KR20060057569A - 알파7 니코틴계 아세틸콜린 수용체와 친화도를 갖는스피로[1-아자비시클로[2.2.2]옥탄-3,5'-옥사졸리딘-2'-온] 유도체 - Google Patents

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Publication number

KR20060057569A

KR20060057569A KR1020067000400A KR20067000400A KR20060057569A KR 20060057569 A KR20060057569 A KR 20060057569A KR 1020067000400 A KR1020067000400 A KR 1020067000400A KR 20067000400 A KR20067000400 A KR 20067000400A KR 20060057569 A KR20060057569 A KR 20060057569A

Authority

KR

South Korea

Prior art keywords

spiro

azabicyclo

octane

thiophen

oxazolidine

Prior art date

2003-07-08

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.)

Ceased

Links

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• 102000047725 alpha7 Nicotinic Acetylcholine Receptor Human genes 0.000 title claims description 6
• 108700006085 alpha7 Nicotinic Acetylcholine Receptor Proteins 0.000 title claims description 6
• TYAGAVRSOFABFO-VIFPVBQESA-N (5s)-spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical class O1C(=O)NC[C@]11C(CC2)CCN2C1 TYAGAVRSOFABFO-VIFPVBQESA-N 0.000 title description 15
• 150000001875 compounds Chemical class 0.000 claims abstract description 254
• 238000000034 method Methods 0.000 claims abstract description 112
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
• 238000004519 manufacturing process Methods 0.000 claims abstract description 24
• 150000003839 salts Chemical class 0.000 claims abstract description 24
• 239000003814 drug Substances 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 229940079593 drug Drugs 0.000 claims abstract description 10
• -1 2-pyrimidyl Chemical group 0.000 claims description 261
• 125000003003 spiro group Chemical group 0.000 claims description 84
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 239000001257 hydrogen Substances 0.000 claims description 51
• 125000004122 cyclic group Chemical group 0.000 claims description 37
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 36
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 31
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 27
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 25
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 25
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 150000002431 hydrogen Chemical class 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• TYAGAVRSOFABFO-UHFFFAOYSA-N spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound O1C(=O)NCC11C(CC2)CCN2C1 TYAGAVRSOFABFO-UHFFFAOYSA-N 0.000 claims description 24
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 150000002367 halogens Chemical class 0.000 claims description 20
• 230000002265 prevention Effects 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 19
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 19
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 18
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• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 230000006735 deficit Effects 0.000 claims description 16
• 125000003118 aryl group Chemical group 0.000 claims description 15
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• 125000004434 sulfur atom Chemical group 0.000 claims description 12
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 10
• 229910052722 tritium Inorganic materials 0.000 claims description 10
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
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• 230000005586 smoking cessation Effects 0.000 claims description 7
• 125000006017 1-propenyl group Chemical group 0.000 claims description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
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• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000006038 hexenyl group Chemical group 0.000 claims description 6
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 6
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 6
• 210000000225 synapse Anatomy 0.000 claims description 6
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
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• ONLUCDBUROZPQZ-QGZVFWFLSA-N (5r)-3-(2-pyridin-3-yl-1,3-thiazol-4-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound C([C@@]1(OC2=O)C3CCN(CC3)C1)N2C(N=1)=CSC=1C1=CC=CN=C1 ONLUCDBUROZPQZ-QGZVFWFLSA-N 0.000 claims description 4
• PLUFRMLMVYJVRA-QGZVFWFLSA-N (5r)-3-(2-pyridin-3-yl-1,3-thiazol-5-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound C([C@@]1(OC2=O)C3CCN(CC3)C1)N2C(S1)=CN=C1C1=CC=CN=C1 PLUFRMLMVYJVRA-QGZVFWFLSA-N 0.000 claims description 4
• JUXGDTBXNQMZFI-HXUWFJFHSA-N (5r)-3-[5-(3-methoxyphenyl)thiophen-2-yl]spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound COC1=CC=CC(C=2SC(=CC=2)N2C(O[C@@]3(C4CCN(CC4)C3)C2)=O)=C1 JUXGDTBXNQMZFI-HXUWFJFHSA-N 0.000 claims description 4
• NJGIYZOSEBWUOK-LJQANCHMSA-N (5r)-3-[5-[3-(trifluoromethoxy)phenyl]thiophen-2-yl]spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound FC(F)(F)OC1=CC=CC(C=2SC(=CC=2)N2C(O[C@@]3(C4CCN(CC4)C3)C2)=O)=C1 NJGIYZOSEBWUOK-LJQANCHMSA-N 0.000 claims description 4
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
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• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
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