JP2001506269A - アミノインダン誘導体 - Google Patents
アミノインダン誘導体Info
- Publication number
- JP2001506269A JP2001506269A JP52804898A JP52804898A JP2001506269A JP 2001506269 A JP2001506269 A JP 2001506269A JP 52804898 A JP52804898 A JP 52804898A JP 52804898 A JP52804898 A JP 52804898A JP 2001506269 A JP2001506269 A JP 2001506269A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- methyl
- compound according
- propargyl
- hydrogen
- 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.)
- Granted
Links
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical class C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 109
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 22
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 21
- 206010012289 Dementia Diseases 0.000 claims abstract description 14
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 4
- 208000009829 Lewy Body Disease Diseases 0.000 claims abstract description 3
- 201000002832 Lewy body dementia Diseases 0.000 claims abstract description 3
- 201000004810 Vascular dementia Diseases 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 2
- -1 amino-substituted carbon atom Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 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 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 5
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- 206010036631 Presenile dementia Diseases 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- 230000000750 progressive effect Effects 0.000 claims description 2
- 230000003068 static effect Effects 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 230000001537 neural effect Effects 0.000 claims 1
- VNAXXPBYEKLMMP-UHFFFAOYSA-N o-[(3-amino-2,3-dihydro-1h-inden-5-yl)] n,n-dimethylcarbamothioate Chemical compound CN(C)C(=S)OC1=CC=C2CCC(N)C2=C1 VNAXXPBYEKLMMP-UHFFFAOYSA-N 0.000 claims 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 abstract description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 abstract description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 abstract description 4
- 229910052736 halogen Inorganic materials 0.000 abstract description 4
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 abstract description 4
- 208000000323 Tourette Syndrome Diseases 0.000 abstract description 2
- 208000016620 Tourette disease Diseases 0.000 abstract description 2
- 150000002367 halogens Chemical group 0.000 abstract description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- 230000000694 effects Effects 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 21
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 229940079593 drug Drugs 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
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- 108010022752 Acetylcholinesterase Proteins 0.000 description 14
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- 229940022698 acetylcholinesterase Drugs 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 102000010909 Monoamine Oxidase Human genes 0.000 description 13
- 108010062431 Monoamine oxidase Proteins 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 208000030886 Traumatic Brain injury Diseases 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 206010021143 Hypoxia Diseases 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 7
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 7
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 7
- 230000000926 neurological effect Effects 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000003414 extremity Anatomy 0.000 description 6
- 230000007954 hypoxia Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 5
- 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 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 5
- 230000021235 carbamoylation Effects 0.000 description 5
- 229940125961 compound 24 Drugs 0.000 description 5
- 229940125846 compound 25 Drugs 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
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- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
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- 238000010254 subcutaneous injection Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000452413 Sabra Species 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
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- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
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- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
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- 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 2
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- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/44—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/58—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式Iの化合物: [ここで、aが0であるとき;bは1又は2であり;aが1であるとき、bは 1であり、mは0から3であり、xは0又はSであり、Yはハロゲンであり、 R1は水素又はC1-4アルキル、R2は水素、C1-4アルキル又は任意に置換され たプロパルギルであり、並びにR3及びR4は夫々独立して水素、各々任意に 置換されたC1-8アルキル、C6-12アリル、C6-12アラルキル又はC6-12シク ロアルキルである]。 2. 請求項1に記載の化合物であって、Xが0である化合物。 3. 請求項1に記載の化合物であって、XがSである化合物。 4. 請求項1に記載の化合物であって、aが0であり、且つbが1である化合物 。 5. 請求項2に記載の化合物であって、aが0であり、且つbが1である化合物 。 6. 請求項3に記載の化合物であって、aが0であり、且つbが1である化合物 。 7. 請求項4に記載の化合物であって、R2が水素、メチル、エチル又は任意に 置換されたプロパルギルからなる群より選択される化合物。 8. 請求項5に記載の化合物であって、R2が水素、メチル、エチル又は任意に 置換されたプロパルギルからなる群より選択される化合物。 9. 請求項6に記載の化合物であって、R2が水素、メチル、エチル又は任意に 置換されたプロパルギルからなる群より選択される化合物。 10. 請求項7に記載の化合物であって、R2がプロパルギルである化合物。 11. 請求項8に記載の化合物であって、R2がプロパルギルである化合物。 12. 請求項9に記載の化合物であって、R2がプロパルギルである化合物。 13. 請求項1に記載の化合物であって、R3又はR4の一方がメチルであり、且 つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル、 ベンジル、又はシクロヘキシルである化合物。 14. 請求項2に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 15. 請求項3に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 16. 請求項4に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 17. 請求項5に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 18. 請求項7に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 19. 請求項10に記載の化合物であって、R3又はR4の一方が、メチルであり、 且つもう一方が水素、メチル、エチル、ブチル、プロピル、ヘキシル、フェニル 、ベンジル又はシクロヘキシルである化合物。 20. 請求項13に記載の化合物であって、前記OC(X)NR3R4基が、該アミノ置換 炭素原子から数えてインダン環の4、6又は7位にある化合物。 21. 請求項14に記載の化合物であって、前記OC(X)NR3R4基が、該アミノ置 炭素原子から数えてインダン環の4、6又は7位にある化合物。 22. 請求項15に記載の化合物であって、前記OC(X)NR3R4基が、該アミノ置換 炭素原子から数えてインダン環の4、6又は7位にある化合物。 23. 請求項16に記載の化合物であって、前記OC(X)NR3R4基が、該アミノ置 換炭素原子から数えてインダン環の4、6又は7位にある化合物。 24. 請求項17に記載の化合物であって、前記OC(X)NR3R4基が、該アミノ置換 炭素原子から数えてインダン環の4、6又は7位にある化合物。 25. 請求項1に記載の化合物であって、前記化合物が光学的活性なエナンチ オマーである化合物。 26. 請求項2に記載の化合物であって、前記化合物が光学的活性なエナンチ オマーである化合物。 27. 請求項3に記戟の化合物であって、前記化合物が光学的活性なエナンチ オマーである化合物。 28. 請求項4に記載の化合物であって、前記化合物が光学的活性なエナンチ オマーである化合物。 29. 以下の化合物からなる群より選択される化合物;(rac)6-(N-メチル,N- エチル-カルバミルオキシ)-N'-プロパルギル-1-アミノインダンHCl;(rec)6-(N, N-ジメチル,カルバミルオキシ)-N'-メチル-N'-プロパルギル-1-アミノインダン HCl;(rac)6-(N-メチル,N-エチル-カルバミルオキシ)-N'-プロパルギル-1-アミ ノテトラリンHCl;(rat)6-(N,N-ジメチル-チオカルバミルオキシ)-1-アミノイン ダンHCl;(rat)6-(N-プロピル-カルバミルオキシ)-N'-プロパルギル-1-アミノイ ンダンHCl;(rac)5-クロロ-6-(N-メチル,N-プロピル-カルバミルオキシ)-N'-プ ロパルギル-1-アミノインダンHCl;(S)-6-(N-メチル,N-プロピル-カルバミルオ キシ)-N'-プロパルギル-1-アミノインダンHCl;及び(R)-6-(N-メチル,N-エチル -カルバミルオキシ)-N-プロパルギル-1-アミノインダン ヘミ-(L)-酒石酸塩。 30. 請求項1に記載の化合物の治療学的有効量と、薬学的に許容される担体 とを含有する薬学的組成物。 31. アルツハイマー病又は痴呆の治療に効果な量の請求項1の化合物を、ア ルツハイマー病又は痴呆に罹患する対象に対して投与することを具備する前記対 象を治療する方法。 32. 請求項31に記載の方法であって、前記痴呆が、静的痴呆、アルツハイマ ー型痴呆、老人性痴呆、初老期痴呆、進行性痴呆、血管性痴呆、又はレーヴィ小 体痴呆を含む方法。 33. 神経外傷の治療に有効な量の請求項1の化合物を、神経外傷に罹患する 対象に投与することを具備する前記対象を治療する方法。 34. 記憶障害の治療に有効な量の請求項1の化合物を、記憶障害に罹患する 対象に投与することを具備する前記対象を治療する方法。
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IL119853 | 1996-12-18 | ||
IL11985396A IL119853A0 (en) | 1996-12-18 | 1996-12-18 | Aminoindan derivatives |
IL12051097A IL120510A0 (en) | 1997-03-24 | 1997-03-24 | Phenylethylamine derivatives |
IL120510 | 1997-03-24 | ||
PCT/US1997/024155 WO1998027055A1 (en) | 1996-12-18 | 1997-12-18 | Aminoindan derivatives |
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-
1997
- 1997-12-18 EP EP05002578A patent/EP1535902B1/en not_active Expired - Lifetime
- 1997-12-18 DE DE69732984T patent/DE69732984T2/de not_active Expired - Lifetime
- 1997-12-18 WO PCT/US1997/024155 patent/WO1998027055A1/en active IP Right Grant
- 1997-12-18 HU HU0101130A patent/HU229507B1/hu unknown
- 1997-12-18 AT AT97953541T patent/ATE292619T1/de not_active IP Right Cessation
- 1997-12-18 JP JP52804898A patent/JP4222632B2/ja not_active Expired - Fee Related
- 1997-12-18 IL IL13052897A patent/IL130528A/en not_active IP Right Cessation
- 1997-12-18 AT AT05002578T patent/ATE377585T1/de not_active IP Right Cessation
- 1997-12-18 PT PT97953541T patent/PT966435E/pt unknown
- 1997-12-18 AU AU57268/98A patent/AU5726898A/en not_active Abandoned
- 1997-12-18 CA CA002275425A patent/CA2275425C/en not_active Expired - Lifetime
- 1997-12-18 DK DK97953541T patent/DK0966435T3/da active
- 1997-12-18 DE DE69738275T patent/DE69738275T2/de not_active Expired - Lifetime
- 1997-12-18 EP EP97953541A patent/EP0966435B1/en not_active Expired - Lifetime
- 1997-12-18 ES ES97953541T patent/ES2241064T3/es not_active Expired - Lifetime
-
1999
- 1999-06-18 US US09/336,493 patent/US6303650B1/en not_active Expired - Lifetime
-
2000
- 2000-06-19 HK HK00103684A patent/HK1024462A1/xx not_active IP Right Cessation
-
2001
- 2001-08-31 US US09/944,912 patent/US6538025B2/en not_active Ceased
- 2001-08-31 US US09/944,850 patent/US6462222B1/en not_active Expired - Lifetime
-
2005
- 2005-03-25 US US11/091,008 patent/USRE39616E1/en not_active Expired - Lifetime
- 2005-11-22 HK HK05110547A patent/HK1076098A1/xx not_active IP Right Cessation
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005523289A (ja) * | 2002-02-27 | 2005-08-04 | テバ ファーマシューティカル インダストリーズ リミティド | 脳選択性mao阻害剤としてのプロパルギルアミノインダン誘導体及びプロパルギルアミノテトラリン誘導体 |
JP2007512319A (ja) * | 2003-11-25 | 2007-05-17 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | 心臓血管障害及び疾患を治療するための組成物及び方法 |
JP2009521402A (ja) * | 2005-11-17 | 2009-06-04 | テバ ファーマシューティカル インダストリーズ リミティド | プロパルギル化アミノインダンの分離のための方法 |
JP2009518433A (ja) * | 2005-12-09 | 2009-05-07 | イッサム リサーチ ディベロップメント カンパニー オブ ザ ヘブライ ユニバーシティー オブ エルサレム | 神経保護用の低用量ラドスチギルの使用 |
Also Published As
Publication number | Publication date |
---|---|
CA2275425A1 (en) | 1998-06-25 |
EP1535902A1 (en) | 2005-06-01 |
WO1998027055A1 (en) | 1998-06-25 |
US6538025B2 (en) | 2003-03-25 |
EP0966435A4 (en) | 2003-04-16 |
USRE39616E1 (en) | 2007-05-08 |
ATE292619T1 (de) | 2005-04-15 |
PT966435E (pt) | 2005-06-30 |
IL130528A (en) | 2004-12-15 |
DE69732984D1 (de) | 2005-05-12 |
HU229507B1 (en) | 2014-01-28 |
JP4222632B2 (ja) | 2009-02-12 |
DE69732984T2 (de) | 2006-02-16 |
HUP0101130A3 (en) | 2003-02-28 |
AU5726898A (en) | 1998-07-15 |
EP0966435A1 (en) | 1999-12-29 |
DK0966435T3 (da) | 2005-08-15 |
DE69738275D1 (de) | 2007-12-20 |
EP0966435B1 (en) | 2005-04-06 |
CA2275425C (en) | 2009-08-04 |
ATE377585T1 (de) | 2007-11-15 |
EP1535902B1 (en) | 2007-11-07 |
HUP0101130A2 (hu) | 2001-08-28 |
DE69738275T2 (de) | 2008-08-28 |
US6303650B1 (en) | 2001-10-16 |
US20020188020A1 (en) | 2002-12-12 |
US6462222B1 (en) | 2002-10-08 |
HK1024462A1 (en) | 2000-10-13 |
ES2241064T3 (es) | 2005-10-16 |
HK1076098A1 (en) | 2006-01-06 |
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