TWI756305B - 化合物 - Google Patents
化合物 Download PDFInfo
- Publication number
- TWI756305B TWI756305B TW106140573A TW106140573A TWI756305B TW I756305 B TWI756305 B TW I756305B TW 106140573 A TW106140573 A TW 106140573A TW 106140573 A TW106140573 A TW 106140573A TW I756305 B TWI756305 B TW I756305B
- Authority
- TW
- Taiwan
- Prior art keywords
- amino
- methyl
- onium
- pyridine
- pyrrolo
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 360
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 220
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 149
- 238000006243 chemical reaction Methods 0.000 claims description 136
- -1 3-{[(tert-butoxy)carbonyl]amino}propyl Chemical group 0.000 claims description 95
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 95
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 38
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000002947 alkylene group Chemical group 0.000 claims description 23
- 150000001450 anions Chemical class 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 230000036961 partial effect Effects 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 239000013543 active substance Substances 0.000 claims description 14
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000001475 halogen functional group Chemical group 0.000 claims description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 10
- 150000001768 cations Chemical class 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000004450 alkenylene group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 8
- 125000004419 alkynylene group Chemical group 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 208000030533 eye disease Diseases 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 208000017520 skin disease Diseases 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 5
- 125000000134 2-(methylsulfanyl)ethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])[*] 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 5
- 238000006268 reductive amination reaction Methods 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 102000003787 Anoctamin-1 Human genes 0.000 claims description 4
- 108090000160 Anoctamin-1 Proteins 0.000 claims description 4
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 4
- 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 4
- 239000000739 antihistaminic agent Substances 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 201000009267 bronchiectasis Diseases 0.000 claims description 4
- 206010006451 bronchitis Diseases 0.000 claims description 4
- 208000007451 chronic bronchitis Diseases 0.000 claims description 4
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical group CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 claims description 4
- 229960002657 orciprenaline Drugs 0.000 claims description 4
- 229960002052 salbutamol Drugs 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 3
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 208000025678 Ciliary Motility disease Diseases 0.000 claims description 3
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
- 206010013774 Dry eye Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 claims description 3
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 claims description 3
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000048 adrenergic agonist Substances 0.000 claims description 3
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 3
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000008937 atopic dermatitis Diseases 0.000 claims description 3
- 229960004574 azelastine Drugs 0.000 claims description 3
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 claims description 3
- 125000005518 carboxamido group Chemical group 0.000 claims description 3
- 229960003291 chlorphenamine Drugs 0.000 claims description 3
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003246 corticosteroid Substances 0.000 claims description 3
- 229960001271 desloratadine Drugs 0.000 claims description 3
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 3
- 229960003592 fexofenadine Drugs 0.000 claims description 3
- XTULMSXFIHGYFS-VLSRWLAYSA-N fluticasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4[C@@H](F)C[C@H]3[C@@H]2C[C@H]1C)C(=O)SCF)C(=O)C1=CC=CO1 XTULMSXFIHGYFS-VLSRWLAYSA-N 0.000 claims description 3
- 229960001469 fluticasone furoate Drugs 0.000 claims description 3
- 206010021198 ichthyosis Diseases 0.000 claims description 3
- 229940039009 isoproterenol Drugs 0.000 claims description 3
- 230000000155 isotopic effect Effects 0.000 claims description 3
- 229960001508 levocetirizine Drugs 0.000 claims description 3
- 229960002744 mometasone furoate Drugs 0.000 claims description 3
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 claims description 3
- 229960005127 montelukast Drugs 0.000 claims description 3
- 229960004618 prednisone Drugs 0.000 claims description 3
- 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 claims description 3
- 201000009266 primary ciliary dyskinesia Diseases 0.000 claims description 3
- 229960004764 zafirlukast Drugs 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
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 claims description 2
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 2
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 claims description 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 229940125715 antihistaminic agent Drugs 0.000 claims description 2
- MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 2
- 229950000210 beclometasone dipropionate Drugs 0.000 claims description 2
- HODFCFXCOMKRCG-UHFFFAOYSA-N bitolterol mesylate Chemical compound CS([O-])(=O)=O.C1=CC(C)=CC=C1C(=O)OC1=CC=C(C(O)C[NH2+]C(C)(C)C)C=C1OC(=O)C1=CC=C(C)C=C1 HODFCFXCOMKRCG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000585 bitolterol mesylate Drugs 0.000 claims description 2
- 229960004436 budesonide Drugs 0.000 claims description 2
- 229960001803 cetirizine Drugs 0.000 claims description 2
- 229960001334 corticosteroids Drugs 0.000 claims description 2
- 229960000676 flunisolide Drugs 0.000 claims description 2
- 229960000289 fluticasone propionate Drugs 0.000 claims description 2
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 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
- 229960004078 indacaterol Drugs 0.000 claims description 2
- QZZUEBNBZAPZLX-QFIPXVFZSA-N indacaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 claims description 2
- 229960001317 isoprenaline Drugs 0.000 claims description 2
- PURKAOJPTOLRMP-UHFFFAOYSA-N ivacaftor Chemical group C1=C(O)C(C(C)(C)C)=CC(C(C)(C)C)=C1NC(=O)C1=CNC2=CC=CC=C2C1=O PURKAOJPTOLRMP-UHFFFAOYSA-N 0.000 claims description 2
- 229960004508 ivacaftor Drugs 0.000 claims description 2
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 2
- 229960003088 loratadine Drugs 0.000 claims description 2
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical group C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 2
- UFSKUSARDNFIRC-UHFFFAOYSA-N lumacaftor Chemical compound N1=C(C=2C=C(C=CC=2)C(O)=O)C(C)=CC=C1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 UFSKUSARDNFIRC-UHFFFAOYSA-N 0.000 claims description 2
- 229960000998 lumacaftor Drugs 0.000 claims description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229960005414 pirbuterol Drugs 0.000 claims description 2
- 229960005205 prednisolone Drugs 0.000 claims description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 2
- QFTLJRFNJYIISH-UHFFFAOYSA-N pyrrolo[2,3-b]pyridine Chemical compound C1=C[N]C2=NC=CC2=C1 QFTLJRFNJYIISH-UHFFFAOYSA-N 0.000 claims description 2
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 claims description 2
- 229960004017 salmeterol Drugs 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229960000195 terbutaline Drugs 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 229950005823 tezacaftor Drugs 0.000 claims 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 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 229960002117 triamcinolone acetonide Drugs 0.000 claims description 2
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 claims description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 2
- 230000001387 anti-histamine Effects 0.000 claims 2
- 229960004754 astemizole Drugs 0.000 claims 2
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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| WO2011079087A1 (en) * | 2009-12-23 | 2011-06-30 | Glaxo Group Limited | Enac blockers |
| TW201204353A (en) * | 2010-06-08 | 2012-02-01 | Vertex Pharma | Formulations of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide |
| WO2015007516A1 (en) * | 2013-07-15 | 2015-01-22 | Boehringer Ingelheim International Gmbh | Novel 5-substituted benzimidazolium compounds |
| WO2016113167A1 (en) * | 2015-01-12 | 2016-07-21 | Boehringer Ingelheim International Gmbh | Substituted benzimidazolium compounds useful in the treatment of respiratory diseases |
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| US20050090505A1 (en) | 2003-08-18 | 2005-04-28 | Johnson Michael R. | Methods of reducing risk of infection from pathogens |
| AU2004264441A1 (en) | 2003-08-18 | 2005-02-24 | Parion Sciences, Inc. | Cyclic pyrazinoylguanidine sodium channel blockers |
| US7745442B2 (en) | 2003-08-20 | 2010-06-29 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens |
| NZ547109A (en) * | 2003-10-28 | 2010-03-26 | Vertex Pharma | Benzimidazoles useful as modulators of ion channels |
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| AU2009246799B2 (en) | 2008-02-26 | 2014-02-27 | Parion Sciences, Inc. | Poly aromatic pyrazinoylguanidine sodium channel blockers |
| JP2011520831A (ja) | 2008-05-13 | 2011-07-21 | ノバルティス アーゲー | ３，５−ジアミノ−６−クロロ−ピラジン−２−カルボン酸誘導体および気道疾患処置用上皮性ナトリウムチャネルブロッカーとしてのその使用 |
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2017
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- 2017-11-22 TW TW106140573A patent/TWI756305B/zh active
- 2017-11-22 EP EP17807900.0A patent/EP3544981B1/en active Active
- 2017-11-22 PT PT178079000T patent/PT3544981T/pt unknown
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- 2017-11-22 MA MA046878A patent/MA46878A/fr unknown
- 2017-11-22 JP JP2019527365A patent/JP6980014B2/ja active Active
- 2017-11-22 KR KR1020197016141A patent/KR102517273B1/ko active Active
- 2017-11-22 HU HUE17807900A patent/HUE055692T2/hu unknown
- 2017-11-22 PL PL17807900T patent/PL3544981T3/pl unknown
- 2017-11-22 DK DK17807900.0T patent/DK3544981T3/da active
- 2017-11-22 ES ES17807900T patent/ES2890226T3/es active Active
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- 2017-11-22 CN CN201780084165.3A patent/CN110214141B/zh active Active
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