CA2452039A1

CA2452039A1 - Beta-hydroxyamine derivatives useful in treatment of alzheimer's disease

Beta-hydroxyamine derivatives useful in treatment of alzheimer's disease Download PDF

Info

Publication number: CA2452039A1
Authority: CA; Canada
Prior art keywords: alkyl; group; optionally substituted; alkoxy; heteroaryl
Prior art date: 2001-06-27
Legal status : Abandoned

Application number

CA002452039A

Other languages

English (en)

French (fr)

Inventor

Varghese John

Roy Hom

John Tucker

Current Assignee

Elan Pharmaceuticals LLC

Pharmacia and Upjohn Co LLC

Original Assignee

Individual

Priority date

2001-06-27

Filing date

2002-06-27

Publication date

2003-01-09

2002-06-27 Application filed by Individual filed Critical Individual

2003-01-09 Publication of CA2452039A1 publication Critical patent/CA2452039A1/en

Status Abandoned legal-status Critical Current

Links

208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 85
238000011282 treatment Methods 0.000 title claims abstract description 35
150000001875 compounds Chemical class 0.000 claims abstract description 246
150000001298 alcohols Chemical class 0.000 claims abstract description 20
-1 dihydronaphthalyl Chemical group 0.000 claims description 156
238000000034 method Methods 0.000 claims description 100
125000001424 substituent group Chemical group 0.000 claims description 92
125000000217 alkyl group Chemical group 0.000 claims description 64
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 61
201000010099 disease Diseases 0.000 claims description 55
125000000753 cycloalkyl group Chemical group 0.000 claims description 47
150000003839 salts Chemical class 0.000 claims description 42
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
125000003545 alkoxy group Chemical group 0.000 claims description 38
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 36
206010012289 Dementia Diseases 0.000 claims description 32
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 30
150000002148 esters Chemical class 0.000 claims description 28
208000010877 cognitive disease Diseases 0.000 claims description 27
208000027061 mild cognitive impairment Diseases 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 25
125000000623 heterocyclic group Chemical group 0.000 claims description 23
208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 21
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 20
229910052799 carbon Inorganic materials 0.000 claims description 20
125000001072 heteroaryl group Chemical group 0.000 claims description 19
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
125000003342 alkenyl group Chemical group 0.000 claims description 18
230000003412 degenerative effect Effects 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 15
125000000304 alkynyl group Chemical group 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
201000010374 Down Syndrome Diseases 0.000 claims description 14
206010044688 Trisomy 21 Diseases 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 14
150000001721 carbon Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
208000018282 ACys amyloidosis Diseases 0.000 claims description 12
208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 12
208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
210000004558 lewy body Anatomy 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
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208000018737 Parkinson disease Diseases 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
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230000001054 cortical effect Effects 0.000 claims description 8
230000007850 degeneration Effects 0.000 claims description 8
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 8
230000000306 recurrent effect Effects 0.000 claims description 8
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 8
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229910052757 nitrogen Inorganic materials 0.000 claims description 7
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 7
125000005309 thioalkoxy group Chemical group 0.000 claims description 7
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125000002757 morpholinyl group Chemical group 0.000 claims description 6
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125000003386 piperidinyl group Chemical group 0.000 claims description 6
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125000005842 heteroatom Chemical group 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
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125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 4
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 4
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 4
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 4
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 4
125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 claims description 4
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125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 claims description 4
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 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 claims description 4
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125000002541 furyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 4
125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 claims description 4
125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 claims description 4
125000005990 isobenzothienyl group Chemical group 0.000 claims description 4
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 4
125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 claims description 4
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 4
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125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 4
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 4
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 4
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 4
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125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
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125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
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125000001544 thienyl group Chemical group 0.000 claims description 4
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125000001425 triazolyl group Chemical group 0.000 claims description 4
125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 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 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
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125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 2
125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 claims description 2
125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 2
RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 2
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125000006413 ring segment Chemical group 0.000 claims description 2
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