CA2522180C - 2-azabicyclo[3.3.1]nonane derivatives as opioid receptor antagonists - Google Patents
2-azabicyclo[3.3.1]nonane derivatives as opioid receptor antagonists Download PDFInfo
- Publication number
- CA2522180C CA2522180C CA002522180A CA2522180A CA2522180C CA 2522180 C CA2522180 C CA 2522180C CA 002522180 A CA002522180 A CA 002522180A CA 2522180 A CA2522180 A CA 2522180A CA 2522180 C CA2522180 C CA 2522180C
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- CA
- Canada
- Prior art keywords
- aza
- bicyclo
- phenyl
- ylmethyl
- methoxy
- 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.)
- Expired - Fee Related
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- ZPAPCUKKKOSLPZ-UHFFFAOYSA-N morphan Chemical class C1CNC2CCCC1C2 ZPAPCUKKKOSLPZ-UHFFFAOYSA-N 0.000 title abstract description 3
- 229940123257 Opioid receptor antagonist Drugs 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 56
- 108090000137 Opioid Receptors Proteins 0.000 claims abstract description 50
- 102000003840 Opioid Receptors Human genes 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 230000001404 mediated effect Effects 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 158
- 150000003839 salts Chemical class 0.000 claims description 62
- -1 indane-2-yl Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 241000124008 Mammalia Species 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 102000005962 receptors Human genes 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- KBPHGUKTJKPERJ-UHFFFAOYSA-N 2-methoxyethanesulfonic acid Chemical compound COCCS(O)(=O)=O KBPHGUKTJKPERJ-UHFFFAOYSA-N 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- WNWOOJRCKNZYEM-UHFFFAOYSA-N n-[3-[2-(cyclopropylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC2CC2)CC3)=C1 WNWOOJRCKNZYEM-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 2
- KEFAFGCJUBWJQM-UHFFFAOYSA-N 2-methoxy-n-[3-(2-octyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]ethanesulfonamide Chemical compound C1CCC(C2)N(CCCCCCCC)CCC21C1=CC=CC(NS(=O)(=O)CCOC)=C1 KEFAFGCJUBWJQM-UHFFFAOYSA-N 0.000 claims description 2
- INCJRISTJIRWIA-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(1h-pyrrol-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC=2NC=CC=2)CC3)=C1 INCJRISTJIRWIA-UHFFFAOYSA-N 0.000 claims description 2
- BSXVWUGGGVSRPU-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(2-methylpropyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC(C)C)CC3)=C1 BSXVWUGGGVSRPU-UHFFFAOYSA-N 0.000 claims description 2
- KYDPDURBBFOTGL-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(3-methylbutyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CCC(C)C)CC3)=C1 KYDPDURBBFOTGL-UHFFFAOYSA-N 0.000 claims description 2
- CRNFTHNQOFPKAE-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CCCC=2C=CC=CC=2)CC3)=C1 CRNFTHNQOFPKAE-UHFFFAOYSA-N 0.000 claims description 2
- ZPDSUULKMSIGFF-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(naphthalen-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC=2C=C4C=CC=CC4=CC=2)CC3)=C1 ZPDSUULKMSIGFF-UHFFFAOYSA-N 0.000 claims description 2
- FRWSCDHYSIEEDU-UHFFFAOYSA-N 2-methoxy-n-[3-[2-(thiophen-3-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC2=CSC=C2)CC3)=C1 FRWSCDHYSIEEDU-UHFFFAOYSA-N 0.000 claims description 2
- ZJGIAPBKSHGFBY-UHFFFAOYSA-N 2-methoxy-n-[3-[2-[(3-methyl-1-benzothiophen-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC2=C(C4=CC=CC=C4S2)C)CC3)=C1 ZJGIAPBKSHGFBY-UHFFFAOYSA-N 0.000 claims description 2
- XDOUPWOTGANRGP-UHFFFAOYSA-N 2-methoxy-n-[3-[2-[(3-phenylcyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC2CC(C2)C=2C=CC=CC=2)CC3)=C1 XDOUPWOTGANRGP-UHFFFAOYSA-N 0.000 claims description 2
- ZQVNKBCHVAFILS-UHFFFAOYSA-N 2-methoxy-n-[3-[2-[(4-methoxyphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC=2C=CC(OC)=CC=2)CC3)=C1 ZQVNKBCHVAFILS-UHFFFAOYSA-N 0.000 claims description 2
- GFMVUCDZLXKXME-UHFFFAOYSA-N 2-methoxy-n-[3-[2-[(4-pyrrolidin-1-ylphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]ethanesulfonamide Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC=2C=CC(=CC=2)N2CCCC2)CC3)=C1 GFMVUCDZLXKXME-UHFFFAOYSA-N 0.000 claims description 2
- FPKXGCIJMWWBNN-UHFFFAOYSA-N 3-(2-ethyl-2-azabicyclo[3.3.1]nonan-5-yl)benzamide Chemical compound C1CCC(C2)N(CC)CCC21C1=CC=CC(C(N)=O)=C1 FPKXGCIJMWWBNN-UHFFFAOYSA-N 0.000 claims description 2
- JGGREPVKZAEUHL-UHFFFAOYSA-N 3-(2-octyl-2-azabicyclo[3.3.1]nonan-5-yl)benzamide Chemical compound C1CCC(C2)N(CCCCCCCC)CCC21C1=CC=CC(C(N)=O)=C1 JGGREPVKZAEUHL-UHFFFAOYSA-N 0.000 claims description 2
- ZMMUWJKQJQCWAR-UHFFFAOYSA-N 3-(2-pentyl-2-azabicyclo[3.3.1]nonan-5-yl)benzamide Chemical compound C1CCC(C2)N(CCCCC)CCC21C1=CC=CC(C(N)=O)=C1 ZMMUWJKQJQCWAR-UHFFFAOYSA-N 0.000 claims description 2
- RZMXZLQPEFQXCN-UHFFFAOYSA-N 3-[2-(1,2,3,4-tetrahydronaphthalen-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2CC4=CC=CC=C4CC2)CC3)=C1 RZMXZLQPEFQXCN-UHFFFAOYSA-N 0.000 claims description 2
- FUGKCDKDPZOJPQ-UHFFFAOYSA-N 3-[2-(1,3-thiazol-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2SC=CN=2)CC3)=C1 FUGKCDKDPZOJPQ-UHFFFAOYSA-N 0.000 claims description 2
- WBEMIDHTHGUGLN-UHFFFAOYSA-N 3-[2-(1h-imidazol-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2NC=CN=2)CC3)=C1 WBEMIDHTHGUGLN-UHFFFAOYSA-N 0.000 claims description 2
- PUOOQBLMNRELHE-UHFFFAOYSA-N 3-[2-(1h-indol-3-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C4=CC=CC=C4NC=2)CC3)=C1 PUOOQBLMNRELHE-UHFFFAOYSA-N 0.000 claims description 2
- VIONGUQMNGHWMU-UHFFFAOYSA-N 3-[2-(1h-pyrrol-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2NC=CC=2)CC3)=C1 VIONGUQMNGHWMU-UHFFFAOYSA-N 0.000 claims description 2
- WSHDVGRJIFWABO-UHFFFAOYSA-N 3-[2-(2-methylpropyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound C1CCC(C2)N(CC(C)C)CCC21C1=CC=CC(C(N)=O)=C1 WSHDVGRJIFWABO-UHFFFAOYSA-N 0.000 claims description 2
- VXVNSRQJWGEWTA-UHFFFAOYSA-N 3-[2-(3-methylbutyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound C1CCC(C2)N(CCC(C)C)CCC21C1=CC=CC(C(N)=O)=C1 VXVNSRQJWGEWTA-UHFFFAOYSA-N 0.000 claims description 2
- YJDSJINCBKULSF-UHFFFAOYSA-N 3-[2-(3-phenylprop-2-ynyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC#CC=2C=CC=CC=2)CC3)=C1 YJDSJINCBKULSF-UHFFFAOYSA-N 0.000 claims description 2
- SQVBTOBQXXNQLI-UHFFFAOYSA-N 3-[2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC=2C=CC=CC=2)CC3)=C1 SQVBTOBQXXNQLI-UHFFFAOYSA-N 0.000 claims description 2
- BVEZPMSUZPKAQO-UHFFFAOYSA-N 3-[2-(9h-fluoren-2-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C=C4C(C5=CC=CC=C5C4)=CC=2)CC3)=C1 BVEZPMSUZPKAQO-UHFFFAOYSA-N 0.000 claims description 2
- LTARZFLOOWJRJZ-UHFFFAOYSA-N 3-[2-(naphthalen-1-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C4=CC=CC=C4C=CC=2)CC3)=C1 LTARZFLOOWJRJZ-UHFFFAOYSA-N 0.000 claims description 2
- KFONPCSQQXFPGZ-UHFFFAOYSA-N 3-[2-(thiophen-3-ylmethyl)-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2=CSC=C2)CC3)=C1 KFONPCSQQXFPGZ-UHFFFAOYSA-N 0.000 claims description 2
- YZMRJTFTIRSULG-UHFFFAOYSA-N 3-[2-[(1-hydroxy-3-phenylcyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC(C2)C=2C=CC=CC=2)CC3)=C1 YZMRJTFTIRSULG-UHFFFAOYSA-N 0.000 claims description 2
- ZDNOWEMLEUNNNV-UHFFFAOYSA-N 3-[2-[(1-hydroxycyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CCC2)CC3)=C1 ZDNOWEMLEUNNNV-UHFFFAOYSA-N 0.000 claims description 2
- UCXJNVUJMZSKQP-UHFFFAOYSA-N 3-[2-[(1-methylindol-3-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound C12=CC=CC=C2N(C)C=C1CN(C(CCC1)C2)CCC21C1=CC=CC(C(N)=O)=C1 UCXJNVUJMZSKQP-UHFFFAOYSA-N 0.000 claims description 2
- VDFMRKLOHOHSJJ-UHFFFAOYSA-N 3-[2-[(1-methylpyrrol-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound CN1C=CC=C1CN1C(C2)CCCC2(C=2C=C(C=CC=2)C(N)=O)CC1 VDFMRKLOHOHSJJ-UHFFFAOYSA-N 0.000 claims description 2
- XWJBBHRGYQANKK-UHFFFAOYSA-N 3-[2-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4C2)CC3)=C1 XWJBBHRGYQANKK-UHFFFAOYSA-N 0.000 claims description 2
- ZCDWSEYWBPLIPE-UHFFFAOYSA-N 3-[2-[(2-hydroxy-3,4-dihydro-1h-naphthalen-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4CC2)CC3)=C1 ZCDWSEYWBPLIPE-UHFFFAOYSA-N 0.000 claims description 2
- KVYKNPRAOIPRSJ-UHFFFAOYSA-N 3-[2-[(3-methyl-1-benzothiophen-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound S1C2=CC=CC=C2C(C)=C1CN(C(CCC1)C2)CCC21C1=CC=CC(C(N)=O)=C1 KVYKNPRAOIPRSJ-UHFFFAOYSA-N 0.000 claims description 2
- WCBUDMVAXZWGCZ-UHFFFAOYSA-N 3-[2-[(3-phenoxyphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C=C(OC=4C=CC=CC=4)C=CC=2)CC3)=C1 WCBUDMVAXZWGCZ-UHFFFAOYSA-N 0.000 claims description 2
- WJVNXORPLRJLJP-UHFFFAOYSA-N 3-[2-[(3-phenylcyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2CC(C2)C=2C=CC=CC=2)CC3)=C1 WJVNXORPLRJLJP-UHFFFAOYSA-N 0.000 claims description 2
- PDPDNZQDARLDLS-UHFFFAOYSA-N 3-[2-[(4-methoxyphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound C1=CC(OC)=CC=C1CN1C(C2)CCCC2(C=2C=C(C=CC=2)C(N)=O)CC1 PDPDNZQDARLDLS-UHFFFAOYSA-N 0.000 claims description 2
- IOIYEORBNAPYQF-UHFFFAOYSA-N 3-[2-[(4-phenylphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C=CC(=CC=2)C=2C=CC=CC=2)CC3)=C1 IOIYEORBNAPYQF-UHFFFAOYSA-N 0.000 claims description 2
- PKUCERRJYPVNGU-UHFFFAOYSA-N 3-[2-[(4-pyrrolidin-1-ylphenyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C=CC(=CC=2)N2CCCC2)CC3)=C1 PKUCERRJYPVNGU-UHFFFAOYSA-N 0.000 claims description 2
- RPZWRBVNMXJMHD-UHFFFAOYSA-N 3-[2-[2-(2-phenylethoxy)ethyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCOCCC=2C=CC=CC=2)CC3)=C1 RPZWRBVNMXJMHD-UHFFFAOYSA-N 0.000 claims description 2
- KDAMUYVTYZYYMY-UHFFFAOYSA-N 3-[2-[3-(1-hydroxycyclohexyl)propyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC2(O)CCCCC2)CC3)=C1 KDAMUYVTYZYYMY-UHFFFAOYSA-N 0.000 claims description 2
- NHGOJBXDOCYYGU-UHFFFAOYSA-N 3-[2-[3-(1-hydroxycyclopentyl)propyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC2(O)CCCC2)CC3)=C1 NHGOJBXDOCYYGU-UHFFFAOYSA-N 0.000 claims description 2
- UASWNWLIOKHFKR-UHFFFAOYSA-N 3-[2-[3-(2,3-dihydro-1h-inden-2-yl)propyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC2CC4=CC=CC=C4C2)CC3)=C1 UASWNWLIOKHFKR-UHFFFAOYSA-N 0.000 claims description 2
- URXOKGGSGHVUBR-UHFFFAOYSA-N 3-[2-[3-(2-hydroxy-1,3-dihydroinden-2-yl)propyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC2(O)CC4=CC=CC=C4C2)CC3)=C1 URXOKGGSGHVUBR-UHFFFAOYSA-N 0.000 claims description 2
- KKQCMNRMKMVFHT-UHFFFAOYSA-N 3-[2-[3-[1-(hydroxymethyl)cyclopentyl]propyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CCCC2(CO)CCCC2)CC3)=C1 KKQCMNRMKMVFHT-UHFFFAOYSA-N 0.000 claims description 2
- QYDCKMCJJCKWKD-UHFFFAOYSA-N 3-[2-[[3-(trifluoromethoxy)phenyl]methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC=2C=C(OC(F)(F)F)C=CC=2)CC3)=C1 QYDCKMCJJCKWKD-UHFFFAOYSA-N 0.000 claims description 2
- FABPZIBCJMUOKN-UHFFFAOYSA-N 3-[2-[[4-(dimethylamino)naphthalen-1-yl]methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1CN(C(CCC1)C2)CCC21C1=CC=CC(C(N)=O)=C1 FABPZIBCJMUOKN-UHFFFAOYSA-N 0.000 claims description 2
- NCNJLWJZUMMRFR-UHFFFAOYSA-N COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC=4C=CC=CC=4)(CCC2)NCC3)=C1 Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC=4C=CC=CC=4)(CCC2)NCC3)=C1 NCNJLWJZUMMRFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- DCQQMWWJGNRUBS-UHFFFAOYSA-N n-[3-(2-ethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]-2-methoxyethanesulfonamide Chemical compound C1CCC(C2)N(CC)CCC21C1=CC=CC(NS(=O)(=O)CCOC)=C1 DCQQMWWJGNRUBS-UHFFFAOYSA-N 0.000 claims description 2
- BQQZXQZPYABUIG-UHFFFAOYSA-N n-[3-(2-heptyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]-2-methoxyethanesulfonamide Chemical compound C1CCC(C2)N(CCCCCCC)CCC21C1=CC=CC(NS(=O)(=O)CCOC)=C1 BQQZXQZPYABUIG-UHFFFAOYSA-N 0.000 claims description 2
- RQIBPTZTWHCWRA-UHFFFAOYSA-N n-[3-(2-heptyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]methanesulfonamide Chemical compound C1CCC(C2)N(CCCCCCC)CCC21C1=CC=CC(NS(C)(=O)=O)=C1 RQIBPTZTWHCWRA-UHFFFAOYSA-N 0.000 claims description 2
- CVCMBUFJKQOLDQ-UHFFFAOYSA-N n-[3-(2-hexyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]methanesulfonamide Chemical compound C1CCC(C2)N(CCCCCC)CCC21C1=CC=CC(NS(C)(=O)=O)=C1 CVCMBUFJKQOLDQ-UHFFFAOYSA-N 0.000 claims description 2
- KCAXVESICDDCRB-UHFFFAOYSA-N n-[3-(2-octyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]methanesulfonamide Chemical compound C1CCC(C2)N(CCCCCCCC)CCC21C1=CC=CC(NS(C)(=O)=O)=C1 KCAXVESICDDCRB-UHFFFAOYSA-N 0.000 claims description 2
- AAEULHMBHHHHSG-UHFFFAOYSA-N n-[3-(2-pentyl-2-azabicyclo[3.3.1]nonan-5-yl)phenyl]methanesulfonamide Chemical compound C1CCC(C2)N(CCCCC)CCC21C1=CC=CC(NS(C)(=O)=O)=C1 AAEULHMBHHHHSG-UHFFFAOYSA-N 0.000 claims description 2
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
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- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
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- JRCXGEWIXMXDPZ-UHFFFAOYSA-N tert-butyl 5-[3-(2-methoxyethylsulfonylamino)phenyl]-2-azabicyclo[3.3.1]nonane-2-carboxylate Chemical compound COCCS(=O)(=O)NC1=CC=CC(C23CC(CCC2)N(CC3)C(=O)OC(C)(C)C)=C1 JRCXGEWIXMXDPZ-UHFFFAOYSA-N 0.000 description 1
- BMHKMSRIOCQAES-UHFFFAOYSA-N tert-butyl 5-[3-(methanesulfonamido)phenyl]-2-azabicyclo[3.3.1]nonane-2-carboxylate Chemical compound C1CCC(C2)N(C(=O)OC(C)(C)C)CCC21C1=CC=CC(NS(C)(=O)=O)=C1 BMHKMSRIOCQAES-UHFFFAOYSA-N 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
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229940072690 valium Drugs 0.000 description 1
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P25/32—Alcohol-abuse
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- A—HUMAN NECESSITIES
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- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
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- Psychiatry (AREA)
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- Pain & Pain Management (AREA)
- Otolaryngology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46260503P | 2003-04-14 | 2003-04-14 | |
| US60/462,605 | 2003-04-14 | ||
| PCT/IB2004/001237 WO2004089909A1 (en) | 2003-04-14 | 2004-04-02 | 2-azabicyclo[3.3.1]nonane derivatives as opioid receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2522180A1 CA2522180A1 (en) | 2004-10-21 |
| CA2522180C true CA2522180C (en) | 2009-12-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002522180A Expired - Fee Related CA2522180C (en) | 2003-04-14 | 2004-04-02 | 2-azabicyclo[3.3.1]nonane derivatives as opioid receptor antagonists |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7056930B2 (https=) |
| EP (1) | EP1615893B1 (https=) |
| JP (1) | JP4493648B2 (https=) |
| AT (1) | ATE449074T1 (https=) |
| BR (1) | BRPI0409369A (https=) |
| CA (1) | CA2522180C (https=) |
| DE (1) | DE602004024188D1 (https=) |
| DK (1) | DK1615893T3 (https=) |
| ES (1) | ES2334570T3 (https=) |
| MX (1) | MXPA05011060A (https=) |
| WO (1) | WO2004089909A1 (https=) |
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| EP1440059B1 (en) * | 2001-10-22 | 2008-04-16 | Pfizer Products Inc. | 3-azabicyclo(3.1.0)hexane derivatives as opioid receptor antagonists |
| BRPI0409307A (pt) * | 2003-04-14 | 2006-04-25 | Pfizer Prod Inc | derivados de 3-azabiciclo[3.2.1]octano |
| US20050043345A1 (en) * | 2003-08-22 | 2005-02-24 | Pfizer Inc | Pharmaceutical composition for the prevention and treatment of addiction in a mammal |
| MY145633A (en) | 2006-03-01 | 2012-03-15 | Theravance Inc | 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| TWI409067B (zh) | 2007-02-28 | 2013-09-21 | Theravance Inc | ８-氮雜雙環〔３．２．１〕辛烷化合物之結晶型 |
| TWI425945B (zh) * | 2007-05-28 | 2014-02-11 | Seldar Pharma Inc | 四氫異喹啉－１－酮衍生物或其鹽 |
| US7947710B2 (en) * | 2007-08-27 | 2011-05-24 | Theravance, Inc. | Disubstituted alkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| WO2009029252A1 (en) * | 2007-08-27 | 2009-03-05 | Theravance, Inc. | Amidoalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| US7691878B2 (en) * | 2007-08-27 | 2010-04-06 | Theravance, Inc. | Heteroarylalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| TWI423801B (zh) * | 2007-08-27 | 2014-01-21 | Theravance Inc | 作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物 |
| GB0721178D0 (en) * | 2007-10-29 | 2007-12-05 | Glaxo Group Ltd | Chemical compounds |
| US20140206667A1 (en) | 2012-11-14 | 2014-07-24 | Michela Gallagher | Methods and compositions for treating schizophrenia |
| US9663463B2 (en) * | 2013-11-20 | 2017-05-30 | Sanwa Kagaku Kenkyusho Co., Ltd. | 3-azabicyclo[3.1.0]hexane derivative and use thereof for medical purpose |
| KR20180004734A (ko) * | 2015-05-20 | 2018-01-12 | 가부시키가이샤산와카가쿠켄큐쇼 | 신규 3-아자비시클로［3.1.0］헥산 유도체의 염의 결정 및 그의 의약 용도 |
| WO2017210105A1 (en) * | 2016-06-02 | 2017-12-07 | Virginia Commonwealth University | Dual modulators of both mu and kappa opioid receptors |
| SG11202007422QA (en) | 2018-02-05 | 2020-09-29 | Alkermes Inc | Compounds for the treatment of pain |
| US11352365B2 (en) | 2018-03-19 | 2022-06-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Biased potent opioid-like agonists as improved medications to treat chronic and acute pain and methods of using the same |
| KR102266854B1 (ko) * | 2019-11-06 | 2021-06-18 | 계명대학교 산학협력단 | 마약 중독 예방 또는 치료용 약학조성물 |
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| US2143145A (en) * | 1934-11-06 | 1939-01-10 | Farnsworth Television Inc | Projection means |
| US6559159B2 (en) * | 2001-02-01 | 2003-05-06 | Research Triangle Institute | Kappa opioid receptor ligands |
-
2004
- 2004-01-22 US US10/762,730 patent/US7056930B2/en not_active Ceased
- 2004-04-02 MX MXPA05011060A patent/MXPA05011060A/es not_active Application Discontinuation
- 2004-04-02 DE DE602004024188T patent/DE602004024188D1/de not_active Expired - Lifetime
- 2004-04-02 CA CA002522180A patent/CA2522180C/en not_active Expired - Fee Related
- 2004-04-02 AT AT04725453T patent/ATE449074T1/de not_active IP Right Cessation
- 2004-04-02 DK DK04725453.7T patent/DK1615893T3/da active
- 2004-04-02 BR BRPI0409369-0A patent/BRPI0409369A/pt not_active IP Right Cessation
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2007
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Also Published As
| Publication number | Publication date |
|---|---|
| JP4493648B2 (ja) | 2010-06-30 |
| MXPA05011060A (es) | 2005-12-12 |
| ATE449074T1 (de) | 2009-12-15 |
| DK1615893T3 (da) | 2010-01-18 |
| EP1615893B1 (en) | 2009-11-18 |
| ES2334570T3 (es) | 2010-03-12 |
| USRE40838E1 (en) | 2009-07-07 |
| CA2522180A1 (en) | 2004-10-21 |
| JP2006522797A (ja) | 2006-10-05 |
| EP1615893A1 (en) | 2006-01-18 |
| DE602004024188D1 (de) | 2009-12-31 |
| BRPI0409369A (pt) | 2006-04-25 |
| US20040204445A1 (en) | 2004-10-14 |
| WO2004089909A1 (en) | 2004-10-21 |
| US7056930B2 (en) | 2006-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |