CA2467798A1 - Amine 1,2- and 1,3-diol compounds and their use for treatment of alzheimer's disease - Google Patents
Amine 1,2- and 1,3-diol compounds and their use for treatment of alzheimer's disease Download PDFInfo
- Publication number
- CA2467798A1 CA2467798A1 CA002467798A CA2467798A CA2467798A1 CA 2467798 A1 CA2467798 A1 CA 2467798A1 CA 002467798 A CA002467798 A CA 002467798A CA 2467798 A CA2467798 A CA 2467798A CA 2467798 A1 CA2467798 A1 CA 2467798A1
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- Prior art keywords
- alkyl
- optionally substituted
- group
- oxide
- alkoxy
- 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.)
- Abandoned
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- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 62
- 238000011282 treatment Methods 0.000 title claims abstract description 33
- -1 1,3-diol compounds Chemical class 0.000 title claims description 1073
- 150000001412 amines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 181
- 238000000034 method Methods 0.000 claims abstract description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 54
- 201000010099 disease Diseases 0.000 claims abstract description 52
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 150000002148 esters Chemical class 0.000 claims abstract description 35
- 125000001424 substituent group Chemical group 0.000 claims description 362
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 352
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 334
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 293
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 264
- 125000000217 alkyl group Chemical group 0.000 claims description 157
- 229910052739 hydrogen Inorganic materials 0.000 claims description 152
- 125000001072 heteroaryl group Chemical group 0.000 claims description 119
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 114
- 125000003118 aryl group Chemical group 0.000 claims description 97
- 125000003342 alkenyl group Chemical group 0.000 claims description 95
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 80
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 80
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 80
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 79
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical group 0.000 claims description 68
- 125000000623 heterocyclic group Chemical group 0.000 claims description 63
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 56
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 56
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 52
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 52
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 50
- 125000002757 morpholinyl group Chemical group 0.000 claims description 44
- 125000004193 piperazinyl group Chemical group 0.000 claims description 44
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 43
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 42
- 125000003386 piperidinyl group Chemical group 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 40
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 40
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 40
- 125000001544 thienyl group Chemical group 0.000 claims description 40
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 38
- 125000002883 imidazolyl group Chemical group 0.000 claims description 36
- 125000002971 oxazolyl group Chemical group 0.000 claims description 36
- 125000000335 thiazolyl group Chemical group 0.000 claims description 36
- 125000004429 atom Chemical group 0.000 claims description 34
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 34
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 34
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 32
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 32
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 32
- 125000002541 furyl group Chemical group 0.000 claims description 32
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 32
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 32
- 125000001041 indolyl group Chemical group 0.000 claims description 32
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 32
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 32
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 32
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 32
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 32
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 32
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 32
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 32
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 32
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 32
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 32
- 125000001425 triazolyl group Chemical group 0.000 claims description 32
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 31
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 31
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 30
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 30
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 30
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 30
- 125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 claims description 30
- 125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 claims description 30
- 125000005990 isobenzothienyl group Chemical group 0.000 claims description 30
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 30
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 30
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 30
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 30
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 29
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 28
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 28
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 28
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 claims description 28
- 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 claims description 28
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 claims description 28
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 28
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 28
- 125000004306 triazinyl group Chemical group 0.000 claims description 28
- 206010012289 Dementia Diseases 0.000 claims description 27
- 239000000460 chlorine Substances 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 claims description 26
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 claims description 26
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 26
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 26
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 claims description 24
- 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 22
- 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 22
- 208000010877 cognitive disease Diseases 0.000 claims description 21
- 208000027061 mild cognitive impairment Diseases 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
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 20
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 20
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 19
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 16
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 15
- 230000003412 degenerative effect Effects 0.000 claims description 14
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 14
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 14
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 14
- 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 12
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
- 125000006413 ring segment Chemical group 0.000 claims description 12
- 201000010374 Down Syndrome Diseases 0.000 claims description 11
- 206010044688 Trisomy 21 Diseases 0.000 claims description 11
- 208000018282 ACys amyloidosis Diseases 0.000 claims description 10
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 10
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 claims description 8
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 8
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 8
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims description 8
- 210000004558 lewy body Anatomy 0.000 claims description 8
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 8
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 230000002792 vascular Effects 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 6
- 208000032843 Hemorrhage Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 230000001054 cortical effect Effects 0.000 claims description 6
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 6
- 230000007850 degeneration Effects 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 6
- 230000000306 recurrent effect Effects 0.000 claims description 6
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims description 4
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 4
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- NEGMMKYAVYNLCG-UHFFFAOYSA-N 5-ethyl-1-methyl-5-phenylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1C1(CC)N(C)C(=O)NC1=O NEGMMKYAVYNLCG-UHFFFAOYSA-N 0.000 claims 5
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 3
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 3
- DOGHYLUQILOTBB-OYUWMTPXSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-(2-methoxyethoxy)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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCOC)=C1 DOGHYLUQILOTBB-OYUWMTPXSA-N 0.000 claims 2
- UCZFIMQPAUYFFA-DCMFLLSESA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-(2-phenylethoxy)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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC=2C=CC=CC=2)=C1 UCZFIMQPAUYFFA-DCMFLLSESA-N 0.000 claims 2
- UDRZWRNKFDAGIU-ZGIBFIJWSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-5-(3,3-dimethylbutoxy)-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC(C)(C)C)=C1 UDRZWRNKFDAGIU-ZGIBFIJWSA-N 0.000 claims 2
- HBZDLVCMSQLKBE-FRXPANAUSA-N 1-n-[(2s,3r,4r)-5-(cyclopentylmethoxy)-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCC2CCCC2)=C1 HBZDLVCMSQLKBE-FRXPANAUSA-N 0.000 claims 2
- UFXFEEUBHIWMBH-UPRLRBBYSA-N 1-n-[(2s,3r,4r)-5-but-3-ynoxy-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC#C)=C1 UFXFEEUBHIWMBH-UPRLRBBYSA-N 0.000 claims 2
- OOBRTCMMRHJIIQ-UPRLRBBYSA-N 1-n-[(2s,3r,4r)-5-cyclobutyloxy-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COC2CCC2)=C1 OOBRTCMMRHJIIQ-UPRLRBBYSA-N 0.000 claims 2
- FJHMHCYYRUWFRP-OJDZSJEKSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-(3-methoxyanilino)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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)CNC=2C=C(OC)C=CC=2)=C1 FJHMHCYYRUWFRP-OJDZSJEKSA-N 0.000 claims 1
- AZIGXLILVYIHGR-ZGIBFIJWSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-(3-methylbut-3-enoxy)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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC(C)=C)=C1 AZIGXLILVYIHGR-ZGIBFIJWSA-N 0.000 claims 1
- ICTPUCMPHWUALV-WIHCDAFUSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-[2-(4-methylphenyl)ethoxy]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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC=2C=CC(C)=CC=2)=C1 ICTPUCMPHWUALV-WIHCDAFUSA-N 0.000 claims 1
- RZEZEKWXDMNHPW-ZGIBFIJWSA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-3,4-dihydroxy-5-pentoxypentan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C([C@@H]([C@@H](O)[C@H](O)COCCCCC)NC(=O)C=1C=C(C=C(C)C=1)C(=O)N(CCC)CCC)C1=CC(F)=CC(F)=C1 RZEZEKWXDMNHPW-ZGIBFIJWSA-N 0.000 claims 1
- VFZGBHXLHNZPGG-DCMFLLSESA-N 1-n-[(2s,3r,4r)-1-(3,5-difluorophenyl)-5-(3-ethylanilino)-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)CNC=2C=C(CC)C=CC=2)=C1 VFZGBHXLHNZPGG-DCMFLLSESA-N 0.000 claims 1
- GYSCIPPQSMAXMI-DCMFLLSESA-N 1-n-[(2s,3r,4r)-5-(2-cyclohexylethoxy)-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC2CCCCC2)=C1 GYSCIPPQSMAXMI-DCMFLLSESA-N 0.000 claims 1
- XXMBUOZQSLSMQV-OJDZSJEKSA-N 1-n-[(2s,3r,4r)-5-(2-cyclopentylethoxy)-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)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@@H](O)[C@H](O)COCCC2CCCC2)=C1 XXMBUOZQSLSMQV-OJDZSJEKSA-N 0.000 claims 1
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- 229960002930 sirolimus Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
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- 229960001603 tamoxifen Drugs 0.000 description 1
- NTQMRNJDSLLFEW-JKSUJKDBSA-N tert-butyl (4s,5r)-4-[(3,5-difluorophenyl)methyl]-5-ethenyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound C=C[C@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1=CC(F)=CC(F)=C1 NTQMRNJDSLLFEW-JKSUJKDBSA-N 0.000 description 1
- LYJZXYGWJRLBSN-LSLKUGRBSA-N tert-butyl n-[(2s)-1-(3,5-difluorophenyl)-3-hydroxypent-4-en-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)C=C)CC1=CC(F)=CC(F)=C1 LYJZXYGWJRLBSN-LSLKUGRBSA-N 0.000 description 1
- ZLCKWHXGRSNFHB-LSDHHAIUSA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxyhex-5-en-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@H](O)CC=C)CC1=CC(F)=CC(F)=C1 ZLCKWHXGRSNFHB-LSDHHAIUSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 229950010938 valspodar Drugs 0.000 description 1
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- 229960001722 verapamil Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
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- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- IHOVFYSQUDPMCN-QKUIIBHLSA-N zosuquidar Chemical compound C([C@H](COC=1C2=CC=CN=C2C=CC=1)O)N(CC1)CCN1C1C2=CC=CC=C2C2C(F)(F)C2C2=CC=CC=C12 IHOVFYSQUDPMCN-QKUIIBHLSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/73—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/77—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/78—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D309/06—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Indole Compounds (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33308101P | 2001-11-19 | 2001-11-19 | |
| US60/333,081 | 2001-11-19 | ||
| US33400001P | 2001-11-28 | 2001-11-28 | |
| US60/334,000 | 2001-11-28 | ||
| US36275202P | 2002-03-08 | 2002-03-08 | |
| US60/362,752 | 2002-03-08 | ||
| PCT/US2002/036999 WO2003043975A1 (en) | 2001-11-19 | 2002-11-19 | Amine 1,2- and 1,3-diol compounds and their use for treatment of alzheimer's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2467798A1 true CA2467798A1 (en) | 2003-05-30 |
Family
ID=27406892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002467798A Abandoned CA2467798A1 (en) | 2001-11-19 | 2002-11-19 | Amine 1,2- and 1,3-diol compounds and their use for treatment of alzheimer's disease |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7388118B2 (https=) |
| EP (1) | EP1453792B1 (https=) |
| JP (1) | JP2005536448A (https=) |
| AT (1) | ATE359995T1 (https=) |
| AU (1) | AU2002362008A1 (https=) |
| BR (1) | BR0214293A (https=) |
| CA (1) | CA2467798A1 (https=) |
| DE (1) | DE60219680T2 (https=) |
| ES (1) | ES2284970T3 (https=) |
| MX (1) | MXPA04004771A (https=) |
| WO (1) | WO2003043975A1 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007516207A (ja) | 2003-06-30 | 2007-06-21 | メルク エンド カムパニー インコーポレーテッド | アルツハイマー病の治療のためのＮ−アルキルフェニルカルボキサミドβ−セクレターゼ阻害剤 |
| ITPD20040151A1 (it) * | 2004-06-15 | 2004-09-15 | Univ Degli Studi Trieste | Inibitori peptidomimetici di proteasi retrovirali e loro uso come antivirali |
| WO2010107384A1 (en) * | 2009-03-19 | 2010-09-23 | Medivir Ab | Aspartyl protease inhibitors |
| EP3623371A1 (en) | 2014-12-16 | 2020-03-18 | Axovant Sciences GmbH | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| CN107847494A (zh) | 2015-06-10 | 2018-03-27 | 阿考温特科学股份有限公司 | 作为α7‑烟碱乙酰胆碱受体激动剂的氨基苯并异噁唑化合物 |
| JP2018523707A (ja) | 2015-08-12 | 2018-08-23 | アクソバント サイエンシズ ゲーエムベーハー | α７−ニコチン性アセチルコリン受容体のアゴニストとしてのジェミナル置換アミノベンゾイソオキサゾール化合物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4864017A (en) | 1986-09-05 | 1989-09-05 | The Upjohn Company | Novel renin inhibiting peptides having a dihyroxyethylene isostere transition state insert |
| DE60124080T2 (de) * | 2000-03-23 | 2007-03-01 | Elan Pharmaceuticals, Inc., San Francisco | Verbindungen und verfahren zur behandlung der alzheimerschen krankheit |
| JP2004502664A (ja) * | 2000-06-30 | 2004-01-29 | イーラン ファーマスーティカルズ、インコーポレイテッド | アルツハイマー病処置用化合物 |
| US6846813B2 (en) * | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| PE20020276A1 (es) * | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| US6906104B2 (en) * | 2001-06-13 | 2005-06-14 | Pharmacia & Upjohn Company | Aminediols for the treatment of Alzheimer's disease |
-
2002
- 2002-11-19 AT AT02797133T patent/ATE359995T1/de not_active IP Right Cessation
- 2002-11-19 ES ES02797133T patent/ES2284970T3/es not_active Expired - Lifetime
- 2002-11-19 EP EP02797133A patent/EP1453792B1/en not_active Expired - Lifetime
- 2002-11-19 BR BR0214293-7A patent/BR0214293A/pt not_active IP Right Cessation
- 2002-11-19 JP JP2003545613A patent/JP2005536448A/ja active Pending
- 2002-11-19 US US10/299,739 patent/US7388118B2/en not_active Expired - Fee Related
- 2002-11-19 AU AU2002362008A patent/AU2002362008A1/en not_active Abandoned
- 2002-11-19 DE DE60219680T patent/DE60219680T2/de not_active Expired - Fee Related
- 2002-11-19 CA CA002467798A patent/CA2467798A1/en not_active Abandoned
- 2002-11-19 MX MXPA04004771A patent/MXPA04004771A/es active IP Right Grant
- 2002-11-19 WO PCT/US2002/036999 patent/WO2003043975A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| DE60219680T2 (de) | 2007-12-27 |
| US7388118B2 (en) | 2008-06-17 |
| ATE359995T1 (de) | 2007-05-15 |
| JP2005536448A (ja) | 2005-12-02 |
| EP1453792B1 (en) | 2007-04-18 |
| ES2284970T3 (es) | 2007-11-16 |
| AU2002362008A1 (en) | 2003-06-10 |
| EP1453792A1 (en) | 2004-09-08 |
| WO2003043975A1 (en) | 2003-05-30 |
| BR0214293A (pt) | 2005-04-19 |
| DE60219680D1 (de) | 2007-05-31 |
| MXPA04004771A (es) | 2004-07-30 |
| US20040039064A1 (en) | 2004-02-26 |
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| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20091119 |