ES2548683T3 - Amidas del ácido 4-(5-isoxazolil o 5-pirrazolil-1,2,4-oxadiazol-3-il)-mandélico como agonistas de receptor de esfingosina-1-fosfato 1 - Google Patents

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Publication number

ES2548683T3

ES2548683T3 ES11717430.0T ES11717430T ES2548683T3 ES 2548683 T3 ES2548683 T3 ES 2548683T3 ES 11717430 T ES11717430 T ES 11717430T ES 2548683 T3 ES2548683 T3 ES 2548683T3

Authority

ES

Spain

Prior art keywords

phenyl

hydroxy

trifluoromethyl

oxadiazol

isoxazol

Prior art date

2010-04-23

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• -1 5-Isoxazolyl Chemical group 0.000 title claims abstract description 434
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title description 18
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title description 18
• 239000000018 receptor agonist Substances 0.000 title description 4
• 229940044601 receptor agonist Drugs 0.000 title description 4
• 229960002510 mandelic acid Drugs 0.000 title description 2
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 326
• 150000001875 compounds Chemical class 0.000 claims abstract description 214
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 124
• 150000003839 salts Chemical class 0.000 claims abstract description 91
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 75
• 125000001424 substituent group Chemical group 0.000 claims abstract description 59
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 48
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 37
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 32
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 32
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 30
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 30
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 28
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 27
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 27
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 23
• 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 23
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 20
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
• 125000004965 chloroalkyl group Chemical group 0.000 claims abstract description 16
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
• 150000002367 halogens Chemical class 0.000 claims abstract description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
• 125000003944 tolyl group Chemical group 0.000 claims abstract description 13
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 12
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 4
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 3
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 128
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 100
• 239000002253 acid Substances 0.000 claims description 44
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 30
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 26
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 19
• XCJLXFIGEMUOEE-UHFFFAOYSA-N acetamide;2,2,2-trifluoroacetic acid Chemical compound CC(N)=O.OC(=O)C(F)(F)F XCJLXFIGEMUOEE-UHFFFAOYSA-N 0.000 claims description 17
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
• 208000023275 Autoimmune disease Diseases 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• WVRKHFSDURCGFL-RSXQAXDFSA-N n-[(1s)-1-cyanoethyl]-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)N[C@@H](C)C#N)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 WVRKHFSDURCGFL-RSXQAXDFSA-N 0.000 claims description 15
• KORQHSDMFVWUTA-UHFFFAOYSA-N N-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C(C)(=O)NC1=CC=C(C=C1)C1=NOC(=N1)C1=C(C(=NO1)C1=CC=CC=C1)C(F)(F)F KORQHSDMFVWUTA-UHFFFAOYSA-N 0.000 claims description 13
• 125000002883 imidazolyl group Chemical group 0.000 claims description 13
• ZHTTYLCDZHOSBW-UHFFFAOYSA-N 2-hydroxy-n-(2-hydroxyethyl)-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)NCCO)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 ZHTTYLCDZHOSBW-UHFFFAOYSA-N 0.000 claims description 12
• DSVUBNIUZPSVHV-UHFFFAOYSA-N 2-hydroxy-n-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound O1C(C)=NN=C1CNC(=O)C(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 DSVUBNIUZPSVHV-UHFFFAOYSA-N 0.000 claims description 12
• OZHGEHHYTPOPTJ-UHFFFAOYSA-N 2-hydroxy-n-[2-(methylamino)-2-oxoethyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)NCC(=O)NC)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 OZHGEHHYTPOPTJ-UHFFFAOYSA-N 0.000 claims description 12
• IUOMDBKIOVJSGI-UHFFFAOYSA-N 3-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]-n,n-dimethylpropanamide Chemical compound C1=CC(C(O)C(=O)NCCC(=O)N(C)C)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 IUOMDBKIOVJSGI-UHFFFAOYSA-N 0.000 claims description 12
• WGHSZGBMDJKIBT-UHFFFAOYSA-N n-[(4-amino-2-methylpyrimidin-5-yl)methyl]-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound NC1=NC(C)=NC=C1CNC(=O)C(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 WGHSZGBMDJKIBT-UHFFFAOYSA-N 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 11
• PAZMJRJAHCBSBO-VGAJERRHSA-N (2s)-2-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]-n,3,3-trimethylbutanamide Chemical compound C1=CC(C(O)C(=O)N[C@H](C(=O)NC)C(C)(C)C)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 PAZMJRJAHCBSBO-VGAJERRHSA-N 0.000 claims description 10
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 9
• NCSSHEINVZSGIO-UHFFFAOYSA-N n-(2-hydroxy-2-methylpropyl)-3-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]propanamide Chemical compound C1=CC(C(O)C(=O)NCCC(=O)NCC(C)(O)C)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 NCSSHEINVZSGIO-UHFFFAOYSA-N 0.000 claims description 9
• RXWTZGGOXAYIKE-UHFFFAOYSA-N 2-hydroxy-n-(2-methylsulfonylethyl)-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)NCCS(=O)(=O)C)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 RXWTZGGOXAYIKE-UHFFFAOYSA-N 0.000 claims description 8
• GGELNVMTYDNTLO-UHFFFAOYSA-N 3-phenyl-4-(trifluoromethyl)-1,2-oxazole Chemical compound FC(F)(F)C1=CON=C1C1=CC=CC=C1 GGELNVMTYDNTLO-UHFFFAOYSA-N 0.000 claims description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
• SGYUYTMWRNCIFM-UHFFFAOYSA-N 2-hydroxy-n-(1,3-oxazol-5-ylmethyl)-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)C(=O)NCC1=CN=CO1 SGYUYTMWRNCIFM-UHFFFAOYSA-N 0.000 claims description 7
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 7
• IPXGWQRYUKVYJS-UHFFFAOYSA-N N-[4-[5-[1-phenyl-5-(trifluoromethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C(C)(=O)NC1=CC=C(C=C1)C1=NOC(=N1)C=1C=NN(C=1C(F)(F)F)C1=CC=CC=C1 IPXGWQRYUKVYJS-UHFFFAOYSA-N 0.000 claims description 7
• LDGOTHYJHKJQQI-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)C(=O)NC1(C#N)CC1 LDGOTHYJHKJQQI-UHFFFAOYSA-N 0.000 claims description 7
• BOGJFNQCPQYQRT-DIAVIDTQSA-N n-[(1s)-1-cyano-2-methylpropyl]-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)N[C@@H](C(C)C)C#N)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 BOGJFNQCPQYQRT-DIAVIDTQSA-N 0.000 claims description 7
• MHLZPTDZPGZIGS-UHFFFAOYSA-N 3-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]propanoic acid Chemical compound C1=CC(C(C(=O)NCCC(O)=O)O)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 MHLZPTDZPGZIGS-UHFFFAOYSA-N 0.000 claims description 6
• 125000002393 azetidinyl group Chemical group 0.000 claims description 6
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• ORJHDSZAMVIOBT-UHFFFAOYSA-N n-(1,3-dihydroxypropan-2-yl)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)NC(CO)CO)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 ORJHDSZAMVIOBT-UHFFFAOYSA-N 0.000 claims description 6
• ULWVKRJZZPZNSJ-UHFFFAOYSA-N n-(cyanomethyl)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(C(=O)NCC#N)O)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 ULWVKRJZZPZNSJ-UHFFFAOYSA-N 0.000 claims description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• OXBPMUDBBYEFPW-UHFFFAOYSA-N 2-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]-n-methylpropanamide Chemical compound C1=CC(C(O)C(=O)NC(C)C(=O)NC)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 OXBPMUDBBYEFPW-UHFFFAOYSA-N 0.000 claims description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000001425 triazolyl group Chemical group 0.000 claims description 5
• 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• FFXCEEXMUIBSJL-UHFFFAOYSA-N 2-hydroxy-n-[(5-methyl-1,2-oxazol-3-yl)methyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound O1C(C)=CC(CNC(=O)C(O)C=2C=CC(=CC=2)C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 FFXCEEXMUIBSJL-UHFFFAOYSA-N 0.000 claims description 4
• VGBQMTYNIIVNJC-UHFFFAOYSA-N 2-hydroxy-n-[(5-methyl-1h-1,2,4-triazol-3-yl)methyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound N1C(C)=NN=C1CNC(=O)C(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 VGBQMTYNIIVNJC-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 4
• XTUJICMPBUFOPE-UHFFFAOYSA-N n-[cyano(phenyl)methyl]-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)C(=O)NC(C#N)C1=CC=CC=C1 XTUJICMPBUFOPE-UHFFFAOYSA-N 0.000 claims description 4
• CVFPVSSFDBNMHH-XADRRFQNSA-N (2s)-2-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]-n-methyl-4-phenylbutanamide Chemical compound C([C@@H](C(=O)NC)NC(=O)C(O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(C(=NO1)C=1C=CC=CC=1)C(F)(F)F)CC1=CC=CC=C1 CVFPVSSFDBNMHH-XADRRFQNSA-N 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• JPZWNFRNVVYOEU-UHFFFAOYSA-N n-(azetidin-3-yl)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)C(=O)NC1CNC1 JPZWNFRNVVYOEU-UHFFFAOYSA-N 0.000 claims description 3
• WVRKHFSDURCGFL-GKOGFXNCSA-N n-[(1r)-1-cyanoethyl]-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound C1=CC(C(O)C(=O)N[C@H](C)C#N)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 WVRKHFSDURCGFL-GKOGFXNCSA-N 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• LWFVBBWRJTULST-UHFFFAOYSA-N 2-hydroxy-2-[4-[5-[1-phenyl-5-(trifluoromethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]phenyl]-n-propylacetamide Chemical compound C1=CC(C(O)C(=O)NCCC)=CC=C1C1=NOC(C2=C(N(N=C2)C=2C=CC=CC=2)C(F)(F)F)=N1 LWFVBBWRJTULST-UHFFFAOYSA-N 0.000 claims description 2
• XQRNOBFSIVNLNY-YTJLLHSVSA-N 2-hydroxy-n-[(1s)-1-(1h-imidazol-2-yl)ethyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound N([C@@H](C)C=1NC=CN=1)C(=O)C(O)C(C=C1)=CC=C1C(N=1)=NOC=1C(=C1C(F)(F)F)ON=C1C1=CC=CC=C1 XQRNOBFSIVNLNY-YTJLLHSVSA-N 0.000 claims description 2
• 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 2
• SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 2
• 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
• 229910052702 rhenium Inorganic materials 0.000 claims description 2
• QDGWCMREKSAGTM-UHFFFAOYSA-N 2-hydroxy-n-[(3-methyl-1,2-oxazol-5-yl)methyl]-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound O1N=C(C)C=C1CNC(=O)C(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 QDGWCMREKSAGTM-UHFFFAOYSA-N 0.000 claims 2
• PQHJKFPHWRAEEE-UHFFFAOYSA-N 3-[[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetyl]amino]-n-methylpropanamide Chemical compound C1=CC(C(O)C(=O)NCCC(=O)NC)=CC=C1C1=NOC(C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)=N1 PQHJKFPHWRAEEE-UHFFFAOYSA-N 0.000 claims 2
• 208000037976 chronic inflammation Diseases 0.000 claims 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 claims 2
• SOBILORTDNTINR-UHFFFAOYSA-N 2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]-n-(2-pyrazin-2-ylethyl)acetamide Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)C(=O)NCCC1=CN=CC=N1 SOBILORTDNTINR-UHFFFAOYSA-N 0.000 claims 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 328
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