CA2771374A1 - 2 -aminodihydro [1, 3] thiazines as bace 2 inhibitors for the treatment of diabetes - Google Patents
2 -aminodihydro [1, 3] thiazines as bace 2 inhibitors for the treatment of diabetes Download PDFInfo
- Publication number
- CA2771374A1 CA2771374A1 CA2771374A CA2771374A CA2771374A1 CA 2771374 A1 CA2771374 A1 CA 2771374A1 CA 2771374 A CA2771374 A CA 2771374A CA 2771374 A CA2771374 A CA 2771374A CA 2771374 A1 CA2771374 A1 CA 2771374A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- alkyl
- halogen
- fluoro
- formula
- 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
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 64
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 29
- 239000003112 inhibitor Substances 0.000 title description 6
- HJXHTTXYWNVHRE-UHFFFAOYSA-N 3,4-dihydro-2h-1,3-thiazin-2-amine Chemical class NC1NCC=CS1 HJXHTTXYWNVHRE-UHFFFAOYSA-N 0.000 title 1
- 101150058765 BACE1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 150000003839 salts Chemical class 0.000 claims abstract description 68
- 101000894883 Homo sapiens Beta-secretase 2 Proteins 0.000 claims abstract description 40
- 102100021277 Beta-secretase 2 Human genes 0.000 claims abstract description 39
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 36
- 230000002265 prevention Effects 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical group 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- -1 hydroxy-C1-7-alkyl Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 230000008878 coupling Effects 0.000 claims description 21
- 238000010168 coupling process Methods 0.000 claims description 21
- 238000005859 coupling reaction Methods 0.000 claims description 21
- 230000005764 inhibitory process Effects 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 20
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- VVZZZUNCWSTIOI-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-methyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C(F)C=1[C@]1(C)CCSC(N)=N1 VVZZZUNCWSTIOI-KRWDZBQOSA-N 0.000 claims description 6
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- UICHXFRUJZAVEZ-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-2-methyl-1,3-thiazole-4-carboxamide Chemical compound C=1C(NC(=O)C=2N=C(C)SC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 UICHXFRUJZAVEZ-KRWDZBQOSA-N 0.000 claims description 4
- RDSUFYJIOASZCK-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-3,6-dichloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC=C(Cl)N=2)Cl)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 RDSUFYJIOASZCK-SFHVURJKSA-N 0.000 claims description 4
- IERFKNQCCQZQQT-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-3-(trifluoromethyl)pyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC=CN=2)C(F)(F)F)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 IERFKNQCCQZQQT-SFHVURJKSA-N 0.000 claims description 4
- QZMDZTRYUFQFQS-DEOSSOPVSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-3-phenylpyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC=CN=2)C=2C=CC=CC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 QZMDZTRYUFQFQS-DEOSSOPVSA-N 0.000 claims description 4
- XDSIMSXFGCMLOD-IBGZPJMESA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-4-chlorobenzamide Chemical compound C=1C(NC(=O)C=2C=CC(Cl)=CC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 XDSIMSXFGCMLOD-IBGZPJMESA-N 0.000 claims description 4
- SJKPPPGAWJAHMR-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-4-chloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC=C(Cl)C=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 SJKPPPGAWJAHMR-SFHVURJKSA-N 0.000 claims description 4
- IQZAZBFFRRDNCK-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-5-chloropyrazine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=NC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 IQZAZBFFRRDNCK-KRWDZBQOSA-N 0.000 claims description 4
- HOGWWCKCEUPPDB-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 HOGWWCKCEUPPDB-SFHVURJKSA-N 0.000 claims description 4
- WPVKZEPJEHYXHL-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-5-chloropyrimidine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=CN=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 WPVKZEPJEHYXHL-KRWDZBQOSA-N 0.000 claims description 4
- XSTKDACIPFNBNB-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-6-chloro-3-(trifluoromethyl)pyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC=C(Cl)N=2)C(F)(F)F)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 XSTKDACIPFNBNB-SFHVURJKSA-N 0.000 claims description 4
- VYPAEEIFCVYBKE-IBGZPJMESA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-6-methylpyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=C(C)C=CC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 VYPAEEIFCVYBKE-IBGZPJMESA-N 0.000 claims description 4
- APSHDJUFQSNKBO-QFIPXVFZSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]isoquinoline-3-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC3=CC=CC=C3C=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 APSHDJUFQSNKBO-QFIPXVFZSA-N 0.000 claims description 4
- VSNFCVOYLALVNG-SFHVURJKSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]pyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC=CC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 VSNFCVOYLALVNG-SFHVURJKSA-N 0.000 claims description 4
- JMKXIABUPUSHBI-FQEVSTJZSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]thieno[2,3-c]pyridine-7-carboxamide Chemical compound C=1C(NC(=O)C=2C=3SC=CC=3C=CN=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 JMKXIABUPUSHBI-FQEVSTJZSA-N 0.000 claims description 4
- JCSINBXDYYFNKC-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-1-methylpyrazole-3-carboxamide Chemical compound C=1C(NC(=O)C2=NN(C)C=C2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 JCSINBXDYYFNKC-KRWDZBQOSA-N 0.000 claims description 3
- JQDIRHGTRXUQDJ-KRWDZBQOSA-N n-[3-[(4s)-2-amino-4-ethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluorophenyl]-2-methyl-1,3-oxazole-4-carboxamide Chemical compound C=1C(NC(=O)C=2N=C(C)OC=2)=CC=C(F)C=1[C@]1(CC)CCSC(N)=N1 JQDIRHGTRXUQDJ-KRWDZBQOSA-N 0.000 claims description 3
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- 229940124639 Selective inhibitor Drugs 0.000 abstract description 3
- VNTNANCAPVJRJP-UHFFFAOYSA-N 3,4-dihydrothiazin-2-amine Chemical class NN1CCC=CS1 VNTNANCAPVJRJP-UHFFFAOYSA-N 0.000 abstract description 2
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- 229920001220 nitrocellulos Polymers 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
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- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JXXCXPRGOXYPJK-HMILPKGGSA-N tert-butyl (3s)-3-[[(r)-tert-butylsulfinyl]amino]-3-(2-fluoro-5-nitrophenyl)pentanoate Chemical compound CC(C)(C)OC(=O)C[C@](CC)(N[S@](=O)C(C)(C)C)C1=CC([N+]([O-])=O)=CC=C1F JXXCXPRGOXYPJK-HMILPKGGSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000004897 thiazines Chemical class 0.000 description 1
- IZOWNOYERNMMAZ-UHFFFAOYSA-N thieno[2,3-c]pyridine-7-carboxylic acid Chemical compound OC(=O)C1=NC=CC2=C1SC=C2 IZOWNOYERNMMAZ-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium(IV) ethoxide Substances [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940007428 victoza Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
- C07D279/06—1,3-Thiazines; Hydrogenated 1,3-thiazines not condensed with other rings
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09170126 | 2009-09-11 | ||
| EP09170126.8 | 2009-09-11 | ||
| EP09172068.0 | 2009-10-02 | ||
| EP09172068 | 2009-10-02 | ||
| PCT/EP2010/063071 WO2011029803A1 (en) | 2009-09-11 | 2010-09-07 | 2 -aminodihydro [1, 3] thiazines as bace 2 inhibitors for the treatment of diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2771374A1 true CA2771374A1 (en) | 2011-03-17 |
Family
ID=43086098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2771374A Abandoned CA2771374A1 (en) | 2009-09-11 | 2010-09-07 | 2 -aminodihydro [1, 3] thiazines as bace 2 inhibitors for the treatment of diabetes |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US20110065695A1 (OSRAM) |
| EP (1) | EP2475658A1 (OSRAM) |
| JP (1) | JP2013503838A (OSRAM) |
| CN (1) | CN102482268B (OSRAM) |
| AR (1) | AR078163A1 (OSRAM) |
| CA (1) | CA2771374A1 (OSRAM) |
| IN (1) | IN2012DN01233A (OSRAM) |
| SG (1) | SG179034A1 (OSRAM) |
| TW (1) | TW201114765A (OSRAM) |
| WO (1) | WO2011029803A1 (OSRAM) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2537898T3 (es) | 2005-10-25 | 2015-06-15 | Shionogi & Co., Ltd. | Derivados de aminotiazolidina y aminotetrahidrotiazepina como inhibidores de BACE 1 |
| EP2689780A1 (en) | 2007-04-24 | 2014-01-29 | Shionogi & Co., Ltd. | Intermediates for aminodihydrothiazine derivatives substituted with a cyclic group |
| WO2008133273A1 (ja) | 2007-04-24 | 2008-11-06 | Shionogi & Co., Ltd. | アルツハイマー症治療用医薬組成物 |
| AU2009258496B8 (en) * | 2008-06-13 | 2014-06-26 | Shionogi & Co., Ltd. | Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity |
| CN102186841A (zh) * | 2008-10-22 | 2011-09-14 | 盐野义制药株式会社 | 具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物 |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| TWI488852B (zh) | 2009-12-11 | 2015-06-21 | Shionogi & Co | 衍生物 |
| JP5766198B2 (ja) | 2010-10-29 | 2015-08-19 | 塩野義製薬株式会社 | 縮合アミノジヒドロピリミジン誘導体 |
| US8927721B2 (en) | 2010-10-29 | 2015-01-06 | Shionogi & Co., Ltd. | Naphthyridine derivative |
| WO2012138734A1 (en) | 2011-04-07 | 2012-10-11 | Merck Sharp & Dohme Corp. | C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| US9145426B2 (en) | 2011-04-07 | 2015-09-29 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
| CN103596939A (zh) * | 2011-04-13 | 2014-02-19 | 默沙东公司 | 作为bace抑制剂的5-取代的亚氨基噻嗪类及其单和二氧化物、组合物及其应用 |
| CA2832473A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 5-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions, and their use |
| JPWO2012147762A1 (ja) | 2011-04-26 | 2014-07-28 | 塩野義製薬株式会社 | ピリジン誘導体およびそれを含有するｂａｃｅ１阻害剤 |
| CN103608345A (zh) | 2011-04-26 | 2014-02-26 | 盐野义制药株式会社 | 噁嗪衍生物和含有该噁嗪衍生物的bace1抑制剂 |
| US8927535B2 (en) | 2011-07-06 | 2015-01-06 | Hoffman-La Roche Inc. | Cyclopropyl-fused-1,3-thiazepines as BACE1 and/or BACE2 inhibitors |
| RU2014111055A (ru) | 2011-08-22 | 2015-09-27 | Мерк Шарп И Доум Корп. | 2-спирозамещенные иминотиазины и их моно- и диоксиды в качестве ингибиторов bace, композиции и их применение |
| WO2013142613A1 (en) | 2012-03-20 | 2013-09-26 | Elan Pharmaceuticals, Inc. | Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof |
| WO2013148130A1 (en) | 2012-03-29 | 2013-10-03 | Oklahoma Medical Research Foundation | Inhibition of memapsin 1 cleavage in the treatment of diabetes |
| SG11201407575PA (en) | 2012-05-24 | 2014-12-30 | Hoffmann La Roche | 5-amino[1,4]thiazines as bace 1 inhibitors |
| BR112014030685A2 (pt) | 2012-06-20 | 2017-06-27 | Hoffmann La Roche | compostos de n-alquiltriazol como antagonistas de lpar |
| WO2014059185A1 (en) | 2012-10-12 | 2014-04-17 | Amgen Inc. | Amino - dihydrothiazine and amino - dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use |
| JP2016501827A (ja) | 2012-10-24 | 2016-01-21 | 塩野義製薬株式会社 | Ｂａｃｅ１阻害作用を有するジヒドロオキサジンまたはオキサゼピン誘導体 |
| US9725469B2 (en) | 2012-11-15 | 2017-08-08 | Amgen, Inc. | Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| CA2902212C (en) | 2013-03-01 | 2020-10-13 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| KR20150124985A (ko) | 2013-03-08 | 2015-11-06 | 암젠 인크 | 베타-세크레타제 억제제로서 퍼플루오르화된 사이클로프로필 융합된 1,3-옥사진-2-아민 화합물 및 그의 사용 방법 |
| CN106795147B (zh) | 2014-08-08 | 2020-09-22 | 美国安进公司 | 作为β-分泌酶抑制剂的环丙基稠合噻嗪-2-胺化合物和使用方法 |
| SG11201707050VA (en) | 2015-03-20 | 2017-10-30 | Hoffmann La Roche | Bace1 inhibitors |
| WO2017024180A1 (en) | 2015-08-06 | 2017-02-09 | Amgen Inc. | Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| MX387729B (es) | 2016-12-15 | 2025-03-18 | Amgen Inc | Derivados de dióxido de 1,4-tiazina y dióxido 1,2,4-tiadiazina como inhibidores de beta-secretasa y métodos de uso. |
| WO2018112083A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Thiazine derivatives as beta-secretase inhibitors and methods of use |
| WO2018112084A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
| MA52722A (fr) | 2016-12-15 | 2021-04-14 | Amgen Inc | Dérivés d'oxazine en tant qu'inhibiteurs de bêta-sécrétase et procédés d'utilisation |
| EP3555085B1 (en) | 2016-12-15 | 2020-12-02 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2537898T3 (es) * | 2005-10-25 | 2015-06-15 | Shionogi & Co., Ltd. | Derivados de aminotiazolidina y aminotetrahidrotiazepina como inhibidores de BACE 1 |
| EP2689780A1 (en) * | 2007-04-24 | 2014-01-29 | Shionogi & Co., Ltd. | Intermediates for aminodihydrothiazine derivatives substituted with a cyclic group |
| WO2008133273A1 (ja) * | 2007-04-24 | 2008-11-06 | Shionogi & Co., Ltd. | アルツハイマー症治療用医薬組成物 |
| CN101952260B (zh) * | 2008-02-18 | 2013-02-13 | 弗·哈夫曼-拉罗切有限公司 | 4,5-二氢-*唑-2-基胺衍生物 |
| WO2010063718A1 (en) * | 2008-12-02 | 2010-06-10 | ETH Zürich | Screening assay for metabolic disease therapeuticals |
-
2010
- 2010-09-02 US US12/874,336 patent/US20110065695A1/en not_active Abandoned
- 2010-09-07 JP JP2012527352A patent/JP2013503838A/ja active Pending
- 2010-09-07 EP EP10771367A patent/EP2475658A1/en not_active Withdrawn
- 2010-09-07 CN CN201080039905.XA patent/CN102482268B/zh not_active Expired - Fee Related
- 2010-09-07 CA CA2771374A patent/CA2771374A1/en not_active Abandoned
- 2010-09-07 IN IN1233DEN2012 patent/IN2012DN01233A/en unknown
- 2010-09-07 SG SG2012016119A patent/SG179034A1/en unknown
- 2010-09-07 WO PCT/EP2010/063071 patent/WO2011029803A1/en active Application Filing
- 2010-09-09 AR ARP100103301A patent/AR078163A1/es unknown
- 2010-09-10 TW TW099130754A patent/TW201114765A/zh unknown
-
2012
- 2012-12-06 US US13/706,394 patent/US20130096107A1/en not_active Abandoned
-
2014
- 2014-04-04 US US14/245,045 patent/US20140221360A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2475658A1 (en) | 2012-07-18 |
| CN102482268B (zh) | 2014-11-26 |
| AR078163A1 (es) | 2011-10-19 |
| US20130096107A1 (en) | 2013-04-18 |
| US20140221360A1 (en) | 2014-08-07 |
| IN2012DN01233A (OSRAM) | 2015-05-15 |
| WO2011029803A1 (en) | 2011-03-17 |
| JP2013503838A (ja) | 2013-02-04 |
| TW201114765A (en) | 2011-05-01 |
| US20110065695A1 (en) | 2011-03-17 |
| SG179034A1 (en) | 2012-04-27 |
| CN102482268A (zh) | 2012-05-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160908 |