A2 (pt) | 2008-12-19 | 2018-09-11 | Sirtris Pharmaceuticals Inc | "composto de tiazolopiridina moduladores de sirtuina, composição farmacêutica compreendendo o mesmo e seu uso." |
| RU2544010C2 (ru) * | 2009-02-27 | 2015-03-10 | Энанта Фармасьютикалс, Инк. | Ингибиторы вируса гепатита с |
| EP2406249A1 (en) | 2009-03-10 | 2012-01-18 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| ES2443016T3 (es) | 2009-08-26 | 2014-02-17 | Sanofi | Nuevos hidratos cristalinos de fluoroglicósidos heteroaromáticos, productos farmacéuticos que comprenden estos compuestos, y su empleo |
| SG10201500639TA (en) | 2010-01-27 | 2015-03-30 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| MX2012012502A (es) * | 2010-04-27 | 2013-01-18 | Hutchison Medipharma Ltd | Compuestos pirimidinil indol. |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| CA2807979A1 (en) * | 2010-08-12 | 2012-02-16 | Sanofi | Process for the preparation of enantiomeric forms of 2,3-diaminopropionic acid derivatives |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| TW201242962A (en) | 2010-12-01 | 2012-11-01 | Sumitomo Chemical Co | Pyrimidine compound and use for pest control thereof |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8710050B2 (en) | 2011-03-08 | 2014-04-29 | Sanofi | Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2683703B1 (de) | 2011-03-08 | 2015-05-27 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| US8809325B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof |
| EP2683701B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120050A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| ES2654177T3 (es) | 2011-07-27 | 2018-02-12 | Astrazeneca Ab | Derivados de 2-(2,4,5-anilino sustituido)pirimidina como moduladores de EGFR útiles para tratar el cáncer |
| SMT201700528T1 (it) * | 2011-08-25 | 2018-01-11 | Medicines For Malaria Venture Mmv | 2-alchil-1-osso-n-fenil-3-eteroaril-1,2,3,4-tetraidroisochinolin-4-carbossammidi sostituite per le terapie antimalariche |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| KR20140103968A (ko) * | 2011-12-06 | 2014-08-27 | 사노피 | 2-(2-메틸아미노-피리미딘-4-일)-1h-인돌-5-카복실산 [(s)-1-카바모일-2-(페닐-피리미딘-2일-아미노)-에틸]-아미드의 결정 형태 |
| EA036521B1 (ru) * | 2012-01-27 | 2020-11-19 | Астразенека Аб | Производные 2-(2,4,5-замещенного анилино)пиримидина в качестве модуляторов egfr, полезных для лечения рака |
| KR101493877B1 (ko) | 2013-03-29 | 2015-02-16 | 농업회사법인 주식회사 생명의나무 | 스피나스테롤 당 유도체를 포함하는 골 질환 예방 또는 치료용 약학 조성물 |
| EP2805705B1 (en) | 2013-05-23 | 2016-11-09 | IP Gesellschaft für Management mbH | Packaging with one or more administration units comprising a sodium salt of (R)-3-[6-amino-pyridin-3-yl]-2-(1-cyclohexyl-1 H-imidazol-4-yl)-propionic acid |
| EP2905282A1 (en) * | 2014-02-05 | 2015-08-12 | AXXAM S.p.A. | Substituted thiazole or oxazole as P2X7 receptor antagonists |
| CN106535899A (zh) | 2014-07-03 | 2017-03-22 | 赛诺菲 | 用于治疗与骨关节炎相关的疼痛的2‑(2‑甲基氨基‑嘧啶‑4‑基)‑1h‑吲哚‑5‑甲酸[(s)‑1‑氨甲酰基‑2‑(苯基‑嘧啶‑2‑基‑氨基)‑乙基]‑酰胺 |
| ES2995737T3 (en) | 2015-01-06 | 2025-02-11 | Arena Pharm Inc | Compound for use in treating conditions related to the s1p1 receptor |
| MA42807A (fr) | 2015-06-22 | 2018-07-25 | Arena Pharm Inc | Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1 |
| EP3290416A1 (en) * | 2016-08-31 | 2018-03-07 | AXXAM S.p.A. | Substituted n-[2-(4-phenoxypiperidin-1-yl)-2-(1,3-thiazol-5-yl)ethyl]benzamide and n-[2-(4-benzyloxypiperidin-1-yl)-2-(1,3-thiazol-5-yl)ethyl]benzamide derivatives and their use as p2x7 receptor antagonist |
| CN106588803A (zh) * | 2016-11-16 | 2017-04-26 | 西南科技大学 | 一种制备5‑乙酰基异噁唑的新方法 |
| CN108299302A (zh) * | 2017-01-11 | 2018-07-20 | 西南科技大学 | 一种制备3-乙酰基吡唑的新方法 |
| WO2018151873A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| EP3801459B1 (en) | 2018-06-06 | 2024-08-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| MX2021011810A (es) | 2019-03-29 | 2021-10-26 | Astrazeneca Ab | Osimertinib para su uso en el tratamiento de cancer de pulmon de celulas no peque?as. |
| US20230116201A1 (en) * | 2020-01-30 | 2023-04-13 | Anima Biotech Inc. | Collagen 1 translation inhibitors and methods of use thereof |
| CN115974849B (zh) * | 2022-12-28 | 2024-06-21 | 中国药科大学 | 一种吲哚氧乙酰胺类衍生物、包含其的药物组合物及其应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU646871B2 (en) * | 1990-06-07 | 1994-03-10 | Astrazeneca Uk Limited | Therapeutic heterocyclic compounds |
| ATE188379T1 (de) | 1992-10-14 | 2000-01-15 | Merck & Co Inc | Fibrinogenrezeptor-antagonisten |
| GB9225141D0 (en) | 1992-12-01 | 1993-01-20 | Smithkline Beecham Corp | Chemical compounds |
| IT1275433B (it) * | 1995-05-19 | 1997-08-07 | Smithkline Beecham Farma | Derivati di diarildiammine |
| FR2763337B1 (fr) * | 1997-05-13 | 1999-08-20 | Sanofi Sa | Nouveaux derives du triazole, un procede pour leur preparation et compositions pharmaceutiques les contenant |
| NZ516348A (en) | 1999-06-23 | 2003-06-30 | Aventis Pharma Gmbh | Substituted benzimidazole |
| DE19951360A1 (de) * | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
| CA2436770A1 (en) | 2001-02-01 | 2002-08-08 | James R. Burke | Methods of treating inflammatory and immune diseases using inhibitors of ikb kinase (ikk) |
| DE10237723A1 (de) * | 2002-08-17 | 2004-07-08 | Aventis Pharma Deutschland Gmbh | Verwendung von IKappaB-Kinase Inhibitoren in der Schmerztherapie |
| US7462638B2 (en) * | 2002-08-17 | 2008-12-09 | Sanofi-Aventis Deutschland Gmbh | Use of IκB-kinase inhibitors in pain therapy |
| DE10237722A1 (de) * | 2002-08-17 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| US7046741B2 (en) * | 2004-04-16 | 2006-05-16 | Data Flow Technologies, Inc. | Single and multiple sinewave modulation and demodulation techniques, apparatus, and communications systems |
-
2002
- 2002-08-17 DE DE10237722A patent/DE10237722A1/de not_active Withdrawn
-
2003
- 2003-05-08 UA UAA200502387A patent/UA78591C2/uk unknown
- 2003-07-23 JO JO200387A patent/JO2764B1/en active
- 2003-08-05 RS YU20050104A patent/RS51902B/sr unknown
- 2003-08-05 AU AU2003263196A patent/AU2003263196B2/en not_active Ceased
- 2003-08-05 RU RU2005107418/04A patent/RU2318820C2/ru not_active IP Right Cessation
- 2003-08-05 SI SI200331971T patent/SI1530568T1/sl unknown
- 2003-08-05 ME MEP-606/08A patent/MEP60608A/xx unknown
- 2003-08-05 PE PE2003000772A patent/PE20040893A1/es not_active Application Discontinuation
- 2003-08-05 AT AT10163200T patent/ATE557018T1/de active
- 2003-08-05 OA OA1200500047A patent/OA12908A/en unknown
- 2003-08-05 DK DK10163200.8T patent/DK2233483T3/da active
- 2003-08-05 BR BRPI0313562-4A patent/BR0313562A/pt not_active Application Discontinuation
- 2003-08-05 ES ES03793685T patent/ES2358795T3/es not_active Expired - Lifetime
- 2003-08-05 DE DE50313372T patent/DE50313372D1/de not_active Expired - Lifetime
- 2003-08-05 PL PL03374229A patent/PL374229A1/xx unknown
- 2003-08-05 MX MXPA05001314A patent/MXPA05001314A/es active IP Right Grant
- 2003-08-05 CN CNB038195437A patent/CN1314683C/zh not_active Expired - Fee Related
- 2003-08-05 PT PT03793685T patent/PT1530568E/pt unknown
- 2003-08-05 AT AT03793685T patent/ATE493402T1/de active
- 2003-08-05 KR KR1020057002707A patent/KR101162046B1/ko not_active Expired - Fee Related
- 2003-08-05 EP EP10163200A patent/EP2233483B1/de not_active Expired - Lifetime
- 2003-08-05 PT PT10163200T patent/PT2233483E/pt unknown
- 2003-08-05 WO PCT/EP2003/008629 patent/WO2004022553A1/de not_active Ceased
- 2003-08-05 SI SI200332173T patent/SI2233483T1/sl unknown
- 2003-08-05 HR HRP20050042AA patent/HRP20050042B1/hr not_active IP Right Cessation
- 2003-08-05 CA CA2498559A patent/CA2498559C/en not_active Expired - Fee Related
- 2003-08-05 JP JP2004533319A patent/JP4504812B2/ja not_active Expired - Fee Related
- 2003-08-05 NZ NZ538296A patent/NZ538296A/en not_active IP Right Cessation
- 2003-08-05 ES ES10163200T patent/ES2387954T3/es not_active Expired - Lifetime
- 2003-08-05 EP EP03793685A patent/EP1530568B1/de not_active Expired - Lifetime
- 2003-08-05 DK DK03793685.3T patent/DK1530568T3/da active
- 2003-08-12 PA PA20038580501A patent/PA8580501A1/es unknown
- 2003-08-14 TW TW092122309A patent/TWI290552B/zh not_active IP Right Cessation
- 2003-08-14 AR ARP030102946A patent/AR040975A1/es not_active Application Discontinuation
- 2003-08-15 HN HN2003000249A patent/HN2003000249A/es unknown
- 2003-08-15 SV SV2003001599A patent/SV2004001599A/es unknown
- 2003-08-15 UY UY27941A patent/UY27941A1/es unknown
- 2003-08-15 MY MYPI20033115A patent/MY140074A/en unknown
- 2003-08-18 US US10/642,970 patent/US7285560B2/en not_active Expired - Lifetime
-
2005
- 2005-01-13 ZA ZA200500322A patent/ZA200500322B/en unknown
- 2005-01-28 CR CR7668A patent/CR7668A/es unknown
- 2005-02-09 IL IL16678505A patent/IL166785A0/xx not_active IP Right Cessation
- 2005-02-15 MA MA28106A patent/MA27382A1/fr unknown
- 2005-02-15 CO CO05013335A patent/CO5690586A2/es active IP Right Grant
- 2005-02-16 TN TNP2005000045A patent/TNSN05045A1/en unknown
- 2005-02-17 EC EC2005005612A patent/ECSP055612A/es unknown
- 2005-03-15 NO NO20051337A patent/NO330981B1/no not_active IP Right Cessation
-
2007
- 2007-06-06 US US11/758,978 patent/US8778955B2/en not_active Expired - Fee Related
-
2011
- 2011-03-02 CY CY20111100246T patent/CY1111692T1/el unknown
-
2012
- 2012-07-24 CY CY20121100658T patent/CY1112991T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE10237722A1 (de) | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase | |
| EP1261601B1 (de) | Substituierte indole zur modulierung von nfkb-aktivität | |
| EP1531819B1 (de) | VERWENDUNG VON I kappa B-KINASE INHIBITOREN IN DER SCHMERZTHERAPIE | |
| EP1194425B1 (de) | Substituierte benzimidazole | |
| EP2102197B1 (de) | 5-([1,3,4]oxadiazol-2-yl)-1h-indazol und 5-([1,3,4]thiadiazol-2-yl)-1h-indazol derivate als sgk-inhibitoren zur behandlung von diabetes | |
| CN102099354A (zh) | 唑类化合物 | |
| JP5897566B2 (ja) | 環式n,n’−ジアリールチオ尿素及びn,n’−ジアリール尿素−アンドロゲン受容体アンタゴニスト、抗癌剤、その調製のための方法及び使用 | |
| EP3412664B1 (en) | Heterocyclic sulfonamide derivative and medicine containing same | |
| DE19928424A1 (de) | Substituierte Benzimidazole | |
| CN114929675B (zh) | 作为粘着斑激酶抑制剂的新型金刚烷衍生物 | |
| CN116102525A (zh) | 苯甲酰胺类衍生物及其用途 | |
| JP2005281309A (ja) | 新規な融合ピラゾリル化合物 | |
| RU2811413C1 (ru) | Метил 4-арил-1-(1,5-диметил-3-оксо-2-фенил-2,3-дигидро-1Н-пиразол-4-ил)-2,3-диоксо-2,3,5,10-тетрагидробензо[b]пирроло[2,3-e][1,4]диазепин-10a(1Н)-карбоксилаты, проявляющие анальгетическую активность, и способ их получения | |
| EP2185525B1 (fr) | Dérivés de pyrazole 3,5-carboxylates, leur préparation et leur application en thérapeutique | |
| DE10006297A1 (de) | Substituierte Benzimidazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8127 | New person/name/address of the applicant |
Owner name: SANOFI-AVENTIS DEUTSCHLAND GMBH, 65929 FRANKFURT, |
|
| 8110 | Request for examination paragraph 44 | ||
| R120 | Application withdrawn or ip right abandoned |
Effective date: 20140121 |