RU2485113C2 - Ингибиторы цитокинов - Google Patents

Info

Publication number

RU2485113C2

RU2485113C2 RU2010122333/04A RU2010122333A RU2485113C2 RU 2485113 C2 RU2485113 C2 RU 2485113C2 RU 2010122333/04 A RU2010122333/04 A RU 2010122333/04A RU 2010122333 A RU2010122333 A RU 2010122333A RU 2485113 C2 RU2485113 C2 RU 2485113C2

Authority

RU

Russia

Prior art keywords

imidazo

phenyl

pyridazin

oxadiazol

methyl

Prior art date

2007-11-02

Links

• Espacenet
• Global Dossier
• Discuss

• 102000004127 Cytokines Human genes 0.000 title claims abstract description 18
• 108090000695 Cytokines Proteins 0.000 title claims abstract description 18
• 239000003112 inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 88
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 76
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 125000001072 heteroaryl group Chemical group 0.000 claims description 43
• -1 (3- (3- (imidazo [1,2-b] pyridazin-2-yl) phenyl) -1,2,4-oxadiazol-5-yl) methyl Chemical group 0.000 claims description 41
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
• 125000001188 haloalkyl group Chemical group 0.000 claims description 25
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 23
• 125000005842 heteroatom Chemical group 0.000 claims description 22
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 150000002367 halogens Chemical class 0.000 claims description 18
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 6
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
• 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 5
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
• 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 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 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
• 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 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
• AEDZVEIUKYDCAB-UHFFFAOYSA-N n-[3-imidazo[1,2-b]pyridazin-2-yl-5-[5-(morpholin-4-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanesulfonamide Chemical compound C=1C(NS(=O)(=O)C)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C(N=1)=NOC=1CN1CCOCC1 AEDZVEIUKYDCAB-UHFFFAOYSA-N 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
• 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
• CDWWZVZYEBPBMQ-UHFFFAOYSA-N 1-[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]-n,n-dimethylmethanamine Chemical compound O1C(CN(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 CDWWZVZYEBPBMQ-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
• 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
• PWDBBZCSOVRMQM-UHFFFAOYSA-N 2-methoxy-n-[[3-[3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]ethanamine Chemical compound O1C(CNCCOC)=NC(C=2C=C(C=CC=2)C=2N=C3SC(C)=CN3C=2)=N1 PWDBBZCSOVRMQM-UHFFFAOYSA-N 0.000 claims description 2
• FDIRZNNHMTZYJV-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)N)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 FDIRZNNHMTZYJV-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
• HGVLPPFRIOCNAA-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-n,n-dimethyl-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)N(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 HGVLPPFRIOCNAA-UHFFFAOYSA-N 0.000 claims description 2
• NDEZROCTPTYFCC-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-n-(2-methoxyethyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)NCCOC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 NDEZROCTPTYFCC-UHFFFAOYSA-N 0.000 claims description 2
• JDQJZWUYXGIHHS-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-n-(thiophen-2-ylmethyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1C(=O)NCC1=CC=CS1 JDQJZWUYXGIHHS-UHFFFAOYSA-N 0.000 claims description 2
• AXXQLSWJYXVVCM-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-n-methyl-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)NC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 AXXQLSWJYXVVCM-UHFFFAOYSA-N 0.000 claims description 2
• YYUWLYIBMVXGOY-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-1,2,4-oxadiazole-5-carboxylic acid Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(C(O)=O)=N1 YYUWLYIBMVXGOY-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
• SZROAHNZSADXEY-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-5-methyl-1,2,4-oxadiazole Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(C)=N1 SZROAHNZSADXEY-UHFFFAOYSA-N 0.000 claims description 2
• AKNJHOUGTCCDSA-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-n-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(C(=O)NCC(F)(F)F)=N1 AKNJHOUGTCCDSA-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
• LUQOFLDYXRZMQC-UHFFFAOYSA-N [2-(3-imidazo[1,2-b]pyridazin-2-ylanilino)pyridin-3-yl]-morpholin-4-ylmethanone Chemical compound C=1C=CN=C(NC=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)C=1C(=O)N1CCOCC1 LUQOFLDYXRZMQC-UHFFFAOYSA-N 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
• IQYHONOVDRUYFW-UHFFFAOYSA-N [3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1C(=O)N1CCCC1 IQYHONOVDRUYFW-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
• 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
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
• IOLGFFULGXBKQW-UHFFFAOYSA-N n'-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]ethane-1,2-diamine Chemical compound O1C(CNCCN)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 IOLGFFULGXBKQW-UHFFFAOYSA-N 0.000 claims description 2
• GOOGZBNBHRZBMM-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)NCCO)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 GOOGZBNBHRZBMM-UHFFFAOYSA-N 0.000 claims description 2
• DCIDXXSRVSHTLE-UHFFFAOYSA-N n-[(3-imidazo[1,2-b]pyridazin-2-ylphenyl)methyl]-2-methoxyacetamide Chemical compound COCC(=O)NCC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 DCIDXXSRVSHTLE-UHFFFAOYSA-N 0.000 claims description 2
• HVSFZPSEGPQGPJ-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)NCCN(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 HVSFZPSEGPQGPJ-UHFFFAOYSA-N 0.000 claims description 2
• VQUCVPMHWBLFCC-UHFFFAOYSA-N n-[3-[5-(aminomethyl)-1,2,4-oxadiazol-3-yl]-5-imidazo[1,2-b]pyridazin-2-ylphenyl]methanesulfonamide Chemical compound C=1C(NS(=O)(=O)C)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(CN)=N1 VQUCVPMHWBLFCC-UHFFFAOYSA-N 0.000 claims description 2
• NROHKVPZUQWXLM-UHFFFAOYSA-N n-[3-[5-[[2-(dimethylamino)ethylamino]methyl]-1,2,4-oxadiazol-3-yl]-5-imidazo[1,2-b]pyridazin-2-ylphenyl]methanesulfonamide Chemical compound O1C(CNCCN(C)C)=NC(C=2C=C(C=C(NS(C)(=O)=O)C=2)C=2N=C3C=CC=NN3C=2)=N1 NROHKVPZUQWXLM-UHFFFAOYSA-N 0.000 claims description 2
• JWHCQCCUBQIHRR-UHFFFAOYSA-N n-[3-imidazo[1,2-b]pyridazin-2-yl-5-[5-(piperazin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanesulfonamide Chemical compound C=1C(NS(=O)(=O)C)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C(N=1)=NOC=1CN1CCNCC1 JWHCQCCUBQIHRR-UHFFFAOYSA-N 0.000 claims description 2
• CNXURQCAZYNLDR-UHFFFAOYSA-N n-[3-imidazo[1,2-b]pyridazin-2-yl-5-[5-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanesulfonamide Chemical compound C=1C(NS(=O)(=O)C)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C(N=1)=NOC=1CN1CCCCC1 CNXURQCAZYNLDR-UHFFFAOYSA-N 0.000 claims description 2
• WSSKWSWVWTXECN-UHFFFAOYSA-N n-[3-imidazo[1,2-b]pyridazin-2-yl-5-[5-[(2-methoxyethylamino)methyl]-1,2,4-oxadiazol-3-yl]phenyl]methanesulfonamide Chemical compound O1C(CNCCOC)=NC(C=2C=C(C=C(NS(C)(=O)=O)C=2)C=2N=C3C=CC=NN3C=2)=N1 WSSKWSWVWTXECN-UHFFFAOYSA-N 0.000 claims description 2
• CVDXTQXKCWDJCS-UHFFFAOYSA-N n-[[3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]methyl]butanamide Chemical compound CCCC(=O)NCC1=CC=CC(C=2N=C3SC(C)=CN3C=2)=C1 CVDXTQXKCWDJCS-UHFFFAOYSA-N 0.000 claims description 2
• LRAKTJWTFRAYJH-UHFFFAOYSA-N n-[[3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]methyl]cyclopropanecarboxamide Chemical compound N1=C2SC(C)=CN2C=C1C(C=1)=CC=CC=1CNC(=O)C1CC1 LRAKTJWTFRAYJH-UHFFFAOYSA-N 0.000 claims description 2
• RABRMNFHQDDOCZ-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]-2-methoxyacetamide Chemical compound O1C(CNC(=O)COC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 RABRMNFHQDDOCZ-UHFFFAOYSA-N 0.000 claims description 2
• OSBITWLZDFBBGY-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]-2-methylpropanamide Chemical compound O1C(CNC(=O)C(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 OSBITWLZDFBBGY-UHFFFAOYSA-N 0.000 claims description 2
• WBHHNGKDPXRDJI-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]-2-morpholin-4-ylethanamine Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1CNCCN1CCOCC1 WBHHNGKDPXRDJI-UHFFFAOYSA-N 0.000 claims description 2
• UZDIPNKXVTURNC-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]cyclopentanecarboxamide Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1CNC(=O)C1CCCC1 UZDIPNKXVTURNC-UHFFFAOYSA-N 0.000 claims description 2
• VTULISXAZGKXEE-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]cyclopropanecarboxamide Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1CNC(=O)C1CC1 VTULISXAZGKXEE-UHFFFAOYSA-N 0.000 claims description 2
• KRMJCXXFKGPNFP-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]ethanamine Chemical compound O1C(CNCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 KRMJCXXFKGPNFP-UHFFFAOYSA-N 0.000 claims description 2
• LVJLBKCRGWMJMW-UHFFFAOYSA-N n-[[3-[3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]-1-(4-methylsulfonylphenyl)methanamine Chemical compound N1=C2SC(C)=CN2C=C1C(C=1)=CC=CC=1C(N=1)=NOC=1CNCC1=CC=C(S(C)(=O)=O)C=C1 LVJLBKCRGWMJMW-UHFFFAOYSA-N 0.000 claims description 2
• JLJDYVUUOWTDJJ-UHFFFAOYSA-N n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]-3-nitrobenzenesulfonamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 JLJDYVUUOWTDJJ-UHFFFAOYSA-N 0.000 claims description 2
• AGKPRBBPMRZAHX-UHFFFAOYSA-N n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]-4-methylbenzenesulfonamide Chemical compound C=1C(C=2N=C3C=CC=NN3C=2)=CC(OCCOC)=CC=1CNS(=O)(=O)C1=CC=C(C)C=C1 AGKPRBBPMRZAHX-UHFFFAOYSA-N 0.000 claims description 2
• MFXYJRWGJADPTB-UHFFFAOYSA-N n-[[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]methyl]acetamide Chemical compound COCCOC1=CC(CNC(C)=O)=CC(C=2N=C3C=CC=NN3C=2)=C1 MFXYJRWGJADPTB-UHFFFAOYSA-N 0.000 claims description 2
• LZUJMFQZUMTEOL-UHFFFAOYSA-N n-cyclopentyl-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1C(=O)NC1CCCC1 LZUJMFQZUMTEOL-UHFFFAOYSA-N 0.000 claims description 2
• OEIQJSZSMZBAPR-UHFFFAOYSA-N n-ethyl-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxamide Chemical compound O1C(C(=O)NCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 OEIQJSZSMZBAPR-UHFFFAOYSA-N 0.000 claims description 2
• 235000001968 nicotinic acid Nutrition 0.000 claims description 2
• 239000011664 nicotinic acid Substances 0.000 claims description 2
• ZEBVDFOGBZJVKC-UHFFFAOYSA-N 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-5-(piperazin-1-ylmethyl)-1,2,4-oxadiazole Chemical compound N=1C(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=NOC=1CN1CCNCC1 ZEBVDFOGBZJVKC-UHFFFAOYSA-N 0.000 claims 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
• 125000005843 halogen group Chemical group 0.000 claims 2
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 2
• LJSGLEVVMDHAGH-UHFFFAOYSA-N [4-chloro-3-(trifluoromethyl)phenyl]urea Chemical compound NC(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 LJSGLEVVMDHAGH-UHFFFAOYSA-N 0.000 claims 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 17
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 17
• 150000002460 imidazoles Chemical class 0.000 abstract description 7
• 230000000694 effects Effects 0.000 abstract description 5
• 239000003814 drug Substances 0.000 abstract description 2
• 239000000126 substance Substances 0.000 abstract 1
• 238000000034 method Methods 0.000 description 91
• 239000000203 mixture Substances 0.000 description 45
• 239000000243 solution Substances 0.000 description 44
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
• 238000010992 reflux Methods 0.000 description 22
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• 239000012267 brine Substances 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• 235000019439 ethyl acetate Nutrition 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• 201000010099 disease Diseases 0.000 description 10
• 239000002244 precipitate Substances 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 8
• LIZGECYXCHZNJQ-UHFFFAOYSA-N 3-imidazo[1,2-b]pyridazin-2-ylbenzonitrile Chemical compound N#CC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 LIZGECYXCHZNJQ-UHFFFAOYSA-N 0.000 description 8
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• YBEQOLPTZPSMNQ-UHFFFAOYSA-N 3-(6-chloroimidazo[1,2-b]pyridazin-2-yl)benzonitrile Chemical compound C=1N2N=C(Cl)C=CC2=NC=1C1=CC=CC(C#N)=C1 YBEQOLPTZPSMNQ-UHFFFAOYSA-N 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• DTXVKPOKPFWSFF-UHFFFAOYSA-N 3(S)-hydroxy-13-cis-eicosenoyl-CoA Chemical compound NC1=CC=C(Cl)N=N1 DTXVKPOKPFWSFF-UHFFFAOYSA-N 0.000 description 6
• 108010063738 Interleukins Proteins 0.000 description 6
• 102000015696 Interleukins Human genes 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 230000016396 cytokine production Effects 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 125000001424 substituent group Chemical group 0.000 description 6
• XWCGNFLHRINYCE-UHFFFAOYSA-N 3-(2-bromoacetyl)benzonitrile Chemical compound BrCC(=O)C1=CC=CC(C#N)=C1 XWCGNFLHRINYCE-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 206010028980 Neoplasm Diseases 0.000 description 5
• 201000011510 cancer Diseases 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000002158 endotoxin Substances 0.000 description 5
• 125000003106 haloaryl group Chemical group 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 239000012188 paraffin wax Substances 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• 208000023275 Autoimmune disease Diseases 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 4
• 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 4
• 229910000564 Raney nickel Inorganic materials 0.000 description 4
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• 239000006071 cream Substances 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 150000002430 hydrocarbons Chemical class 0.000 description 4
• 229920006008 lipopolysaccharide Polymers 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000002674 ointment Substances 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• PGRSVEKUGDKYID-UHFFFAOYSA-N (3-imidazo[1,2-b]pyridazin-2-ylphenyl)methanamine Chemical compound NCC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 PGRSVEKUGDKYID-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 235000019489 Almond oil Nutrition 0.000 description 3
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 0 COC(c1cc(C*)cc(N)c1)=O Chemical compound COC(c1cc(C*)cc(N)c1)=O 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
• 108010057466 NF-kappa B Proteins 0.000 description 3
• 102000003945 NF-kappa B Human genes 0.000 description 3
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 239000008168 almond oil Substances 0.000 description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 238000010586 diagram Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• FUXUMOOJLAEGAX-UHFFFAOYSA-N methyl 3-carbamoyl-5-nitrobenzoate Chemical compound COC(=O)C1=CC(C(N)=O)=CC([N+]([O-])=O)=C1 FUXUMOOJLAEGAX-UHFFFAOYSA-N 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• YKMGXOPWGUUDBM-UHFFFAOYSA-N n-(3-acetyl-5-cyanophenyl)methanesulfonamide Chemical compound CC(=O)C1=CC(NS(C)(=O)=O)=CC(C#N)=C1 YKMGXOPWGUUDBM-UHFFFAOYSA-N 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• QAVXTTXNXCCJOW-UHFFFAOYSA-N n-[3-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-5-cyanophenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(C#N)=CC(C=2N=C3C=CC(Cl)=NN3C=2)=C1 QAVXTTXNXCCJOW-UHFFFAOYSA-N 0.000 description 3
• TVIROOGVIATJHM-UHFFFAOYSA-N n-[3-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]-5-imidazo[1,2-b]pyridazin-2-ylphenyl]methanesulfonamide Chemical compound C=1C(NS(=O)(=O)C)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(CCl)=N1 TVIROOGVIATJHM-UHFFFAOYSA-N 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 238000010898 silica gel chromatography Methods 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• RUWMBEULHIETND-UHFFFAOYSA-N 3-(2-bromoacetyl)-5-(2-methoxyethoxy)benzonitrile Chemical compound COCCOC1=CC(C#N)=CC(C(=O)CBr)=C1 RUWMBEULHIETND-UHFFFAOYSA-N 0.000 description 2
• FNJCYMZMVFVWQN-UHFFFAOYSA-N 3-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-5-(2-methoxyethoxy)benzonitrile Chemical compound COCCOC1=CC(C#N)=CC(C=2N=C3C=CC(Cl)=NN3C=2)=C1 FNJCYMZMVFVWQN-UHFFFAOYSA-N 0.000 description 2
• ZCRNIIJXDRYWDU-UHFFFAOYSA-N 3-(methoxycarbonyl)-5-nitrobenzoic acid Chemical compound COC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 ZCRNIIJXDRYWDU-UHFFFAOYSA-N 0.000 description 2
• MXQKGRCOVRXHKJ-UHFFFAOYSA-N 3-[6-(methylamino)imidazo[1,2-b]pyridazin-2-yl]benzonitrile Chemical compound C=1N2N=C(NC)C=CC2=NC=1C1=CC=CC(C#N)=C1 MXQKGRCOVRXHKJ-UHFFFAOYSA-N 0.000 description 2
• ITMUIADEHAABGE-UHFFFAOYSA-N 3-acetyl-5-(2-methoxyethoxy)benzonitrile Chemical compound COCCOC1=CC(C#N)=CC(C(C)=O)=C1 ITMUIADEHAABGE-UHFFFAOYSA-N 0.000 description 2
• SMOBWEMJNQETAC-UHFFFAOYSA-N 3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)benzonitrile Chemical compound COCCOC1=CC(C#N)=CC(C=2N=C3C=CC=NN3C=2)=C1 SMOBWEMJNQETAC-UHFFFAOYSA-N 0.000 description 2
• ZBMUVPXXSONFSB-UHFFFAOYSA-N 3-imidazo[1,2-b]pyridazin-2-ylaniline Chemical compound NC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 ZBMUVPXXSONFSB-UHFFFAOYSA-N 0.000 description 2
• BFICWRQBEHUQFU-UHFFFAOYSA-N 3-imidazo[1,2-b]pyridazin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 BFICWRQBEHUQFU-UHFFFAOYSA-N 0.000 description 2
• VDMWCEVJILEBCJ-UHFFFAOYSA-N 3-methoxycarbonyl-5-(2-methoxyethoxy)benzoic acid Chemical compound COCCOC1=CC(C(O)=O)=CC(C(=O)OC)=C1 VDMWCEVJILEBCJ-UHFFFAOYSA-N 0.000 description 2
• TVWCCNMOIUBAOR-UHFFFAOYSA-N 5-(chloromethyl)-3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole Chemical compound O1C(CCl)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 TVWCCNMOIUBAOR-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• 108010002350 Interleukin-2 Proteins 0.000 description 2
• 108090001005 Interleukin-6 Proteins 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 229910006124 SOCl2 Inorganic materials 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 235000013871 bee wax Nutrition 0.000 description 2
• 239000012166 beeswax Substances 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• QDKPTPYNAUYXOC-UHFFFAOYSA-N dimethyl 5-(2-methoxyethoxy)benzene-1,3-dicarboxylate Chemical compound COCCOC1=CC(C(=O)OC)=CC(C(=O)OC)=C1 QDKPTPYNAUYXOC-UHFFFAOYSA-N 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
• PPZURVIPLHMVBO-UHFFFAOYSA-N methyl 3-carbamoyl-5-(2-methoxyethoxy)benzoate Chemical compound COCCOC1=CC(C(N)=O)=CC(C(=O)OC)=C1 PPZURVIPLHMVBO-UHFFFAOYSA-N 0.000 description 2
• MPNUATLSGYZGIE-UHFFFAOYSA-N methyl 3-cyano-5-(2-methoxyethoxy)benzoate Chemical compound COCCOC1=CC(C#N)=CC(C(=O)OC)=C1 MPNUATLSGYZGIE-UHFFFAOYSA-N 0.000 description 2
• QOPRZOZWRJUFRI-UHFFFAOYSA-N methyl 3-cyano-5-(methanesulfonamido)benzoate Chemical compound COC(=O)C1=CC(NS(C)(=O)=O)=CC(C#N)=C1 QOPRZOZWRJUFRI-UHFFFAOYSA-N 0.000 description 2
• ZMVKXPKHCOWFDJ-UHFFFAOYSA-N methyl 3-cyano-5-nitrobenzoate Chemical compound COC(=O)C1=CC(C#N)=CC([N+]([O-])=O)=C1 ZMVKXPKHCOWFDJ-UHFFFAOYSA-N 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 2
• RHNJTGKUBIHAHH-UHFFFAOYSA-N n-(3-cyano-5-imidazo[1,2-b]pyridazin-2-ylphenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(C#N)=CC(C=2N=C3C=CC=NN3C=2)=C1 RHNJTGKUBIHAHH-UHFFFAOYSA-N 0.000 description 2
• XYNQVWVANFCXTM-UHFFFAOYSA-N n-[3-(2-bromoacetyl)-5-cyanophenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(C#N)=CC(C(=O)CBr)=C1 XYNQVWVANFCXTM-UHFFFAOYSA-N 0.000 description 2
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 239000000651 prodrug Substances 0.000 description 2
• 229940002612 prodrug Drugs 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 239000002511 suppository base Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• DXHZANUZJMWMQU-UHFFFAOYSA-N tert-butyl n-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C=2N=C3C=CC=NN3C=2)=C1 DXHZANUZJMWMQU-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
• LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
• STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
• IOQORVDNYPOZPL-VQTJNVASSA-N (5S,6R)-5-(4-chlorophenyl)-6-cyclopropyl-3-[6-methoxy-5-(4-methylimidazol-1-yl)pyridin-2-yl]-5,6-dihydro-2H-1,2,4-oxadiazine Chemical compound ClC1=CC=C(C=C1)[C@@H]1NC(=NO[C@@H]1C1CC1)C1=NC(=C(C=C1)N1C=NC(=C1)C)OC IOQORVDNYPOZPL-VQTJNVASSA-N 0.000 description 1
• VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 description 1
• 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• ZYZCALPXKGUGJI-DDVDASKDSA-M (e,3r,5s)-7-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C=1C=C(F)C=CC=1N1C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C(C)C)N=C1C1=CC=CC=C1 ZYZCALPXKGUGJI-DDVDASKDSA-M 0.000 description 1
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
• FZQXMGLQANXZRP-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)-3-(3-imidazol-1-ylpropyl)thiourea Chemical compound C1=C(OC)C(OC)=CC=C1NC(=S)NCCCN1C=NC=C1 FZQXMGLQANXZRP-UHFFFAOYSA-N 0.000 description 1
• MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• FONOMEOLFOKZTG-UHFFFAOYSA-N 2,2,2-trifluoro-n-methyl-n-[2-[3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]imidazo[1,2-b]pyridazin-6-yl]acetamide Chemical compound C=1N2N=C(N(C(=O)C(F)(F)F)C)C=CC2=NC=1C(C=1)=CC=CC=1C1=NOC(C(F)(F)F)=N1 FONOMEOLFOKZTG-UHFFFAOYSA-N 0.000 description 1
• WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
• FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
• QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
• FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
• ZQZAHPFFZWEUCL-UHFFFAOYSA-N 2-chloropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1Cl ZQZAHPFFZWEUCL-UHFFFAOYSA-N 0.000 description 1
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
• RYPRUBNQCXNMJF-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-1,2,4-oxadiazole-5-carboxamide Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C1=NOC(C(N)=O)=N1 RYPRUBNQCXNMJF-UHFFFAOYSA-N 0.000 description 1
• ZSWASTFTCOIAQY-UHFFFAOYSA-N 3-[3-imidazo[1,2-b]pyridazin-2-yl-5-(2-methoxyethoxy)phenyl]-n-pyridin-2-yl-1,2,4-oxadiazole-5-carboxamide Chemical compound C=1C(OCCOC)=CC(C=2N=C3C=CC=NN3C=2)=CC=1C(N=1)=NOC=1C(=O)NC1=CC=CC=N1 ZSWASTFTCOIAQY-UHFFFAOYSA-N 0.000 description 1
• SBCFGFDAZCTSRH-UHFFFAOYSA-N 3-acetylbenzonitrile Chemical compound CC(=O)C1=CC=CC(C#N)=C1 SBCFGFDAZCTSRH-UHFFFAOYSA-N 0.000 description 1
• WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
• MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
• XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
• RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
• 125000005865 C2-C10alkynyl group Chemical group 0.000 description 1
• TVNWLRLEXUXSKN-VOTSOKGWSA-N CC/C=C(\C=C)/NS(C)(=O)=O Chemical compound CC/C=C(\C=C)/NS(C)(=O)=O TVNWLRLEXUXSKN-VOTSOKGWSA-N 0.000 description 1
• HVXJDNYRQITHFR-UHFFFAOYSA-N CCC(N)N1N=CC=CC1=N Chemical compound CCC(N)N1N=CC=CC1=N HVXJDNYRQITHFR-UHFFFAOYSA-N 0.000 description 1
• IHSYIVAZIINDFR-UHFFFAOYSA-N CNc(cc1)nnc1Cl Chemical compound CNc(cc1)nnc1Cl IHSYIVAZIINDFR-UHFFFAOYSA-N 0.000 description 1
• WJAFDZGPQAWRHX-UHFFFAOYSA-N COC(c1cc(CN)cc([N+]([O-])=O)c1)=O Chemical compound COC(c1cc(CN)cc([N+]([O-])=O)c1)=O WJAFDZGPQAWRHX-UHFFFAOYSA-N 0.000 description 1
• PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 206010007558 Cardiac failure chronic Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 229940126639 Compound 33 Drugs 0.000 description 1
• 229940127007 Compound 39 Drugs 0.000 description 1
• 229920000858 Cyclodextrin Polymers 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
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000003777 Interleukin-1 beta Human genes 0.000 description 1
• 108090000193 Interleukin-1 beta Proteins 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• 229930064664 L-arginine Natural products 0.000 description 1
• 235000014852 L-arginine Nutrition 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• QZCGUGNUPJXUST-UHFFFAOYSA-N N/C(/c1cccc(-c2c[n]3ncccc3n2)c1)=N\O Chemical compound N/C(/c1cccc(-c2c[n]3ncccc3n2)c1)=N\O QZCGUGNUPJXUST-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 206010033647 Pancreatitis acute Diseases 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
• SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
• IOSLINNLJFQMFF-XMMPIXPASA-N [(2R)-1-[[4-[[3-[(4-fluorophenyl)methylsulfanyl]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound FC1=CC=C(CSC=2C=C(OCC3=CC=C(CN4[C@H](CCC4)CO)C=C3)C=CC=2)C=C1 IOSLINNLJFQMFF-XMMPIXPASA-N 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 201000003229 acute pancreatitis Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 125000004442 acylamino group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000005277 alkyl imino group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 235000020224 almond Nutrition 0.000 description 1
• 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 125000004467 aryl imino group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 201000004983 autoimmune atherosclerosis Diseases 0.000 description 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 229910001424 calcium ion Inorganic materials 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000010261 cell growth Effects 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
• 125000003636 chemical group Chemical group 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125810 compound 20 Drugs 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125833 compound 23 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 229940127204 compound 29 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 229940125878 compound 36 Drugs 0.000 description 1
• 229940125807 compound 37 Drugs 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 229940126540 compound 41 Drugs 0.000 description 1
• 229940125936 compound 42 Drugs 0.000 description 1
• 229940125844 compound 46 Drugs 0.000 description 1
• 229940127271 compound 49 Drugs 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 229940126545 compound 53 Drugs 0.000 description 1
• 229940127113 compound 57 Drugs 0.000 description 1
• 229940125900 compound 59 Drugs 0.000 description 1
• 229940126179 compound 72 Drugs 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 125000004986 diarylamino group Chemical group 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• DOSDTCPDBPRFHQ-UHFFFAOYSA-N dimethyl 5-hydroxybenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(O)=CC(C(=O)OC)=C1 DOSDTCPDBPRFHQ-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• OQORVHMMUBEIGD-UHFFFAOYSA-N ethyl 3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazole-5-carboxylate Chemical compound O1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 OQORVHMMUBEIGD-UHFFFAOYSA-N 0.000 description 1
• GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
• OBGGSKKTMFPQTO-UHFFFAOYSA-N ethyl 3-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methylamino]-3-oxopropanoate Chemical compound O1C(CNC(=O)CC(=O)OCC)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 OBGGSKKTMFPQTO-UHFFFAOYSA-N 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
• 125000005216 haloheteroaryl group Chemical group 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 150000002473 indoazoles Chemical class 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910001425 magnesium ion Inorganic materials 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 1
• IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 1
• 230000001333 moisturizer Effects 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
• RTNJZCUIXZSJQF-UHFFFAOYSA-N n-[[3-(3-imidazo[1,2-b]pyridazin-2-ylphenyl)-1,2,4-oxadiazol-5-yl]methyl]-n',n'-dimethylethane-1,2-diamine Chemical compound O1C(CNCCN(C)C)=NC(C=2C=C(C=CC=2)C=2N=C3C=CC=NN3C=2)=N1 RTNJZCUIXZSJQF-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004957 naphthylene group Chemical group 0.000 description 1
• IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 230000003448 neutrophilic effect Effects 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• BNIXVQGCZULYKV-UHFFFAOYSA-N pentachloroethane Chemical compound ClC(Cl)C(Cl)(Cl)Cl BNIXVQGCZULYKV-UHFFFAOYSA-N 0.000 description 1
• 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 201000001245 periodontitis Diseases 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 125000005561 phenanthryl group Chemical group 0.000 description 1
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 230000004983 pleiotropic effect Effects 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000015323 positive regulation of phagocytosis Effects 0.000 description 1
• 229910001414 potassium ion Inorganic materials 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 125000001725 pyrenyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 235000012752 quinoline yellow Nutrition 0.000 description 1
• 229940051201 quinoline yellow Drugs 0.000 description 1
• FZUOVNMHEAPVBW-UHFFFAOYSA-L quinoline yellow ws Chemical compound [Na+].[Na+].O=C1C2=CC=CC=C2C(=O)C1C1=NC2=C(S([O-])(=O)=O)C=C(S(=O)(=O)[O-])C=C2C=C1 FZUOVNMHEAPVBW-UHFFFAOYSA-L 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 229910001415 sodium ion Inorganic materials 0.000 description 1
• KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000003441 thioacyl group Chemical group 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1