KR20100101581A - 사이토카인 억제제 - Google Patents

Info

Publication number

KR20100101581A

KR20100101581A KR1020107011579A KR20107011579A KR20100101581A KR 20100101581 A KR20100101581 A KR 20100101581A KR 1020107011579 A KR1020107011579 A KR 1020107011579A KR 20107011579 A KR20107011579 A KR 20107011579A KR 20100101581 A KR20100101581 A KR 20100101581A

Authority

KR

South Korea

Prior art keywords

alkyl

imidazo

phenyl

pyridazin

heteroaryl

Prior art date

2007-11-02

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 102000004127 Cytokines Human genes 0.000 title claims abstract description 29
• 108090000695 Cytokines Proteins 0.000 title claims abstract description 29
• 239000003112 inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 93
• 238000000034 method Methods 0.000 claims abstract description 62
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 208000035475 disorder Diseases 0.000 claims abstract description 14
• 238000012261 overproduction Methods 0.000 claims abstract description 8
• 230000001404 mediated effect Effects 0.000 claims abstract description 6
• 150000002460 imidazoles Chemical class 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 175
• 125000003118 aryl group Chemical group 0.000 claims description 111
• 125000001072 heteroaryl group Chemical group 0.000 claims description 109
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 83
• -1 (3- (3- (imidazo [1,2-b] pyridazin-2-yl) phenyl) -1,2,4-oxadiazol-5-yl) methyl Chemical group 0.000 claims description 76
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 68
• 229910052739 hydrogen Inorganic materials 0.000 claims description 62
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 61
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 58
• 229910052799 carbon Inorganic materials 0.000 claims description 54
• 125000005843 halogen group Chemical group 0.000 claims description 48
• 125000001188 haloalkyl group Chemical group 0.000 claims description 47
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 39
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 34
• 125000003106 haloaryl group Chemical group 0.000 claims description 23
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 22
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
• 239000002904 solvent Substances 0.000 claims description 19
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 16
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 15
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 108010063738 Interleukins Proteins 0.000 claims description 11
• 102000015696 Interleukins Human genes 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 10
• 125000003282 alkyl amino group Chemical group 0.000 claims description 9
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 150000003839 salts Chemical class 0.000 claims description 9
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• MYVSUIXAYJQREI-UHFFFAOYSA-N 4-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]morpholine Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1CN1CCOCC1 MYVSUIXAYJQREI-UHFFFAOYSA-N 0.000 claims description 6
• 208000023275 Autoimmune disease Diseases 0.000 claims description 6
• 108010002350 Interleukin-2 Proteins 0.000 claims description 6
• 108090001005 Interleukin-6 Proteins 0.000 claims description 6
• 230000008878 coupling Effects 0.000 claims description 6
• 238000010168 coupling process Methods 0.000 claims description 6
• 238000005859 coupling reaction Methods 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 230000001603 reducing effect Effects 0.000 claims description 4
• JXFACLVJTUIGDP-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-methyl-1,2,4-oxadiazole Chemical compound O1C(C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 JXFACLVJTUIGDP-UHFFFAOYSA-N 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 206010020751 Hypersensitivity Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
• SFXRLQPKVCNPMK-UHFFFAOYSA-N [3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methanamine Chemical compound COCCOC1=CC(CN)=CC(C=2N=C3C=CC=NN3C=2)=C1 SFXRLQPKVCNPMK-UHFFFAOYSA-N 0.000 claims description 3
• 230000007815 allergy Effects 0.000 claims description 3
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• PJAUUXPPCYUOSC-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]-2-methoxyethanamine Chemical compound O1C(CNCCOC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 PJAUUXPPCYUOSC-UHFFFAOYSA-N 0.000 claims description 3
• ZZQLGVCPIFVVSV-UHFFFAOYSA-N n-methyl-2-[3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]imidazo[1,2-b]pyridazin-6-amine Chemical compound C=1N2N=C(NC)C=CC2=NC=1C(C=1)=CC=CC=1C1=NOC(C(F)(F)F)=N1 ZZQLGVCPIFVVSV-UHFFFAOYSA-N 0.000 claims description 3
• XFGCZYZMCZITNG-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methanone Chemical compound C1CN(CC)CCN1C(=O)C1=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NO1 XFGCZYZMCZITNG-UHFFFAOYSA-N 0.000 claims description 2
• VOBIYBSROYKPSK-UHFFFAOYSA-N 1-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]-3-(2-methoxyethyl)urea Chemical compound COCCNC(=O)NCC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 VOBIYBSROYKPSK-UHFFFAOYSA-N 0.000 claims description 2
• RHWJKWDPCFRAQY-UHFFFAOYSA-N 1-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]-3-(2-morpholin-4-ylethyl)urea Chemical compound C=1C=CC(C=2N=C3C=CC=NN3C=2)=CC=1CNC(=O)NCCN1CCOCC1 RHWJKWDPCFRAQY-UHFFFAOYSA-N 0.000 claims description 2
• HFPOAOPFFCFTLR-UHFFFAOYSA-N 1-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]-3-(thiophen-2-ylmethyl)urea Chemical compound C=1C=CC(C=2N=C3C=CC=NN3C=2)=CC=1CNC(=O)NCC1=CC=CS1 HFPOAOPFFCFTLR-UHFFFAOYSA-N 0.000 claims description 2
• SXGYCEMPBZRAHN-UHFFFAOYSA-N 2,2,2-trifluoro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]acetamide Chemical compound COCCOC1=CC(CNC(=O)C(F)(F)F)=CC(C=2N=C3C=CC=NN3C=2)=C1 SXGYCEMPBZRAHN-UHFFFAOYSA-N 0.000 claims description 2
• YRSHVROIXDMERP-UHFFFAOYSA-N 2-[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]-n-methylacetamide Chemical compound O1C(CC(=O)NC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 YRSHVROIXDMERP-UHFFFAOYSA-N 0.000 claims description 2
• BZDZOSZSWXOIKS-UHFFFAOYSA-N 2-[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]acetamide Chemical compound O1C(CC(=O)N)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 BZDZOSZSWXOIKS-UHFFFAOYSA-N 0.000 claims description 2
• XHFNBOHOMFRLBA-UHFFFAOYSA-N 2-[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]acetic acid Chemical compound O1C(CC(=O)O)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 XHFNBOHOMFRLBA-UHFFFAOYSA-N 0.000 claims description 2
• BNUIDEHBQILQPB-UHFFFAOYSA-N 2-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methylamino]ethanol Chemical compound O1C(CNCCO)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 BNUIDEHBQILQPB-UHFFFAOYSA-N 0.000 claims description 2
• NNSNDWIWJGASMJ-UHFFFAOYSA-N 2-chloro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]acetamide Chemical compound COCCOC1=CC(CNC(=O)CCl)=CC(C=2N=C3C=CC=NN3C=2)=C1 NNSNDWIWJGASMJ-UHFFFAOYSA-N 0.000 claims description 2
• QSWWINLYWVHBSN-UHFFFAOYSA-N 2-fluoro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzenesulfonamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNS(=O)(=O)C1=CC=CC=C1F QSWWINLYWVHBSN-UHFFFAOYSA-N 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• UDDTTWFCVWUKNL-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxylic acid Chemical compound O1C(C(=O)O)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 UDDTTWFCVWUKNL-UHFFFAOYSA-N 0.000 claims description 2
• DMJPSDAEGZSGDL-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-(methoxymethyl)-1,2,4-oxadiazole Chemical compound O1C(COC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 DMJPSDAEGZSGDL-UHFFFAOYSA-N 0.000 claims description 2
• QJQRWLCIESXICZ-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-(methylsulfanylmethyl)-1,2,4-oxadiazole Chemical compound O1C(CSC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 QJQRWLCIESXICZ-UHFFFAOYSA-N 0.000 claims description 2
• XVCAOEBVIBRRMU-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-(methylsulfonylmethyl)-1,2,4-oxadiazole Chemical compound O1C(CS(=O)(=O)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 XVCAOEBVIBRRMU-UHFFFAOYSA-N 0.000 claims description 2
• OHFCRYSWZDMFLV-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound O1C(C(F)(F)F)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 OHFCRYSWZDMFLV-UHFFFAOYSA-N 0.000 claims description 2
• PUEFFLRBJGCSSM-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-propan-2-yl-1,2,4-oxadiazole Chemical compound O1C(C(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 PUEFFLRBJGCSSM-UHFFFAOYSA-N 0.000 claims description 2
• MUCPHMGJNFHLTC-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-5-(methoxymethyl)-1,2,4-oxadiazole Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(COC)=N1 MUCPHMGJNFHLTC-UHFFFAOYSA-N 0.000 claims description 2
• XHNHQZXUVYGKNU-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(C(F)(F)F)=N1 XHNHQZXUVYGKNU-UHFFFAOYSA-N 0.000 claims description 2
• ZHDPBEHUMASYKB-UHFFFAOYSA-N 3-[[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methylamino]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CNCC=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=C1 ZHDPBEHUMASYKB-UHFFFAOYSA-N 0.000 claims description 2
• NDXIYLGWDGOLAZ-UHFFFAOYSA-N 3-bromo-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNC(=O)C1=CC=CC(Br)=C1 NDXIYLGWDGOLAZ-UHFFFAOYSA-N 0.000 claims description 2
• JMXXXKFPHFKOBA-UHFFFAOYSA-N 3-chloro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzenesulfonamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNS(=O)(=O)C1=CC=CC(Cl)=C1 JMXXXKFPHFKOBA-UHFFFAOYSA-N 0.000 claims description 2
• GNYBPMZJPCAJEQ-UHFFFAOYSA-N 3-cyano-n-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]benzenesulfonamide Chemical compound C=1C=CC(C=2N=C3C=CC=NN3C=2)=CC=1CNS(=O)(=O)C1=CC=CC(C#N)=C1 GNYBPMZJPCAJEQ-UHFFFAOYSA-N 0.000 claims description 2
• BYJYYWFRADTTPM-UHFFFAOYSA-N 4-chloro-n-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 BYJYYWFRADTTPM-UHFFFAOYSA-N 0.000 claims description 2
• OLQKHGCRUFSLNI-UHFFFAOYSA-N 4-chloro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNC(=O)C1=CC=C(Cl)C=C1 OLQKHGCRUFSLNI-UHFFFAOYSA-N 0.000 claims description 2
• YTLCTVVDXMWMOP-UHFFFAOYSA-N 4-cyano-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNC(=O)C1=CC=C(C#N)C=C1 YTLCTVVDXMWMOP-UHFFFAOYSA-N 0.000 claims description 2
• OOXDRBHANHMILT-UHFFFAOYSA-N 4-fluoro-n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]benzenesulfonamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNS(=O)(=O)C1=CC=C(F)C=C1 OOXDRBHANHMILT-UHFFFAOYSA-N 0.000 claims description 2
• RCGIORZRZAUVAC-UHFFFAOYSA-N 5-(ethoxymethyl)-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound O1C(COCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 RCGIORZRZAUVAC-UHFFFAOYSA-N 0.000 claims description 2
• CUNUPDZFTBJWHW-UHFFFAOYSA-N 5-(ethoxymethyl)-3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-1,2,4-oxadiazole Chemical compound O1C(COCC)=NC(C=2C=C(C=C(OCCOC)C=2)C=2N=C3C=CC=NN3C=2)=N1 CUNUPDZFTBJWHW-UHFFFAOYSA-N 0.000 claims description 2
• XBQAZEXDFFJFNN-UHFFFAOYSA-N 5-(fluoromethyl)-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound O1C(CF)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 XBQAZEXDFFJFNN-UHFFFAOYSA-N 0.000 claims description 2
• ZXJRZUTUVXBIRE-UHFFFAOYSA-N 5-(fluoromethyl)-3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-1,2,4-oxadiazole Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(CF)=N1 ZXJRZUTUVXBIRE-UHFFFAOYSA-N 0.000 claims description 2
• JPWLGKSCPIYEIN-UHFFFAOYSA-N 5-[(4-fluorophenoxy)methyl]-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound C1=CC(F)=CC=C1OCC1=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NO1 JPWLGKSCPIYEIN-UHFFFAOYSA-N 0.000 claims description 2
• PTTOHJPVEZOABW-UHFFFAOYSA-N 5-cyclopropyl-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound C1CC1C1=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NO1 PTTOHJPVEZOABW-UHFFFAOYSA-N 0.000 claims description 2
• DAIHEXRLOPDCQK-UHFFFAOYSA-N 5-ethyl-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound O1C(CC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 DAIHEXRLOPDCQK-UHFFFAOYSA-N 0.000 claims description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
• 206010040070 Septic Shock Diseases 0.000 claims description 2
• NNHNTWIYBDZKND-UHFFFAOYSA-N [2-(3-imidazo[1,2-b]pyridazin-2-ylanilino)pyridin-3-yl]-pyrrolidin-1-ylmethanone Chemical compound C=1C=CN=C(NC=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)C=1C(=O)N1CCCC1 NNHNTWIYBDZKND-UHFFFAOYSA-N 0.000 claims description 2
• VVYOCCRJBICVAO-UHFFFAOYSA-N [3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]-morpholin-4-ylmethanone Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1C(=O)N1CCOCC1 VVYOCCRJBICVAO-UHFFFAOYSA-N 0.000 claims description 2
• WPEACOCTYYOQIK-UHFFFAOYSA-N [3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methanol Chemical compound O1C(CO)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 WPEACOCTYYOQIK-UHFFFAOYSA-N 0.000 claims description 2
• HEGUKUBMSVANSO-UHFFFAOYSA-N [3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-1,2,4-oxadiazol-5-yl]methanol Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(CO)=N1 HEGUKUBMSVANSO-UHFFFAOYSA-N 0.000 claims description 2
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
• 239000004202 carbamide Substances 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• LKXJXDCNHQUSAE-UHFFFAOYSA-N ethyl 2-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methylamino]-2-oxoacetate Chemical compound O1C(CNC(=O)C(=O)OCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 LKXJXDCNHQUSAE-UHFFFAOYSA-N 0.000 claims description 2
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