CA2450205A1

CA2450205A1 - Aminediols for the treatment of alzheimer's disease

Aminediols for the treatment of alzheimer's disease Download PDF

Info

Publication number: CA2450205A1
Authority: CA; Canada
Prior art keywords: amino; alkyl; methyl; methylsulfonyl; carbonyl
Prior art date: 2001-06-13
Legal status : Abandoned

Application number

CA002450205A

Other languages

English (en)

French (fr)

Inventor

Heinrich Josef Schostarez

Robert Alan Chrusciel

Current Assignee

Elan Pharmaceuticals LLC

Pharmacia and Upjohn Co LLC

Original Assignee

Individual

Priority date

2001-06-13

Filing date

2002-06-13

Publication date

2002-12-19

2002-06-13 Application filed by Individual filed Critical Individual

2002-12-19 Publication of CA2450205A1 publication Critical patent/CA2450205A1/en

Status Abandoned legal-status Critical Current

Links

208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 78
238000011282 treatment Methods 0.000 title claims abstract description 37
150000001875 compounds Chemical class 0.000 claims abstract description 297
238000000034 method Methods 0.000 claims abstract description 105
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 60
201000010099 disease Diseases 0.000 claims abstract description 55
-1 -C1-C3 alkoxy Chemical group 0.000 claims description 284
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 195
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 194
229910052736 halogen Inorganic materials 0.000 claims description 125
150000002367 halogens Chemical class 0.000 claims description 118
125000000753 cycloalkyl group Chemical group 0.000 claims description 100
125000000217 alkyl group Chemical group 0.000 claims description 78
125000003118 aryl group Chemical group 0.000 claims description 69
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 63
125000000623 heterocyclic group Chemical group 0.000 claims description 50
125000004663 dialkyl amino group Chemical group 0.000 claims description 49
125000001072 heteroaryl group Chemical group 0.000 claims description 45
150000003839 salts Chemical class 0.000 claims description 40
125000000304 alkynyl group Chemical group 0.000 claims description 37
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 36
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 36
206010012289 Dementia Diseases 0.000 claims description 33
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 31
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 28
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 24
238000004519 manufacturing process Methods 0.000 claims description 24
208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 22
208000010877 cognitive disease Diseases 0.000 claims description 22
208000027061 mild cognitive impairment Diseases 0.000 claims description 22
230000003412 degenerative effect Effects 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 16
HEBKCHPVOIAQTA-NGQZWQHPSA-N d-xylitol Chemical compound OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 claims description 16
FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 claims description 16
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 14
201000010374 Down Syndrome Diseases 0.000 claims description 14
206010044688 Trisomy 21 Diseases 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 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
239000003814 drug Substances 0.000 claims description 11
125000002877 alkyl aryl group Chemical group 0.000 claims description 10
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 10
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 10
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
230000002792 vascular Effects 0.000 claims description 10
208000018737 Parkinson disease Diseases 0.000 claims description 9
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
230000001054 cortical effect Effects 0.000 claims description 9
230000007850 degeneration Effects 0.000 claims description 9
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
210000004558 lewy body Anatomy 0.000 claims description 7
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 6
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
229910052799 carbon Inorganic materials 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
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 5
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
230000002265 prevention Effects 0.000 claims description 5
125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 4
125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
125000004438 haloalkoxy group Chemical group 0.000 claims description 3
RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
125000003386 piperidinyl group Chemical group 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
125000001422 pyrrolinyl group Chemical group 0.000 claims description 3
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
VOTQNKMWMRRTNF-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-phenylnon-8-yn-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CCCC#C)=C1 VOTQNKMWMRRTNF-UHFFFAOYSA-N 0.000 claims description 2
HITDTRFWXBCZJF-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-phenylnonan-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=CC=C1 HITDTRFWXBCZJF-UHFFFAOYSA-N 0.000 claims description 2
ALCHLYSYYJLTFT-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-phenylnonan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=CC=C1 ALCHLYSYYJLTFT-UHFFFAOYSA-N 0.000 claims description 2
AAVKAKMEABDNQS-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-phenyloctan-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=CC=C1 AAVKAKMEABDNQS-UHFFFAOYSA-N 0.000 claims description 2
IYXJKKSOTIEAPD-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-phenyloctan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=CC=C1 IYXJKKSOTIEAPD-UHFFFAOYSA-N 0.000 claims description 2
PXEPFHWUNYEJHE-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-ylnon-8-yn-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=CN=CC=2)C(O)C(O)CCCC#C)=C1 PXEPFHWUNYEJHE-UHFFFAOYSA-N 0.000 claims description 2
WPAMKXTYYVGJER-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-ylnon-8-yn-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CN=CC=2)C(O)C(O)CCCC#C)=C1 WPAMKXTYYVGJER-UHFFFAOYSA-N 0.000 claims description 2
FQTFDCDCWYHFGN-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-ylnonan-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=NC=C1 FQTFDCDCWYHFGN-UHFFFAOYSA-N 0.000 claims description 2
BDPAFFSKXNRJTJ-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-ylnonan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=NC=C1 BDPAFFSKXNRJTJ-UHFFFAOYSA-N 0.000 claims description 2
WZCUDEDCAQCUCE-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-yloctan-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=NC=C1 WZCUDEDCAQCUCE-UHFFFAOYSA-N 0.000 claims description 2
ORAIVINDYDGYIZ-UHFFFAOYSA-N 1-n-(3,4-dihydroxy-1-pyridin-4-yloctan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=NC=C1 ORAIVINDYDGYIZ-UHFFFAOYSA-N 0.000 claims description 2
DWNXUJOGMRSHQU-UHFFFAOYSA-N 1-n-(5-cyano-3,4-dihydroxy-1-phenylpentan-2-yl)-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CC#N)=C1 DWNXUJOGMRSHQU-UHFFFAOYSA-N 0.000 claims description 2
LZGBDIBWWSFJNJ-UHFFFAOYSA-N 1-n-(5-cyano-3,4-dihydroxy-1-pyridin-4-ylpentan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CN=CC=2)C(O)C(O)CC#N)=C1 LZGBDIBWWSFJNJ-UHFFFAOYSA-N 0.000 claims description 2
SSFQIVVDFOMWBB-UHFFFAOYSA-N 1-n-(6-cyano-3,4-dihydroxy-1-phenylhexan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CCC#N)=C1 SSFQIVVDFOMWBB-UHFFFAOYSA-N 0.000 claims description 2
LLXIOCMEBLSORL-UHFFFAOYSA-N 1-n-(7-cyano-3,4-dihydroxy-1-phenylheptan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CCCC#N)=C1 LLXIOCMEBLSORL-UHFFFAOYSA-N 0.000 claims description 2
AOSMPTJYBUOPRJ-UHFFFAOYSA-N 1-n-(7-cyano-3,4-dihydroxy-1-pyridin-4-ylheptan-2-yl)-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CN=CC=2)C(O)C(O)CCCC#N)=C1 AOSMPTJYBUOPRJ-UHFFFAOYSA-N 0.000 claims description 2
RWJSXDABPVWKTG-GMQQYTKMSA-N 1-n-[(2s,3r,4s)-1-(3,5-difluorophenyl)-3,4-dihydroxyoctan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C([C@@H]([C@@H](O)[C@@H](O)CCCC)NC(=O)C=1C=C(C=C(C)C=1)C(=O)N(CCC)CCC)C1=CC(F)=CC(F)=C1 RWJSXDABPVWKTG-GMQQYTKMSA-N 0.000 claims description 2
IYXJKKSOTIEAPD-GMQQYTKMSA-N 1-n-[(2s,3r,4s)-3,4-dihydroxy-1-phenyloctan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C([C@@H]([C@@H](O)[C@@H](O)CCCC)NC(=O)C=1C=C(C=C(C)C=1)C(=O)N(CCC)CCC)C1=CC=CC=C1 IYXJKKSOTIEAPD-GMQQYTKMSA-N 0.000 claims description 2
UWSGMOGLUPCWSD-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3,4-dihydroxynon-8-yn-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)C(O)CCCC#C)=C1 UWSGMOGLUPCWSD-UHFFFAOYSA-N 0.000 claims description 2
YHNUDRUAWHFWDB-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3,4-dihydroxynon-8-yn-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)C(O)CCCC#C)=C1 YHNUDRUAWHFWDB-UHFFFAOYSA-N 0.000 claims description 2
WMDGYQCKMSZYOG-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3,4-dihydroxynonan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC(F)=CC(F)=C1 WMDGYQCKMSZYOG-UHFFFAOYSA-N 0.000 claims description 2
LZVSRTMEGVYLGF-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3,4-dihydroxyoctan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC(F)=CC(F)=C1 LZVSRTMEGVYLGF-UHFFFAOYSA-N 0.000 claims description 2
KUZDLJRJBFYMTC-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)non-8-yn-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CCCC#C)=C1 KUZDLJRJBFYMTC-UHFFFAOYSA-N 0.000 claims description 2
ZJWHWUVMSFIIDS-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)non-8-yn-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CCCC#C)=C1 ZJWHWUVMSFIIDS-UHFFFAOYSA-N 0.000 claims description 2
FFWPOAJMONBVEC-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)nonan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=C(O)C=C1 FFWPOAJMONBVEC-UHFFFAOYSA-N 0.000 claims description 2
MNTOBJNGQLGOEM-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)nonan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC=C(O)C=C1 MNTOBJNGQLGOEM-UHFFFAOYSA-N 0.000 claims description 2
XRDRGVGVJHIFRA-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)octan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound C=1C(C(N)=O)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=C(O)C=C1 XRDRGVGVJHIFRA-UHFFFAOYSA-N 0.000 claims description 2
GCKMFOCAAVSDHT-UHFFFAOYSA-N 1-n-[3,4-dihydroxy-1-(4-hydroxyphenyl)octan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C)=CC(C(=O)N(CCC)CCC)=CC=1C(=O)NC(C(O)C(O)CCCC)CC1=CC=C(O)C=C1 GCKMFOCAAVSDHT-UHFFFAOYSA-N 0.000 claims description 2
WKQXXNSIQNTDHQ-UHFFFAOYSA-N 1-n-[5-cyano-1-(3,5-difluorophenyl)-3,4-dihydroxypentan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)C(O)CC#N)=C1 WKQXXNSIQNTDHQ-UHFFFAOYSA-N 0.000 claims description 2
YJMNLGJZBOJSET-UHFFFAOYSA-N 1-n-[5-cyano-1-(3,5-difluorophenyl)-3,4-dihydroxypentan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)C(O)CC#N)=C1 YJMNLGJZBOJSET-UHFFFAOYSA-N 0.000 claims description 2
UGCJMVNJFWNPBL-UHFFFAOYSA-N 1-n-[5-cyano-3,4-dihydroxy-1-(4-hydroxyphenyl)pentan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CC#N)=C1 UGCJMVNJFWNPBL-UHFFFAOYSA-N 0.000 claims description 2
SYOXZQFZLVFTSJ-UHFFFAOYSA-N 1-n-[5-cyano-3,4-dihydroxy-1-(4-hydroxyphenyl)pentan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CC#N)=C1 SYOXZQFZLVFTSJ-UHFFFAOYSA-N 0.000 claims description 2
SOTYKCOPLDKSEZ-UHFFFAOYSA-N 1-n-[6-cyano-3,4-dihydroxy-1-(4-hydroxyphenyl)hexan-2-yl]-3-n,3-n-dipropylbenzene-1,3,5-tricarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C(N)=O)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CCC#N)=C1 SOTYKCOPLDKSEZ-UHFFFAOYSA-N 0.000 claims description 2
HWVLPHLSQWMMCY-UHFFFAOYSA-N 1-n-[6-cyano-3,4-dihydroxy-1-(4-hydroxyphenyl)hexan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CCC#N)=C1 HWVLPHLSQWMMCY-UHFFFAOYSA-N 0.000 claims description 2
AHOBFZPTLKVJOP-UHFFFAOYSA-N 1-n-[7-cyano-1-(3,5-difluorophenyl)-3,4-dihydroxyheptan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)C(O)CCCC#N)=C1 AHOBFZPTLKVJOP-UHFFFAOYSA-N 0.000 claims description 2
QPVXVENZJINNGY-UHFFFAOYSA-N 1-n-[7-cyano-3,4-dihydroxy-1-(4-hydroxyphenyl)heptan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=CC(O)=CC=2)C(O)C(O)CCCC#N)=C1 QPVXVENZJINNGY-UHFFFAOYSA-N 0.000 claims description 2
MNJRFOQXRKWYNK-JIMJEQGWSA-N 5-bromo-1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxyoctan-2-yl]-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C([C@@H]([C@@H](O)[C@H](O)CCCC)NC(=O)C=1C=C(C=C(Br)C=1)C(=O)N(CCC)CCC)C1=CC(F)=CC(F)=C1 MNJRFOQXRKWYNK-JIMJEQGWSA-N 0.000 claims description 2
RJEBHTRBRCSTAU-ISJGIBHGSA-N 5-bromo-1-n-[(2s,3r,4r)-3,4-dihydroxy-6-methylsulfanyl-1-phenylhexan-2-yl]-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(Br)=CC(C(=O)N[C@@H](CC=2C=CC=CC=2)[C@@H](O)[C@H](O)CCSC)=C1 RJEBHTRBRCSTAU-ISJGIBHGSA-N 0.000 claims description 2
125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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PIZGCXNUIKRZSS-UHFFFAOYSA-N n-(3,4-dihydroxy-1-phenylnon-8-yn-2-yl)-2-(methanesulfonamido)-1,3-thiazole-4-carboxamide Chemical compound S1C(NS(=O)(=O)C)=NC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CCCC#C)=C1 PIZGCXNUIKRZSS-UHFFFAOYSA-N 0.000 claims description 2
SFEPQHQILIEWBE-UHFFFAOYSA-N n-(3,4-dihydroxy-1-phenylnon-8-yn-2-yl)-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide Chemical compound O1C(N(C)S(C)(=O)=O)=NC(C(=O)NC(CC=2C=CC=CC=2)C(O)C(O)CCCC#C)=C1 SFEPQHQILIEWBE-UHFFFAOYSA-N 0.000 claims description 2
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FXHVXXFIVVWDAT-UHFFFAOYSA-N n-[1-(3,5-difluorophenyl)-3,4-dihydroxynonan-2-yl]-2-(methanesulfonamido)-1,3-oxazole-4-carboxamide Chemical compound C=1OC(NS(C)(=O)=O)=NC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC(F)=CC(F)=C1 FXHVXXFIVVWDAT-UHFFFAOYSA-N 0.000 claims description 2
PIRNVDSLNDTNIK-UHFFFAOYSA-N n-[1-(3,5-difluorophenyl)-3,4-dihydroxynonan-2-yl]-2-(methanesulfonamido)-1,3-thiazole-4-carboxamide Chemical compound C=1SC(NS(C)(=O)=O)=NC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC(F)=CC(F)=C1 PIRNVDSLNDTNIK-UHFFFAOYSA-N 0.000 claims description 2
XUZGKHJXZKERHR-UHFFFAOYSA-N n-[1-(3,5-difluorophenyl)-3,4-dihydroxynonan-2-yl]-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide Chemical compound C=1OC(N(C)S(C)(=O)=O)=NC=1C(=O)NC(C(O)C(O)CCCCC)CC1=CC(F)=CC(F)=C1 XUZGKHJXZKERHR-UHFFFAOYSA-N 0.000 claims description 2
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108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 abstract description 103
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