JP2009504768A - ムスカリン性アセチルコリン受容体アンタゴニスト - Google Patents
ムスカリン性アセチルコリン受容体アンタゴニスト Download PDFInfo
- Publication number
- JP2009504768A JP2009504768A JP2008527135A JP2008527135A JP2009504768A JP 2009504768 A JP2009504768 A JP 2009504768A JP 2008527135 A JP2008527135 A JP 2008527135A JP 2008527135 A JP2008527135 A JP 2008527135A JP 2009504768 A JP2009504768 A JP 2009504768A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- diphenyl
- azoniabicyclo
- hydroxy
- heptane bromide
- 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.)
- Pending
Links
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title claims abstract description 42
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title claims abstract description 42
- 229940121683 Acetylcholine receptor antagonist Drugs 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 52
- 150000001875 compounds Chemical class 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- -1 trifluoroacetate ion Chemical class 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 23
- 229940079593 drug Drugs 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 229960004373 acetylcholine Drugs 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 239000004305 biphenyl Substances 0.000 claims description 10
- 235000010290 biphenyl Nutrition 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 9
- 125000006267 biphenyl group Chemical group 0.000 claims description 9
- 102000005962 receptors Human genes 0.000 claims description 9
- 108020003175 receptors Proteins 0.000 claims description 9
- 230000009471 action Effects 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 229940112141 dry powder inhaler Drugs 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 229940071648 metered dose inhaler Drugs 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- BXQZGQXBRYYDAC-UHFFFAOYSA-M [1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 BXQZGQXBRYYDAC-UHFFFAOYSA-M 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 238000003860 storage Methods 0.000 claims description 4
- PDJGIOVYWCVUTC-UHFFFAOYSA-M (1-ethyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-diphenylmethanol;bromide Chemical compound [Br-].C1C[N+](CC)(C2)CCC12C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 PDJGIOVYWCVUTC-UHFFFAOYSA-M 0.000 claims description 3
- YENBEILOHOLUOO-UHFFFAOYSA-M 2-[1-(3-methoxypropyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C1C[N+](CCCOC)(C2)CCC12C(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 YENBEILOHOLUOO-UHFFFAOYSA-M 0.000 claims description 3
- MXMVOGBLQLSFLG-UHFFFAOYSA-N 2-[3-[4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.1]heptan-1-yl]propoxy]phenol;bromide Chemical compound [Br-].OC1=CC=CC=C1OCCC[N+]1(C2)CCC2(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MXMVOGBLQLSFLG-UHFFFAOYSA-N 0.000 claims description 3
- OQDYATWZZXSYBS-UHFFFAOYSA-M 2-[4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.1]heptan-1-yl]ethyl benzoate;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCOC(=O)C=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 OQDYATWZZXSYBS-UHFFFAOYSA-M 0.000 claims description 3
- FVWNDVASSKEXHZ-UHFFFAOYSA-M 6-[4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.1]heptan-1-yl]hexan-1-ol;bromide Chemical compound [Br-].C1C[N+](CCCCCCO)(C2)CCC12C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 FVWNDVASSKEXHZ-UHFFFAOYSA-M 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- KMRVAHIHUIKLNB-UHFFFAOYSA-M [1-(3-naphthalen-2-yloxypropyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOC=3C=C4C=CC=CC4=CC=3)(CC1)C2)(O)C1=CC=CC=C1 KMRVAHIHUIKLNB-UHFFFAOYSA-M 0.000 claims description 3
- JACIGCRJLAQOAG-UHFFFAOYSA-M [1-(4-phenoxybutyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCCOC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 JACIGCRJLAQOAG-UHFFFAOYSA-M 0.000 claims description 3
- QNHNXNPIPCSLBP-UHFFFAOYSA-M [1-[2-[(3-methoxyphenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].COC1=CC=CC(COCC[N+]23CCC(CC2)(C3)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 QNHNXNPIPCSLBP-UHFFFAOYSA-M 0.000 claims description 3
- AXBOBELJLQOWPL-UHFFFAOYSA-M [1-[3-(3-chlorophenoxy)propyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOC=3C=C(Cl)C=CC=3)(CC1)C2)(O)C1=CC=CC=C1 AXBOBELJLQOWPL-UHFFFAOYSA-M 0.000 claims description 3
- AWFAZKNPXWIEBQ-UHFFFAOYSA-M [1-[3-(4-nitrophenoxy)propyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOC=3C=CC(=CC=3)[N+]([O-])=O)(CC1)C2)(O)C1=CC=CC=C1 AWFAZKNPXWIEBQ-UHFFFAOYSA-M 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 208000007451 chronic bronchitis Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- SUVOQQBXZFXBFI-UHFFFAOYSA-M diphenyl-[1-(2-phenylethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]methanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 SUVOQQBXZFXBFI-UHFFFAOYSA-M 0.000 claims description 3
- VEXJMDRECRGFAV-UHFFFAOYSA-M diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]methanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCOCC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 VEXJMDRECRGFAV-UHFFFAOYSA-M 0.000 claims description 3
- PFCWMSURHUQAQA-UHFFFAOYSA-M diphenyl-[1-[[4-(trifluoromethoxy)phenyl]methyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]methanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CC=3C=CC(OC(F)(F)F)=CC=3)(CC1)C2)(O)C1=CC=CC=C1 PFCWMSURHUQAQA-UHFFFAOYSA-M 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- ACCBVLDMNMOXDN-UHFFFAOYSA-N heptane;hydrobromide Chemical compound Br.CCCCCCC ACCBVLDMNMOXDN-UHFFFAOYSA-N 0.000 claims description 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 229940085991 phosphate ion Drugs 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- QTOYIMYSNVABAB-UHFFFAOYSA-M (1-nonyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-diphenylmethanol;bromide Chemical compound [Br-].C1C[N+](CCCCCCCCC)(C2)CCC12C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 QTOYIMYSNVABAB-UHFFFAOYSA-M 0.000 claims description 2
- KDPYXAKZNYGSFT-UHFFFAOYSA-M 2,2-diphenyl-2-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]acetonitrile;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCOCC=3C=CC=CC=3)(CC1)C2)(C#N)C1=CC=CC=C1 KDPYXAKZNYGSFT-UHFFFAOYSA-M 0.000 claims description 2
- IXIBREPTIQOQGP-UHFFFAOYSA-M 2,2-diphenyl-2-[1-(3-phenylpropyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]acetonitrile;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCC=3C=CC=CC=3)(CC1)C2)(C#N)C1=CC=CC=C1 IXIBREPTIQOQGP-UHFFFAOYSA-M 0.000 claims description 2
- OETZWJYIMJQDRQ-UHFFFAOYSA-M 2-(1-ethyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C1C[N+](CC)(C2)CCC12C(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 OETZWJYIMJQDRQ-UHFFFAOYSA-M 0.000 claims description 2
- SEDAKDQHHDXQQE-UHFFFAOYSA-M 2-(1-hexyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C1C[N+](CCCCCC)(C2)CCC12C(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 SEDAKDQHHDXQQE-UHFFFAOYSA-M 0.000 claims description 2
- ANIPEIJJIGNLCU-UHFFFAOYSA-M 2-[1-(2-hydroxyethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C1C[N+](CCO)(C2)CCC12C(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 ANIPEIJJIGNLCU-UHFFFAOYSA-M 0.000 claims description 2
- FPVHGDXLYQQKRZ-UHFFFAOYSA-M 2-[1-(cyclohexylmethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CC3CCCCC3)(CC1)C2)(C#N)C1=CC=CC=C1 FPVHGDXLYQQKRZ-UHFFFAOYSA-M 0.000 claims description 2
- ZHMBONPBHCQABZ-UHFFFAOYSA-M 2-[1-[2-(1h-indol-2-yl)ethyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCC=3NC4=CC=CC=C4C=3)(CC1)C2)(C#N)C1=CC=CC=C1 ZHMBONPBHCQABZ-UHFFFAOYSA-M 0.000 claims description 2
- PFVDQAVJJJSHDR-UHFFFAOYSA-M 4-[4-[cyano(diphenyl)methyl]-1-azoniabicyclo[2.2.1]heptan-1-yl]butanenitrile;bromide Chemical compound [Br-].C1C[N+](CCCC#N)(C2)CCC12C(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 PFVDQAVJJJSHDR-UHFFFAOYSA-M 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 206010061876 Obstruction Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- YBLDQQDCSJWQIC-UHFFFAOYSA-M [1-(2-methoxyethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C1C[N+](CCOC)(C2)CCC12C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 YBLDQQDCSJWQIC-UHFFFAOYSA-M 0.000 claims description 2
- OTSMGVLZNNGFKG-UHFFFAOYSA-M [1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCOC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 OTSMGVLZNNGFKG-UHFFFAOYSA-M 0.000 claims description 2
- URCMEQZIXFRGBA-UHFFFAOYSA-M [1-(cyclohexylmethyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CC3CCCCC3)(CC1)C2)(O)C1=CC=CC=C1 URCMEQZIXFRGBA-UHFFFAOYSA-M 0.000 claims description 2
- UOQCSFHGPNSHSG-UHFFFAOYSA-M [1-[(3-methoxyphenyl)methyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].COC1=CC=CC(C[N+]23CCC(CC2)(C3)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 UOQCSFHGPNSHSG-UHFFFAOYSA-M 0.000 claims description 2
- NGTQNKCGHRSIPQ-UHFFFAOYSA-M [1-[3-(4-bromophenoxy)propyl]-1-azoniabicyclo[2.2.1]heptan-4-yl]-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOC=3C=CC(Br)=CC=3)(CC1)C2)(O)C1=CC=CC=C1 NGTQNKCGHRSIPQ-UHFFFAOYSA-M 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- ONHJTLAXELJOER-UHFFFAOYSA-M diphenyl-[1-(3-phenylmethoxypropyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]methanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCOCC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 ONHJTLAXELJOER-UHFFFAOYSA-M 0.000 claims description 2
- LRNNXNVGBVUJLH-UHFFFAOYSA-M diphenyl-[1-(4-phenylmethoxybutyl)-1-azoniabicyclo[2.2.1]heptan-4-yl]methanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCCOCC=3C=CC=CC=3)(CC1)C2)(O)C1=CC=CC=C1 LRNNXNVGBVUJLH-UHFFFAOYSA-M 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
- 230000010807 negative regulation of binding Effects 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- BPURUAIDMARGPI-UHFFFAOYSA-M (1-hex-5-enyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-diphenylmethanol;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CCCCC=C)(CC1)C2)(O)C1=CC=CC=C1 BPURUAIDMARGPI-UHFFFAOYSA-M 0.000 claims 1
- BUQWNAIAQSJBGF-UHFFFAOYSA-M (1-hexyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-diphenylmethanol;bromide Chemical compound [Br-].C1C[N+](CCCCCC)(C2)CCC12C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 BUQWNAIAQSJBGF-UHFFFAOYSA-M 0.000 claims 1
- ZUFGHLIVMMFQLU-UHFFFAOYSA-M 2-(1-benzyl-1-azoniabicyclo[2.2.1]heptan-4-yl)-2,2-diphenylacetonitrile;bromide Chemical compound [Br-].C=1C=CC=CC=1C(C12CC[N+](CC=3C=CC=CC=3)(CC1)C2)(C#N)C1=CC=CC=C1 ZUFGHLIVMMFQLU-UHFFFAOYSA-M 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 description 39
- 239000000047 product Substances 0.000 description 37
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- NAYNOSVXIWVKDH-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-4-yl(diphenyl)methanol Chemical compound C=1C=CC=CC=1C(C12CCN(CC1)C2)(O)C1=CC=CC=C1 NAYNOSVXIWVKDH-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- 210000004072 lung Anatomy 0.000 description 15
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- FUNWFHKWYDSNOO-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.1]heptan-4-yl)-2,2-diphenylacetonitrile Chemical compound C=1C=CC=CC=1C(C12CCN(CC1)C2)(C#N)C1=CC=CC=C1 FUNWFHKWYDSNOO-UHFFFAOYSA-N 0.000 description 11
- 239000000443 aerosol Substances 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 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 8
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 8
- 229960004484 carbachol Drugs 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
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- 210000001186 vagus nerve Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70930105P | 2005-08-18 | 2005-08-18 | |
| PCT/US2006/032138 WO2007022351A2 (en) | 2005-08-18 | 2006-08-17 | Muscarinic acetylcholine receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009504768A true JP2009504768A (ja) | 2009-02-05 |
| JP2009504768A5 JP2009504768A5 (enExample) | 2009-10-01 |
Family
ID=37758395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008527135A Pending JP2009504768A (ja) | 2005-08-18 | 2006-08-17 | ムスカリン性アセチルコリン受容体アンタゴニスト |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US7767691B2 (enExample) |
| EP (1) | EP1937068A4 (enExample) |
| JP (1) | JP2009504768A (enExample) |
| WO (1) | WO2007022351A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019506384A (ja) * | 2016-01-08 | 2019-03-07 | セロン ファーマシューティカルズ， インク | ７−アゾニアビシクロ［２．２．１］ヘプタン誘導体の乾燥粉末吸入器組成物 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200519108A (en) | 2003-07-17 | 2005-06-16 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| CN101230061A (zh) | 2003-10-14 | 2008-07-30 | 葛兰素集团有限公司 | 蕈毒碱性乙酰胆碱受体拮抗剂 |
| TW200524577A (en) | 2003-11-04 | 2005-08-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| WO2005087236A1 (en) * | 2004-03-11 | 2005-09-22 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
| WO2005095407A1 (en) | 2004-03-17 | 2005-10-13 | Glaxo Group Limited | M3 muscarinic acetylcholine receptor antagonists |
| AR050902A1 (es) | 2004-04-27 | 2006-12-06 | Glaxo Group Ltd | Compuesto de quinuclidina, composicion farmaceutica que lo comprende y su usopara preparar dicha composicion |
| EP1747219A4 (en) * | 2004-05-13 | 2010-05-26 | Glaxo Group Ltd | Antagonists of muscarinic acetylcholine receptor |
| KR101495708B1 (ko) | 2007-02-23 | 2015-02-25 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 무스카린 수용체 안타고니스트로 유용한 4차 암모늄 디페닐메틸 화합물 |
| CA2682032A1 (en) | 2007-04-24 | 2008-11-06 | Theravance, Inc. | Quaternary ammonium compounds useful as muscarinic receptor antagonists |
| CL2009000249A1 (es) | 2008-02-06 | 2009-09-11 | Glaxo Group Ltd | Compuestos derivados de pirazolo[3,4-b] piridin-butanodiamida; composicion farmaceutica; y su uso en el tratamiento del asma, enfermedad pulmonar obstructiva cronica, rinitis, dermatitis atopica, psoriasis. |
| UY31637A1 (es) | 2008-02-06 | 2009-08-03 | Farmacoforos duales-antagonistas muscarinicos de pde4 | |
| AR070564A1 (es) | 2008-02-06 | 2010-04-21 | Glaxo Group Ltd | Derivados de 1h-pirazolo[3,4-b]piridin-5-ilo,inhibidores de fosfodiesterasas pde4 y antagonistas de receptores muscarinicos de acetilcolina(machr), utiles en el tratamiento y/o profilaxis de enfermedades respiratorias y alergicas,y composiciones farmaceuticas que los comprenden |
| WO2010094643A1 (en) | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
| TWI904157B (zh) | 2020-04-30 | 2025-11-11 | 瑞士商愛杜西亞製藥有限公司 | Ccr6受體調節劑 |
| WO2023057548A1 (en) | 2021-10-07 | 2023-04-13 | Idorsia Pharmaceuticals Ltd | Ccr6 receptor modulators |
| JP2024539987A (ja) | 2021-10-26 | 2024-10-31 | イドルシア・ファーマシューティカルズ・リミテッド | Ｃｃｒ６受容体調節剤 |
| ES3073199T3 (en) | 2021-10-28 | 2026-07-09 | Idorsia Pharmaceuticals Ltd | Ccr6 receptor modulators |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5780466A (en) * | 1995-01-30 | 1998-07-14 | Sanofi | Substituted heterocyclic compounds method of preparing them and pharmaceutical compositions in which they are present |
| JP2003504368A (ja) * | 1999-07-14 | 2003-02-04 | アルミラル・プロデスフアルマ・エス・エイ | キヌクリジン誘導体およびそれらのムスカリンｍ３レセプターリガンドとしての使用 |
| JP2007525478A (ja) * | 2003-07-17 | 2007-09-06 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| JP2007534769A (ja) * | 2004-04-27 | 2007-11-29 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| JP2008501020A (ja) * | 2004-05-28 | 2008-01-17 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2800481A (en) | 1955-07-01 | 1957-07-23 | Smith Kline French Lab | Tertiary alcohol derivatives of 8-alkylnortropanes and the acid and quaternary ammonium salts thereof |
| US2800478A (en) | 1955-07-01 | 1957-07-23 | Smith Kline French Lab | 3-substituted-8-alkylnortropanes and the acid and quaternary ammonium salts thereof |
| AT298118B (de) | 1967-06-08 | 1972-04-25 | Siemens Ag | Verfahren zur Umsetzung von Spannungen in digitale Werte und Vorrichtung zur Durchführung des Verfahrens |
| CY1308A (en) | 1979-12-06 | 1985-12-06 | Glaxo Group Ltd | Device for dispensing medicaments |
| EP0069715B1 (en) | 1981-07-08 | 1986-11-05 | Aktiebolaget Draco | Powder inhalator |
| GB2169265B (en) | 1982-10-08 | 1987-08-12 | Glaxo Group Ltd | Pack for medicament |
| DK172541B1 (da) | 1982-10-08 | 1998-12-07 | Glaxo Group Ltd | Apparat til administrering af medikamenter til patienter og en medikamentpakning til brug i apparatet |
| AU591152B2 (en) | 1985-07-30 | 1989-11-30 | Glaxo Group Limited | Devices for administering medicaments to patients |
| IT1204826B (it) | 1986-03-04 | 1989-03-10 | Chiesi Farma Spa | Composizioni farmaceutiche per inalazione |
| EP0363085A3 (en) * | 1988-10-03 | 1991-03-27 | Beecham Group Plc | Novel compounds |
| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| IL117149A0 (en) * | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| WO1998024788A1 (en) | 1996-12-02 | 1998-06-11 | Georgetown University | Tropane derivatives and method for their synthesis |
| US6248752B1 (en) | 1998-02-27 | 2001-06-19 | Charles Duane Smith | Azabicyclooctane compositions and methods for enhancing chemotherapy |
| US6262066B1 (en) | 1998-07-27 | 2001-07-17 | Schering Corporation | High affinity ligands for nociceptin receptor ORL-1 |
| RU2004110717A (ru) | 2001-10-17 | 2005-10-20 | Юсиби, С.А. (Be) | Производные хинуклидина, способы их получения и их применение в качестве и нгибиторов м2- и/или м3- мускариновых рецепторов |
| US6696462B2 (en) | 2002-01-31 | 2004-02-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics, processes for the preparation thereof, and pharmaceutical compositions |
| UY27927A1 (es) | 2002-08-06 | 2003-12-31 | Glaxo Group Ltd | Antagonistas del receptor muscarínico m3 de acetilcolina |
| WO2004091482A2 (en) | 2003-04-07 | 2004-10-28 | Glaxo Group Limited | M3 muscarinic acetylcholine receptor antagonists |
| PE20050711A1 (es) | 2003-07-17 | 2005-09-10 | Glaxo Group Ltd | Compuestos 8-azoniabiciclo[3.2.1] octanos como antagonistas de los receptores muscarinicos de la acetilcolina |
| CN101230061A (zh) | 2003-10-14 | 2008-07-30 | 葛兰素集团有限公司 | 蕈毒碱性乙酰胆碱受体拮抗剂 |
| MXPA06004242A (es) | 2003-10-17 | 2006-06-28 | Glaxo Group Ltd | Antagonistas del receptor muscarinico de la acetilcolina. |
| TW200524577A (en) | 2003-11-04 | 2005-08-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| ES2329586T3 (es) | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| PE20050861A1 (es) | 2003-12-03 | 2005-12-10 | Glaxo Group Ltd | Derivados de sales ciclicas de amonio cuaternario como antagonistas del receptor muscarinico de acetilcolina |
| UY28645A1 (es) | 2003-12-03 | 2005-06-30 | Glaxo Group Ltd | Nuevos antagonistas del receptor muscarinico m3 de acetilcolina |
| US20070185088A1 (en) | 2004-03-17 | 2007-08-09 | Jakob Busch-Petersen | M3 muscarinic acetylchoine receptor antagonists |
| WO2005095407A1 (en) | 2004-03-17 | 2005-10-13 | Glaxo Group Limited | M3 muscarinic acetylcholine receptor antagonists |
| US20070185090A1 (en) | 2004-03-17 | 2007-08-09 | Jakob Busch-Petersen | Muscarinic acetylchoine receptor antagonists |
| WO2005094251A2 (en) | 2004-03-17 | 2005-10-13 | Glaxo Group Limited | M3muscarinic acetylcholine receptor antagonists |
| EP1747219A4 (en) * | 2004-05-13 | 2010-05-26 | Glaxo Group Ltd | Antagonists of muscarinic acetylcholine receptor |
| JP2008520579A (ja) | 2004-11-15 | 2008-06-19 | グラクソ グループ リミテッド | 新規ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| WO2006055503A2 (en) | 2004-11-15 | 2006-05-26 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
| PE20060826A1 (es) | 2004-12-06 | 2006-10-08 | Smithkline Beecham Corp | Derivado oleofinico de 8-azoniabiciclo[3.2.1]octano y combinacion farmaceutica que lo comprende |
| PE20061162A1 (es) | 2004-12-06 | 2006-10-14 | Smithkline Beecham Corp | Compuestos derivados olefinicos de 8-azoniabiciclo[3.2.1]octanos |
| WO2006065755A2 (en) | 2004-12-13 | 2006-06-22 | Glaxo Group Limited | Quaternary ammonium salts of fused hetearomatic amines as novel muscarinic acetylcholine receptor antagonists |
| WO2006065788A2 (en) | 2004-12-13 | 2006-06-22 | Glaxo Group Limited | Novel muscarinic acetylcholine receptor antagonists |
| WO2007018508A1 (en) | 2005-07-28 | 2007-02-15 | Glaxo Group Limited | Novel m3 muscarinic acetycholine receptor antagonists |
| WO2007018514A1 (en) | 2005-07-28 | 2007-02-15 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
-
2006
- 2006-08-17 US US12/063,719 patent/US7767691B2/en not_active Expired - Fee Related
- 2006-08-17 WO PCT/US2006/032138 patent/WO2007022351A2/en not_active Ceased
- 2006-08-17 JP JP2008527135A patent/JP2009504768A/ja active Pending
- 2006-08-17 EP EP06801732A patent/EP1937068A4/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5780466A (en) * | 1995-01-30 | 1998-07-14 | Sanofi | Substituted heterocyclic compounds method of preparing them and pharmaceutical compositions in which they are present |
| JP2003504368A (ja) * | 1999-07-14 | 2003-02-04 | アルミラル・プロデスフアルマ・エス・エイ | キヌクリジン誘導体およびそれらのムスカリンｍ３レセプターリガンドとしての使用 |
| JP2007525478A (ja) * | 2003-07-17 | 2007-09-06 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| JP2007534769A (ja) * | 2004-04-27 | 2007-11-29 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| JP2008501020A (ja) * | 2004-05-28 | 2008-01-17 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019506384A (ja) * | 2016-01-08 | 2019-03-07 | セロン ファーマシューティカルズ， インク | ７−アゾニアビシクロ［２．２．１］ヘプタン誘導体の乾燥粉末吸入器組成物 |
| JP7015549B2 (ja) | 2016-01-08 | 2022-02-03 | セロン ファーマシューティカルズ， インク | ７－アゾニアビシクロ［２．２．１］ヘプタン誘導体の乾燥粉末吸入器組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1937068A4 (en) | 2010-08-04 |
| WO2007022351A3 (en) | 2007-10-04 |
| US7767691B2 (en) | 2010-08-03 |
| WO2007022351A2 (en) | 2007-02-22 |
| US20080194618A1 (en) | 2008-08-14 |
| EP1937068A2 (en) | 2008-07-02 |
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