ZA200506242B - Cytokine inhibitors - Google Patents
Cytokine inhibitors Download PDFInfo
- Publication number
- ZA200506242B ZA200506242B ZA200506242A ZA200506242A ZA200506242B ZA 200506242 B ZA200506242 B ZA 200506242B ZA 200506242 A ZA200506242 A ZA 200506242A ZA 200506242 A ZA200506242 A ZA 200506242A ZA 200506242 B ZA200506242 B ZA 200506242B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- phenyl
- methoxy
- amide
- indole
- Prior art date
Links
- 102000004127 Cytokines Human genes 0.000 title claims description 42
- 108090000695 Cytokines Proteins 0.000 title claims description 42
- 239000003112 inhibitor Substances 0.000 title description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 131
- -1 fury] Chemical group 0.000 claims description 70
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 46
- 201000010099 disease Diseases 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000002252 acyl group Chemical group 0.000 claims description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 22
- 125000003386 piperidinyl group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000002757 morpholinyl group Chemical group 0.000 claims description 19
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004193 piperazinyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 230000001404 mediated effect Effects 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004442 acylamino group Chemical group 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- HCUARRIEZVDMPT-UHFFFAOYSA-N indolyl-2-carboxylic acid Natural products C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 claims description 6
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004069 aziridinyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 claims description 3
- 230000000771 oncological effect Effects 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 2
- ZVMXSTNOWNAJGL-UHFFFAOYSA-N 1-methyl-7-pyrimidin-4-yloxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC1=CC=NC=N1 ZVMXSTNOWNAJGL-UHFFFAOYSA-N 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 2
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004276 dioxalanyl group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 2
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 2
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 2
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
- XNPVTUDLRVNVLW-UHFFFAOYSA-N n-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulfonamide Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1NS(C)(=O)=O XNPVTUDLRVNVLW-UHFFFAOYSA-N 0.000 claims 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 5
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 3
- 230000008878 coupling Effects 0.000 claims 3
- 238000010168 coupling process Methods 0.000 claims 3
- 238000005859 coupling reaction Methods 0.000 claims 3
- ZMXOQQOGKXDESA-UHFFFAOYSA-N 2-methoxy-3-(morpholin-4-ylmethyl)-5-(trifluoromethyl)aniline Chemical compound COC1=C(N)C=C(C(F)(F)F)C=C1CN1CCOCC1 ZMXOQQOGKXDESA-UHFFFAOYSA-N 0.000 claims 2
- NOMATNAAIHROAR-UHFFFAOYSA-N 3-amino-5-tert-butyl-2-methoxybenzamide Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1C(N)=O NOMATNAAIHROAR-UHFFFAOYSA-N 0.000 claims 2
- LERLXXIEBXXATD-UHFFFAOYSA-N n-[3-amino-2-methoxy-5-(trifluoromethyl)phenyl]methanesulfonamide Chemical compound COC1=C(N)C=C(C(F)(F)F)C=C1NS(C)(=O)=O LERLXXIEBXXATD-UHFFFAOYSA-N 0.000 claims 2
- GMDHEGQVKCIECG-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-1h-indole-2-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC2=CC=CC=C2N1 GMDHEGQVKCIECG-UHFFFAOYSA-N 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- RYQIIUMRNCAPJK-UHFFFAOYSA-N 1-methyl-7-(2-piperazin-1-ylpyrimidin-4-yl)oxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC(N=1)=CC=NC=1N1CCNCC1 RYQIIUMRNCAPJK-UHFFFAOYSA-N 0.000 claims 1
- CDKZKAUOODOSCT-UHFFFAOYSA-N 1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=NC=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=N1 CDKZKAUOODOSCT-UHFFFAOYSA-N 0.000 claims 1
- VLOFGQCLIXJRJZ-UHFFFAOYSA-N 1-methyl-7-[2-(methylamino)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound CNC1=NC=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=N1 VLOFGQCLIXJRJZ-UHFFFAOYSA-N 0.000 claims 1
- JARRSYNKGJUCJY-UHFFFAOYSA-N 1-methyl-7-[2-(morpholin-4-ylmethyl)pyridin-4-yl]oxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC(C=1)=CC=NC=1CN1CCOCC1 JARRSYNKGJUCJY-UHFFFAOYSA-N 0.000 claims 1
- QUOOAOSCXXVFPS-UHFFFAOYSA-N 1-methyl-7-[2-(morpholin-4-ylmethyl)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC(N=1)=CC=NC=1CN1CCOCC1 QUOOAOSCXXVFPS-UHFFFAOYSA-N 0.000 claims 1
- JNFIHXJPZSKVII-UHFFFAOYSA-N 1-methyl-7-pyridin-4-yloxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC1=CC=NC=C1 JNFIHXJPZSKVII-UHFFFAOYSA-N 0.000 claims 1
- MAHAMBLNIDMREX-UHFFFAOYSA-N 1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1 MAHAMBLNIDMREX-UHFFFAOYSA-N 0.000 claims 1
- NINKYSPOVVXLTC-UHFFFAOYSA-N 3-N,3-N-dibenzyl-5-tert-butyl-2-methoxybenzene-1,3-diamine Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 NINKYSPOVVXLTC-UHFFFAOYSA-N 0.000 claims 1
- HEXCBHCGMLQXRT-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-2-methoxy-5-(trifluoromethyl)aniline Chemical compound COC1=C(N)C=C(C(F)(F)F)C=C1CN(C)C HEXCBHCGMLQXRT-UHFFFAOYSA-N 0.000 claims 1
- PVTVYZZZTYRCSU-UHFFFAOYSA-N 3-amino-5-tert-butyl-2-methoxy-N-(2-morpholin-4-ylethyl)benzamide Chemical compound NC=1C(=C(C(=O)NCCN2CCOCC2)C=C(C=1)C(C)(C)C)OC PVTVYZZZTYRCSU-UHFFFAOYSA-N 0.000 claims 1
- MLJDNAYTLKOGIC-UHFFFAOYSA-N 5-(1,1,1,3,3,3-hexafluoropropan-2-yl)-2-methoxyaniline Chemical compound COC1=CC=C(C(C(F)(F)F)C(F)(F)F)C=C1N MLJDNAYTLKOGIC-UHFFFAOYSA-N 0.000 claims 1
- WBYNKKCDCNTOIU-UHFFFAOYSA-N 5-tert-butyl-2-methoxy-3-(morpholin-4-ylmethyl)aniline Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1CN1CCOCC1 WBYNKKCDCNTOIU-UHFFFAOYSA-N 0.000 claims 1
- KTFVFDZWYXSQFH-UHFFFAOYSA-N 5-tert-butyl-2-methoxy-3-(pyrrolidin-1-ylmethyl)aniline Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1CN1CCCC1 KTFVFDZWYXSQFH-UHFFFAOYSA-N 0.000 claims 1
- SIHGOFIDKYNTLV-UHFFFAOYSA-N 7-[2-(1,2-dihydroxyethyl)pyrimidin-4-yl]oxy-1-methylindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC1=CC=NC(C(O)CO)=N1 SIHGOFIDKYNTLV-UHFFFAOYSA-N 0.000 claims 1
- SGLSEMJAUPSIID-UHFFFAOYSA-N 7-[2-[(4-tert-butylpiperazin-1-yl)methyl]pyrimidin-4-yl]oxy-1-methylindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC(N=1)=CC=NC=1CN1CCN(C(C)(C)C)CC1 SGLSEMJAUPSIID-UHFFFAOYSA-N 0.000 claims 1
- PQAPXLVMTSLHFL-UHFFFAOYSA-N 7-[2-[(dimethylamino)methyl]pyridin-4-yl]oxy-1-methylindole-2-carboxylic acid Chemical compound C1=NC(CN(C)C)=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=C1 PQAPXLVMTSLHFL-UHFFFAOYSA-N 0.000 claims 1
- 101710126670 Apoptosis regulator BHRF1 Proteins 0.000 claims 1
- ANSIURAXIQUPEP-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CC(C)(C)N(CC1)CCN1C1=NC=CC(OC2=C3N(C)C(C(O)=O)=CC3=CC=C2)=N1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CC(C)(C)N(CC1)CCN1C1=NC=CC(OC2=C3N(C)C(C(O)=O)=CC3=CC=C2)=N1 ANSIURAXIQUPEP-UHFFFAOYSA-N 0.000 claims 1
- DNNCSQQFFVAMHF-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=CC(CN2CCN(C)CC2)=NC=C1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=CC(CN2CCN(C)CC2)=NC=C1 DNNCSQQFFVAMHF-UHFFFAOYSA-N 0.000 claims 1
- QPLHYEMENYPJQM-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(CN2CCOCC2)=NC=C1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(CN2CCOCC2)=NC=C1 QPLHYEMENYPJQM-UHFFFAOYSA-N 0.000 claims 1
- VVZQENIVKDHYMZ-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(NCCN2CCCC2)=NC=C1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(NCCN2CCCC2)=NC=C1 VVZQENIVKDHYMZ-UHFFFAOYSA-N 0.000 claims 1
- OLVOUIUFAQEIJB-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(OCCN2C=NC=C2)=NC=C1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(N)=C1OC.CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(OCCN2C=NC=C2)=NC=C1 OLVOUIUFAQEIJB-UHFFFAOYSA-N 0.000 claims 1
- MBADFRUMVBAWKT-UHFFFAOYSA-N CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(OCCN2C=NC=C2)=NC=C1.COC(C(NS(C)(=O)=O)=CC(C(F)(F)F)=C1)=C1N Chemical compound CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(OCCN2C=NC=C2)=NC=C1.COC(C(NS(C)(=O)=O)=CC(C(F)(F)F)=C1)=C1N MBADFRUMVBAWKT-UHFFFAOYSA-N 0.000 claims 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 1
- KOPQOQBYHQAVII-UHFFFAOYSA-N N-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulfonamide 1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1NS(C)(=O)=O.C1CN(C)CCN1C1=NC=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=N1 KOPQOQBYHQAVII-UHFFFAOYSA-N 0.000 claims 1
- OYBNVWHWGVKQQB-UHFFFAOYSA-N N-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulfonamide 1-methyl-7-[2-[2-(4-methylpiperazin-1-yl)ethyl]pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1NS(C)(=O)=O.C1CN(C)CCN1CCC1=NC=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=N1 OYBNVWHWGVKQQB-UHFFFAOYSA-N 0.000 claims 1
- FSTYXMBHSHUKPV-UHFFFAOYSA-N N-[3-amino-2-methoxy-5-(trifluoromethyl)phenyl]methanesulfonamide 1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound CN(C(C(O)=O)=CC1=CC=C2)C1=C2OC1=NC(N2CCN(C)CC2)=NC=C1.COC(C(NS(C)(=O)=O)=CC(C(F)(F)F)=C1)=C1N FSTYXMBHSHUKPV-UHFFFAOYSA-N 0.000 claims 1
- POULVPJYLDLUKJ-UHFFFAOYSA-N N1=CN=C(C=C1)OC=1C=CC=C2C=C(NC12)C(=O)O.C(C)(C)(C)C=1C=C(C(=C(C1)NC(=O)C1=CC2=C(S1)C(=CC=C2)OC2=NC=NC=C2)OC)NS(=O)(=O)C Chemical compound N1=CN=C(C=C1)OC=1C=CC=C2C=C(NC12)C(=O)O.C(C)(C)(C)C=1C=C(C(=C(C1)NC(=O)C1=CC2=C(S1)C(=CC=C2)OC2=NC=NC=C2)OC)NS(=O)(=O)C POULVPJYLDLUKJ-UHFFFAOYSA-N 0.000 claims 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 150000001412 amines Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
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| EP1867646A1 (en) * | 2004-05-03 | 2007-12-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| US7470692B2 (en) * | 2004-08-25 | 2008-12-30 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
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- 2004-03-02 EP EP04775820A patent/EP1631567A2/en not_active Withdrawn
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- 2004-03-02 CA CA2518774A patent/CA2518774C/en not_active Expired - Fee Related
- 2004-03-02 CN CNA2008100835053A patent/CN101239972A/zh active Pending
- 2004-03-02 KR KR1020057016939A patent/KR101084961B1/ko not_active IP Right Cessation
- 2004-03-02 CN CN2004800063518A patent/CN1759114B/zh not_active Expired - Fee Related
- 2004-03-02 JP JP2006508971A patent/JP4954701B2/ja not_active Expired - Fee Related
- 2004-03-02 BR BRPI0408228-1A patent/BRPI0408228A/pt not_active IP Right Cessation
- 2004-03-02 MX MXPA05009554A patent/MXPA05009554A/es active IP Right Grant
- 2004-03-02 WO PCT/US2004/006264 patent/WO2005016918A2/en active Application Filing
- 2004-03-08 TW TW093106043A patent/TWI369354B/zh not_active IP Right Cessation
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| RU2394029C2 (ru) | 2010-07-10 |
| WO2005016918A2 (en) | 2005-02-24 |
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| US20040186114A1 (en) | 2004-09-23 |
| CN101239972A (zh) | 2008-08-13 |
| CN1759114A (zh) | 2006-04-12 |
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| TWI369354B (en) | 2012-08-01 |
| CL2004000469A1 (es) | 2005-01-14 |
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| PE20050308A1 (es) | 2005-06-07 |
| RU2008107879A (ru) | 2009-09-10 |
| AU2004264409A1 (en) | 2005-02-24 |
| JP2006519861A (ja) | 2006-08-31 |
| AU2004264409B2 (en) | 2010-08-19 |
| CN1759114B (zh) | 2013-04-10 |
| KR101084961B1 (ko) | 2011-11-23 |
| MY138373A (en) | 2009-05-29 |
| BRPI0408228A (pt) | 2006-02-21 |
| NZ542775A (en) | 2008-08-29 |
| EP1631567A2 (en) | 2006-03-08 |
| KR20050107792A (ko) | 2005-11-15 |
| US20060235017A1 (en) | 2006-10-19 |
| IL170740A (en) | 2011-06-30 |
| WO2005016918A3 (en) | 2005-04-07 |
| TW200508225A (en) | 2005-03-01 |
| JP4954701B2 (ja) | 2012-06-20 |
| CA2518774C (en) | 2013-08-27 |
| CA2518774A1 (en) | 2005-02-24 |
| UY28222A1 (es) | 2004-11-08 |
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