JP2004535424A

JP2004535424A - アルツハイマー病の治療に有用な置換アミノアルコール

アルツハイマー病の治療に有用な置換アミノアルコール Download PDF

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Publication number: JP2004535424A
Authority: JP; Japan
Prior art keywords: alkyl; optionally substituted; group; aryl; heteroaryl
Prior art date: 2001-06-11
Legal status : Pending

Application number

JP2003503590A

Other languages

English (en)

Japanese (ja)

Other versions

JP2004535424A5 (https=

Inventor

マイラード、マイケル

タッカー、ジョン、アラン

Current Assignee

Pharmacia and Upjohn Co

Original Assignee

Pharmacia and Upjohn Co

Priority date

2001-06-11

Filing date

2002-06-11

Publication date

2004-11-25

2002-06-11 Application filed by Pharmacia and Upjohn Co filed Critical Pharmacia and Upjohn Co

2004-11-25 Publication of JP2004535424A publication Critical patent/JP2004535424A/ja

2006-01-05 Publication of JP2004535424A5 publication Critical patent/JP2004535424A5/ja

Status Pending legal-status Critical Current

Links

208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 82
150000001414 amino alcohols Chemical class 0.000 title claims description 14
150000001875 compounds Chemical class 0.000 claims abstract description 190
238000000034 method Methods 0.000 claims abstract description 73
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
201000010099 disease Diseases 0.000 claims abstract description 40
125000001424 substituent group Chemical group 0.000 claims description 248
-1 dihydronaphthalyl Chemical group 0.000 claims description 185
125000001072 heteroaryl group Chemical group 0.000 claims description 171
229910052799 carbon Inorganic materials 0.000 claims description 164
125000000217 alkyl group Chemical group 0.000 claims description 148
229910052739 hydrogen Inorganic materials 0.000 claims description 148
125000003118 aryl group Chemical group 0.000 claims description 143
125000000753 cycloalkyl group Chemical group 0.000 claims description 125
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 104
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 72
229910052736 halogen Inorganic materials 0.000 claims description 68
150000002367 halogens Chemical class 0.000 claims description 68
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
125000003545 alkoxy group Chemical group 0.000 claims description 50
206010012289 Dementia Diseases 0.000 claims description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
229910052740 iodine Inorganic materials 0.000 claims description 46
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 44
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 44
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 44
229910052801 chlorine Inorganic materials 0.000 claims description 41
229910052731 fluorine Inorganic materials 0.000 claims description 40
239000001257 hydrogen Substances 0.000 claims description 39
150000001721 carbon Chemical group 0.000 claims description 37
125000004432 carbon atom Chemical group C* 0.000 claims description 35
125000000623 heterocyclic group Chemical group 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 31
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 28
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
208000010877 cognitive disease Diseases 0.000 claims description 26
125000004663 dialkyl amino group Chemical group 0.000 claims description 26
208000027061 mild cognitive impairment Diseases 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
125000000304 alkynyl group Chemical group 0.000 claims description 21
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 18
229910052717 sulfur Inorganic materials 0.000 claims description 18
150000002148 esters Chemical class 0.000 claims description 17
229910052760 oxygen Inorganic materials 0.000 claims description 17
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 16
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 16
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 16
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 16
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 16
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 16
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 16
230000003412 degenerative effect Effects 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 14
125000002837 carbocyclic group Chemical group 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 11
206010008111 Cerebral haemorrhage Diseases 0.000 claims description 10
230000002490 cerebral effect Effects 0.000 claims description 10
230000007850 degeneration Effects 0.000 claims description 10
208000032843 Hemorrhage Diseases 0.000 claims description 9
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210000004227 basal ganglia Anatomy 0.000 claims description 9
238000004393 prognosis Methods 0.000 claims description 9
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125000004429 atom Chemical group 0.000 claims description 8
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 8
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 8
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 8
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 8
125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 8
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 8
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 8
230000001054 cortical effect Effects 0.000 claims description 8
125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 claims description 8
125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 8
150000002431 hydrogen Chemical group 0.000 claims description 8
125000002883 imidazolyl group Chemical group 0.000 claims description 8
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 8
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 8
125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 claims description 8
125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 claims description 8
125000005990 isobenzothienyl group Chemical group 0.000 claims description 8
125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 claims description 8
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 8
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 8
125000005956 isoquinolyl group Chemical group 0.000 claims description 8
125000001786 isothiazolyl group Chemical group 0.000 claims description 8
125000000842 isoxazolyl group Chemical group 0.000 claims description 8
210000004558 lewy body Anatomy 0.000 claims description 8
125000002757 morpholinyl group Chemical group 0.000 claims description 8
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 8
125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
125000002971 oxazolyl group Chemical group 0.000 claims description 8
125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 8
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 8
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 8
125000003373 pyrazinyl group Chemical group 0.000 claims description 8
125000003226 pyrazolyl group Chemical group 0.000 claims description 8
125000002098 pyridazinyl group Chemical group 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
125000001422 pyrrolinyl group Chemical group 0.000 claims description 8
125000000168 pyrrolyl group Chemical group 0.000 claims description 8
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 8
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
229910052705 radium Inorganic materials 0.000 claims description 8
125000006413 ring segment Chemical group 0.000 claims description 8
229910052701 rubidium Inorganic materials 0.000 claims description 8
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 8
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 8
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125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 8
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125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
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125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 7
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 5
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SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 5
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 4
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 2
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