JP2006526613A - β２−アドレナリン受容体アゴニストとしての２−（６−アミノ−ピリジン−３−イル）−２−ヒドロキシエチルアミン誘導体 - Google Patents
β２−アドレナリン受容体アゴニストとしての２−（６−アミノ−ピリジン−３−イル）−２−ヒドロキシエチルアミン誘導体 Download PDFInfo
- Publication number
- JP2006526613A JP2006526613A JP2006508431A JP2006508431A JP2006526613A JP 2006526613 A JP2006526613 A JP 2006526613A JP 2006508431 A JP2006508431 A JP 2006508431A JP 2006508431 A JP2006508431 A JP 2006508431A JP 2006526613 A JP2006526613 A JP 2006526613A
- Authority
- JP
- Japan
- Prior art keywords
- propyl
- amino
- hydroxy
- phenyl
- aminopyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 title claims description 15
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 title claims description 15
- CVRVRWYCBRWOLQ-UHFFFAOYSA-N 2-amino-1-(6-aminopyridin-3-yl)ethanol Chemical class NCC(O)C1=CC=C(N)N=C1 CVRVRWYCBRWOLQ-UHFFFAOYSA-N 0.000 title 1
- 239000000048 adrenergic agonist Substances 0.000 title 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 302
- 238000000034 method Methods 0.000 claims abstract description 119
- 239000000203 mixture Substances 0.000 claims abstract description 93
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 208000035475 disorder Diseases 0.000 claims abstract description 9
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 8
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 5
- -1 3- {2-[(2R) -2- (6-amino-pyridin-3-yl) -2-hydroxy-ethylamino] -propyl} -phenyl Chemical group 0.000 claims description 222
- 238000004519 manufacturing process Methods 0.000 claims description 98
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 79
- 150000001412 amines Chemical class 0.000 claims description 68
- 239000002253 acid Substances 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 41
- 208000006673 asthma Diseases 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 206010006451 bronchitis Diseases 0.000 claims description 29
- 229940124748 beta 2 agonist Drugs 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 229940079593 drug Drugs 0.000 claims description 18
- 201000009267 bronchiectasis Diseases 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 239000005557 antagonist Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 150000003930 2-aminopyridines Chemical class 0.000 claims description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 201000010659 intrinsic asthma Diseases 0.000 claims description 6
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 6
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 6
- 206010006482 Bronchospasm Diseases 0.000 claims description 5
- 206010014561 Emphysema Diseases 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 5
- 230000007885 bronchoconstriction Effects 0.000 claims description 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000000884 Airway Obstruction Diseases 0.000 claims description 4
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 claims description 4
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 claims description 4
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 239000000812 cholinergic antagonist Substances 0.000 claims description 4
- 208000007451 chronic bronchitis Diseases 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 208000024711 extrinsic asthma Diseases 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 230000002458 infectious effect Effects 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- HLUFJKVIOGXFLE-CJAUYULYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(2,3-dihydro-1h-inden-2-yl)acetamide Chemical compound C1([C@@H](O)CN[C@@H](CC=2C=C(CC(=O)NC3CC4=CC=CC=C4C3)C=CC=2)C)=CC=C(N)N=C1 HLUFJKVIOGXFLE-CJAUYULYSA-N 0.000 claims description 3
- MMZJKMJQAVXSPB-DVECYGJZSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(2-phenylethyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC=C1 MMZJKMJQAVXSPB-DVECYGJZSA-N 0.000 claims description 3
- XESNJJXNSNRFDW-NLFFAJNJSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(3-phenylpropyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCCCC1=CC=CC=C1 XESNJJXNSNRFDW-NLFFAJNJSA-N 0.000 claims description 3
- XGAOFZOAEPBTRU-DVECYGJZSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(2-ethoxyphenyl)methyl]acetamide Chemical compound CCOC1=CC=CC=C1CNC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 XGAOFZOAEPBTRU-DVECYGJZSA-N 0.000 claims description 3
- OEBAFKHZOOOJFF-JPYJTQIMSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(2-methoxyphenyl)methyl]acetamide Chemical compound COC1=CC=CC=C1CNC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 OEBAFKHZOOOJFF-JPYJTQIMSA-N 0.000 claims description 3
- AEFMLSXFSRUOAN-MWTRTKDXSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(3,4-dichlorophenyl)methyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCC1=CC=C(Cl)C(Cl)=C1 AEFMLSXFSRUOAN-MWTRTKDXSA-N 0.000 claims description 3
- SBGFKFIFWKTORP-NLFFAJNJSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(3,4-dimethylphenyl)methyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCC1=CC=C(C)C(C)=C1 SBGFKFIFWKTORP-NLFFAJNJSA-N 0.000 claims description 3
- FTFZJGUKLJRXDO-JPYJTQIMSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-benzylacetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCC1=CC=CC=C1 FTFZJGUKLJRXDO-JPYJTQIMSA-N 0.000 claims description 3
- LQBJKTDDUSJZEW-VWLOTQADSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(2,3-dihydro-1h-inden-2-yl)acetamide Chemical compound C1([C@@H](O)CNC(C)(CC=2C=C(CC(=O)NC3CC4=CC=CC=C4C3)C=CC=2)C)=CC=C(N)N=C1 LQBJKTDDUSJZEW-VWLOTQADSA-N 0.000 claims description 3
- FRSKICZSOVEZJD-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(2-phenylethyl)acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC=C1 FRSKICZSOVEZJD-DEOSSOPVSA-N 0.000 claims description 3
- KANMKKLTVIMZTE-VWLOTQADSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(3-phenylpropyl)acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCCCC1=CC=CC=C1 KANMKKLTVIMZTE-VWLOTQADSA-N 0.000 claims description 3
- JWMKEGVOSSRVSG-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(2-ethoxyphenyl)methyl]acetamide Chemical compound CCOC1=CC=CC=C1CNC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 JWMKEGVOSSRVSG-DEOSSOPVSA-N 0.000 claims description 3
- ZCMOQGZWQJCPTB-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3,4-dichlorophenyl)methyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC=C(Cl)C(Cl)=C1 ZCMOQGZWQJCPTB-QHCPKHFHSA-N 0.000 claims description 3
- KLJXQQGRQKJFCX-VWLOTQADSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3,4-dimethylphenyl)methyl]acetamide Chemical compound C1=C(C)C(C)=CC=C1CNC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 KLJXQQGRQKJFCX-VWLOTQADSA-N 0.000 claims description 3
- XKWFZRDOLVRRPS-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3,5-dichlorophenyl)methyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC(Cl)=CC(Cl)=C1 XKWFZRDOLVRRPS-QHCPKHFHSA-N 0.000 claims description 3
- RRLWLBPLXJRHKE-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(4-sulfamoylphenyl)methyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 RRLWLBPLXJRHKE-QHCPKHFHSA-N 0.000 claims description 3
- BOZURQMZWFCEBE-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-benzylacetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC=CC=C1 BOZURQMZWFCEBE-QHCPKHFHSA-N 0.000 claims description 3
- UJVLSKFICSPQNU-VXLWULRPSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(4-hydroxy-3-methoxyphenyl)methyl]acetamide Chemical compound C1=C(O)C(OC)=CC(CNC(=O)CC=2C=C(CC(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 UJVLSKFICSPQNU-VXLWULRPSA-N 0.000 claims description 3
- VLQAVCAPEAIPRO-QHCPKHFHSA-N 2-[4-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(2,6-dimethoxyphenyl)methyl]acetamide Chemical compound COC1=CC=CC(OC)=C1CNC(=O)CC(C=C1)=CC=C1CC(C)(C)NC[C@H](O)C1=CC=C(N)N=C1 VLQAVCAPEAIPRO-QHCPKHFHSA-N 0.000 claims description 3
- PJBCMWNFRRXAKY-DEOSSOPVSA-N 2-[4-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3-methoxyphenyl)methyl]acetamide Chemical compound COC1=CC=CC(CNC(=O)CC=2C=CC(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)=CC=2)=C1 PJBCMWNFRRXAKY-DEOSSOPVSA-N 0.000 claims description 3
- 229940122086 Adenosine A2a receptor agonist Drugs 0.000 claims description 3
- 206010011224 Cough Diseases 0.000 claims description 3
- 229940122694 Muscarinic M3 receptor antagonist Drugs 0.000 claims description 3
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 3
- 239000002465 adenosine A2a receptor agonist Substances 0.000 claims description 3
- 239000013566 allergen Substances 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 239000003681 muscarinic M3 receptor antagonist Substances 0.000 claims description 3
- 230000008506 pathogenesis Effects 0.000 claims description 3
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 3
- 229960000278 theophylline Drugs 0.000 claims description 3
- YSKQGPMDXPBBJY-HXOBKFHXSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(2-hydroxy-5-methylphenyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NC1=CC(C)=CC=C1O YSKQGPMDXPBBJY-HXOBKFHXSA-N 0.000 claims description 2
- NURBGMGWUKIAHK-MWTRTKDXSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(3-hydroxy-2-methylphenyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NC1=CC=CC(O)=C1C NURBGMGWUKIAHK-MWTRTKDXSA-N 0.000 claims description 2
- UUIIWUKNVUTSNE-ZHRRBRCNSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(3-hydroxy-4-methoxyphenyl)acetamide Chemical compound C1=C(O)C(OC)=CC=C1NC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 UUIIWUKNVUTSNE-ZHRRBRCNSA-N 0.000 claims description 2
- CTDHMZSZPKBCHL-HXOBKFHXSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(3-hydroxy-4-methylphenyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NC1=CC=C(C)C(O)=C1 CTDHMZSZPKBCHL-HXOBKFHXSA-N 0.000 claims description 2
- IGKRIIXFWGRSBG-ZHRRBRCNSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(4-hydroxyphenyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NC1=CC=C(O)C=C1 IGKRIIXFWGRSBG-ZHRRBRCNSA-N 0.000 claims description 2
- DEBJXINLCPCOPT-ZNSGIYGDSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-(5-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide Chemical compound C1([C@@H](O)CN[C@@H](CC=2C=C(CC(=O)NC3C4=CC=CC(O)=C4CCC3)C=CC=2)C)=CC=C(N)N=C1 DEBJXINLCPCOPT-ZNSGIYGDSA-N 0.000 claims description 2
- PDJGWJMYBHXWOF-CJAUYULYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(2-chloro-4-hydroxyphenyl)methyl]-n-ethylacetamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CC1=CC=C(O)C=C1Cl PDJGWJMYBHXWOF-CJAUYULYSA-N 0.000 claims description 2
- NNYXUZGPRTZSFE-CJAUYULYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(2-chloro-5-hydroxyphenyl)methyl]-n-ethylacetamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CC1=CC(O)=CC=C1Cl NNYXUZGPRTZSFE-CJAUYULYSA-N 0.000 claims description 2
- BOBQZGKXKNTVCI-CLOONOSVSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-(3-ethoxy-4-hydroxyphenyl)ethyl]acetamide Chemical compound C1=C(O)C(OCC)=CC(CCNC(=O)CC=2C=C(C[C@@H](C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 BOBQZGKXKNTVCI-CLOONOSVSA-N 0.000 claims description 2
- YSWKWILLLWJXAR-KOSHJBKYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-(3-hydroxy-4-methoxyphenyl)ethyl]acetamide Chemical compound C1=C(O)C(OC)=CC=C1CCNC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 YSWKWILLLWJXAR-KOSHJBKYSA-N 0.000 claims description 2
- ICCCLQJQCUTXGH-KOSHJBKYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-(3-hydroxyphenyl)ethyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC(O)=C1 ICCCLQJQCUTXGH-KOSHJBKYSA-N 0.000 claims description 2
- NDFUIKXWIDLZFV-KOSHJBKYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-(4-hydroxyphenyl)ethyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCCC1=CC=C(O)C=C1 NDFUIKXWIDLZFV-KOSHJBKYSA-N 0.000 claims description 2
- MQIBAVICCOQAET-GBTGNHPCSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-hydroxy-2-(3-hydroxyphenyl)ethyl]-n-methylacetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)N(C)CC(O)C1=CC=CC(O)=C1 MQIBAVICCOQAET-GBTGNHPCSA-N 0.000 claims description 2
- JLGQTJOFCNKMEQ-IBVKSMDESA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[4-(4-hydroxyphenyl)butyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)NCCCCC1=CC=C(O)C=C1 JLGQTJOFCNKMEQ-IBVKSMDESA-N 0.000 claims description 2
- ZDIXLQJXKQNWEO-IBVKSMDESA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-ethyl-n-[2-(4-hydroxyphenyl)ethyl]acetamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CCC1=CC=C(O)C=C1 ZDIXLQJXKQNWEO-IBVKSMDESA-N 0.000 claims description 2
- YSMQNXNKVKMIEO-QFIPXVFZSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(2-chloro-4-hydroxyphenyl)acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NC1=CC=C(O)C=C1Cl YSMQNXNKVKMIEO-QFIPXVFZSA-N 0.000 claims description 2
- UGOVZVKGYPLUHL-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(2-hydroxy-5-methylphenyl)acetamide Chemical compound CC1=CC=C(O)C(NC(=O)CC=2C=C(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 UGOVZVKGYPLUHL-QHCPKHFHSA-N 0.000 claims description 2
- HBVGZGDXVFDMMT-QFIPXVFZSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(3-hydroxy-4-methoxyphenyl)acetamide Chemical compound C1=C(O)C(OC)=CC=C1NC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 HBVGZGDXVFDMMT-QFIPXVFZSA-N 0.000 claims description 2
- GDMGRJIFDPWGIY-QHCPKHFHSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(3-hydroxy-4-methylphenyl)acetamide Chemical compound C1=C(O)C(C)=CC=C1NC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 GDMGRJIFDPWGIY-QHCPKHFHSA-N 0.000 claims description 2
- CLWHSZIEGPPJNF-QFIPXVFZSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(3-hydroxyphenyl)acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NC1=CC=CC(O)=C1 CLWHSZIEGPPJNF-QFIPXVFZSA-N 0.000 claims description 2
- IBUUBNWFBXNQKJ-VWLOTQADSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(2-chloro-5-hydroxyphenyl)methyl]-n-ethylacetamide Chemical compound C=1C=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CC1=CC(O)=CC=C1Cl IBUUBNWFBXNQKJ-VWLOTQADSA-N 0.000 claims description 2
- MXQFFUMAHVUEDV-VWLOTQADSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3-chloro-5-hydroxyphenyl)methyl]-n-ethylacetamide Chemical compound C=1C=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CC1=CC(O)=CC(Cl)=C1 MXQFFUMAHVUEDV-VWLOTQADSA-N 0.000 claims description 2
- KYMUUNDNWSTEFU-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[2-(2-hydroxyphenyl)ethyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC=C1O KYMUUNDNWSTEFU-DEOSSOPVSA-N 0.000 claims description 2
- BPDKQVGOGABPQR-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[2-(3-hydroxyphenyl)ethyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC(O)=C1 BPDKQVGOGABPQR-DEOSSOPVSA-N 0.000 claims description 2
- PEKSPLVVZVXYLE-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acetamide Chemical compound C1=C(O)C(OC)=CC(CCNC(=O)CC=2C=C(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 PEKSPLVVZVXYLE-DEOSSOPVSA-N 0.000 claims description 2
- WBCALGARQBBOKQ-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[2-(4-hydroxyphenyl)ethyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)NCCC1=CC=C(O)C=C1 WBCALGARQBBOKQ-DEOSSOPVSA-N 0.000 claims description 2
- GRSHAUZEQUXADF-LJAQVGFWSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-benzyl-n-(4-hydroxyphenyl)acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1CC(=O)N(C=1C=CC(O)=CC=1)CC1=CC=CC=C1 GRSHAUZEQUXADF-LJAQVGFWSA-N 0.000 claims description 2
- RJEOZSVBWMVGDN-DEOSSOPVSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-ethyl-n-(3-hydroxyphenyl)acetamide Chemical compound C1([C@@H](O)CNC(C)(C)CC=2C=CC=C(C=2)CC(=O)N(CC)C=2C=C(O)C=CC=2)=CC=C(N)N=C1 RJEOZSVBWMVGDN-DEOSSOPVSA-N 0.000 claims description 2
- XIUIDNNUSWLERE-IMMUGOHXSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(3,4,5-trimethoxyphenyl)methyl]acetamide Chemical compound COC1=C(OC)C(OC)=CC(CNC(=O)CC=2C=C(CC(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 XIUIDNNUSWLERE-IMMUGOHXSA-N 0.000 claims description 2
- PYIRKRDWPLLOFQ-VXLWULRPSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[[3-(trifluoromethoxy)phenyl]methyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC=CC(OC(F)(F)F)=C1 PYIRKRDWPLLOFQ-VXLWULRPSA-N 0.000 claims description 2
- 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- UVFVAKJMQXHLIL-ZHRRBRCNSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(2-hydroxy-5-methylphenyl)benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NC1=CC(C)=CC=C1O UVFVAKJMQXHLIL-ZHRRBRCNSA-N 0.000 claims description 2
- QTINNCGAARTPJK-QRQCRPRQSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(3-hydroxy-2-methylphenyl)benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NC1=CC=CC(O)=C1C QTINNCGAARTPJK-QRQCRPRQSA-N 0.000 claims description 2
- BXTQSBJWMMSWBU-VFNWGFHPSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(3-hydroxy-4-methoxyphenyl)benzamide Chemical compound C1=C(O)C(OC)=CC=C1NC(=O)C1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 BXTQSBJWMMSWBU-VFNWGFHPSA-N 0.000 claims description 2
- APPVRYWZAFXGQX-VFNWGFHPSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(3-hydroxyphenyl)benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NC1=CC=CC(O)=C1 APPVRYWZAFXGQX-VFNWGFHPSA-N 0.000 claims description 2
- CPBMOWXLMAIYRD-VFNWGFHPSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(4-hydroxyphenyl)benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NC1=CC=C(O)C=C1 CPBMOWXLMAIYRD-VFNWGFHPSA-N 0.000 claims description 2
- UUEQNTWXVVSGRW-QFSZVTIDSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-(5-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide Chemical compound C1([C@@H](O)CN[C@@H](CC=2C=C(C=CC=2)C(=O)NC2C3=CC=CC(O)=C3CCC2)C)=CC=C(N)N=C1 UUEQNTWXVVSGRW-QFSZVTIDSA-N 0.000 claims description 2
- FBSQYSNPBGQPDZ-HXOBKFHXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[(2-hydroxyphenyl)methyl]-n-methylbenzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)N(C)CC1=CC=CC=C1O FBSQYSNPBGQPDZ-HXOBKFHXSA-N 0.000 claims description 2
- GEIDDDLGOYNGHJ-HXOBKFHXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-(2-hydroxyphenyl)ethyl]benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NCCC1=CC=CC=C1O GEIDDDLGOYNGHJ-HXOBKFHXSA-N 0.000 claims description 2
- RXUAFTFQOLCYMJ-KOSHJBKYSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-(3-ethoxy-4-hydroxyphenyl)ethyl]benzamide Chemical compound C1=C(O)C(OCC)=CC(CCNC(=O)C=2C=C(C[C@@H](C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 RXUAFTFQOLCYMJ-KOSHJBKYSA-N 0.000 claims description 2
- FXOIAKRUYZIEHK-HXOBKFHXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-(3-hydroxy-4-methoxyphenyl)ethyl]benzamide Chemical compound C1=C(O)C(OC)=CC=C1CCNC(=O)C1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 FXOIAKRUYZIEHK-HXOBKFHXSA-N 0.000 claims description 2
- JBTSTUYGGAJQOD-HXOBKFHXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NCCC1=CC=C(O)C=C1 JBTSTUYGGAJQOD-HXOBKFHXSA-N 0.000 claims description 2
- MUZSNANGMLHJMO-GYUIMPAFSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-hydroxy-2-(3-hydroxyphenyl)ethyl]-n-methylbenzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)N(C)CC(O)C1=CC=CC(O)=C1 MUZSNANGMLHJMO-GYUIMPAFSA-N 0.000 claims description 2
- ZNIROZAZMOKJEV-MWTRTKDXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[[3-hydroxy-5-(trifluoromethyl)phenyl]methyl]-n-methylbenzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)N(C)CC1=CC(O)=CC(C(F)(F)F)=C1 ZNIROZAZMOKJEV-MWTRTKDXSA-N 0.000 claims description 2
- NLKDZJIWBSKQGE-CLOONOSVSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-ethyl-n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1C(=O)N(CC)CCC1=CC=C(O)C=C1 NLKDZJIWBSKQGE-CLOONOSVSA-N 0.000 claims description 2
- YOVAQOWIQHPGMV-QFIPXVFZSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-(3-hydroxy-2-methylphenyl)benzamide Chemical compound CC1=C(O)C=CC=C1NC(=O)C1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 YOVAQOWIQHPGMV-QFIPXVFZSA-N 0.000 claims description 2
- PYAZXKBJXIIIGU-NRFANRHFSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-(3-hydroxy-4-methoxyphenyl)benzamide Chemical compound C1=C(O)C(OC)=CC=C1NC(=O)C1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 PYAZXKBJXIIIGU-NRFANRHFSA-N 0.000 claims description 2
- IBZYJGDVZKUAIG-QFIPXVFZSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-(3-hydroxy-4-methylphenyl)benzamide Chemical compound C1=C(O)C(C)=CC=C1NC(=O)C1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 IBZYJGDVZKUAIG-QFIPXVFZSA-N 0.000 claims description 2
- XKGMBJQFLBSAMN-NRFANRHFSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-(3-hydroxyphenyl)benzamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1C(=O)NC1=CC=CC(O)=C1 XKGMBJQFLBSAMN-NRFANRHFSA-N 0.000 claims description 2
- SSWLFPMRFKJPMA-DEOSSOPVSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(3-ethoxy-4-hydroxyphenyl)ethyl]benzamide Chemical compound C1=C(O)C(OCC)=CC(CCNC(=O)C=2C=C(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 SSWLFPMRFKJPMA-DEOSSOPVSA-N 0.000 claims description 2
- KSBHWBHZCIMXGZ-QHCPKHFHSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(3-hydroxy-4-methoxyphenyl)ethyl]benzamide Chemical compound C1=C(O)C(OC)=CC=C1CCNC(=O)C1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 KSBHWBHZCIMXGZ-QHCPKHFHSA-N 0.000 claims description 2
- PFZWHJXQOCKLDN-QHCPKHFHSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(3-hydroxyphenyl)ethyl]benzamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1C(=O)NCCC1=CC=CC(O)=C1 PFZWHJXQOCKLDN-QHCPKHFHSA-N 0.000 claims description 2
- SJAWPIAGCDYKTR-QFIPXVFZSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(4-hydroxy-3,5-dimethoxyphenyl)ethyl]benzamide Chemical compound COC1=C(O)C(OC)=CC(CCNC(=O)C=2C=C(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 SJAWPIAGCDYKTR-QFIPXVFZSA-N 0.000 claims description 2
- HJMNGJSWXXAYTN-QHCPKHFHSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(4-hydroxy-3-methoxyphenyl)ethyl]benzamide Chemical compound C1=C(O)C(OC)=CC(CCNC(=O)C=2C=C(CC(C)(C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 HJMNGJSWXXAYTN-QHCPKHFHSA-N 0.000 claims description 2
- KZUREFTZDXQSIH-UXMRNZNESA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-hydroxy-2-(3-hydroxyphenyl)ethyl]-n-methylbenzamide Chemical compound C=1C=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1C(=O)N(C)CC(O)C1=CC=CC(O)=C1 KZUREFTZDXQSIH-UXMRNZNESA-N 0.000 claims description 2
- 102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 claims description 2
- 108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 claims description 2
- 206010003557 Asthma exercise induced Diseases 0.000 claims description 2
- 206010003645 Atopy Diseases 0.000 claims description 2
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 206010006448 Bronchiolitis Diseases 0.000 claims description 2
- 229940124638 COX inhibitor Drugs 0.000 claims description 2
- 206010011416 Croup infectious Diseases 0.000 claims description 2
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 2
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 claims description 2
- 102000015554 Dopamine receptor Human genes 0.000 claims description 2
- 108050004812 Dopamine receptor Proteins 0.000 claims description 2
- 208000000059 Dyspnea Diseases 0.000 claims description 2
- 206010013975 Dyspnoeas Diseases 0.000 claims description 2
- 229940122858 Elastase inhibitor Drugs 0.000 claims description 2
- 208000004657 Exercise-Induced Asthma Diseases 0.000 claims description 2
- 206010017533 Fungal infection Diseases 0.000 claims description 2
- 229940122236 Histamine receptor antagonist Drugs 0.000 claims description 2
- 206010020565 Hyperaemia Diseases 0.000 claims description 2
- 239000003458 I kappa b kinase inhibitor Substances 0.000 claims description 2
- 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 2
- 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 2
- 108010093008 Kinins Proteins 0.000 claims description 2
- 102000002397 Kinins Human genes 0.000 claims description 2
- 102000005741 Metalloproteases Human genes 0.000 claims description 2
- 108010006035 Metalloproteases Proteins 0.000 claims description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 claims description 2
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims description 2
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims description 2
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 claims description 2
- 208000010362 Protozoan Infections Diseases 0.000 claims description 2
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 claims description 2
- 102000003141 Tachykinin Human genes 0.000 claims description 2
- 206010054094 Tumour necrosis Diseases 0.000 claims description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- BEBVPOOJGRKIJO-VWLOTQADSA-N [3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-(8-hydroxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl)methanone Chemical compound C1([C@@H](O)CNC(C)(CC=2C=C(C=CC=2)C(=O)N2CC3=CC(O)=CC=C3CCC2)C)=CC=C(N)N=C1 BEBVPOOJGRKIJO-VWLOTQADSA-N 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 239000000533 adrenergic alpha-1 receptor agonist Substances 0.000 claims description 2
- 239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 claims description 2
- 230000010085 airway hyperresponsiveness Effects 0.000 claims description 2
- 201000009961 allergic asthma Diseases 0.000 claims description 2
- 230000000954 anitussive effect Effects 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000000259 anti-tumor effect Effects 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 239000000739 antihistaminic agent Substances 0.000 claims description 2
- 229940124584 antitussives Drugs 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims description 2
- 229940111134 coxibs Drugs 0.000 claims description 2
- 229960000265 cromoglicic acid Drugs 0.000 claims description 2
- 201000010549 croup Diseases 0.000 claims description 2
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 claims description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 claims description 2
- 239000003602 elastase inhibitor Substances 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 claims description 2
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 2
- 230000001861 immunosuppressant effect Effects 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 230000002427 irreversible effect Effects 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 238000002483 medication Methods 0.000 claims description 2
- CEBFCNJSOSKIGH-QHCPKHFHSA-N methyl 4-[[2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetyl]amino]-3-hydroxybenzoate Chemical compound OC1=CC(C(=O)OC)=CC=C1NC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(N)=CC=2)=C1 CEBFCNJSOSKIGH-QHCPKHFHSA-N 0.000 claims description 2
- 230000000510 mucolytic effect Effects 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 208000007892 occupational asthma Diseases 0.000 claims description 2
- 230000001991 pathophysiological effect Effects 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 claims description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 230000000750 progressive effect Effects 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 108060008037 tachykinin Proteins 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
- 229960005356 urokinase Drugs 0.000 claims description 2
- 239000005526 vasoconstrictor agent Substances 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- DVNRJVHCQZTSEB-VXLWULRPSA-N 2-[3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[[4-(trifluoromethoxy)phenyl]methyl]acetamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)CC(C=1)=CC=CC=1CC(=O)NCC1=CC=C(OC(F)(F)F)C=C1 DVNRJVHCQZTSEB-VXLWULRPSA-N 0.000 claims 1
- YPVODFPCTDEFJD-OSPHWJPCSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[(2-chloro-4-hydroxyphenyl)methyl]-n-ethylbenzamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1C(=O)N(CC)CC1=CC=C(O)C=C1Cl YPVODFPCTDEFJD-OSPHWJPCSA-N 0.000 claims 1
- ZMZRHPKCSOPLNR-OSPHWJPCSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[(2-chloro-5-hydroxyphenyl)methyl]-n-ethylbenzamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1C(=O)N(CC)CC1=CC(O)=CC=C1Cl ZMZRHPKCSOPLNR-OSPHWJPCSA-N 0.000 claims 1
- OXYMFVCGRSKNLM-OSPHWJPCSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[(3-chloro-5-hydroxyphenyl)methyl]-n-ethylbenzamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1C(=O)N(CC)CC1=CC(O)=CC(Cl)=C1 OXYMFVCGRSKNLM-OSPHWJPCSA-N 0.000 claims 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims 1
- 230000003325 follicular Effects 0.000 claims 1
- 230000001717 pathogenic effect Effects 0.000 claims 1
- 230000002889 sympathetic effect Effects 0.000 claims 1
- 125000006493 trifluoromethyl benzyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 180
- 239000000543 intermediate Substances 0.000 abstract description 9
- 230000000172 allergic effect Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 3
- 208000026935 allergic disease Diseases 0.000 abstract description 2
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- 239000000243 solution Substances 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 239000002904 solvent Substances 0.000 description 53
- 239000007787 solid Substances 0.000 description 50
- 239000011734 sodium Substances 0.000 description 47
- 239000003921 oil Substances 0.000 description 43
- 235000019198 oils Nutrition 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
- 238000009472 formulation Methods 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 34
- 239000006260 foam Substances 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 150000002148 esters Chemical class 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 229910021529 ammonia Inorganic materials 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 150000001408 amides Chemical class 0.000 description 16
- 239000003826 tablet Substances 0.000 description 16
- 239000002552 dosage form Substances 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 229960001317 isoprenaline Drugs 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 11
- 239000012299 nitrogen atmosphere Substances 0.000 description 11
- 150000002924 oxiranes Chemical class 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000013270 controlled release Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000010561 standard procedure Methods 0.000 description 7
- 238000013268 sustained release Methods 0.000 description 7
- 239000012730 sustained-release form Substances 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 230000003111 delayed effect Effects 0.000 description 6
- 239000010408 film Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 150000003509 tertiary alcohols Chemical class 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- 0 CC1(*C(*)=O)C=CC(CC(*)(*)NCC(c(cc2)cnc2N)O)=CC=C1 Chemical compound CC1(*C(*)=O)C=CC(CC(*)(*)NCC(c(cc2)cnc2N)O)=CC=C1 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 4
- 239000012607 strong cation exchange resin Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 3
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 3
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 3
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000001270 agonistic effect Effects 0.000 description 3
- 208000028004 allergic respiratory disease Diseases 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 150000001502 aryl halides Chemical class 0.000 description 3
- 229940040544 bromides Drugs 0.000 description 3
- 150000001649 bromium compounds Chemical class 0.000 description 3
- 230000007883 bronchodilation Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- KJGLZJQPMKQFIK-UHFFFAOYSA-N methanolate;tributylstannanylium Chemical compound CCCC[Sn](CCCC)(CCCC)OC KJGLZJQPMKQFIK-UHFFFAOYSA-N 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000006199 nebulizer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000012799 strong cation exchange Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000003419 tautomerization reaction Methods 0.000 description 3
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 2
- KYLUAQBYONVMCP-UHFFFAOYSA-N (2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P KYLUAQBYONVMCP-UHFFFAOYSA-N 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VUJANHVNFQTFTH-UHFFFAOYSA-N 1-(3-bromophenyl)-2-methylpropan-2-amine Chemical compound CC(C)(N)CC1=CC=CC(Br)=C1 VUJANHVNFQTFTH-UHFFFAOYSA-N 0.000 description 2
- PAPNRQCYSFBWDI-UHFFFAOYSA-N 2,5-Dimethyl-1H-pyrrole Chemical compound CC1=CC=C(C)N1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 description 2
- WIACAMZSZVKRLO-UHFFFAOYSA-N 2-(4-hydroxy-2,5-dimethylphenyl)acetonitrile Chemical compound CC1=CC(CC#N)=C(C)C=C1O WIACAMZSZVKRLO-UHFFFAOYSA-N 0.000 description 2
- RRPZLLRACDYRDD-XLDIYJRPSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetic acid Chemical compound C([C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)NC(C)CC1=CC=CC(CC(O)=O)=C1 RRPZLLRACDYRDD-XLDIYJRPSA-N 0.000 description 2
- 125000006185 3,4-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])[H])C([H])([H])* 0.000 description 2
- CEDPVRBUFIXTAG-UHFFFAOYSA-N 4-(2-aminoethyl)-2,5-dimethylphenol Chemical compound CC1=CC(CCN)=C(C)C=C1O CEDPVRBUFIXTAG-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 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 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 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 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000005107 Premature Birth Diseases 0.000 description 2
- 206010036590 Premature baby Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 102000000551 Syk Kinase Human genes 0.000 description 2
- 108010016672 Syk Kinase Proteins 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000004044 bronchoconstricting agent Substances 0.000 description 2
- 230000003435 bronchoconstrictive effect Effects 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000009109 curative therapy Methods 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 230000010250 cytokine signaling pathway Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- UXZDUBJVCLRIMS-HXOBKFHXSA-N methyl 2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 UXZDUBJVCLRIMS-HXOBKFHXSA-N 0.000 description 2
- HJPHWPILRQHHBR-SECBINFHSA-N methyl 2-[3-[(2r)-2-aminopropyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(C[C@@H](C)N)=C1 HJPHWPILRQHHBR-SECBINFHSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000002638 palliative care Methods 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000010902 straw Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 239000006068 taste-masking agent Substances 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- LKGNAVZFUZDIMS-LBPRGKRZSA-N (1r)-2-amino-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanol Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CN)C=N1 LKGNAVZFUZDIMS-LBPRGKRZSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 1
- AYKYOOPFBCOXSL-UHFFFAOYSA-N (4-hydroxyphenyl)acetonitrile Chemical compound OC1=CC=C(CC#N)C=C1 AYKYOOPFBCOXSL-UHFFFAOYSA-N 0.000 description 1
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 1
- DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000005859 (C1-C6)alkanoyloxymethyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-M 1,1-dioxo-1,2-benzothiazol-3-olate Chemical compound C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-M 0.000 description 1
- FQIZFAJMBXZVOL-UHFFFAOYSA-N 1-(3-bromophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=CC(Br)=C1 FQIZFAJMBXZVOL-UHFFFAOYSA-N 0.000 description 1
- DXXPWEKAYXAOPR-UHFFFAOYSA-N 1-(4-bromophenyl)-2-methylpropan-2-amine Chemical compound CC(C)(N)CC1=CC=C(Br)C=C1 DXXPWEKAYXAOPR-UHFFFAOYSA-N 0.000 description 1
- GXRFHTZJNUGYSI-UHFFFAOYSA-N 1-(4-bromophenyl)-2-methylpropan-2-ol Chemical compound CC(C)(O)CC1=CC=C(Br)C=C1 GXRFHTZJNUGYSI-UHFFFAOYSA-N 0.000 description 1
- CFMMTXJMIJRUSH-UHFFFAOYSA-N 1-(4-bromophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(Br)C=C1 CFMMTXJMIJRUSH-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- VSWPGAIWKHPTKX-UHFFFAOYSA-N 1-methyl-10-[2-(4-methyl-1-piperazinyl)-1-oxoethyl]-5H-thieno[3,4-b][1,5]benzodiazepin-4-one Chemical compound C1CN(C)CCN1CC(=O)N1C2=CC=CC=C2NC(=O)C2=CSC(C)=C21 VSWPGAIWKHPTKX-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- XGHBKRKXZTUREB-LBPRGKRZSA-N 2-(2,5-dimethylpyrrol-1-yl)-5-[(2r)-oxiran-2-yl]pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C([C@H]2OC2)C=N1 XGHBKRKXZTUREB-LBPRGKRZSA-N 0.000 description 1
- KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 1
- ZONYHDJJTKXZPC-UHFFFAOYSA-N 2-(4-hydroxy-2,3-dimethylphenyl)acetonitrile Chemical compound CC1=C(C)C(CC#N)=CC=C1O ZONYHDJJTKXZPC-UHFFFAOYSA-N 0.000 description 1
- PKVGVGHNOSEAMZ-UHFFFAOYSA-N 2-(4-hydroxy-3-methylphenyl)acetonitrile Chemical compound CC1=CC(CC#N)=CC=C1O PKVGVGHNOSEAMZ-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- VJYKILPDSJBHEA-UHFFFAOYSA-N 2-(4-methoxy-2,3-dimethylphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C(C)=C1C VJYKILPDSJBHEA-UHFFFAOYSA-N 0.000 description 1
- XPKNQRIEXCGMHA-UHFFFAOYSA-N 2-(4-methoxy-2,5-dimethylphenyl)acetonitrile Chemical compound COC1=CC(C)=C(CC#N)C=C1C XPKNQRIEXCGMHA-UHFFFAOYSA-N 0.000 description 1
- QOMACJMHUFTRJI-UHFFFAOYSA-N 2-(4-methoxy-3-methylphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C=C1C QOMACJMHUFTRJI-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- QJPCGQFEWBIKAU-SFHVURJKSA-N 2-[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]isoindole-1,3-dione Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CN2C(C3=CC=CC=C3C2=O)=O)C=N1 QJPCGQFEWBIKAU-SFHVURJKSA-N 0.000 description 1
- CFLNUXVFVYCBHB-UHFFFAOYSA-N 2-[1-(4-bromophenyl)-2-methylpropan-2-yl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(C)(C)CC1=CC=C(Br)C=C1 CFLNUXVFVYCBHB-UHFFFAOYSA-N 0.000 description 1
- BHGFHTPCVUDLDS-UHFFFAOYSA-N 2-[3-(2-ethoxy-2-oxoethyl)phenyl]acetic acid Chemical compound CCOC(=O)CC1=CC=CC(CC(O)=O)=C1 BHGFHTPCVUDLDS-UHFFFAOYSA-N 0.000 description 1
- LNMRKNQYHPBGEF-UHFFFAOYSA-N 2-[3-(2-hydroxy-2-methylpropyl)phenyl]acetic acid Chemical compound CC(C)(O)CC1=CC=CC(CC(O)=O)=C1 LNMRKNQYHPBGEF-UHFFFAOYSA-N 0.000 description 1
- CRXLBXIEPHJAOV-CJAUYULYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[(3-chloro-5-hydroxyphenyl)methyl]-n-ethylacetamide Chemical compound C=1C=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(N)=CC=2)=CC=1CC(=O)N(CC)CC1=CC(O)=CC(Cl)=C1 CRXLBXIEPHJAOV-CJAUYULYSA-N 0.000 description 1
- CFMCVVNBOUEDMY-KOSHJBKYSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acetamide Chemical compound C1=C(O)C(OC)=CC(CCNC(=O)CC=2C=C(C[C@@H](C)NC[C@H](O)C=3C=NC(N)=CC=3)C=CC=2)=C1 CFMCVVNBOUEDMY-KOSHJBKYSA-N 0.000 description 1
- DVDLFFFJRPSGBQ-OSPHWJPCSA-N 2-[3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-n-[[3-hydroxy-5-(trifluoromethyl)phenyl]methyl]-n-methylacetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1CC(=O)N(C)CC1=CC(O)=CC(C(F)(F)F)=C1 DVDLFFFJRPSGBQ-OSPHWJPCSA-N 0.000 description 1
- URPKQMDGUQVCGY-DJUQAAIZSA-N 2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]-n-(2-phenylethyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C(C=1)=CC=CC=1CC(=O)NCCC1=CC=CC=C1 URPKQMDGUQVCGY-DJUQAAIZSA-N 0.000 description 1
- XXBLHXXJJIWHHK-XJFCNFDWSA-N 2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]-n-(3-phenylpropyl)acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C(C=1)=CC=CC=1CC(=O)NCCCC1=CC=CC=C1 XXBLHXXJJIWHHK-XJFCNFDWSA-N 0.000 description 1
- NYYYCSSDXVZDDQ-DJUQAAIZSA-N 2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]-n-[(2-ethoxyphenyl)methyl]acetamide Chemical compound CCOC1=CC=CC=C1CNC(=O)CC1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 NYYYCSSDXVZDDQ-DJUQAAIZSA-N 0.000 description 1
- RRPZLLRACDYRDD-ZHRRBRCNSA-N 2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetic acid Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C1=CC=CC(CC(O)=O)=C1 RRPZLLRACDYRDD-ZHRRBRCNSA-N 0.000 description 1
- UQNLWWFJRHNKDQ-UHFFFAOYSA-N 2-[3-[2-[(2-chloroacetyl)amino]-2-methylpropyl]phenyl]acetic acid Chemical compound ClCC(=O)NC(C)(C)CC1=CC=CC(CC(O)=O)=C1 UQNLWWFJRHNKDQ-UHFFFAOYSA-N 0.000 description 1
- TWFHUVKSAPZITJ-PMERELPUSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(2-phenylethyl)acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCCC=3C=CC=CC=3)C=CC=2)C=N1 TWFHUVKSAPZITJ-PMERELPUSA-N 0.000 description 1
- AHGUYMNZKMQDNM-HKBQPEDESA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-(3-phenylpropyl)acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCCCC=3C=CC=CC=3)C=CC=2)C=N1 AHGUYMNZKMQDNM-HKBQPEDESA-N 0.000 description 1
- QVGULSCUUWNXQD-PMERELPUSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(2-ethoxyphenyl)methyl]acetamide Chemical compound CCOC1=CC=CC=C1CNC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 QVGULSCUUWNXQD-PMERELPUSA-N 0.000 description 1
- YZSGHDWKHDFFLT-LJAQVGFWSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(4-sulfamoylphenyl)methyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCC=3C=CC(=CC=3)S(N)(=O)=O)C=CC=2)C=N1 YZSGHDWKHDFFLT-LJAQVGFWSA-N 0.000 description 1
- JSKVFGYNBLDXBP-QFIPXVFZSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetic acid Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(O)=O)C=CC=2)C=N1 JSKVFGYNBLDXBP-QFIPXVFZSA-N 0.000 description 1
- PIRHWRDZPDSLAA-TXMUIZFDSA-N 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]-n-[(4-hydroxy-3-methoxyphenyl)methyl]acetamide Chemical compound C1=C(O)C(OC)=CC(CNC(=O)CC=2C=C(CC(C)NC[C@H](O)C=3C=NC(=CC=3)N3C(=CC=C3C)C)C=CC=2)=C1 PIRHWRDZPDSLAA-TXMUIZFDSA-N 0.000 description 1
- SBBXSLSOQJIGDN-PMERELPUSA-N 2-[4-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]-n-[(3-methoxyphenyl)methyl]acetamide Chemical compound COC1=CC=CC(CNC(=O)CC=2C=CC(CC(C)(C)NC[C@H](O)C=3C=NC(=CC=3)N3C(=CC=C3C)C)=CC=2)=C1 SBBXSLSOQJIGDN-PMERELPUSA-N 0.000 description 1
- VWZCMBPLSSGMNZ-QFIPXVFZSA-N 2-[4-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetic acid Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=CC(CC(O)=O)=CC=2)C=N1 VWZCMBPLSSGMNZ-QFIPXVFZSA-N 0.000 description 1
- DPKJNRKIIXFDLG-UHFFFAOYSA-N 2-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-2-methylpropanenitrile Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(C(C)(C)C#N)C=C1 DPKJNRKIIXFDLG-UHFFFAOYSA-N 0.000 description 1
- YCGQTWPHDJMYPC-UHFFFAOYSA-N 2-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]acetonitrile Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(CC#N)C=C1 YCGQTWPHDJMYPC-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- SCOJKGRNQDKFRP-UHFFFAOYSA-N 2-chloro-n-methoxy-n-methylacetamide Chemical compound CON(C)C(=O)CCl SCOJKGRNQDKFRP-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- OCUAPVNNQFAQSM-UHFFFAOYSA-N 3-Methyl-3-butenyl acetate Chemical compound CC(=C)CCOC(C)=O OCUAPVNNQFAQSM-UHFFFAOYSA-N 0.000 description 1
- KDBGZBPJZJSLSK-HXOBKFHXSA-N 3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]-n-[2-(3-hydroxyphenyl)ethyl]benzamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(N)=CC=1)C(C=1)=CC=CC=1C(=O)NCCC1=CC=CC(O)=C1 KDBGZBPJZJSLSK-HXOBKFHXSA-N 0.000 description 1
- DGYNNLSUTQZBCO-VFNWGFHPSA-N 3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]benzoic acid Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C1=CC=CC(C(O)=O)=C1 DGYNNLSUTQZBCO-VFNWGFHPSA-N 0.000 description 1
- FBSYEHFNUGYOJB-QHCPKHFHSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1C(=O)NCCC1=CC=C(O)C=C1 FBSYEHFNUGYOJB-QHCPKHFHSA-N 0.000 description 1
- YDDAPOFZRXSTOU-LJAQVGFWSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-[[4-(4-hydroxyphenyl)-2-methylphenyl]methyl]benzamide Chemical compound C1([C@@H](O)CNC(C)(C)CC=2C=CC=C(C=2)C(=O)NCC2=CC=C(C=C2C)C=2C=CC(O)=CC=2)=CC=C(N)N=C1 YDDAPOFZRXSTOU-LJAQVGFWSA-N 0.000 description 1
- DQLKMLQGESIYHZ-NRFANRHFSA-N 3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]benzoic acid Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(C=CC=2)C(O)=O)C=N1 DQLKMLQGESIYHZ-NRFANRHFSA-N 0.000 description 1
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
- IGXYXEJKBOICPG-UHFFFAOYSA-N 4-(2-aminoethyl)-2,3-dimethylphenol Chemical compound CC1=C(C)C(CCN)=CC=C1O IGXYXEJKBOICPG-UHFFFAOYSA-N 0.000 description 1
- XUUUAVMDYPPDOI-UHFFFAOYSA-N 4-(2-aminoethyl)-2-methylphenol Chemical compound CC1=CC(CCN)=CC=C1O XUUUAVMDYPPDOI-UHFFFAOYSA-N 0.000 description 1
- ZRMIETZFPZGBEB-UHFFFAOYSA-N 4-(4-hydroxyphenyl)benzonitrile Chemical compound C1=CC(O)=CC=C1C1=CC=C(C#N)C=C1 ZRMIETZFPZGBEB-UHFFFAOYSA-N 0.000 description 1
- AMPBOCAQBJUJBP-UHFFFAOYSA-N 4-[3-(aminomethyl)phenyl]phenol Chemical compound NCC1=CC=CC(C=2C=CC(O)=CC=2)=C1 AMPBOCAQBJUJBP-UHFFFAOYSA-N 0.000 description 1
- HXEDNOYUBKSWOW-UHFFFAOYSA-N 4-[4-(aminomethyl)phenyl]phenol;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1C1=CC=C(O)C=C1 HXEDNOYUBKSWOW-UHFFFAOYSA-N 0.000 description 1
- LAOZSCRCYVBSJA-UHFFFAOYSA-N 5,5-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CC1(C)C(=O)NC(=O)NC1=O LAOZSCRCYVBSJA-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 102000035121 Adrenergic receptor subfamily Human genes 0.000 description 1
- 108020000586 Adrenergic receptor subfamily Proteins 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 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 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 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 description 1
- KCICIERONJJKMJ-UHFFFAOYSA-N CC(C)(C)OC(NC(C)(C)Cc1cc(Br)ccc1)=O Chemical compound CC(C)(C)OC(NC(C)(C)Cc1cc(Br)ccc1)=O KCICIERONJJKMJ-UHFFFAOYSA-N 0.000 description 1
- VZKRUPOKFSGKQS-UHFFFAOYSA-N CC(C)(Cc(cc1)ccc1[Br]=C)O Chemical compound CC(C)(Cc(cc1)ccc1[Br]=C)O VZKRUPOKFSGKQS-UHFFFAOYSA-N 0.000 description 1
- WMJVAKVSYDTYIN-QFIPXVFZSA-N CC(C)(Cc1cc(C(OC)=O)ccc1)NC[C@@H](c1ccc(-[n]2c(C)ccc2C)nc1)O Chemical compound CC(C)(Cc1cc(C(OC)=O)ccc1)NC[C@@H](c1ccc(-[n]2c(C)ccc2C)nc1)O WMJVAKVSYDTYIN-QFIPXVFZSA-N 0.000 description 1
- WFKBBUXWYIDQCJ-UHFFFAOYSA-N CC(C)(Cc1cccc(C(OC)=O)c1)N=N Chemical compound CC(C)(Cc1cccc(C(OC)=O)c1)N=N WFKBBUXWYIDQCJ-UHFFFAOYSA-N 0.000 description 1
- DYZSRIMVHIZMIY-UHFFFAOYSA-N CC(CCC(C)=O)=O.BrC=1C=CC(=NC1)N1C(=CC=C1C)C Chemical compound CC(CCC(C)=O)=O.BrC=1C=CC(=NC1)N1C(=CC=C1C)C DYZSRIMVHIZMIY-UHFFFAOYSA-N 0.000 description 1
- 102000017925 CHRM3 Human genes 0.000 description 1
- 101150060249 CHRM3 gene Proteins 0.000 description 1
- NOPKGRZRPFWWKG-IPBJYNAHSA-N C[C@H](Cc1cc(C(NCCc(cc2C)c(C)cc2O)=O)ccc1)NC[C@@H](c1ccc(-[n]2c(C)ccc2C)nc1)O Chemical compound C[C@H](Cc1cc(C(NCCc(cc2C)c(C)cc2O)=O)ccc1)NC[C@@H](c1ccc(-[n]2c(C)ccc2C)nc1)O NOPKGRZRPFWWKG-IPBJYNAHSA-N 0.000 description 1
- FZFCGMNRSIAHCZ-SUYFMZKJSA-N C[C@H](Cc1cc(CC(NCc2cc(-c(cc3)ccc3O)ccc2)=O)ccc1)NCC(c1ccc(-[n]2c(C)ccc2C)nc1)O Chemical compound C[C@H](Cc1cc(CC(NCc2cc(-c(cc3)ccc3O)ccc2)=O)ccc1)NCC(c1ccc(-[n]2c(C)ccc2C)nc1)O FZFCGMNRSIAHCZ-SUYFMZKJSA-N 0.000 description 1
- RRPZLLRACDYRDD-XESZBRCGSA-N C[C@H](Cc1cc(CC(O)=O)ccc1)NCC(c1ccc(-[n]2c(C)ccc2C)nc1)O Chemical compound C[C@H](Cc1cc(CC(O)=O)ccc1)NCC(c1ccc(-[n]2c(C)ccc2C)nc1)O RRPZLLRACDYRDD-XESZBRCGSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 101000959437 Homo sapiens Beta-2 adrenergic receptor Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- VFIDUCMKNJIJTO-BBRMVZONSA-N ICI 118551 Chemical compound CC(C)N[C@@H](C)[C@@H](O)COC1=CC=C(C)C2=C1CCC2 VFIDUCMKNJIJTO-BBRMVZONSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 101100269376 Mus musculus Agfg2 gene Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- QVCDBOQTJPSXRP-UHFFFAOYSA-N NCc(cc1)ccc1-c(cc1)ccc1O Chemical compound NCc(cc1)ccc1-c(cc1)ccc1O QVCDBOQTJPSXRP-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- RJYCRBQHCZBJOP-CJAUYULYSA-N [3-[(2r)-2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]propyl]phenyl]-(8-hydroxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl)methanone Chemical compound C1([C@@H](O)CN[C@@H](CC=2C=C(C=CC=2)C(=O)N2CC3=CC(O)=CC=C3CCC2)C)=CC=C(N)N=C1 RJYCRBQHCZBJOP-CJAUYULYSA-N 0.000 description 1
- ZPOVYOWNOUWWAU-UHFFFAOYSA-N acetyl chloride;methyl 2-(3-bromophenyl)acetate Chemical compound CC(Cl)=O.COC(=O)CC1=CC=CC(Br)=C1 ZPOVYOWNOUWWAU-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 210000005057 airway smooth muscle cell Anatomy 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000002590 anti-leukotriene effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 102000016967 beta-1 Adrenergic Receptors Human genes 0.000 description 1
- 108010014494 beta-1 Adrenergic Receptors Proteins 0.000 description 1
- 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 description 1
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical compound C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- MLBCEUNLSMADIP-UHFFFAOYSA-N carbamic acid hydroiodide Chemical compound I.C(N)(O)=O MLBCEUNLSMADIP-UHFFFAOYSA-N 0.000 description 1
- 229940077731 carbohydrate nutrients Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 150000004777 chromones Chemical class 0.000 description 1
- 229960003728 ciclesonide Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229950010286 diolamine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940110377 dl- arginine Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- URZKCMPZWPHMAF-UHFFFAOYSA-N ethyl 1,3-dioxoisoindole-4-carboxylate Chemical compound CCOC(=O)C1=CC=CC2=C1C(=O)NC2=O URZKCMPZWPHMAF-UHFFFAOYSA-N 0.000 description 1
- KTKVMMGGETYZIP-UHFFFAOYSA-N ethyl 2-[3-(2-amino-2-methylpropyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(CC(C)(C)N)=C1 KTKVMMGGETYZIP-UHFFFAOYSA-N 0.000 description 1
- KYMQZZUIUHRDHM-DEOSSOPVSA-N ethyl 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(CC(C)(C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 KYMQZZUIUHRDHM-DEOSSOPVSA-N 0.000 description 1
- FSEWAWXEVDQMHB-UHFFFAOYSA-N ethyl 2-[4-(2-amino-2-methylpropyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(CC(C)(C)N)C=C1 FSEWAWXEVDQMHB-UHFFFAOYSA-N 0.000 description 1
- PBUWFVXLMAJJGU-UHFFFAOYSA-N ethyl 2-[4-[2-(1,3-dioxoisoindol-2-yl)-2-methylpropyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1CC(C)(C)N1C(=O)C2=CC=CC=C2C1=O PBUWFVXLMAJJGU-UHFFFAOYSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- 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 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000005283 haloketone group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 229950000177 hibenzate Drugs 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- PYFDZOCGFHIRST-UHFFFAOYSA-N hydron;(3-iodophenyl)methanamine;chloride Chemical compound Cl.NCC1=CC=CC(I)=C1 PYFDZOCGFHIRST-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical class O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- XXIKYCPRDXIMQM-UHFFFAOYSA-N isoprenyl acetate Natural products CC(C)=CCOC(C)=O XXIKYCPRDXIMQM-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000012731 long-acting form Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- CCUFJSRTMDUHLG-UHFFFAOYSA-N methyl 2-[3-(2-oxopropyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(CC(C)=O)=C1 CCUFJSRTMDUHLG-UHFFFAOYSA-N 0.000 description 1
- BPGREBLIYAFVNF-HZPDHXFCSA-N methyl 2-[3-[(2r)-2-[[(1r)-1-phenylethyl]amino]propyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(C[C@@H](C)N[C@H](C)C=2C=CC=CC=2)=C1 BPGREBLIYAFVNF-HZPDHXFCSA-N 0.000 description 1
- JNTKZSCMCFEPFO-QNBGGDODSA-N methyl 2-[3-[(2r)-2-[[(1r)-1-phenylethyl]amino]propyl]phenyl]acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=CC(C[C@@H](C)N[C@H](C)C=2C=CC=CC=2)=C1 JNTKZSCMCFEPFO-QNBGGDODSA-N 0.000 description 1
- GSHVZYGTLAOAND-SBSPUUFOSA-N methyl 2-[3-[(2r)-2-aminopropyl]phenyl]acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=CC(C[C@@H](C)N)=C1 GSHVZYGTLAOAND-SBSPUUFOSA-N 0.000 description 1
- UXZDUBJVCLRIMS-VXLWULRPSA-N methyl 2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(CC(C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 UXZDUBJVCLRIMS-VXLWULRPSA-N 0.000 description 1
- UOLXYVYPXZMYIG-QHCPKHFHSA-N methyl 2-[4-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1CC(C)(C)NC[C@H](O)C1=CC=C(N2C(=CC=C2C)C)N=C1 UOLXYVYPXZMYIG-QHCPKHFHSA-N 0.000 description 1
- OXPMIJUPVHVHHE-UHFFFAOYSA-N methyl 3-(2-amino-2-methylpropyl)benzoate Chemical compound COC(=O)C1=CC=CC(CC(C)(C)N)=C1 OXPMIJUPVHVHHE-UHFFFAOYSA-N 0.000 description 1
- OIQIRDNTYVKGFX-ZHRRBRCNSA-N methyl 3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]benzoate Chemical compound COC(=O)C1=CC=CC(C[C@@H](C)NC[C@H](O)C=2C=NC(=CC=2)N2C(=CC=C2C)C)=C1 OIQIRDNTYVKGFX-ZHRRBRCNSA-N 0.000 description 1
- JNDQVKXBGOMTBZ-UHFFFAOYSA-N methyl 3-[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]benzoate Chemical compound COC(=O)C1=CC=CC(CC(C)(C)NC(=O)OC(C)(C)C)=C1 JNDQVKXBGOMTBZ-UHFFFAOYSA-N 0.000 description 1
- KMFJVYMFCAIRAN-UHFFFAOYSA-N methyl 3-bromobenzoate Chemical compound COC(=O)C1=CC=CC(Br)=C1 KMFJVYMFCAIRAN-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone 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)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- IQRDSUDNTKPZKH-UVDDSOTQSA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetamide Chemical compound N1=CC([C@@H](O)CN[C@@H](CC=2C=C(CC(=O)NC3CC4=CC=CC=C4C3)C=CC=2)C)=CC=C1N1C(C)=CC=C1C IQRDSUDNTKPZKH-UVDDSOTQSA-N 0.000 description 1
- BKYPNSXMYPSPOM-HKBQPEDESA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NC3CC4=CC=CC=C4C3)C=CC=2)C=N1 BKYPNSXMYPSPOM-HKBQPEDESA-N 0.000 description 1
- AXKXCFSMORNYEY-HKBQPEDESA-N n-[(2,3-dimethylphenyl)methyl]-2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCC=3C(=C(C)C=CC=3)C)C=CC=2)C=N1 AXKXCFSMORNYEY-HKBQPEDESA-N 0.000 description 1
- UMAQDLHPFISFBX-LJAQVGFWSA-N n-[(2,6-dimethoxyphenyl)methyl]-2-[4-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound COC1=CC=CC(OC)=C1CNC(=O)CC(C=C1)=CC=C1CC(C)(C)NC[C@H](O)C1=CC=C(N2C(=CC=C2C)C)N=C1 UMAQDLHPFISFBX-LJAQVGFWSA-N 0.000 description 1
- YZJCAEBMSOBNCF-LJAQVGFWSA-N n-[(3,4-dichlorophenyl)methyl]-2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCC=3C=C(Cl)C(Cl)=CC=3)C=CC=2)C=N1 YZJCAEBMSOBNCF-LJAQVGFWSA-N 0.000 description 1
- XXEWSGIGMOIZOD-XJFCNFDWSA-N n-[(3,4-dimethylphenyl)methyl]-2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C(C=1)=CC=CC=1CC(=O)NCC1=CC=C(C)C(C)=C1 XXEWSGIGMOIZOD-XJFCNFDWSA-N 0.000 description 1
- RYPOUAWGCUIRRE-LJAQVGFWSA-N n-[(3,5-dichlorophenyl)methyl]-2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCC=3C=C(Cl)C=C(Cl)C=3)C=CC=2)C=N1 RYPOUAWGCUIRRE-LJAQVGFWSA-N 0.000 description 1
- UAPBPSRAYCIVQB-UHFFFAOYSA-N n-[[4-[tert-butyl(dimethyl)silyl]oxynaphthalen-1-yl]methyl]prop-2-en-1-amine Chemical compound C1=CC=C2C(O[Si](C)(C)C(C)(C)C)=CC=C(CNCC=C)C2=C1 UAPBPSRAYCIVQB-UHFFFAOYSA-N 0.000 description 1
- FTXQZWSEYONITC-MNNSJKJDSA-N n-benzyl-2-[3-[(2r)-2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]propyl]phenyl]acetamide Chemical compound C([C@@H](C)NC[C@H](O)C=1C=NC(=CC=1)N1C(=CC=C1C)C)C(C=1)=CC=CC=1CC(=O)NCC1=CC=CC=C1 FTXQZWSEYONITC-MNNSJKJDSA-N 0.000 description 1
- IPQRTQMKTWLBTJ-LJAQVGFWSA-N n-benzyl-2-[3-[2-[[(2r)-2-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl]amino]-2-methylpropyl]phenyl]acetamide Chemical compound CC1=CC=C(C)N1C1=CC=C([C@@H](O)CNC(C)(C)CC=2C=C(CC(=O)NCC=3C=CC=CC=3)C=CC=2)C=N1 IPQRTQMKTWLBTJ-LJAQVGFWSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000002353 niosome Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical group CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229950004864 olamine Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical class 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-M orotate Chemical compound [O-]C(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-M 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000003544 oxime group Chemical group 0.000 description 1
- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical class CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
- 229960004633 pirenzepine Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 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 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229950004351 telenzepine Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- 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 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0312832.9A GB0312832D0 (en) | 2003-06-04 | 2003-06-04 | 2-amino-pyridine derivatives useful for the treatment of diseases |
| PCT/IB2004/001850 WO2004108676A1 (en) | 2003-06-04 | 2004-06-01 | 2-(6-amino-pyridin-3-yl)-2-hydroxyethylamine derivatives as beta 2-adrenoceptors agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006526613A true JP2006526613A (ja) | 2006-11-24 |
| JP2006526613A5 JP2006526613A5 (enExample) | 2007-06-14 |
Family
ID=9959308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006508431A Withdrawn JP2006526613A (ja) | 2003-06-04 | 2004-06-01 | β２−アドレナリン受容体アゴニストとしての２−（６−アミノ−ピリジン−３−イル）−２−ヒドロキシエチルアミン誘導体 |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1633715B1 (enExample) |
| JP (1) | JP2006526613A (enExample) |
| AR (1) | AR044475A1 (enExample) |
| AT (1) | ATE372321T1 (enExample) |
| BR (1) | BRPI0410946A (enExample) |
| CA (1) | CA2527788A1 (enExample) |
| CL (1) | CL2004001366A1 (enExample) |
| DE (1) | DE602004008773T2 (enExample) |
| ES (1) | ES2291882T3 (enExample) |
| GB (1) | GB0312832D0 (enExample) |
| GT (1) | GT200400116A (enExample) |
| MX (1) | MXPA05012840A (enExample) |
| NL (1) | NL1026329C2 (enExample) |
| PA (1) | PA8604301A1 (enExample) |
| PE (1) | PE20050628A1 (enExample) |
| TW (1) | TW200524603A (enExample) |
| UY (1) | UY28339A1 (enExample) |
| WO (1) | WO2004108676A1 (enExample) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
| UA87854C2 (en) * | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
| EP1830837B1 (en) | 2004-09-20 | 2013-09-04 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-coa desaturase enzymes |
| AU2005286728A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
| AR051090A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| JP5149009B2 (ja) | 2004-09-20 | 2013-02-20 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトステアロイル−ＣｏＡデサチュラーゼを阻害するためのピリダジン誘導体 |
| MX2007003332A (es) | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa-desaturasa. |
| MX2007003325A (es) | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores estearoil-coa-desaturasa. |
| AR051093A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa desaturasa |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| EP2029138A1 (en) | 2005-06-03 | 2009-03-04 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| RU2442771C2 (ru) | 2005-08-08 | 2012-02-20 | Арджента Дискавери Лтд | Производные бицикло[2,2,1]гепт-7-иламина и их применения |
| MY144906A (en) | 2005-10-21 | 2011-11-30 | Novartis Ag | Human antibodies against il13 and therapeutic uses |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| AR060607A1 (es) | 2006-04-21 | 2008-07-02 | Novartis Ag | Derivados de purina,composiciones farmaceuticas que los contienen, metodo de preparacion y usos en enfermedades obstructivas o inflamatorias de las vias respiratorias. |
| US8163758B2 (en) * | 2006-06-09 | 2012-04-24 | Parion Sciences, Inc. | Phenyl substituted pyrazinoylguanidine sodium channel blockers possessing beta agonist activity |
| EP2535330A3 (en) | 2006-10-23 | 2012-12-26 | Takeda Pharmaceutical Company Limited | Iminopyridine derivative and use thereof |
| AU2008248598B2 (en) | 2007-05-07 | 2011-11-17 | Novartis Ag | Organic compounds |
| ES2654395T3 (es) | 2007-12-10 | 2018-02-13 | Novartis Ag | Análogos de amilorida espirocíclicos como bloqueantes de ENaC |
| JP5584138B2 (ja) | 2008-01-11 | 2014-09-03 | ノバルティス アーゲー | キナーゼ阻害剤としてのピリミジン類 |
| US8481569B2 (en) | 2008-04-23 | 2013-07-09 | Takeda Pharmaceutical Company Limited | Iminopyridine derivatives and use thereof |
| EP2300010B1 (en) | 2008-06-10 | 2015-03-04 | Novartis AG | Pyrazine derivatives as epithelial sodium channel blockers |
| US8236786B2 (en) | 2008-08-07 | 2012-08-07 | Pulmagen Therapeutics (Inflammation) Limited | Respiratory disease treatment |
| DE102008049675A1 (de) | 2008-09-30 | 2010-04-01 | Markus Dr. Heinrich | Verfahren zur Herstellung von 3-Aminobiphenylen |
| WO2010076553A1 (en) | 2008-12-30 | 2010-07-08 | Dr. Reddy's Laboratories Ltd | Sulfonamide compounds for the treatment of respiratory disorders |
| WO2010150014A1 (en) | 2009-06-24 | 2010-12-29 | Pulmagen Therapeutics (Inflammation) Limited | 5r- 5 -deuterated glitazones for respiratory disease treatment |
| MX2012004792A (es) | 2009-10-22 | 2013-02-01 | Vertex Pharma | Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas. |
| GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
| GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
| GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| WO2011098746A1 (en) | 2010-02-09 | 2011-08-18 | Pulmagen Therapeutics (Inflammation) Limited | Crystalline acid addition salts of ( 5r) -enanti0mer of pioglitazone |
| GB201002224D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| GB201002243D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| JP5959541B2 (ja) | 2011-02-25 | 2016-08-02 | ノバルティス アーゲー | Ｔｒｋ阻害剤としてのピラゾロ［１，５−ａ］ピリジン |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| US9034879B2 (en) | 2011-09-16 | 2015-05-19 | Novartis Ag | Heterocyclic compounds for the treatment of CF |
| ES2882807T3 (es) | 2011-09-16 | 2021-12-02 | Novartis Ag | Heterociclil carboxamidas N-sustituidas |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| WO2015162461A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| MX2016013812A (es) | 2014-04-24 | 2017-03-09 | Novartis Ag | Derivados de amino-pirazina como inhibidores de fosfatidil-inositol-3-cinasa. |
| EA201692140A1 (ru) | 2014-04-24 | 2017-04-28 | Новартис Аг | Производные аминопиридина в качестве ингибиторов фосфатидилинозитол 3-киназы |
| JP2022537667A (ja) | 2019-06-10 | 2022-08-29 | ノバルティス アーゲー | Ｃｆ、ｃｏｐｄ、及び気管支拡張症の治療のためのピリジン及びピラジン誘導体 |
| EP4021572A1 (en) | 2019-08-28 | 2022-07-06 | Novartis AG | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4358455A (en) * | 1980-12-23 | 1982-11-09 | Merck & Co., Inc. | Aralkylamindethanol heterocyclic compounds |
| WO1996035671A1 (en) * | 1995-05-10 | 1996-11-14 | Pfizer Inc. | β-ADRENERGIC AGONISTS |
| EP1078924B1 (en) * | 1999-07-23 | 2004-10-20 | Pfizer Products Inc. | Intermediates and a process for producing beta-adrenergic receptor agonists |
| TWI249515B (en) * | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| GB0217225D0 (en) * | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicinal compounds |
| DE60320439T2 (de) * | 2002-10-11 | 2009-05-20 | Pfizer Inc. | INDOLDERIVATE ALS ß2-AGONISTEN |
-
2003
- 2003-06-04 GB GBGB0312832.9A patent/GB0312832D0/en not_active Ceased
-
2004
- 2004-06-01 DE DE602004008773T patent/DE602004008773T2/de not_active Expired - Fee Related
- 2004-06-01 PE PE2004000553A patent/PE20050628A1/es not_active Application Discontinuation
- 2004-06-01 BR BRPI0410946-5A patent/BRPI0410946A/pt not_active IP Right Cessation
- 2004-06-01 EP EP04735621A patent/EP1633715B1/en not_active Expired - Lifetime
- 2004-06-01 JP JP2006508431A patent/JP2006526613A/ja not_active Withdrawn
- 2004-06-01 CA CA002527788A patent/CA2527788A1/en not_active Abandoned
- 2004-06-01 AT AT04735621T patent/ATE372321T1/de not_active IP Right Cessation
- 2004-06-01 ES ES04735621T patent/ES2291882T3/es not_active Expired - Lifetime
- 2004-06-01 MX MXPA05012840A patent/MXPA05012840A/es unknown
- 2004-06-01 WO PCT/IB2004/001850 patent/WO2004108676A1/en not_active Ceased
- 2004-06-02 UY UY28339A patent/UY28339A1/es not_active Application Discontinuation
- 2004-06-03 CL CL200401366A patent/CL2004001366A1/es unknown
- 2004-06-03 GT GT200400116A patent/GT200400116A/es unknown
- 2004-06-03 PA PA20048604301A patent/PA8604301A1/es unknown
- 2004-06-03 AR ARP040101904A patent/AR044475A1/es unknown
- 2004-06-03 TW TW093115990A patent/TW200524603A/zh unknown
- 2004-06-03 NL NL1026329A patent/NL1026329C2/nl not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1633715A1 (en) | 2006-03-15 |
| UY28339A1 (es) | 2005-01-31 |
| DE602004008773D1 (de) | 2007-10-18 |
| MXPA05012840A (es) | 2006-02-13 |
| GB0312832D0 (en) | 2003-07-09 |
| CA2527788A1 (en) | 2004-12-16 |
| CL2004001366A1 (es) | 2005-05-06 |
| NL1026329C2 (nl) | 2005-07-26 |
| NL1026329A1 (nl) | 2004-12-07 |
| PE20050628A1 (es) | 2005-08-30 |
| WO2004108676A1 (en) | 2004-12-16 |
| PA8604301A1 (es) | 2004-12-16 |
| GT200400116A (es) | 2005-03-03 |
| ES2291882T3 (es) | 2008-03-01 |
| ATE372321T1 (de) | 2007-09-15 |
| DE602004008773T2 (de) | 2008-01-10 |
| BRPI0410946A (pt) | 2006-06-27 |
| EP1633715B1 (en) | 2007-09-05 |
| TW200524603A (en) | 2005-08-01 |
| AR044475A1 (es) | 2005-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2006526613A (ja) | β２−アドレナリン受容体アゴニストとしての２−（６−アミノ−ピリジン−３−イル）−２−ヒドロキシエチルアミン誘導体 | |
| US8013019B2 (en) | Sulfonamide derivatives for the treatment of diseases | |
| JP4036343B2 (ja) | 疾患の治療のためのスルフォンアミド誘導体 | |
| JP3966897B2 (ja) | ベータ２アゴニストとしての（２−ヒドロキシ−２−（４−ヒドロキシ−３−ヒドロキシメチルフェニル）−エチルアミノ）−プロピル−フェニル誘導体 | |
| WO2005092861A1 (en) | Quinolinone derivatives pharmaceutical compositions containing them and their use | |
| JP2006526604A (ja) | β−２アドレナリン受容体アゴニストとしての２−アミノ−ピリジン誘導体 | |
| JP4108117B2 (ja) | 疾患を処置するための化合物 | |
| JP2007529499A (ja) | β２受容体アゴニストとしてのフェニルアミノエタノール誘導体 | |
| NL1028599C2 (nl) | Verbindingen voor de behandeling van ziekten. | |
| JP4054366B2 (ja) | 疾患の治療のために有用な化合物 | |
| EP1577291A1 (en) | Phenylethanolamine derivatives as beta-2 agonists | |
| US7375100B2 (en) | 2-amino-pyridine derivatives useful for the treatment of diseases | |
| JP2010539154A (ja) | ムスカリン様受容体アンタゴニストとして活性な新規化合物 | |
| US20050215542A1 (en) | Compounds for the treatment of diseases | |
| EP1574501A1 (en) | Quinolinone derivatives, pharmaceutical compositions containing them and their use | |
| JP4819770B2 (ja) | アドレナリン受容体として有用なホルムアミド誘導体 | |
| CN100548976C (zh) | 用于治疗疾病的磺酰胺衍生物 | |
| JP2008174555A (ja) | 疾患を処置するための化合物 | |
| HK1096379B (en) | Sulfonamide derivatives for the treatment of diseases | |
| HK1096379A1 (zh) | 用於治疗疾病的磺酰胺衍生物 | |
| MXPA06008311A (en) | Sulfonamide derivatives for the treatment of diseases | |
| MXPA06010629A (en) | Phenylaminoethanol derivates as beta2 receptor agonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070413 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070413 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20090210 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20090218 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090313 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20090507 |