ES2260300T3 - Compuestos tetraciclicos sustituidos con amino utiles como agentes antiinflamatorios y composiciones farmaceuticas que comprenden los mismos. - Google Patents
Compuestos tetraciclicos sustituidos con amino utiles como agentes antiinflamatorios y composiciones farmaceuticas que comprenden los mismos.Info
- Publication number
- ES2260300T3 ES2260300T3 ES01979911T ES01979911T ES2260300T3 ES 2260300 T3 ES2260300 T3 ES 2260300T3 ES 01979911 T ES01979911 T ES 01979911T ES 01979911 T ES01979911 T ES 01979911T ES 2260300 T3 ES2260300 T3 ES 2260300T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- substituted
- methyl
- compound
- nitrogen
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 108
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- -1 AMINO Chemical group 0.000 title description 60
- 239000002260 anti-inflammatory agent Substances 0.000 title description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 99
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- 125000003118 aryl group Chemical group 0.000 claims abstract description 21
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical group 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 10
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 125000005605 benzo group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- ODFIBXFJCDPCHA-UHFFFAOYSA-N 1-methyl-4-methylaminobenzo(g)imidazo(4,5-c)quinoline Chemical compound C1=CC=C2C=C(C3=C(C(NC)=N4)N=CN3C)C4=CC2=C1 ODFIBXFJCDPCHA-UHFFFAOYSA-N 0.000 claims description 2
- WTPHYSIDMNOBOL-UHFFFAOYSA-N 12-thia-14,17-diazatetracyclo[8.7.0.03,8.011,15]heptadeca-1,3,5,7,9,11(15),13,16-octaene Chemical compound C1=CC=CC2=CC3=C(SC=N4)C4=CN=C3C=C21 WTPHYSIDMNOBOL-UHFFFAOYSA-N 0.000 claims description 2
- ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical compound C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- KFIFSKNSIUVOCG-UHFFFAOYSA-N chembl230185 Chemical compound N=1C2=CC3=CC=CC=C3C=C2N2C(C)=CN=C2C=1NCCN1CCCCC1 KFIFSKNSIUVOCG-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 4
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- HYIUUGVUYIIERY-UHFFFAOYSA-N CNC1=NC2=CC3=CC=CC=C3C=C2C2=C1N=C[S+]2C Chemical compound CNC1=NC2=CC3=CC=CC=C3C=C2C2=C1N=C[S+]2C HYIUUGVUYIIERY-UHFFFAOYSA-N 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- UMGOIQFASVFXBU-UHFFFAOYSA-N chembl230184 Chemical compound C1=CC=C2C=C(N3C(C)=CN=C3C(NCCO)=N3)C3=CC2=C1 UMGOIQFASVFXBU-UHFFFAOYSA-N 0.000 claims 1
- 210000000987 immune system Anatomy 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 208000014239 psoriasis 11 Diseases 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 7
- 108091008648 NR7C Proteins 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 239000000203 mixture Substances 0.000 description 50
- 238000002360 preparation method Methods 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 239000002253 acid Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000002619 bicyclic group Chemical group 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
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- 230000007062 hydrolysis Effects 0.000 description 6
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- 125000002950 monocyclic group Chemical group 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
- JJFAGUZOWDICTQ-UHFFFAOYSA-N 4-chloro-1-methylbenzo[g]imidazo[1,2-a]quinoxaline Chemical compound C1=CC=C2C=C(N3C(C)=CN=C3C(Cl)=N3)C3=CC2=C1 JJFAGUZOWDICTQ-UHFFFAOYSA-N 0.000 description 5
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- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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- 150000004820 halides Chemical class 0.000 description 5
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 5
- 150000003141 primary amines Chemical class 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
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- 229940124597 therapeutic agent Drugs 0.000 description 5
- LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
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- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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- 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)
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- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US22330400P | 2000-10-03 | 2000-10-03 | |
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| EP (1) | EP1325009B1 (enExample) |
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| CA (1) | CA2424303A1 (enExample) |
| DE (1) | DE60117835T2 (enExample) |
| ES (1) | ES2260300T3 (enExample) |
| HU (1) | HUP0302925A3 (enExample) |
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| MXPA03003599A (es) | 2000-10-26 | 2003-08-01 | Tularik Inc | Agentes antiinflamatorios. |
| EP1363993A4 (en) * | 2001-02-01 | 2008-11-12 | Bristol Myers Squibb Co | METHOD FOR THE TREATMENT OF INFLAMMATORY AND IMMUNE DISEASES USING I KAPPA B KINASE (IKK) |
| AU2002365611A1 (en) | 2001-12-05 | 2003-06-17 | F. Hoffmann - La Roche Ag | Inflammation modulators |
| US7199119B2 (en) | 2002-10-31 | 2007-04-03 | Amgen Inc. | Antiinflammation agents |
| 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 |
| TW200626142A (en) | 2004-09-21 | 2006-08-01 | Glaxo Group Ltd | Chemical compounds |
| US8063071B2 (en) | 2007-10-31 | 2011-11-22 | GlaxoSmithKline, LLC | Chemical compounds |
| MX2007016541A (es) | 2005-06-30 | 2008-03-07 | Smithkline Beecham Corp | Compuestos quimicos. |
| DK1928887T3 (en) | 2005-08-05 | 2015-03-23 | Senhwa Biosciences Inc | Methods for preparing quinolonanaloger |
| US20090175852A1 (en) | 2006-06-06 | 2009-07-09 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| KR101563103B1 (ko) * | 2006-12-13 | 2015-10-23 | 아스카 세이야쿠 가부시키가이샤 | 퀴녹살린 유도체 |
| PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
| CN102171204B (zh) | 2008-10-02 | 2014-08-20 | 旭化成制药株式会社 | 8位取代异喹啉衍生物及其用途 |
| WO2010102968A1 (en) | 2009-03-10 | 2010-09-16 | Glaxo Group Limited | Indole derivatives as ikk2 inhibitors |
| CN102288753A (zh) * | 2011-05-10 | 2011-12-21 | 重庆市科学技术研究院 | 快速检测四环素、金霉素、土霉素与多西环素残留的四联胶体金免疫层析试纸条及其制备方法 |
| PE20170131A1 (es) * | 2014-05-09 | 2017-03-19 | Pimera Inc | Composiciones novedosas usos y metodos para hacerlas |
| US9758518B2 (en) | 2015-03-04 | 2017-09-12 | Pimera, Inc. | Compositions, uses and methods for making them |
| JP2020512975A (ja) * | 2017-03-28 | 2020-04-30 | ピメラ，インク． | Ｐｏｌ１阻害剤の新規な結晶形態 |
| JOP20180094A1 (ar) | 2017-10-18 | 2019-04-18 | Hk Inno N Corp | مركب حلقي غير متجانس كمثبط بروتين كيناز |
| KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
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| US4160097A (en) | 1977-01-07 | 1979-07-03 | Westwind Pharmaceuticals, Inc. | 1-(2-Phenylureylene)imidazoles |
| US4225724A (en) | 1977-01-07 | 1980-09-30 | Westwood Pharmaceuticals, Inc. | 1-(2-Phenylureylene)imidazoles |
| US4236015A (en) | 1977-01-07 | 1980-11-25 | Westwood Pharmaceuticals, Inc. | 1-(2-Acylaminophenyl)imidazoles |
| US5153196A (en) * | 1991-06-05 | 1992-10-06 | Eli Lilly And Company | Excitatory amino acid receptor antagonists and methods for the use thereof |
| US5196421A (en) | 1991-06-05 | 1993-03-23 | Eli Lilly And Company | Excitatory amino acid receptor antagonists in methods for the use thereof |
| US5182386A (en) | 1991-08-27 | 1993-01-26 | Neurogen Corporation | Certain imidazoquinoxalinones; a new class of gaba brain receptor ligands |
| US5266575A (en) * | 1991-11-06 | 1993-11-30 | Minnesota Mining And Manufacturing Company | 2-ethyl 1H-imidazo[4,5-ciquinolin-4-amines |
| FR2696466B1 (fr) | 1992-10-02 | 1994-11-25 | Rhone Poulenc Rorer Sa | Dérivés de 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one, leur préparation et les médicaments les contenant. |
| IT1276167B1 (it) | 1995-11-24 | 1997-10-27 | Foscama Biomed Chim Farma | Imidazo(1,2-alfa)chinossalin-4-ammine attivi come antagonisti adenosinici,procedimento per la loro preparazione e loro composizioni |
| US6235740B1 (en) | 1997-08-25 | 2001-05-22 | Bristol-Myers Squibb Co. | Imidazoquinoxaline protein tyrosine kinase inhibitors |
| CA2322311C (en) | 1998-03-04 | 2009-10-13 | Bristol-Myers Squibb Company | Heterocyclo-substituted imidazopyrazine protein tyrosine kinase inhibitors |
| US6869956B2 (en) * | 2000-10-03 | 2005-03-22 | Bristol-Myers Squibb Company | Methods of treating inflammatory and immune diseases using inhibitors of IκB kinase (IKK) |
| EP1363993A4 (en) * | 2001-02-01 | 2008-11-12 | Bristol Myers Squibb Co | METHOD FOR THE TREATMENT OF INFLAMMATORY AND IMMUNE DISEASES USING I KAPPA B KINASE (IKK) |
-
2001
- 2001-09-27 ES ES01979911T patent/ES2260300T3/es not_active Expired - Lifetime
- 2001-09-27 AU AU1182702A patent/AU1182702A/xx active Pending
- 2001-09-27 HU HU0302925A patent/HUP0302925A3/hu unknown
- 2001-09-27 CA CA002424303A patent/CA2424303A1/en not_active Abandoned
- 2001-09-27 WO PCT/US2001/042387 patent/WO2002028860A2/en not_active Ceased
- 2001-09-27 JP JP2002532443A patent/JP5021148B2/ja not_active Expired - Fee Related
- 2001-09-27 AU AU2002211827A patent/AU2002211827B2/en not_active Ceased
- 2001-09-27 EP EP01979911A patent/EP1325009B1/en not_active Expired - Lifetime
- 2001-09-27 AT AT01979911T patent/ATE319713T1/de not_active IP Right Cessation
- 2001-09-27 US US09/965,977 patent/US6960585B2/en not_active Expired - Lifetime
- 2001-09-27 DE DE60117835T patent/DE60117835T2/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0302925A2 (hu) | 2003-12-29 |
| CA2424303A1 (en) | 2002-04-11 |
| EP1325009B1 (en) | 2006-03-08 |
| EP1325009A2 (en) | 2003-07-09 |
| DE60117835T2 (de) | 2006-10-19 |
| US6960585B2 (en) | 2005-11-01 |
| ATE319713T1 (de) | 2006-03-15 |
| JP5021148B2 (ja) | 2012-09-05 |
| AU2002211827B2 (en) | 2006-12-14 |
| AU1182702A (en) | 2002-04-15 |
| US20020072523A1 (en) | 2002-06-13 |
| WO2002028860A3 (en) | 2002-09-06 |
| JP2004512281A (ja) | 2004-04-22 |
| HUP0302925A3 (en) | 2004-10-28 |
| WO2002028860A2 (en) | 2002-04-11 |
| DE60117835D1 (de) | 2006-05-04 |
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