ES2953576T3 - Moduladores del receptor beta-3 adrenérgico útiles para el tratamiento o la prevención de la insuficiencia cardíaca y los trastornos relacionados con la misma - Google Patents

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Publication number

ES2953576T3

ES2953576T3 ES18822236T ES18822236T ES2953576T3 ES 2953576 T3 ES2953576 T3 ES 2953576T3 ES 18822236 T ES18822236 T ES 18822236T ES 18822236 T ES18822236 T ES 18822236T ES 2953576 T3 ES2953576 T3 ES 2953576T3

Authority

ES

Spain

Prior art keywords

methyl

phenyl

ílo

pyridin

dihydro

Prior art date

2017-12-06

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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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 106
• 206010019280 Heart failures Diseases 0.000 title claims abstract description 80
• 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 title claims abstract description 76
• 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 title claims abstract description 76
• 238000011282 treatment Methods 0.000 title abstract description 34
• 230000002265 prevention Effects 0.000 title description 12
• 150000001875 compounds Chemical class 0.000 claims abstract description 814
• 238000000034 method Methods 0.000 claims abstract description 60
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 59
• 230000001404 mediated effect Effects 0.000 claims abstract description 57
• -1 hydroxycarbamimidol Chemical group 0.000 claims description 2688
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 402
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 157
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 149
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 144
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 119
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 95
• 125000001424 substituent group Chemical group 0.000 claims description 95
• 208000035475 disorder Diseases 0.000 claims description 90
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 85
• 125000004043 oxo group Chemical group O=* 0.000 claims description 80
• 150000003839 salts Chemical class 0.000 claims description 52
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 50
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
• 239000012453 solvate Substances 0.000 claims description 46
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
• 125000000623 heterocyclic group Chemical group 0.000 claims description 44
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 42
• 150000004677 hydrates Chemical class 0.000 claims description 41
• 239000000203 mixture Substances 0.000 claims description 40
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 39
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 35
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
• 125000005605 benzo group Chemical group 0.000 claims description 34
• 150000003857 carboxamides Chemical class 0.000 claims description 32
• 239000011737 fluorine Substances 0.000 claims description 32
• 229910052731 fluorine Inorganic materials 0.000 claims description 32
• 125000001072 heteroaryl group Chemical group 0.000 claims description 32
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 31
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 31
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 229940127557 pharmaceutical product Drugs 0.000 claims description 30
• 210000002216 heart Anatomy 0.000 claims description 29
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 27
• 229910052736 halogen Inorganic materials 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 27
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 23
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 22
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
• 125000004076 pyridyl group Chemical group 0.000 claims description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
• 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims description 18
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 18
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 17
• 208000010125 myocardial infarction Diseases 0.000 claims description 17
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 16
• 206010007556 Cardiac failure acute Diseases 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 16
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 15
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 15
• 125000004104 aryloxy group Chemical group 0.000 claims description 15
• 238000009472 formulation Methods 0.000 claims description 14
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 14
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 13
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 claims description 13
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 13
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 13
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 12
• 206010024119 Left ventricular failure Diseases 0.000 claims description 12
• 150000001412 amines Chemical class 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 12
• 229940079593 drug Drugs 0.000 claims description 12
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
• 125000006516 2-(benzyloxy)ethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 11
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 11
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 11
• 125000001624 naphthyl group Chemical group 0.000 claims description 11
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 11
• 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 claims description 11
• 125000005899 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl group Chemical group 0.000 claims description 10
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 10
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
• 241000282414 Homo sapiens Species 0.000 claims description 10
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 10
• 125000002883 imidazolyl group Chemical group 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
• 230000002861 ventricular Effects 0.000 claims description 10
• 125000005955 1H-indazolyl group Chemical group 0.000 claims description 9
• 125000005900 2,3-dihydrofuro[2,3-b]pyridinyl group Chemical group 0.000 claims description 9
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 claims description 9
• 241001465754 Metazoa Species 0.000 claims description 9
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• 125000001246 bromo group Chemical group Br* 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 125000001041 indolyl group Chemical group 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 9
• CSBIAJTULAQKAD-UHFFFAOYSA-N n-fluoroethanamine Chemical compound CCNF CSBIAJTULAQKAD-UHFFFAOYSA-N 0.000 claims description 9
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 150000001204 N-oxides Chemical class 0.000 claims description 8
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 8
• 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims description 8
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 230000000747 cardiac effect Effects 0.000 claims description 8
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
• 125000002541 furyl group Chemical group 0.000 claims description 8
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
• 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 8
• 238000002560 therapeutic procedure Methods 0.000 claims description 8
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
• 125000006798 (C1-C6) haloalkylamino group Chemical group 0.000 claims description 7
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 7
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 7
• RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 claims description 7
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
• YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 claims description 6
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 claims description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
• 206010067125 Liver injury Diseases 0.000 claims description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
• 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 238000002592 echocardiography Methods 0.000 claims description 6
• 210000003709 heart valve Anatomy 0.000 claims description 6
• 231100000753 hepatic injury Toxicity 0.000 claims description 6
• 230000008816 organ damage Effects 0.000 claims description 6
• 230000033764 rhythmic process Effects 0.000 claims description 6
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 5
• UDHXJZHVNHGCEC-UHFFFAOYSA-N Chlorophacinone Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)C(=O)C1C(=O)C2=CC=CC=C2C1=O UDHXJZHVNHGCEC-UHFFFAOYSA-N 0.000 claims description 5
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims description 5
• 238000002583 angiography Methods 0.000 claims description 5
• 239000004202 carbamide Substances 0.000 claims description 5
• 235000013877 carbamide Nutrition 0.000 claims description 5
• 229960001330 hydroxycarbamide Drugs 0.000 claims description 5
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 5
• 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• GVWISOJSERXQBM-UHFFFAOYSA-N n-methylpropan-1-amine Chemical compound CCCNC GVWISOJSERXQBM-UHFFFAOYSA-N 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000001984 thiazolidinyl group Chemical group 0.000 claims description 5
• IAKOZHOLGAGEJT-UHFFFAOYSA-N 1,1,1-trichloro-2,2-bis(p-methoxyphenyl)-Ethane Chemical compound C1=CC(OC)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(OC)C=C1 IAKOZHOLGAGEJT-UHFFFAOYSA-N 0.000 claims description 4
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 4
• 239000004305 biphenyl Substances 0.000 claims description 4
• 235000010290 biphenyl Nutrition 0.000 claims description 4
• FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 4
• 229910052751 metal Inorganic materials 0.000 claims description 4
• 239000002184 metal Substances 0.000 claims description 4
• 238000002156 mixing Methods 0.000 claims description 4
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 3
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 3
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 3
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