LV12495B - COMPOUNDS AND COMPOSITIONS FOR TREATMENT OF TRIPTASE ACTIVITIES \ t - Google Patents

Info

Publication number

LV12495B

LV12495B LVP-99-153A LV990153A LV12495B LV 12495 B LV12495 B LV 12495B LV 990153 A LV990153 A LV 990153A LV 12495 B LV12495 B LV 12495B

Authority

LV

Latvia

Prior art keywords

compound

ethyl

alkyl

methyl

benzoimidazol

Prior art date

1997-04-07

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 417
• 239000000203 mixture Substances 0.000 title claims abstract description 155
• 108060005989 Tryptase Proteins 0.000 title abstract description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 28
• 201000010099 disease Diseases 0.000 title description 25
• 102000001400 Tryptase Human genes 0.000 title description 22
• 230000000694 effects Effects 0.000 title description 10
• 102000012479 Serine Proteases Human genes 0.000 title description 4
• 108010022999 Serine Proteases Proteins 0.000 title description 4
• 238000000034 method Methods 0.000 claims abstract description 42
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 22
• 206010010741 Conjunctivitis Diseases 0.000 claims abstract description 6
• 210000002345 respiratory system Anatomy 0.000 claims abstract description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 349
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 191
• -1 amino, carboxyl Chemical group 0.000 claims description 170
• 125000000217 alkyl group Chemical group 0.000 claims description 158
• 239000001257 hydrogen Substances 0.000 claims description 85
• 229910052739 hydrogen Inorganic materials 0.000 claims description 85
• 125000005842 heteroatom Chemical group 0.000 claims description 83
• 125000003118 aryl group Chemical group 0.000 claims description 71
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
• 239000005711 Benzoic acid Substances 0.000 claims description 63
• 235000010233 benzoic acid Nutrition 0.000 claims description 63
• 150000003839 salts Chemical class 0.000 claims description 52
• 125000001424 substituent group Chemical group 0.000 claims description 52
• 125000003545 alkoxy group Chemical group 0.000 claims description 50
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 46
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 45
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 44
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
• 125000004429 atom Chemical group 0.000 claims description 42
• 125000002947 alkylene group Chemical group 0.000 claims description 40
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 39
• 125000005843 halogen group Chemical group 0.000 claims description 37
• 239000000651 prodrug Chemical class 0.000 claims description 35
• 229940002612 prodrug Drugs 0.000 claims description 35
• 125000001931 aliphatic group Chemical group 0.000 claims description 29
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
• 150000002431 hydrogen Chemical group 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 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 27
• 150000001204 N-oxides Chemical class 0.000 claims description 25
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 24
• 125000003282 alkyl amino group Chemical group 0.000 claims description 22
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• 125000004432 carbon atom Chemical group C* 0.000 claims description 21
• 125000004423 acyloxy group Chemical group 0.000 claims description 20
• 125000002723 alicyclic group Chemical group 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 239000000443 aerosol Substances 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 125000003943 azolyl group Chemical group 0.000 claims description 13
• 229940079593 drug Drugs 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 11
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 239000000843 powder Substances 0.000 claims description 6
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
• 125000001118 alkylidene group Chemical group 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 238000000926 separation method Methods 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 3
• 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 3
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
• 229960001022 fenoterol Drugs 0.000 claims description 3
• 229960002848 formoterol Drugs 0.000 claims description 3
• 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 3
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
• 125000001072 heteroaryl group Chemical group 0.000 claims description 3
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 3
• 229960002052 salbutamol Drugs 0.000 claims description 3
• 229960000195 terbutaline Drugs 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
• 125000004474 heteroalkylene group Chemical group 0.000 claims description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
• 230000009385 viral infection Effects 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 20
• 125000006413 ring segment Chemical group 0.000 claims 19
• 229910052736 halogen Inorganic materials 0.000 claims 15
• 150000002367 halogens Chemical class 0.000 claims 14
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 11
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 7
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 6
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 5
• 239000002243 precursor Substances 0.000 claims 5
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 4
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 3
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 3
• QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical group NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 claims 3
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
• KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-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
• 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
• 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 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
• SYWNNHDBRIRLIJ-UHFFFAOYSA-N 2-[2-[[2-[1-(5-ethanimidoyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoic acid Chemical compound N=1C=2CN(C(C)=N)CCC=2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=CC=C1C(O)=O SYWNNHDBRIRLIJ-UHFFFAOYSA-N 0.000 claims 1
• 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 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
• OSRVVWZHRVQALB-UHFFFAOYSA-N 2-[[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]methyl]-3-(2-hydroxyethyl)-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)CCO)CC=3NC4=CC=C(C=C4N=3)NC(=N)N)=CC=CC2=C1 OSRVVWZHRVQALB-UHFFFAOYSA-N 0.000 claims 1
• MWIKGVWTRMUKJV-UHFFFAOYSA-N 2-[[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]methyl]-3-(3-hydroxypropyl)-n-(2-naphthalen-1-ylethyl)benzimidazole-5-carboxamide Chemical compound C1=CC=C2C(CCNC(=O)C3=CC=C4N=C(N(C4=C3)CCCO)CC=3NC4=CC=C(C=C4N=3)NC(=N)N)=CC=CC2=C1 MWIKGVWTRMUKJV-UHFFFAOYSA-N 0.000 claims 1
• XMLXFJVPVNLPCA-UHFFFAOYSA-N 2-[[6-(diaminomethylideneamino)-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(NC(N)=N)C=C6N=5)N(C4=C3)C)=CC=CC2=C1 XMLXFJVPVNLPCA-UHFFFAOYSA-N 0.000 claims 1
• XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical compound CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• PCCUPAKWDDHPKB-UHFFFAOYSA-N 5-chloro-2-[2-[[2-[1-[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]ethyl]-3-methylbenzimidazole-5-carbonyl]amino]ethoxy]benzoic acid Chemical compound N=1C2=CC(NC(N)=N)=CC=C2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=C(Cl)C=C1C(O)=O PCCUPAKWDDHPKB-UHFFFAOYSA-N 0.000 claims 1
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 1
• 125000005138 alkoxysulfonyl group Chemical group 0.000 claims 1
• KZOWNALBTMILAP-JBMRGDGGSA-N ancitabine hydrochloride Chemical compound Cl.N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 KZOWNALBTMILAP-JBMRGDGGSA-N 0.000 claims 1
• 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 1
• 239000004202 carbamide Substances 0.000 claims 1
• 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 1
• KBLIYEFDOMCUBC-UHFFFAOYSA-N ethyl 2-[3-[[2-[1-[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]ethyl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carbonyl]amino]propoxy]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1OCCCNC(=O)N1CC(N=C(N2)C(C)C=3NC4=CC=C(NC(N)=N)C=C4N=3)=C2CC1 KBLIYEFDOMCUBC-UHFFFAOYSA-N 0.000 claims 1
• LSLYOANBFKQKPT-UHFFFAOYSA-N fenoterol Chemical compound C=1C(O)=CC(O)=CC=1C(O)CNC(C)CC1=CC=C(O)C=C1 LSLYOANBFKQKPT-UHFFFAOYSA-N 0.000 claims 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
• 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
• FJUZLZZFUIJKRF-UHFFFAOYSA-N n-[2-(2-carbamoyl-4-chlorophenoxy)ethyl]-2-[1-[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]ethyl]-3-methylbenzimidazole-5-carboxamide Chemical compound N=1C2=CC(NC(N)=N)=CC=C2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=C(Cl)C=C1C(N)=O FJUZLZZFUIJKRF-UHFFFAOYSA-N 0.000 claims 1
• WURDECGZGWCLLG-UHFFFAOYSA-N n-[2-(2-carbamoylphenoxy)ethyl]-2-[1-[6-(diaminomethylideneamino)-1h-benzimidazol-2-yl]ethyl]-3-methylbenzimidazole-5-carboxamide Chemical compound N=1C2=CC(NC(N)=N)=CC=C2NC=1C(C)C(N(C1=C2)C)=NC1=CC=C2C(=O)NCCOC1=CC=CC=C1C(N)=O WURDECGZGWCLLG-UHFFFAOYSA-N 0.000 claims 1
• 125000005592 polycycloalkyl group Polymers 0.000 claims 1
• 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 1
• 201000003068 rheumatic fever Diseases 0.000 claims 1
• 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
• 208000006673 asthma Diseases 0.000 abstract description 27
• 238000002360 preparation method Methods 0.000 abstract description 9
• 230000002265 prevention Effects 0.000 abstract description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 6
• 206010039085 Rhinitis allergic Diseases 0.000 abstract description 5
• 201000010105 allergic rhinitis Diseases 0.000 abstract description 5
• 230000000699 topical effect Effects 0.000 abstract description 4
• 210000003630 histaminocyte Anatomy 0.000 abstract description 3
• 230000001404 mediated effect Effects 0.000 abstract description 3
• 230000003389 potentiating effect Effects 0.000 abstract description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 abstract description 2
• 229940124639 Selective inhibitor Drugs 0.000 abstract description 2
• 230000003612 virological effect Effects 0.000 abstract 1
• 238000001819 mass spectrum Methods 0.000 description 205
• 229940087827 biolon Drugs 0.000 description 164
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 100
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 96
• 238000005481 NMR spectroscopy Methods 0.000 description 83
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
• 239000000243 solution Substances 0.000 description 56
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
• 239000002244 precipitate Substances 0.000 description 39
• 239000007787 solid Substances 0.000 description 37
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
• 150000003254 radicals Chemical class 0.000 description 28
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