JP7333793B2 - 化合物 - Google Patents
化合物 Download PDFInfo
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- JP7333793B2 JP7333793B2 JP2020564577A JP2020564577A JP7333793B2 JP 7333793 B2 JP7333793 B2 JP 7333793B2 JP 2020564577 A JP2020564577 A JP 2020564577A JP 2020564577 A JP2020564577 A JP 2020564577A JP 7333793 B2 JP7333793 B2 JP 7333793B2
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- 150000001875 compounds Chemical class 0.000 title claims description 397
- 238000006243 chemical reaction Methods 0.000 claims description 163
- -1 isotopes thereof Chemical class 0.000 claims description 112
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 51
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 31
- 125000002947 alkylene group Chemical group 0.000 claims description 30
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 23
- 150000001450 anions Chemical class 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 20
- 208000023504 respiratory system disease Diseases 0.000 claims description 20
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 239000013543 active substance Substances 0.000 claims description 17
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 17
- 230000007062 hydrolysis Effects 0.000 claims description 17
- 238000006460 hydrolysis reaction Methods 0.000 claims description 17
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 16
- 125000001475 halogen functional group Chemical group 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 13
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 10
- 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 10
- 125000004450 alkenylene group Chemical group 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical group CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 229960002657 orciprenaline Drugs 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229960002052 salbutamol Drugs 0.000 claims description 10
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 9
- 125000004419 alkynylene group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 229940044551 receptor antagonist Drugs 0.000 claims description 9
- 239000002464 receptor antagonist Substances 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 8
- 102000003787 Anoctamin-1 Human genes 0.000 claims description 7
- 108090000160 Anoctamin-1 Proteins 0.000 claims description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 7
- 239000000048 adrenergic agonist Substances 0.000 claims description 7
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 7
- 239000000739 antihistaminic agent Substances 0.000 claims description 7
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 claims description 7
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 claims description 7
- 239000003246 corticosteroid Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000003623 enhancer Substances 0.000 claims description 7
- 235000019256 formaldehyde Nutrition 0.000 claims description 7
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 7
- 238000006268 reductive amination reaction Methods 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 229940125715 antihistaminic agent Drugs 0.000 claims description 6
- 201000009267 bronchiectasis Diseases 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 229960001334 corticosteroids Drugs 0.000 claims description 6
- 229960000533 dornase alfa Drugs 0.000 claims description 6
- 108010067396 dornase alfa Proteins 0.000 claims description 6
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 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 5
- 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 5
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 claims description 5
- 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 5
- 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 5
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical group 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 5
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 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 5
- 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 5
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 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 5
- 229960004574 azelastine Drugs 0.000 claims description 5
- 229950000210 beclometasone dipropionate Drugs 0.000 claims description 5
- 229960000585 bitolterol mesylate Drugs 0.000 claims description 5
- 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 5
- 229960004436 budesonide Drugs 0.000 claims description 5
- 229960001803 cetirizine Drugs 0.000 claims description 5
- 229960003291 chlorphenamine Drugs 0.000 claims description 5
- 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 5
- 229960001271 desloratadine Drugs 0.000 claims description 5
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- 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 5
- 229960003592 fexofenadine Drugs 0.000 claims description 5
- 229960000676 flunisolide Drugs 0.000 claims description 5
- 229960001469 fluticasone furoate Drugs 0.000 claims description 5
- 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 5
- 229960000289 fluticasone propionate Drugs 0.000 claims description 5
- 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 5
- 229960002848 formoterol Drugs 0.000 claims description 5
- 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 5
- 229960004078 indacaterol Drugs 0.000 claims description 5
- 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 5
- 229960001317 isoprenaline Drugs 0.000 claims description 5
- 229940039009 isoproterenol Drugs 0.000 claims description 5
- 229960001508 levocetirizine Drugs 0.000 claims description 5
- 229960003088 loratadine Drugs 0.000 claims description 5
- 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 5
- 229960002744 mometasone furoate Drugs 0.000 claims description 5
- 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 5
- 229960005127 montelukast Drugs 0.000 claims description 5
- 229960005414 pirbuterol Drugs 0.000 claims description 5
- 229960005205 prednisolone Drugs 0.000 claims description 5
- 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 5
- 229960004618 prednisone Drugs 0.000 claims description 5
- 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 5
- 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 5
- 229960004017 salmeterol Drugs 0.000 claims description 5
- 229960000195 terbutaline Drugs 0.000 claims description 5
- 229960002117 triamcinolone acetonide Drugs 0.000 claims description 5
- 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 5
- 229960004764 zafirlukast Drugs 0.000 claims description 5
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 4
- 206010006451 bronchitis Diseases 0.000 claims description 4
- 125000002091 cationic group Chemical group 0.000 claims description 4
- 208000007451 chronic bronchitis Diseases 0.000 claims description 4
- 229960001340 histamine Drugs 0.000 claims description 4
- 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 3
- PATZPRFLFADDLW-UHFFFAOYSA-O 6-amino-N-[(1,3-diethyl-5-methoxybenzimidazol-1-ium-2-yl)methyl]-3-methyl-2H-pyrazolo[3,4-b]pyrazine-5-carboxamide Chemical compound NC1=C(N=C2C(=N1)NN=C2C)C(=O)NCC1=[N+](C2=C(N1CC)C=C(C=C2)OC)CC PATZPRFLFADDLW-UHFFFAOYSA-O 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- MNIUKQPQDJZNCP-UHFFFAOYSA-N CCN1C(C=C(C=C2)C([O-])=O)=C2[N+](CC)=C1CNC(C1=C(N)N=C2NN=C(C)C2=N1)=O Chemical compound CCN1C(C=C(C=C2)C([O-])=O)=C2[N+](CC)=C1CNC(C1=C(N)N=C2NN=C(C)C2=N1)=O MNIUKQPQDJZNCP-UHFFFAOYSA-N 0.000 claims description 3
- ZUBYYSFAQHMAPZ-UHFFFAOYSA-N CCN1C(C=C(C=C2)C([O-])=O)=C2[N+](CC)=C1CNC(C1=C(N)N=C2NN=CC2=N1)=O Chemical compound CCN1C(C=C(C=C2)C([O-])=O)=C2[N+](CC)=C1CNC(C1=C(N)N=C2NN=CC2=N1)=O ZUBYYSFAQHMAPZ-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary 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
- 206010014561 Emphysema Diseases 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000008937 atopic dermatitis Diseases 0.000 claims description 3
- 206010021198 ichthyosis Diseases 0.000 claims description 3
- UFSKUSARDNFIRC-UHFFFAOYSA-N lumacaftor Chemical group 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 3
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- 125000004765 (C1-C4) haloalkyl 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
- 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
- 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- 238000006467 substitution reaction Methods 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
- 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
- 230000003115 biocidal effect Effects 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 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 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- 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 1
- 230000001387 anti-histamine Effects 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 322
- 239000007787 solid Substances 0.000 description 275
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 251
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- CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
- CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
- VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 1
- UGWNXCGBAYNDHB-UHFFFAOYSA-N tert-butyl 4-(9H-fluoren-9-ylmethoxycarbonylamino)piperidine-1-carboxylate Chemical compound C1(CCN(CC1)C(=O)OC(C)(C)C)NC(=O)OCC1C2=C(C=CC=C2)C2=C1C=CC=C2 UGWNXCGBAYNDHB-UHFFFAOYSA-N 0.000 description 1
- KEMODIOXOLUTTF-UHFFFAOYSA-N tert-butyl 4-[1,3-diethyl-2-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]benzimidazol-1-ium-5-yl]piperidine-1-carboxylate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)N1CCC(CC1)C=1C=CC2=C(N(C(=[N+]2CC)CNC(=O)OCC2C3=CC=CC=C3C=3C=CC=CC2=3)CC)C=1 KEMODIOXOLUTTF-UHFFFAOYSA-N 0.000 description 1
- NZGPQMFPLPNIOD-UHFFFAOYSA-N tert-butyl 4-[2-[(1,3-dioxoisoindol-2-yl)methyl]-3-ethylbenzimidazol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound CCn1c(CN2C(=O)c3ccccc3C2=O)nc2ccc(cc12)C1=CCN(CC1)C(=O)OC(C)(C)C NZGPQMFPLPNIOD-UHFFFAOYSA-N 0.000 description 1
- QSQWENQPOSRWLP-UHFFFAOYSA-N tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(B2OC(C)(C)C(C)(C)O2)=C1 QSQWENQPOSRWLP-UHFFFAOYSA-N 0.000 description 1
- XROWMPUMSXLCSG-UHFFFAOYSA-M tert-butyl 4-[4-[2-[(1,3-dioxoisoindol-2-yl)methyl]-1,3-diethylbenzimidazol-1-ium-5-yl]pyrazol-1-yl]piperidine-1-carboxylate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)N1CCC(CC1)N1N=CC(=C1)C=1C=CC2=C(N(C(=[N+]2CC)CN2C(C3=CC=CC=C3C2=O)=O)CC)C=1 XROWMPUMSXLCSG-UHFFFAOYSA-M 0.000 description 1
- DLPCWGXCBSURFK-UHFFFAOYSA-N tert-butyl 4-[4-[2-[(1,3-dioxoisoindol-2-yl)methyl]-3-ethylbenzimidazol-5-yl]pyrazol-1-yl]piperidine-1-carboxylate Chemical compound O=C1N(C(C2=CC=CC=C12)=O)CC1=NC2=C(N1CC)C=C(C=C2)C=1C=NN(C=1)C1CCN(CC1)C(=O)OC(C)(C)C DLPCWGXCBSURFK-UHFFFAOYSA-N 0.000 description 1
- ZFQUOKRSEWPRIO-LBPRGKRZSA-N tert-butyl N-[(2S)-1-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxobutan-2-yl]-N-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC[C@H](N(CCCN)C(=O)OC(C)(C)C)C(N)=O ZFQUOKRSEWPRIO-LBPRGKRZSA-N 0.000 description 1
- DBOAIDSTXJLMOS-UHFFFAOYSA-N tert-butyl N-[(3-ethyl-5-fluoro-1-methylbenzimidazol-1-ium-2-yl)methyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCC1=[N+](C2=C(N1CC)C=C(C=C2)F)C DBOAIDSTXJLMOS-UHFFFAOYSA-N 0.000 description 1
- VHFBUPUSMYRMAC-UHFFFAOYSA-N tert-butyl N-[2-[1,3-diethyl-2-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]benzimidazol-1-ium-5-yl]oxyethyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCCOC=1C=CC2=C(N(C(=[N+]2CC)CNC(=O)OCC2C3=CC=CC=C3C=3C=CC=CC2=3)CC)C=1 VHFBUPUSMYRMAC-UHFFFAOYSA-N 0.000 description 1
- KRBUFAMNUUIVDT-UHFFFAOYSA-N tert-butyl N-[2-[2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]ethoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCOCCOCCNC(=O)OCC1c2ccccc2-c2ccccc12 KRBUFAMNUUIVDT-UHFFFAOYSA-N 0.000 description 1
- WQMVXZWIKVFFJQ-UHFFFAOYSA-N tert-butyl N-[2-[4-[4-(2-aminoethyl)phenyl]phenyl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCc1ccc(cc1)-c1ccc(CCN)cc1 WQMVXZWIKVFFJQ-UHFFFAOYSA-N 0.000 description 1
- YWPCTUISODBHNP-UHFFFAOYSA-N tert-butyl N-[2-[4-[4-(cyanomethyl)phenyl]phenyl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCc1ccc(cc1)-c1ccc(CC#N)cc1 YWPCTUISODBHNP-UHFFFAOYSA-N 0.000 description 1
- GBGMSVNDPGCWFZ-BBHRNUBPSA-N tert-butyl N-[2-[4-[bis[(2S,3R)-2,3-dihydroxy-3-[(4R,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl]propyl]amino]piperidin-1-yl]ethyl]carbamate Chemical compound O[C@@H](CN(C1CCN(CC1)CCNC(OC(C)(C)C)=O)C[C@@H]([C@@H](O)[C@@H]1OC(OC[C@H]1O)C1=CC=CC=C1)O)[C@H]([C@@H]1OC(OC[C@H]1O)C1=CC=CC=C1)O GBGMSVNDPGCWFZ-BBHRNUBPSA-N 0.000 description 1
- REKMSBNVDQANNP-UHFFFAOYSA-N tert-butyl N-[3-[1,3-diethyl-2-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]benzimidazol-1-ium-5-yl]oxypropyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCCCOC=1C=CC2=C(N(C(=[N+]2CC)CNC(=O)OCC2C3=CC=CC=C3C=3C=CC=CC2=3)CC)C=1 REKMSBNVDQANNP-UHFFFAOYSA-N 0.000 description 1
- RKTCMTICQHGORC-UHFFFAOYSA-N tert-butyl N-[3-[2-[(1,3-dioxoisoindol-2-yl)methyl]-1,3-diethylbenzimidazol-1-ium-5-yl]propyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCCCC=1C=CC2=C(N(C(=[N+]2CC)CN2C(C3=CC=CC=C3C2=O)=O)CC)C=1 RKTCMTICQHGORC-UHFFFAOYSA-N 0.000 description 1
- DBNUGBNDOLDISE-UHFFFAOYSA-N tert-butyl N-[3-[3-(ethylamino)-4-nitrophenoxy]propyl]carbamate Chemical compound C(C)NC=1C=C(OCCCNC(OC(C)(C)C)=O)C=CC=1[N+](=O)[O-] DBNUGBNDOLDISE-UHFFFAOYSA-N 0.000 description 1
- ZYQDUZXGRVKQIH-XBXGWEOASA-N tert-butyl N-[3-[bis[(2S,3R)-2,3-dihydroxy-3-[(4R,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl]propyl]amino]propyl]-N-methylcarbamate Chemical compound O[C@@H](CN(CCCN(C(OC(C)(C)C)=O)C)C[C@@H]([C@@H](O)[C@@H]1OC(OC[C@H]1O)C1=CC=CC=C1)O)[C@H]([C@@H]1OC(OC[C@H]1O)C1=CC=CC=C1)O ZYQDUZXGRVKQIH-XBXGWEOASA-N 0.000 description 1
- MSHOAQSFIWPSPV-UHFFFAOYSA-N tert-butyl N-[[1-(2-amino-2-oxoethyl)-3-ethyl-5-methoxybenzimidazol-1-ium-2-yl]methyl]carbamate bromide Chemical compound [Br-].C(C)(C)(C)OC(=O)NCC1=[N+](C2=C(N1CC)C=C(C=C2)OC)CC(N)=O MSHOAQSFIWPSPV-UHFFFAOYSA-N 0.000 description 1
- HPNDBOMABMIFJH-UHFFFAOYSA-N tert-butyl N-[[1-benzyl-3-ethyl-5-(trifluoromethyl)benzimidazol-1-ium-2-yl]methyl]carbamate bromide Chemical compound [Br-].C(C1=CC=CC=C1)[N+]1=C(N(C2=C1C=CC(=C2)C(F)(F)F)CC)CNC(=O)OC(C)(C)C HPNDBOMABMIFJH-UHFFFAOYSA-N 0.000 description 1
- BQPZWGLCJFYKEP-UHFFFAOYSA-N tert-butyl N-[[3-ethyl-1-methyl-5-(trifluoromethoxy)benzimidazol-1-ium-2-yl]methyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCC1=[N+](C2=C(N1CC)C=C(C=C2)OC(F)(F)F)C BQPZWGLCJFYKEP-UHFFFAOYSA-N 0.000 description 1
- FFADXYFYSIYRHP-UHFFFAOYSA-N tert-butyl N-[[3-ethyl-1-methyl-5-(trifluoromethyl)benzimidazol-1-ium-2-yl]methyl]carbamate iodide Chemical compound [I-].C(C)(C)(C)OC(=O)NCC1=[N+](C2=C(N1CC)C=C(C=C2)C(F)(F)F)C FFADXYFYSIYRHP-UHFFFAOYSA-N 0.000 description 1
- WRAOGDJKTDDORV-UHFFFAOYSA-N tert-butyl n-(1h-benzimidazol-2-ylmethyl)carbamate Chemical compound C1=CC=C2NC(CNC(=O)OC(C)(C)C)=NC2=C1 WRAOGDJKTDDORV-UHFFFAOYSA-N 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- PNQYAMWGTGWJDW-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)-n-methylcarbamate Chemical compound NCCCN(C)C(=O)OC(C)(C)C PNQYAMWGTGWJDW-UHFFFAOYSA-N 0.000 description 1
- POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 1
- VHYXAWLOJGIJPC-UHFFFAOYSA-N tert-butyl n-(piperidin-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNCC1 VHYXAWLOJGIJPC-UHFFFAOYSA-N 0.000 description 1
- KNGLRBULSKPMHY-UHFFFAOYSA-N tert-butyl n-[(1-benzylbenzimidazol-2-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=NC2=CC=CC=C2N1CC1=CC=CC=C1 KNGLRBULSKPMHY-UHFFFAOYSA-N 0.000 description 1
- YBOWCGQWAVIWQT-LURJTMIESA-N tert-butyl n-[(3s)-3,4-diamino-4-oxobutyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC[C@H](N)C(N)=O YBOWCGQWAVIWQT-LURJTMIESA-N 0.000 description 1
- NXAKRVADEMLOPT-UHFFFAOYSA-N tert-butyl n-[2-(4-aminopiperidin-1-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCN1CCC(N)CC1 NXAKRVADEMLOPT-UHFFFAOYSA-N 0.000 description 1
- MRQBIMZMDWOQLF-UHFFFAOYSA-N tert-butyl n-[2-(4-bromophenyl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1=CC=C(Br)C=C1 MRQBIMZMDWOQLF-UHFFFAOYSA-N 0.000 description 1
- CUPBLDPRUBNAIE-UHFFFAOYSA-N tert-butyl n-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCOCCOCCN CUPBLDPRUBNAIE-UHFFFAOYSA-N 0.000 description 1
- UBRZVFBAPAUSBV-UHFFFAOYSA-N tert-butyl n-[3-(9h-fluoren-9-ylmethoxycarbonylamino)propyl]carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCNC(=O)OC(C)(C)C)C3=CC=CC=C3C2=C1 UBRZVFBAPAUSBV-UHFFFAOYSA-N 0.000 description 1
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 239000008181 tonicity modifier Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/02—Formic acid
- C07C53/06—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
- C07C53/16—Halogenated acetic acids
- C07C53/18—Halogenated acetic acids containing fluorine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1808093.7A GB201808093D0 (en) | 2018-05-18 | 2018-05-18 | Compounds |
| GB1808093.7 | 2018-05-18 | ||
| PCT/GB2019/051383 WO2019220147A1 (en) | 2018-05-18 | 2019-05-17 | Compounds |
Publications (4)
| Publication Number | Publication Date |
|---|---|
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| PH12021553110A1 (en) | 2019-06-12 | 2022-08-01 | Tmem16A Ltd | Compounds for treating respiratory disease |
| EP4259607A1 (en) | 2020-12-11 | 2023-10-18 | Tmem16A Limited | Benzimidazole derivatives for treating respiratory disease |
| US12414916B2 (en) | 2021-06-10 | 2025-09-16 | Belhaven BioPharma Inc. | Dry powder formulations of epinephrine and associated methods |
| US11932648B2 (en) | 2021-06-28 | 2024-03-19 | Blueprint Medicines Corporation | CDK2 inhibitors |
| CN117946013B (zh) * | 2024-01-25 | 2024-07-02 | 白银康寓信生物科技有限公司 | 一锅法合成5,6-二卤代-3-氨基吡嗪-2-甲酸甲酯的方法 |
| US20260108686A1 (en) | 2024-10-21 | 2026-04-23 | Belhaven BioPharma Inc. | Compositions, devices, and methods for intranasal delivery of dry powder epinephrine |
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| US20210188855A1 (en) | 2021-06-24 |
| EP3794002A1 (en) | 2021-03-24 |
| JP2021524453A (ja) | 2021-09-13 |
| EP3794002B1 (en) | 2023-08-02 |
| GB201808093D0 (en) | 2018-07-04 |
| WO2019220147A1 (en) | 2019-11-21 |
| US12037336B2 (en) | 2024-07-16 |
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