CA2285454A1 - Compounds and compositions for treating diseases associated with serine protease, particularly tryptase, activity - Google Patents

Info

Publication number

CA2285454A1

CA2285454A1 CA002285454A CA2285454A CA2285454A1 CA 2285454 A1 CA2285454 A1 CA 2285454A1 CA 002285454 A CA002285454 A CA 002285454A CA 2285454 A CA2285454 A CA 2285454A CA 2285454 A1 CA2285454 A1 CA 2285454A1

Authority

CA

Canada

Prior art keywords

benzoimidazol

alkyl

compound

ethyl

methyl

Prior art date

1997-04-07

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

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 360
• 239000000203 mixture Substances 0.000 title claims abstract description 143
• 108060005989 Tryptase Proteins 0.000 title abstract description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 26
• 201000010099 disease Diseases 0.000 title description 23
• 102000001400 Tryptase Human genes 0.000 title description 22
• 230000000694 effects Effects 0.000 title description 9
• 102000012479 Serine Proteases Human genes 0.000 title description 4
• 108010022999 Serine Proteases Proteins 0.000 title description 4
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 81
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 70
• 239000001257 hydrogen Substances 0.000 claims abstract description 69
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 48
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 47
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 46
• 238000000034 method Methods 0.000 claims abstract description 39
• 125000001424 substituent group Chemical group 0.000 claims abstract description 33
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 19
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 15
• 125000003943 azolyl group Chemical group 0.000 claims abstract description 14
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 11
• 210000002345 respiratory system Anatomy 0.000 claims abstract description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 5
• 230000000699 topical effect Effects 0.000 claims abstract description 4
• 206010010741 Conjunctivitis Diseases 0.000 claims abstract description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 35
• 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims abstract 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 6
• -1 amino, carboxy, carbamoyl Chemical group 0.000 claims description 284
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 224
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 108
• 125000005842 heteroatom Chemical group 0.000 claims description 75
• 125000003118 aryl group Chemical group 0.000 claims description 65
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 44
• 239000005711 Benzoic acid Substances 0.000 claims description 42
• 235000010233 benzoic acid Nutrition 0.000 claims description 42
• 125000002947 alkylene group Chemical group 0.000 claims description 38
• 150000003839 salts Chemical class 0.000 claims description 38
• 125000004429 atom Chemical group 0.000 claims description 37
• 125000005843 halogen group Chemical group 0.000 claims description 32
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
• 239000000651 prodrug Substances 0.000 claims description 27
• 229940002612 prodrug Drugs 0.000 claims description 27
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 25
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
• 125000001931 aliphatic group Chemical group 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• FNLQDVXHDNFXIY-UHFFFAOYSA-N 3h-benzimidazole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=NC2=C1 FNLQDVXHDNFXIY-UHFFFAOYSA-N 0.000 claims description 18
• 125000002723 alicyclic group Chemical group 0.000 claims description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 16
• 125000004423 acyloxy group Chemical group 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 150000001204 N-oxides Chemical class 0.000 claims description 14
• SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 14
• OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 claims description 12
• 239000000443 aerosol Substances 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 9
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 9
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 230000009385 viral infection Effects 0.000 claims description 6
• 125000001118 alkylidene group Chemical group 0.000 claims description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 239000000843 powder Substances 0.000 claims description 4
• QLSPZJGUNBXVHU-UHFFFAOYSA-N 2-[2-[[2-[1-(5,6-difluoro-1h-benzimidazol-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoic acid Chemical compound N=1C2=CC(F)=C(F)C=C2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=CC=C1C(O)=O QLSPZJGUNBXVHU-UHFFFAOYSA-N 0.000 claims description 3
• 239000000048 adrenergic agonist Substances 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 3
• MRZUPMMOAMHPRD-UHFFFAOYSA-N ethyl 2-[2-[[2-[1-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC=3CCN(CC=3N=2)C(C)=N)N2C)C2=C1 MRZUPMMOAMHPRD-UHFFFAOYSA-N 0.000 claims description 3
• ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
• XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 2
• JAPCFBJCLMYVSK-UHFFFAOYSA-N 2-[(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)methyl]-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)C)CC=3NC=4CCN(CC=4N=3)C(=N)C)=CC=CC2=C1 JAPCFBJCLMYVSK-UHFFFAOYSA-N 0.000 claims description 2
• MTWFINXLTMNGCU-UHFFFAOYSA-N 2-[2-[[3-methyl-2-[1-(4,6,7-trifluoro-1h-benzimidazol-2-yl)ethyl]benzimidazole-5-carbonyl]amino]ethoxy]benzoic acid Chemical compound N=1C2=C(F)C=C(F)C(F)=C2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=CC=C1C(O)=O MTWFINXLTMNGCU-UHFFFAOYSA-N 0.000 claims description 2
• SEUKIEPOEJRKFB-UHFFFAOYSA-N 2-methylpropyl 2-[2-[[2-[1-(6-hydroxy-1h-benzimidazol-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CC(C)COC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC3=CC=C(O)C=C3N=2)N2C)C2=C1 SEUKIEPOEJRKFB-UHFFFAOYSA-N 0.000 claims description 2
• LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
• DXESMANYHPHJKC-UHFFFAOYSA-N butyl 2-[2-[[2-[1-(6-hydroxy-1h-benzimidazol-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CCCCOC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC3=CC=C(O)C=C3N=2)N2C)C2=C1 DXESMANYHPHJKC-UHFFFAOYSA-N 0.000 claims description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
• 229960001022 fenoterol Drugs 0.000 claims description 2
• 229960002848 formoterol Drugs 0.000 claims description 2
• BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• ITLXLUOKKNJLRA-UHFFFAOYSA-N propyl 2-[2-[[2-[1-(6-hydroxy-1h-benzimidazol-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC3=CC=C(O)C=C3N=2)N2C)C2=C1 ITLXLUOKKNJLRA-UHFFFAOYSA-N 0.000 claims description 2
• 229960002052 salbutamol Drugs 0.000 claims description 2
• 229960000195 terbutaline Drugs 0.000 claims description 2
• 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 2
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 18
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 10
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 6
• WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 claims 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 2
• XMGODZOTGXEKCX-UHFFFAOYSA-N 2-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridine-2-carbonyl)-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)C)C(=O)C=3NC=4CCN(CC=4N=3)C(=N)C)=CC=CC2=C1 XMGODZOTGXEKCX-UHFFFAOYSA-N 0.000 claims 1
• GIHLYBBKNGKPHR-UHFFFAOYSA-N 2-[(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)methyl]-n-(2-hydroxy-2-naphthalen-1-ylethyl)-3-methylbenzimidazole-5-carboxamide Chemical compound C1=CC=C2C(C(O)CNC(=O)C3=CC=C4N=C(N(C4=C3)C)CC=3NC=4CCN(CC=4N=3)C(=N)C)=CC=CC2=C1 GIHLYBBKNGKPHR-UHFFFAOYSA-N 0.000 claims 1
• NWAXVDHKLJWHNU-UHFFFAOYSA-N 2-[(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)methyl]-n-[2-(2-hydroxynaphthalen-1-yl)ethyl]-3-methylbenzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)C)CC=3NC=4CCN(CC=4N=3)C(=N)C)=C(O)C=CC2=C1 NWAXVDHKLJWHNU-UHFFFAOYSA-N 0.000 claims 1
• MISQWHLQAZBBHJ-UHFFFAOYSA-N 2-[(5-methanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)methyl]-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(CC=5NC=6CCN(CC=6N=5)C=N)N(C4=C3)C)=CC=CC2=C1 MISQWHLQAZBBHJ-UHFFFAOYSA-N 0.000 claims 1
• WIQOYAJMCNMJPP-UHFFFAOYSA-N 2-[1-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)ethyl]-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)C)C(C=3NC=4CCN(CC=4N=3)C(C)=N)C)=CC=CC2=C1 WIQOYAJMCNMJPP-UHFFFAOYSA-N 0.000 claims 1
• GYSBOTYZJCZKQQ-UHFFFAOYSA-N 2-[1-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)ethyl]-3-methyl-n-[2-[2-(2h-tetrazol-5-yl)phenoxy]ethyl]benzimidazole-5-carboxamide Chemical compound N=1C=2CN(C(C)=N)CCC=2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=CC=C1C1=NN=NN1 GYSBOTYZJCZKQQ-UHFFFAOYSA-N 0.000 claims 1
• FTNBVAOKBGAXCR-UHFFFAOYSA-N 2-[2-[[2-[1-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)ethyl]-3-(2-methoxyethyl)benzimidazole-5-carbonyl]amino]ethoxy]benzoic acid Chemical compound C1=C2N(CCOC)C(C(C)C=3NC=4CCN(CC=4N=3)C(C)=N)=NC2=CC=C1C(=O)NCCOC1=CC=CC=C1C(O)=O FTNBVAOKBGAXCR-UHFFFAOYSA-N 0.000 claims 1
• JAHYJFMHHBGDKR-UHFFFAOYSA-N 2-[[6-(aminomethyl)-1h-benzimidazol-2-yl]methyl]-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(CC=5NC6=CC=C(CN)C=C6N=5)N(C4=C3)C)=CC=CC2=C1 JAHYJFMHHBGDKR-UHFFFAOYSA-N 0.000 claims 1
• HAKZKUZTXPGYRU-UHFFFAOYSA-N 2-[[6-(aminomethyl)-4,5,6,7-tetrahydro-1h-benzimidazol-2-yl]methyl]-3-methyl-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(CC=5NC=6CCC(CN)CC=6N=5)N(C4=C3)C)=CC=CC2=C1 HAKZKUZTXPGYRU-UHFFFAOYSA-N 0.000 claims 1
• 125000000172 C5-C10 aryl group Chemical group 0.000 claims 1
• 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims 1
• 125000000815 N-oxide group Chemical group 0.000 claims 1
• 229910019999 S(O)2O Inorganic materials 0.000 claims 1
• QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 claims 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
• 208000006673 asthma Diseases 0.000 abstract description 26
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• 125000001475 halogen functional group Chemical group 0.000 abstract 2
• 229940124639 Selective inhibitor Drugs 0.000 abstract 1
• 230000003612 virological effect Effects 0.000 abstract 1
• 238000001819 mass spectrum Methods 0.000 description 205
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 101
• 238000005160 1H NMR spectroscopy Methods 0.000 description 92
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• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
• 239000000243 solution Substances 0.000 description 57
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
• 239000000454 talc Substances 0.000 description 49
• 229910052623 talc Inorganic materials 0.000 description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• 239000007787 solid Substances 0.000 description 40
• 239000002244 precipitate Substances 0.000 description 39
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• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• 229920006395 saturated elastomer Polymers 0.000 description 27
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
• 235000019441 ethanol Nutrition 0.000 description 25
• 150000003254 radicals Chemical class 0.000 description 25
• BOEBOCVQDLZVBD-UHFFFAOYSA-N C1=CC=C2C(CCC3=NC4=CC=C(C=C4N3)C(=O)N)=CC=CC2=C1 Chemical compound C1=CC=C2C(CCC3=NC4=CC=C(C=C4N3)C(=O)N)=CC=CC2=C1 BOEBOCVQDLZVBD-UHFFFAOYSA-N 0.000 description 24
• 229910052757 nitrogen Inorganic materials 0.000 description 24
• 238000001914 filtration Methods 0.000 description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• 241001494479 Pecora Species 0.000 description 14
• 229940087827 biolon Drugs 0.000 description 14
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• HLNQMMZXAQRKIS-UHFFFAOYSA-N ethyl 2-[2-[[2-[1-(6-hydroxy-1h-benzimidazol-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC3=CC=C(O)C=C3N=2)N2C)C2=C1 HLNQMMZXAQRKIS-UHFFFAOYSA-N 0.000 description 1
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• WCUVKRBCXZSASQ-UHFFFAOYSA-N ethyl 2-[2-[[2-[1-[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1OCCNC(=O)C1=CC=C(N=C(C(C)C=2NC3=CC=C(NC(N)=N)C=C3N=2)N2C)C2=C1 WCUVKRBCXZSASQ-UHFFFAOYSA-N 0.000 description 1
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