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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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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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 |
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| ES2432529T3 (es) | 2003-08-18 | 2013-12-04 | Parion Sciences, Inc. | Bloqueadores del canal de sodio de pirazinoilguanidina rematada |
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| EP1678145A2 (en) * | 2003-10-28 | 2006-07-12 | Vertex Pharmaceuticals Incorporated | Benzimidazoles useful as modulators of ion channels |
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| JP2011522860A (ja) | 2008-06-10 | 2011-08-04 | ノバルティス アーゲー | 上皮性ナトリウムチャネルブロッカーとしてのピラジン誘導体 |
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2016
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2017
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- 2017-11-22 CA CA3043132A patent/CA3043132A1/en active Pending
- 2017-11-22 WO PCT/GB2017/053499 patent/WO2018096325A1/en not_active Ceased
- 2017-11-22 PT PT178079000T patent/PT3544981T/pt unknown
- 2017-11-22 MA MA046878A patent/MA46878A/fr unknown
- 2017-11-22 HU HUE17807900A patent/HUE055692T2/hu unknown
- 2017-11-22 TW TW106140573A patent/TWI756305B/zh active
- 2017-11-22 MX MX2019005934A patent/MX389496B/es unknown
- 2017-11-22 JP JP2019527365A patent/JP6980014B2/ja active Active
- 2017-11-22 AU AU2017364308A patent/AU2017364308B2/en active Active
- 2017-11-22 EA EA201991253A patent/EA039607B1/ru unknown
- 2017-11-22 CN CN201780084165.3A patent/CN110214141B/zh active Active
- 2017-11-22 ES ES17807900T patent/ES2890226T3/es active Active
- 2017-11-22 PL PL17807900T patent/PL3544981T3/pl unknown
- 2017-11-22 DK DK17807900.0T patent/DK3544981T3/da active
- 2017-11-22 KR KR1020197016141A patent/KR102517273B1/ko active Active
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2023
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