ZA200502841B - Thiazole compounds for the treatment of neurodegenerative disorders - Google Patents
Thiazole compounds for the treatment of neurodegenerative disorders Download PDFInfo
- Publication number
- ZA200502841B ZA200502841B ZA200502841A ZA200502841A ZA200502841B ZA 200502841 B ZA200502841 B ZA 200502841B ZA 200502841 A ZA200502841 A ZA 200502841A ZA 200502841 A ZA200502841 A ZA 200502841A ZA 200502841 B ZA200502841 B ZA 200502841B
- Authority
- ZA
- South Africa
- Prior art keywords
- thiazol
- acetylamino
- phenyl
- amide
- difluoro
- Prior art date
Links
- 208000015122 neurodegenerative disease Diseases 0.000 title description 4
- 150000003557 thiazoles Chemical class 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 140
- 125000003118 aryl group Chemical group 0.000 claims description 81
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 73
- CIVHYONOTJEXAY-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)CC1=CC(F)=CC(F)=C1 CIVHYONOTJEXAY-UHFFFAOYSA-N 0.000 claims description 72
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 67
- 150000001875 compounds Chemical class 0.000 claims description 65
- 125000001072 heteroaryl group Chemical group 0.000 claims description 61
- 229910052731 fluorine Inorganic materials 0.000 claims description 58
- 239000011737 fluorine Substances 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- -1 wherein said alkyi Chemical group 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 40
- 125000001153 fluoro group Chemical group F* 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 125000001246 bromo group Chemical group Br* 0.000 claims description 32
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 31
- 229940080818 propionamide Drugs 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 20
- 125000004104 aryloxy group Chemical group 0.000 claims description 19
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- URQBSSXANXPCBK-UHFFFAOYSA-N 2-[(2-hydroxy-3,3-dimethylbutanoyl)amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)C(O)C(C)(C)C URQBSSXANXPCBK-UHFFFAOYSA-N 0.000 claims description 12
- NGEWQZIDQIYUNV-UHFFFAOYSA-N 2-hydroxy-3-methylbutyric acid Chemical compound CC(C)C(O)C(O)=O NGEWQZIDQIYUNV-UHFFFAOYSA-N 0.000 claims description 12
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- GJWSUKYXUMVMGX-UHFFFAOYSA-N citronellic acid Chemical compound OC(=O)CC(C)CCC=C(C)C GJWSUKYXUMVMGX-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- YRKKUQJRDOKSKD-UHFFFAOYSA-N 2-[(2-hydroxy-3-methylbutanoyl)amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)C(O)C(C)C YRKKUQJRDOKSKD-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- HZKUNVGMGAVTPO-UHFFFAOYSA-N 2-[(2-hydroxy-2-phenylacetyl)amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)C(O)C1=CC=CC=C1 HZKUNVGMGAVTPO-UHFFFAOYSA-N 0.000 claims description 4
- GVQLGDFAYXUYPQ-UHFFFAOYSA-N 2-[(2-oxo-2-thiophen-2-ylacetyl)amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)C(=O)C1=CC=CS1 GVQLGDFAYXUYPQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 3
- GUABFMPMKJGSBQ-UHFFFAOYSA-N 5-methyl-1,3-thiazol-2-amine Chemical compound CC1=CN=C(N)S1 GUABFMPMKJGSBQ-UHFFFAOYSA-N 0.000 claims description 3
- 201000010374 Down Syndrome Diseases 0.000 claims description 3
- 102000029797 Prion Human genes 0.000 claims description 3
- 108091000054 Prion Proteins 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 206010044688 Trisomy 21 Diseases 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 229910052805 deuterium Inorganic materials 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- ZHMRGFNMPNFNPW-UHFFFAOYSA-N 1,3-thiazole-2,5-diamine Chemical compound NC1=CN=C(N)S1 ZHMRGFNMPNFNPW-UHFFFAOYSA-N 0.000 claims description 2
- LYNZEVPXFDEQTD-UHFFFAOYSA-N 1-(3,5-difluorophenyl)cyclopentane-1-carboxylic acid Chemical compound C=1C(F)=CC(F)=CC=1C1(C(=O)O)CCCC1 LYNZEVPXFDEQTD-UHFFFAOYSA-N 0.000 claims description 2
- PJMNELZSKDFVIU-UHFFFAOYSA-N 2-[(2-cyclohexyl-2-hydroxyacetyl)amino]-n-(5-methyl-1,3-thiazol-2-yl)pentanamide Chemical compound N=1C=C(C)SC=1NC(=O)C(CCC)NC(=O)C(O)C1CCCCC1 PJMNELZSKDFVIU-UHFFFAOYSA-N 0.000 claims description 2
- IGFWVOSQAWAMJK-UHFFFAOYSA-N 2-[2-[[2-(3,5-difluorophenyl)acetyl]amino]pentanoylamino]-1,3-thiazole-5-carboxamide Chemical compound N=1C=C(C(N)=O)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 IGFWVOSQAWAMJK-UHFFFAOYSA-N 0.000 claims description 2
- WAELWYPFVWUEPY-UHFFFAOYSA-N 2-[[2-(5-bromopyridin-3-yl)acetyl]amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)CC1=CN=CC(Br)=C1 WAELWYPFVWUEPY-UHFFFAOYSA-N 0.000 claims description 2
- RQDNLKKGYGNSAR-UHFFFAOYSA-N 3,3-dimethyl-2-oxo-n-[1-oxo-1-[(5-propan-2-yl-1,3-thiazol-2-yl)amino]pentan-2-yl]butanamide Chemical compound CC(C)(C)C(=O)C(=O)NC(CCC)C(=O)NC1=NC=C(C(C)C)S1 RQDNLKKGYGNSAR-UHFFFAOYSA-N 0.000 claims description 2
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
- NYGMDZBALVBWJR-UHFFFAOYSA-N n-(4,5-dimethyl-1,3-thiazol-2-yl)-2-[(2-hydroxy-2-phenylacetyl)amino]pentanamide Chemical compound N=1C(C)=C(C)SC=1NC(=O)C(CCC)NC(=O)C(O)C1=CC=CC=C1 NYGMDZBALVBWJR-UHFFFAOYSA-N 0.000 claims description 2
- XLBDLZDPPVQYPO-UHFFFAOYSA-N n-(5-butyl-1,3-thiazol-2-yl)-2-[[2-(3-phenoxyphenyl)acetyl]amino]pentanamide Chemical compound S1C(CCCC)=CN=C1NC(=O)C(CCC)NC(=O)CC1=CC=CC(OC=2C=CC=CC=2)=C1 XLBDLZDPPVQYPO-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 11
- 239000003795 chemical substances by application Substances 0.000 claims 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 8
- 230000002401 inhibitory effect Effects 0.000 claims 5
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims 4
- 239000000935 antidepressant agent Substances 0.000 claims 4
- 239000003963 antioxidant agent Substances 0.000 claims 4
- 239000000164 antipsychotic agent Substances 0.000 claims 4
- 239000002249 anxiolytic agent Substances 0.000 claims 4
- 230000000949 anxiolytic effect Effects 0.000 claims 4
- 235000012000 cholesterol Nutrition 0.000 claims 4
- 230000006993 memory improvement Effects 0.000 claims 4
- 229940125707 sleep disorder agent Drugs 0.000 claims 4
- 239000002220 antihypertensive agent Substances 0.000 claims 3
- GLFYGFRFAGFJIF-UHFFFAOYSA-N n-(5-acetyl-1,3-thiazol-2-yl)-2-[[2-(3,5-difluorophenyl)acetyl]amino]pentanamide Chemical compound N=1C=C(C(C)=O)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 GLFYGFRFAGFJIF-UHFFFAOYSA-N 0.000 claims 3
- 208000018282 ACys amyloidosis Diseases 0.000 claims 2
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims 2
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims 2
- 201000008319 inclusion body myositis Diseases 0.000 claims 2
- KPXFNVJTISERBU-UHFFFAOYSA-N n-[1-[(5-acetyl-1,3-thiazol-2-yl)amino]-1-oxopentan-2-yl]-2-hydroxy-3,3-dimethylbutanamide Chemical compound CC(C)(C)C(O)C(=O)NC(CCC)C(=O)NC1=NC=C(C(C)=O)S1 KPXFNVJTISERBU-UHFFFAOYSA-N 0.000 claims 2
- IYODMMGZTGSKGN-UHFFFAOYSA-N n-[5-[1-(butylamino)ethyl]-1,3-thiazol-2-yl]-2-[[2-(3,5-difluorophenyl)acetyl]amino]pentanamide Chemical compound S1C(C(C)NCCCC)=CN=C1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 IYODMMGZTGSKGN-UHFFFAOYSA-N 0.000 claims 2
- 208000023516 stroke disease Diseases 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- PKUKCASRNJIQNU-UHFFFAOYSA-N 1-(2-amino-4-methyl-1,3-thiazol-5-yl)ethanone Chemical compound CC(=O)C=1SC(N)=NC=1C PKUKCASRNJIQNU-UHFFFAOYSA-N 0.000 claims 1
- CJYQOFOUNKKDSA-UHFFFAOYSA-N 2-[(2-hydroxy-2-phenylacetyl)amino]-n-[5-(2,2,2-trifluoroacetyl)-1,3-thiazol-2-yl]pentanamide Chemical compound N=1C=C(C(=O)C(F)(F)F)SC=1NC(=O)C(CCC)NC(=O)C(O)C1=CC=CC=C1 CJYQOFOUNKKDSA-UHFFFAOYSA-N 0.000 claims 1
- LFVULWZSYZBQOP-UHFFFAOYSA-N 2-[(2-hydroxy-2-phenylacetyl)amino]-n-[5-(6-methylhept-5-en-2-yl)-1,3-thiazol-2-yl]pentanamide Chemical compound N=1C=C(C(C)CCC=C(C)C)SC=1NC(=O)C(CCC)NC(=O)C(O)C1=CC=CC=C1 LFVULWZSYZBQOP-UHFFFAOYSA-N 0.000 claims 1
- BGPGKMPFTDJIJH-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-n-(5-pentan-3-yl-1,3-thiazol-2-yl)pentanamide Chemical compound N=1C=C(C(CC)CC)SC=1NC(=O)C(CCC)NC(=O)C(O)C1=CC(F)=CC(F)=C1 BGPGKMPFTDJIJH-UHFFFAOYSA-N 0.000 claims 1
- FKDBSPSPIWYLFQ-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)butanamide Chemical compound N=1C=2CCCCC=2SC=1NC(=O)C(CC)NC(=O)CC1=CC(F)=CC(F)=C1 FKDBSPSPIWYLFQ-UHFFFAOYSA-N 0.000 claims 1
- JRRXABKYGVGWKK-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(4-phenyl-1,3-thiazol-2-yl)butanamide Chemical compound N=1C(C=2C=CC=CC=2)=CSC=1NC(=O)C(CC)NC(=O)CC1=CC(F)=CC(F)=C1 JRRXABKYGVGWKK-UHFFFAOYSA-N 0.000 claims 1
- LDKWNNMWSLWBRB-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-2-yl)butanamide Chemical compound N=1C=2CCCCCC=2SC=1NC(=O)C(CC)NC(=O)CC1=CC(F)=CC(F)=C1 LDKWNNMWSLWBRB-UHFFFAOYSA-N 0.000 claims 1
- ZFSPCKGRLFLVFF-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(5-ethyl-4-methyl-1,3-thiazol-2-yl)pentanamide Chemical compound N=1C(C)=C(CC)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 ZFSPCKGRLFLVFF-UHFFFAOYSA-N 0.000 claims 1
- NZWGYMXLWIUGSM-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(5-methyl-1,3-thiazol-2-yl)pentanamide Chemical compound N=1C=C(C)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 NZWGYMXLWIUGSM-UHFFFAOYSA-N 0.000 claims 1
- BVEDHYNKKKTYLJ-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(5-nitro-1,3-thiazol-2-yl)pentanamide Chemical compound N=1C=C([N+]([O-])=O)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 BVEDHYNKKKTYLJ-UHFFFAOYSA-N 0.000 claims 1
- KXNXDNZVEFNURK-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(6-methoxy-1,3-benzothiazol-2-yl)butanamide Chemical compound N=1C2=CC=C(OC)C=C2SC=1NC(=O)C(CC)NC(=O)CC1=CC(F)=CC(F)=C1 KXNXDNZVEFNURK-UHFFFAOYSA-N 0.000 claims 1
- FHDMVLCSHDHBHT-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[4-methyl-5-[1-(propylamino)ethyl]-1,3-thiazol-2-yl]pentanamide Chemical compound CC1=C(C(C)NCCC)SC(NC(=O)C(CCC)NC(=O)CC=2C=C(F)C=C(F)C=2)=N1 FHDMVLCSHDHBHT-UHFFFAOYSA-N 0.000 claims 1
- KHYSMADOOWVRNB-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[5-(1-hydroxyethyl)-1,3-thiazol-2-yl]pentanamide Chemical compound N=1C=C(C(C)O)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 KHYSMADOOWVRNB-UHFFFAOYSA-N 0.000 claims 1
- VXGBCGAZVMUESH-UHFFFAOYSA-N 2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[5-[1-(3,3-dimethylbutylamino)-2,2,2-trifluoroethyl]-1,3-thiazol-2-yl]pentanamide Chemical compound N=1C=C(C(NCCC(C)(C)C)C(F)(F)F)SC=1NC(=O)C(CCC)NC(=O)CC1=CC(F)=CC(F)=C1 VXGBCGAZVMUESH-UHFFFAOYSA-N 0.000 claims 1
- VASRJGMOUPSMKZ-UHFFFAOYSA-N 2-[[2-(3-phenoxyphenyl)acetyl]amino]pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)CC1=CC=CC(OC=2C=CC=CC=2)=C1 VASRJGMOUPSMKZ-UHFFFAOYSA-N 0.000 claims 1
- BTJLPORGNBDFMK-UHFFFAOYSA-N 2-hydroxy-n-[1-[[5-(6-hydroxy-6-methylheptan-2-yl)-1,3-thiazol-2-yl]amino]-1-oxopentan-2-yl]-3,3-dimethylbutanamide Chemical compound CC(C)(C)C(O)C(=O)NC(CCC)C(=O)NC1=NC=C(C(C)CCCC(C)(C)O)S1 BTJLPORGNBDFMK-UHFFFAOYSA-N 0.000 claims 1
- ADQNFRCBALIWBF-UHFFFAOYSA-N 2-hydroxy-n-[1-[[5-(6-hydroxy-6-methylheptan-2-yl)-1,3-thiazol-2-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide Chemical compound CC(C)C(O)C(=O)NC(C)C(=O)NC1=NC=C(C(C)CCCC(C)(C)O)S1 ADQNFRCBALIWBF-UHFFFAOYSA-N 0.000 claims 1
- VHXIDVVMADGPED-UHFFFAOYSA-N 3-(2-amino-1,3-thiazol-5-yl)pentan-3-ol Chemical compound CCC(O)(CC)C1=CN=C(N)S1 VHXIDVVMADGPED-UHFFFAOYSA-N 0.000 claims 1
- HUKBELGUWQLEFD-UHFFFAOYSA-N 5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-2-amine Chemical compound C1CCC2=C1N=C(N)S2 HUKBELGUWQLEFD-UHFFFAOYSA-N 0.000 claims 1
- WLMHDICPCCYJBP-UHFFFAOYSA-N 5-(4,4-dimethylpentan-2-yl)-1,3-thiazol-2-amine Chemical compound CC(C)(C)CC(C)C1=CN=C(N)S1 WLMHDICPCCYJBP-UHFFFAOYSA-N 0.000 claims 1
- XWRQHPFDMUNUQU-UHFFFAOYSA-N 5-[(dimethylamino)methyl]-1,3-thiazol-2-amine Chemical compound CN(C)CC1=CN=C(N)S1 XWRQHPFDMUNUQU-UHFFFAOYSA-N 0.000 claims 1
- QXQBIQGCASOUDZ-UHFFFAOYSA-N 5-[1-(2-methoxyethylamino)ethyl]-1,3-thiazol-2-amine Chemical compound COCCNC(C)C1=CN=C(N)S1 QXQBIQGCASOUDZ-UHFFFAOYSA-N 0.000 claims 1
- MENMPXBUKLPJKR-UHFFFAOYSA-N 5-propan-2-yl-1,3-thiazol-2-amine Chemical compound CC(C)C1=CN=C(N)S1 MENMPXBUKLPJKR-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000002704 decyl 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])* 0.000 claims 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ACJVYBFJMQMOOB-UHFFFAOYSA-N ethyl 2-[2-[2-[[2-(3,5-difluorophenyl)acetyl]amino]butanoylamino]-1,3-thiazol-4-yl]-2-methoxyiminoacetate Chemical compound CCOC(=O)C(=NOC)C1=CSC(NC(=O)C(CC)NC(=O)CC=2C=C(F)C=C(F)C=2)=N1 ACJVYBFJMQMOOB-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/54—Nitrogen and either oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (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)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41740002P | 2002-10-09 | 2002-10-09 |
Publications (1)
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|---|---|
| ZA200502841B true ZA200502841B (en) | 2006-03-29 |
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| ZA200502841A ZA200502841B (en) | 2002-10-09 | 2006-01-17 | Thiazole compounds for the treatment of neurodegenerative disorders |
Country Status (28)
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| US (1) | US20040152747A1 (nl) |
| EP (1) | EP1551815A1 (nl) |
| JP (1) | JP2006504796A (nl) |
| KR (1) | KR20050070046A (nl) |
| CN (1) | CN1688557A (nl) |
| AP (1) | AP2005003274A0 (nl) |
| AR (1) | AR043051A1 (nl) |
| AU (1) | AU2003265068A1 (nl) |
| BR (1) | BR0314611A (nl) |
| CA (1) | CA2501803A1 (nl) |
| CO (1) | CO5550435A2 (nl) |
| CR (1) | CR7785A (nl) |
| EC (1) | ECSP055719A (nl) |
| GT (1) | GT200300219A (nl) |
| IS (1) | IS7738A (nl) |
| MA (1) | MA27451A1 (nl) |
| MX (1) | MXPA05002420A (nl) |
| NL (1) | NL1024499C2 (nl) |
| NO (1) | NO20052223L (nl) |
| OA (1) | OA12937A (nl) |
| PA (1) | PA8585001A1 (nl) |
| PE (1) | PE20040640A1 (nl) |
| PL (1) | PL376171A1 (nl) |
| TN (1) | TNSN05104A1 (nl) |
| TW (1) | TW200420550A (nl) |
| UY (1) | UY28011A1 (nl) |
| WO (1) | WO2004033439A1 (nl) |
| ZA (1) | ZA200502841B (nl) |
Families Citing this family (35)
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| FR2842523A1 (fr) * | 2002-07-17 | 2004-01-23 | Sanofi Synthelabo | Derives d'acylaminothiazole, leur preparation et leur application en therapeutique |
| WO2004099200A1 (en) | 2003-05-12 | 2004-11-18 | Pfizer Products Inc. | Isoxazole and isothiazole compounds for the treatment of neurodegenerative disorders |
| EP1653952A4 (en) * | 2003-08-06 | 2007-04-04 | Pfizer Prod Inc | OXAZOLE COMPOUNDS FOR THE TREATMENT OF NEURODEEGENERATIVE DISORDER |
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| WO1992021360A1 (en) * | 1991-05-28 | 1992-12-10 | Merck & Co., Inc. | Substituted n-carboxyalkylpeptidyl derivatives as antidegenerative active agents |
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| BR9910092A (pt) * | 1998-05-01 | 2002-01-22 | Abbott Lab | Inibidores de beta-aminoácido substituìdo de metionina aminopeptidase-2 |
| WO2000024392A1 (fr) * | 1998-10-26 | 2000-05-04 | Sumitomo Pharmaceuticals Company, Limited | Inhibiteur de la formation de beta-amyloide |
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| FR2842523A1 (fr) * | 2002-07-17 | 2004-01-23 | Sanofi Synthelabo | Derives d'acylaminothiazole, leur preparation et leur application en therapeutique |
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2003
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- 2003-09-29 AU AU2003265068A patent/AU2003265068A1/en not_active Abandoned
- 2003-09-29 PL PL03376171A patent/PL376171A1/xx not_active Application Discontinuation
- 2003-09-29 BR BR0314611-1A patent/BR0314611A/pt not_active IP Right Cessation
- 2003-09-29 CA CA002501803A patent/CA2501803A1/en not_active Abandoned
- 2003-09-29 WO PCT/IB2003/004330 patent/WO2004033439A1/en active Application Filing
- 2003-09-29 OA OA1200500098A patent/OA12937A/en unknown
- 2003-09-29 EP EP03807933A patent/EP1551815A1/en not_active Withdrawn
- 2003-09-29 AP AP2005003274A patent/AP2005003274A0/xx unknown
- 2003-09-29 CN CNA038240106A patent/CN1688557A/zh active Pending
- 2003-09-29 MX MXPA05002420A patent/MXPA05002420A/es not_active Application Discontinuation
- 2003-10-03 TW TW092127495A patent/TW200420550A/zh unknown
- 2003-10-07 PE PE2003001021A patent/PE20040640A1/es not_active Application Discontinuation
- 2003-10-08 AR ARP030103662A patent/AR043051A1/es unknown
- 2003-10-08 PA PA20038585001A patent/PA8585001A1/es unknown
- 2003-10-08 US US10/682,686 patent/US20040152747A1/en not_active Abandoned
- 2003-10-09 GT GT200300219A patent/GT200300219A/es unknown
- 2003-10-09 NL NL1024499A patent/NL1024499C2/nl not_active IP Right Cessation
- 2003-10-09 UY UY28011A patent/UY28011A1/es not_active Application Discontinuation
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- 2005-03-10 IS IS7738A patent/IS7738A/is unknown
- 2005-04-07 EC EC2005005719A patent/ECSP055719A/es unknown
- 2005-04-07 CR CR7785A patent/CR7785A/es not_active Application Discontinuation
- 2005-04-08 CO CO05031337A patent/CO5550435A2/es not_active Application Discontinuation
- 2005-04-08 MA MA28206A patent/MA27451A1/fr unknown
- 2005-04-08 TN TNP2005000104A patent/TNSN05104A1/fr unknown
- 2005-05-06 NO NO20052223A patent/NO20052223L/no unknown
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2006
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| NO20052223D0 (no) | 2005-05-06 |
| BR0314611A (pt) | 2005-07-26 |
| US20040152747A1 (en) | 2004-08-05 |
| EP1551815A1 (en) | 2005-07-13 |
| GT200300219A (es) | 2004-05-18 |
| CA2501803A1 (en) | 2004-04-22 |
| NL1024499A1 (nl) | 2004-04-13 |
| PA8585001A1 (es) | 2004-12-16 |
| NL1024499C2 (nl) | 2004-10-13 |
| MA27451A1 (fr) | 2005-07-01 |
| KR20050070046A (ko) | 2005-07-05 |
| TNSN05104A1 (fr) | 2007-05-14 |
| MXPA05002420A (es) | 2005-10-05 |
| PL376171A1 (en) | 2005-12-27 |
| WO2004033439A1 (en) | 2004-04-22 |
| TW200420550A (en) | 2004-10-16 |
| CO5550435A2 (es) | 2005-08-31 |
| CR7785A (es) | 2005-07-08 |
| NO20052223L (no) | 2005-07-04 |
| AU2003265068A1 (en) | 2004-05-04 |
| ECSP055719A (es) | 2005-07-06 |
| IS7738A (is) | 2005-03-10 |
| AR043051A1 (es) | 2005-07-13 |
| OA12937A (en) | 2006-10-13 |
| PE20040640A1 (es) | 2004-09-15 |
| UY28011A1 (es) | 2004-04-30 |
| AP2005003274A0 (en) | 2005-06-30 |
| CN1688557A (zh) | 2005-10-26 |
| JP2006504796A (ja) | 2006-02-09 |
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