TWI629278B - 橋聯哌啶衍生物 - Google Patents
橋聯哌啶衍生物 Download PDFInfo
- Publication number
- TWI629278B TWI629278B TW105140951A TW105140951A TWI629278B TW I629278 B TWI629278 B TW I629278B TW 105140951 A TW105140951 A TW 105140951A TW 105140951 A TW105140951 A TW 105140951A TW I629278 B TWI629278 B TW I629278B
- Authority
- TW
- Taiwan
- Prior art keywords
- triazolo
- amine
- azabicyclo
- oct
- pyridin
- Prior art date
Links
- 150000003053 piperidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 386
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 239000002253 acid Substances 0.000 claims abstract description 33
- 230000003287 optical effect Effects 0.000 claims abstract description 23
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 17
- 206010012289 Dementia Diseases 0.000 claims abstract description 15
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims abstract description 10
- 201000010374 Down Syndrome Diseases 0.000 claims abstract description 7
- 206010061216 Infarction Diseases 0.000 claims abstract description 7
- 208000036536 dutch type ABeta amyloidosis Diseases 0.000 claims abstract description 7
- 230000007574 infarction Effects 0.000 claims abstract description 7
- 238000011282 treatment Methods 0.000 claims abstract description 6
- -1 3-methyl-1,2,4-thiadiazol-5-yl Chemical group 0.000 claims description 365
- 229910052799 carbon Inorganic materials 0.000 claims description 133
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 63
- 150000002367 halogens Chemical group 0.000 claims description 63
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 150000001412 amines Chemical class 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
- IBANRDPEOYZVGW-UHFFFAOYSA-N 3-methyl-1,2,4-thiadiazole Chemical compound CC=1N=CSN=1 IBANRDPEOYZVGW-UHFFFAOYSA-N 0.000 claims description 21
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 17
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- QGCRJRVFQZXCAZ-UHFFFAOYSA-N 1h-triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC=CC2=CN(N)NN21 QGCRJRVFQZXCAZ-UHFFFAOYSA-N 0.000 claims description 7
- DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 claims description 6
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims description 5
- GLAYEAGOETWDPL-UHFFFAOYSA-N 1H-triazolo[1,5-a]pyrazin-2-amine Chemical compound N1N(C=C2N1C=CN=C2)N GLAYEAGOETWDPL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 206010002022 amyloidosis Diseases 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 208000019553 vascular disease Diseases 0.000 claims description 2
- 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 claims 3
- DPPHNCGGFCAZGX-UHFFFAOYSA-N 1,1-difluorocyclobutane Chemical compound FC1(F)CCC1 DPPHNCGGFCAZGX-UHFFFAOYSA-N 0.000 claims 2
- 102100026456 POU domain, class 3, transcription factor 3 Human genes 0.000 claims 2
- 101710133393 POU domain, class 3, transcription factor 3 Proteins 0.000 claims 2
- AQUUOVJBMHLVNI-UHFFFAOYSA-N 5-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC=C(OCC(F)(F)F)N2N=C(N)N=C21 AQUUOVJBMHLVNI-UHFFFAOYSA-N 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000018282 ACys amyloidosis Diseases 0.000 abstract description 5
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 abstract description 5
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 description 225
- 239000007787 solid Substances 0.000 description 193
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 187
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- 238000005859 coupling reaction Methods 0.000 description 120
- 230000008878 coupling Effects 0.000 description 117
- 238000010168 coupling process Methods 0.000 description 117
- 239000011541 reaction mixture Substances 0.000 description 112
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 98
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 70
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 64
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- UXRZLDREKITWRO-UHFFFAOYSA-N P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 Chemical compound P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 UXRZLDREKITWRO-UHFFFAOYSA-N 0.000 description 63
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 52
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 51
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 49
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- 238000003818 flash chromatography Methods 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- 239000013058 crude material Substances 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- WOTIUKDGJBXFLG-UHFFFAOYSA-N 3-methyl-1,2-thiazole Chemical compound CC=1C=CSN=1 WOTIUKDGJBXFLG-UHFFFAOYSA-N 0.000 description 32
- 229910052786 argon Inorganic materials 0.000 description 32
- 239000012141 concentrate Substances 0.000 description 32
- 235000008504 concentrate Nutrition 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 27
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 26
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 20
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 20
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 20
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 20
- CUICPJOPYVMUPK-UHFFFAOYSA-N ethyl n-tert-butylcarbamate Chemical compound CCOC(=O)NC(C)(C)C CUICPJOPYVMUPK-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 18
- 229910052794 bromium Inorganic materials 0.000 description 18
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 17
- 239000008346 aqueous phase Substances 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- 229940086542 triethylamine Drugs 0.000 description 16
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 15
- FZAXBPZVVJOFKX-UHFFFAOYSA-N 3-methyl-1,2,4-oxadiazole Chemical compound CC=1N=CON=1 FZAXBPZVVJOFKX-UHFFFAOYSA-N 0.000 description 14
- 229910052801 chlorine Inorganic materials 0.000 description 14
- BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical compound CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- ZMSIFDIKIXVLDF-UHFFFAOYSA-N 2-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=CO1 ZMSIFDIKIXVLDF-UHFFFAOYSA-N 0.000 description 12
- CUMCMYMKECWGHO-UHFFFAOYSA-N 3-methyl-1,2-oxazole Chemical compound CC=1C=CON=1 CUMCMYMKECWGHO-UHFFFAOYSA-N 0.000 description 12
- LVILGAOSPDLNRM-UHFFFAOYSA-N 4-methylpyrimidine Chemical compound CC1=CC=NC=N1 LVILGAOSPDLNRM-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 239000011737 fluorine Substances 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 241000208340 Araliaceae Species 0.000 description 10
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 10
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 10
- 235000003140 Panax quinquefolius Nutrition 0.000 description 10
- 235000008434 ginseng Nutrition 0.000 description 10
- SGQFQIOHTBBYFS-UHFFFAOYSA-N octylcarbamic acid Chemical compound CCCCCCCCNC(O)=O SGQFQIOHTBBYFS-UHFFFAOYSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
- GCSKOIZKVFVVCY-UHFFFAOYSA-N 2-bromo-8-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)COC1=CC=C(N2N=C(Br)N=C12)C(F)(F)F GCSKOIZKVFVVCY-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 8
- KDWQLICBSFIDRM-UHFFFAOYSA-N 1,1,1-trifluoropropane Chemical compound CCC(F)(F)F KDWQLICBSFIDRM-UHFFFAOYSA-N 0.000 description 8
- VZWOXDYRBDIHMA-UHFFFAOYSA-N 2-methyl-1,3-thiazole Chemical compound CC1=NC=CS1 VZWOXDYRBDIHMA-UHFFFAOYSA-N 0.000 description 8
- SVYZUHSGVZDUDT-UHFFFAOYSA-N FC(F)(F)COC1=CC=CN2N=C(Br)N=C12 Chemical compound FC(F)(F)COC1=CC=CN2N=C(Br)N=C12 SVYZUHSGVZDUDT-UHFFFAOYSA-N 0.000 description 8
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 8
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- KJLKRLDWQPENMK-UHFFFAOYSA-N 5-iodo-3-methyl-1,2-oxazole Chemical compound CC=1C=C(I)ON=1 KJLKRLDWQPENMK-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- WBDSUXMAQJTMCG-UHFFFAOYSA-N 2-bromo-8-(2,2,3,3,3-pentafluoropropoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=NN2C(C(=CC=C2)OCC(C(F)(F)F)(F)F)=N1 WBDSUXMAQJTMCG-UHFFFAOYSA-N 0.000 description 6
- QBPDSKPWYWIHGA-UHFFFAOYSA-N 3-hydroxy-2-nitropyridine Chemical class OC1=CC=CN=C1[N+]([O-])=O QBPDSKPWYWIHGA-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 239000007937 lozenge Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 6
- 235000019798 tripotassium phosphate Nutrition 0.000 description 6
- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 5
- AHKRDLDYFJZNLJ-UHFFFAOYSA-N 2-bromo-5-cyclopropyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)COC1=CC=C(C2CC2)N2N=C(Br)N=C12 AHKRDLDYFJZNLJ-UHFFFAOYSA-N 0.000 description 5
- ZBCSZYVDLLOFMU-UHFFFAOYSA-N 4-fluoropyrimidine Chemical compound FC1=CC=NC=N1 ZBCSZYVDLLOFMU-UHFFFAOYSA-N 0.000 description 5
- PENVYHXKYYCYML-UHFFFAOYSA-N 4-methoxypyrimidine Chemical compound COC1=CC=NC=N1 PENVYHXKYYCYML-UHFFFAOYSA-N 0.000 description 5
- AENHEFDZKPSDCK-UHFFFAOYSA-N 6-methyl-2-nitro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound CC1=CC=C(C(=N1)[N+](=O)[O-])OCC(F)(F)F AENHEFDZKPSDCK-UHFFFAOYSA-N 0.000 description 5
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 235000005074 zinc chloride Nutrition 0.000 description 5
- 239000011592 zinc chloride Substances 0.000 description 5
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 4
- WFHYFKBQGLFGRQ-UHFFFAOYSA-N 2-bromo-8-(1,1,1-trifluoropropan-2-yloxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC(Oc1cccn2nc(Br)nc12)C(F)(F)F WFHYFKBQGLFGRQ-UHFFFAOYSA-N 0.000 description 4
- SMHORIXQSMDYEY-UHFFFAOYSA-N 2-ethylheptanenitrile Chemical compound CCCCCC(CC)C#N SMHORIXQSMDYEY-UHFFFAOYSA-N 0.000 description 4
- KSPDSMOWMQFPBL-UHFFFAOYSA-N 5-fluoropyrimidine Chemical compound FC1=CN=CN=C1 KSPDSMOWMQFPBL-UHFFFAOYSA-N 0.000 description 4
- WEIOIYMBZDYIMX-UHFFFAOYSA-N 6-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-amine Chemical compound CC1=CC=C(OCC(F)(F)F)C(N)=N1 WEIOIYMBZDYIMX-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- ACONPURZGJUVLW-UHFFFAOYSA-N chloroform;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl ACONPURZGJUVLW-UHFFFAOYSA-N 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- ZYIBENCKBXFJSL-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate Chemical compound FC(F)(F)C(C)OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F ZYIBENCKBXFJSL-UHFFFAOYSA-N 0.000 description 3
- LWXKUSABFFMNTJ-UHFFFAOYSA-N 2-[2-bromo-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]propan-2-ol Chemical compound CC(C)(O)C1=CC=C(OCC(F)(F)F)C2=NC(Br)=NN12 LWXKUSABFFMNTJ-UHFFFAOYSA-N 0.000 description 3
- PMBVLZFLKMSSSD-UHFFFAOYSA-N 2-bromo-8-(2,2-difluoroethoxy)-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)COC1=CC=C(N2N=C(Br)N=C12)C(F)(F)F PMBVLZFLKMSSSD-UHFFFAOYSA-N 0.000 description 3
- IHRVUZCZXRPKHM-UHFFFAOYSA-N 2-bromo-8-(4,4,4-trifluorobutoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)CCCOC1=CC=CN2N=C(Br)N=C12 IHRVUZCZXRPKHM-UHFFFAOYSA-N 0.000 description 3
- WFHYFKBQGLFGRQ-YFKPBYRVSA-N 2-bromo-8-[(2S)-1,1,1-trifluoropropan-2-yl]oxy-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=NN2C(C(=CC=C2)O[C@H](C(F)(F)F)C)=N1 WFHYFKBQGLFGRQ-YFKPBYRVSA-N 0.000 description 3
- DDHWDLRJQMMXTF-UHFFFAOYSA-N 2-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-ol Chemical compound OC1=CC=CN2N=C(Br)N=C12 DDHWDLRJQMMXTF-UHFFFAOYSA-N 0.000 description 3
- LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 description 3
- AEVSSZHXGJAPIE-UHFFFAOYSA-N 3-chloropyrazin-2-amine Chemical compound NC1=NC=CN=C1Cl AEVSSZHXGJAPIE-UHFFFAOYSA-N 0.000 description 3
- WZMGQHIBXUAYGS-UHFFFAOYSA-N 3-hydroxy-6-methyl-2-nitropyridine Chemical compound CC1=CC=C(O)C([N+]([O-])=O)=N1 WZMGQHIBXUAYGS-UHFFFAOYSA-N 0.000 description 3
- BKDUWMJFLCNPKP-UHFFFAOYSA-N 4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC=N1 BKDUWMJFLCNPKP-UHFFFAOYSA-N 0.000 description 3
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 3
- RRYZGWSWNSXSSN-UHFFFAOYSA-N 6-acetamido-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid Chemical compound C(C)(=O)NC1=C(C=CC(=N1)C(=O)O)OCC(F)(F)F RRYZGWSWNSXSSN-UHFFFAOYSA-N 0.000 description 3
- FEAHWDFLOPGKGG-UHFFFAOYSA-N 6-cyclopropyl-3-(2,2,2-trifluoroethoxy)pyridin-2-amine Chemical compound C1(CC1)C1=CC=C(C(=N1)N)OCC(F)(F)F FEAHWDFLOPGKGG-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 108010050254 Presenilins Proteins 0.000 description 3
- 238000000297 Sandmeyer reaction Methods 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000001211 (E)-4-phenylbut-3-en-2-one Substances 0.000 description 2
- GILIYJDBJZWGBG-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-ol Chemical compound CC(O)C(F)(F)F GILIYJDBJZWGBG-UHFFFAOYSA-N 0.000 description 2
- VOGSDFLJZPNWHY-UHFFFAOYSA-N 2,2-difluoroethanol Chemical compound OCC(F)F VOGSDFLJZPNWHY-UHFFFAOYSA-N 0.000 description 2
- YHPDMEBZIOVFAE-UHFFFAOYSA-N 2-bromo-5-(trifluoromethyl)-8-(1,1,1-trifluoropropan-2-yloxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=NN2C(C(=CC=C2C(F)(F)F)OC(C(F)(F)F)C)=N1 YHPDMEBZIOVFAE-UHFFFAOYSA-N 0.000 description 2
- KEMOFOZJLYPYRA-UHFFFAOYSA-N 2-bromo-5-methyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC1=CC=C(OCC(F)(F)F)C2=NC(Br)=NN12 KEMOFOZJLYPYRA-UHFFFAOYSA-N 0.000 description 2
- LYLUTRSUSIAVDH-UHFFFAOYSA-N 2-bromo-8-(2,2,3,3,3-pentafluoropropoxy)-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound FC(F)(F)C(F)(F)COC1=NC=CN2N=C(Br)N=C12 LYLUTRSUSIAVDH-UHFFFAOYSA-N 0.000 description 2
- WFHYFKBQGLFGRQ-RXMQYKEDSA-N 2-bromo-8-[(2R)-1,1,1-trifluoropropan-2-yl]oxy-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=NN2C(C(=CC=C2)O[C@@H](C(F)(F)F)C)=N1 WFHYFKBQGLFGRQ-RXMQYKEDSA-N 0.000 description 2
- DKZPZRXERKEHRF-UHFFFAOYSA-N 2-bromo-8-chloro-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound ClC1=NC=CN2N=C(Br)N=C12 DKZPZRXERKEHRF-UHFFFAOYSA-N 0.000 description 2
- XIVQRQUKDKSBHD-UHFFFAOYSA-N 2-nitro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound [O-][N+](=O)C1=NC=CC=C1OCC(F)(F)F XIVQRQUKDKSBHD-UHFFFAOYSA-N 0.000 description 2
- HXBKWYLESFBHEC-UHFFFAOYSA-N 2-nitro-3-(3,3,3-trifluoropropoxy)pyridine Chemical compound [O-][N+](=O)C1=NC=CC=C1OCCC(F)(F)F HXBKWYLESFBHEC-UHFFFAOYSA-N 0.000 description 2
- HCALTEGTIZHQEZ-UHFFFAOYSA-N 3-(2,2-difluoroethoxy)pyrazin-2-amine Chemical compound FC(COC=1C(=NC=CN=1)N)F HCALTEGTIZHQEZ-UHFFFAOYSA-N 0.000 description 2
- KHHWISYSQWIMSZ-UHFFFAOYSA-N 3-(4,4,4-trifluorobutoxy)pyridin-2-amine Chemical compound FC(CCCOC=1C(=NC=CC=1)N)(F)F KHHWISYSQWIMSZ-UHFFFAOYSA-N 0.000 description 2
- MCLDVUCSDZGNRR-UHFFFAOYSA-N 4,6-difluoropyrimidine Chemical compound FC1=CC(F)=NC=N1 MCLDVUCSDZGNRR-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QSFGQHQXDKLATK-UHFFFAOYSA-N 4-chloro-5-fluoro-2-methylpyrimidine Chemical compound CC1=NC=C(F)C(Cl)=N1 QSFGQHQXDKLATK-UHFFFAOYSA-N 0.000 description 2
- DUNVDIOORQSZHX-UHFFFAOYSA-N 5-cyclopropyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(OCC(F)(F)F)=CC=C2C1CC1 DUNVDIOORQSZHX-UHFFFAOYSA-N 0.000 description 2
- KGSHUSTZRNJJMD-UHFFFAOYSA-N 5-methyl-2-nitro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound CC=1C=C(C(=NC=1)[N+](=O)[O-])OCC(F)(F)F KGSHUSTZRNJJMD-UHFFFAOYSA-N 0.000 description 2
- XKWDTBXOOOUTKY-UHFFFAOYSA-N 5-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-amine Chemical compound CC=1C=C(C(=NC=1)N)OCC(F)(F)F XKWDTBXOOOUTKY-UHFFFAOYSA-N 0.000 description 2
- WTIBMXCTMHKOHG-UHFFFAOYSA-N 5-methyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound CC1=CC=C(OCC(F)(F)F)C2=NC(N)=NN12 WTIBMXCTMHKOHG-UHFFFAOYSA-N 0.000 description 2
- FGJGJGMNXQPQKP-UHFFFAOYSA-N 5-methyl-8-(2,2,3,3,3-pentafluoropropoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound CC1=CC=C(OCC(F)(F)C(F)(F)F)C2=NC(N)=NN12 FGJGJGMNXQPQKP-UHFFFAOYSA-N 0.000 description 2
- AJSRUPTXYSCBFT-UHFFFAOYSA-N 6-bromo-2-nitro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound BrC1=CC=C(C(=N1)[N+](=O)[O-])OCC(F)(F)F AJSRUPTXYSCBFT-UHFFFAOYSA-N 0.000 description 2
- GSGNTVQLHGOEMB-UHFFFAOYSA-N 6-bromo-2-nitropyridin-3-ol Chemical compound OC1=CC=C(Br)N=C1[N+]([O-])=O GSGNTVQLHGOEMB-UHFFFAOYSA-N 0.000 description 2
- LTQGFWUMZSPNAI-UHFFFAOYSA-N 6-cyclopropyl-2-nitro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound C1(CC1)C1=CC=C(C(=N1)[N+](=O)[O-])OCC(F)(F)F LTQGFWUMZSPNAI-UHFFFAOYSA-N 0.000 description 2
- GSRWGAUVZVIBDI-UHFFFAOYSA-N 6-methyl-2-nitro-3-(2,2,3,3,3-pentafluoropropoxy)pyridine Chemical compound CC1=CC=C(C(=N1)[N+](=O)[O-])OCC(C(F)(F)F)(F)F GSRWGAUVZVIBDI-UHFFFAOYSA-N 0.000 description 2
- ZGWJCPLWSGWKII-UHFFFAOYSA-N 6-methyl-3-(2,2,3,3,3-pentafluoropropoxy)pyridin-2-amine Chemical compound CC1=CC=C(C(=N1)N)OCC(C(F)(F)F)(F)F ZGWJCPLWSGWKII-UHFFFAOYSA-N 0.000 description 2
- LASUHPKLRHJZAK-UHFFFAOYSA-N 6-methyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound CC1=CN2N=C(N)N=C2C(OCC(F)(F)F)=C1 LASUHPKLRHJZAK-UHFFFAOYSA-N 0.000 description 2
- UIWJIQYXUKFLSE-UHFFFAOYSA-N 8-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(OCC(F)(F)F)=CC=C2C(F)(F)F UIWJIQYXUKFLSE-UHFFFAOYSA-N 0.000 description 2
- HSWZSZNHAANMGK-UHFFFAOYSA-N 8-(2,2-difluoroethoxy)-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(OCC(F)F)=CC=C2C(F)(F)F HSWZSZNHAANMGK-UHFFFAOYSA-N 0.000 description 2
- MYMYPGIKEVRYOM-UHFFFAOYSA-N 8-(2,2-difluoroethoxy)-[1,2,4]triazolo[1,5-a]pyrazin-2-amine Chemical compound NC1=NN2C=CN=C(OCC(F)F)C2=N1 MYMYPGIKEVRYOM-UHFFFAOYSA-N 0.000 description 2
- PHQMHFVGWVBDOX-UHFFFAOYSA-N 8-(3,3,3-trifluoropropoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C=CC=C(OCCC(F)(F)F)C2=N1 PHQMHFVGWVBDOX-UHFFFAOYSA-N 0.000 description 2
- GFMHXVKQHYKWKE-UHFFFAOYSA-N 8-(4,4,4-trifluorobutoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C=CC=C(OCCCC(F)(F)F)C2=N1 GFMHXVKQHYKWKE-UHFFFAOYSA-N 0.000 description 2
- XCKQBAUSPDKKOZ-UHFFFAOYSA-N 8-(trifluoromethoxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C=CC=C(OC(F)(F)F)C2=N1 XCKQBAUSPDKKOZ-UHFFFAOYSA-N 0.000 description 2
- HRCKNYWKHBWFJH-UHFFFAOYSA-N 8-bromo-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(Br)=CC=C2C(F)(F)F HRCKNYWKHBWFJH-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VRGMTAQNFBYTJZ-UHFFFAOYSA-N N=1C(NN2C1C=CC=C2)=O Chemical compound N=1C(NN2C1C=CC=C2)=O VRGMTAQNFBYTJZ-UHFFFAOYSA-N 0.000 description 2
- WHYHTLNCDLTIPE-UHFFFAOYSA-N NC1=NN2C=CC=C(OCC(F)(F)F)C2=N1 Chemical compound NC1=NN2C=CC=C(OCC(F)(F)F)C2=N1 WHYHTLNCDLTIPE-UHFFFAOYSA-N 0.000 description 2
- 102000005650 Notch Receptors Human genes 0.000 description 2
- 108010070047 Notch Receptors Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000006933 amyloid-beta aggregation Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 229930008407 benzylideneacetone Natural products 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- UFEIWEXHHOXPGP-UHFFFAOYSA-M sodium;(4,6-dimethoxypyrimidin-2-yl)carbamoyl-[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonylazanide Chemical compound [Na+].COC1=CC(OC)=NC(NC(=O)[N-]S(=O)(=O)C=2C(=CC=CN=2)OCC(F)(F)F)=N1 UFEIWEXHHOXPGP-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- BWHOZHOGCMHOBV-BQYQJAHWSA-N trans-benzylideneacetone Chemical compound CC(=O)\C=C\C1=CC=CC=C1 BWHOZHOGCMHOBV-BQYQJAHWSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- VMFCTZUYOILUMY-UHFFFAOYSA-N 1,1-difluoro-2-iodoethane Chemical compound FC(F)CI VMFCTZUYOILUMY-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- LPUCHTNHUHOTRY-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)ethanamine Chemical compound C1CC2C(C(N)C)CC1C2 LPUCHTNHUHOTRY-UHFFFAOYSA-N 0.000 description 1
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
- SZVOULWPEYQUJX-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyridine Chemical compound FC1=CN=C(Cl)C=C1Cl SZVOULWPEYQUJX-UHFFFAOYSA-N 0.000 description 1
- WUGTXQVNSRFDNV-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine Chemical compound CC1=CC(Cl)=CC(Cl)=N1 WUGTXQVNSRFDNV-UHFFFAOYSA-N 0.000 description 1
- DZVISWVJDSJKSN-UHFFFAOYSA-N 2-bromo-5-(trifluoromethyl)-8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)C1=CC=C(OCC2(CC2)C(F)(F)F)C2=NC(Br)=NN12 DZVISWVJDSJKSN-UHFFFAOYSA-N 0.000 description 1
- KLFIDXBWKMWDOF-UHFFFAOYSA-N 2-bromo-5-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=C(Br)O1 KLFIDXBWKMWDOF-UHFFFAOYSA-N 0.000 description 1
- AWEBOJDWBVHJQA-UHFFFAOYSA-N 2-bromo-5-methyl-8-(2,2,3,3,3-pentafluoropropoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC1=CC=C(OCC(F)(F)C(F)(F)F)C2=NC(Br)=NN12 AWEBOJDWBVHJQA-UHFFFAOYSA-N 0.000 description 1
- PIJPIQNUGHNVDV-UHFFFAOYSA-N 2-bromo-6-chloro-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)COC1=CC(Cl)=CN2N=C(Br)N=C12 PIJPIQNUGHNVDV-UHFFFAOYSA-N 0.000 description 1
- IRSPAKSRCUQZQB-UHFFFAOYSA-N 2-bromo-6-fluoro-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=NN2C(C(=CC(=C2)F)OCC(F)(F)F)=N1 IRSPAKSRCUQZQB-UHFFFAOYSA-N 0.000 description 1
- YGKKBLOKOLYQQT-UHFFFAOYSA-N 2-bromo-6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-8-ol Chemical compound OC1=CC(F)=CN2N=C(Br)N=C12 YGKKBLOKOLYQQT-UHFFFAOYSA-N 0.000 description 1
- UUUBWRZJUSTBEH-UHFFFAOYSA-N 2-bromo-6-methyl-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC1=CN2N=C(Br)N=C2C(OCC(F)(F)F)=C1 UUUBWRZJUSTBEH-UHFFFAOYSA-N 0.000 description 1
- LKMZLWZDHHVLJN-UHFFFAOYSA-N 2-bromo-8-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound FC(F)(F)C(Oc1nccn2nc(Br)nc12)C(F)(F)F LKMZLWZDHHVLJN-UHFFFAOYSA-N 0.000 description 1
- OUWFQETWLYNNKL-UHFFFAOYSA-N 2-bromo-8-(1,1,1-trifluoropropan-2-yloxy)-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound CC(Oc1nccn2nc(Br)nc12)C(F)(F)F OUWFQETWLYNNKL-UHFFFAOYSA-N 0.000 description 1
- XQNGMKTZZZJONA-UHFFFAOYSA-N 2-bromo-8-(2,2-difluoroethoxy)-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound FC(F)COC1=NC=CN2N=C(Br)N=C12 XQNGMKTZZZJONA-UHFFFAOYSA-N 0.000 description 1
- AEKFIZOJMSFUIT-UHFFFAOYSA-N 2-bromo-8-(2,2-difluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)COC1=CC=CN2N=C(Br)N=C12 AEKFIZOJMSFUIT-UHFFFAOYSA-N 0.000 description 1
- VGFAIMRGTMAJBN-UHFFFAOYSA-N 2-bromo-8-(3,3,3-trifluoropropoxy)-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound FC(F)(F)CCOC1=NC=CN2N=C(Br)N=C12 VGFAIMRGTMAJBN-UHFFFAOYSA-N 0.000 description 1
- NHRPUHHRADTMRC-UHFFFAOYSA-N 2-bromo-8-(3,3,3-trifluoropropoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)CCOC1=CC=CN2N=C(Br)N=C12 NHRPUHHRADTMRC-UHFFFAOYSA-N 0.000 description 1
- DCKSDPDINWUBLR-UHFFFAOYSA-N 2-bromo-8-(trifluoromethoxy)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)OC1=CC=CN2N=C(Br)N=C12 DCKSDPDINWUBLR-UHFFFAOYSA-N 0.000 description 1
- BVEBEJIQEVOQDI-UHFFFAOYSA-N 2-bromo-8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC(F)(F)C1(COC2=CC=CN3N=C(Br)N=C23)CC1 BVEBEJIQEVOQDI-UHFFFAOYSA-N 0.000 description 1
- LEWVYKYYCKLYSJ-UHFFFAOYSA-N 2-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine Chemical compound COC1=CC=CN2N=C(Br)N=C12 LEWVYKYYCKLYSJ-UHFFFAOYSA-N 0.000 description 1
- FGSAQRJRWCZLOB-UHFFFAOYSA-N 2-chloro-4-fluoropyridine Chemical compound FC1=CC=NC(Cl)=C1 FGSAQRJRWCZLOB-UHFFFAOYSA-N 0.000 description 1
- BAXHQKADZZPFNR-UHFFFAOYSA-N 2-cyclopropylpentanoic acid Chemical compound CCCC(C(O)=O)C1CC1 BAXHQKADZZPFNR-UHFFFAOYSA-N 0.000 description 1
- GGDYAKVUZMZKRV-UHFFFAOYSA-N 2-fluoroethanol Chemical compound OCCF GGDYAKVUZMZKRV-UHFFFAOYSA-N 0.000 description 1
- IODBYQLNMHFIQR-UHFFFAOYSA-N 2-methyl-5-(2,2,2-trifluoroethoxy)pyridine Chemical compound CC1=CC=C(OCC(F)(F)F)C=N1 IODBYQLNMHFIQR-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- UVISNPMCMWCENB-UHFFFAOYSA-N 2-nitro-1h-pyridin-2-ol Chemical class [O-][N+](=O)C1(O)NC=CC=C1 UVISNPMCMWCENB-UHFFFAOYSA-N 0.000 description 1
- YBNHJIVKJLUHIV-UHFFFAOYSA-N 2-nitro-3-(4,4,4-trifluorobutoxy)pyridine Chemical compound [N+](=O)([O-])C1=NC=CC=C1OCCCC(F)(F)F YBNHJIVKJLUHIV-UHFFFAOYSA-N 0.000 description 1
- JSIAIROWMJGMQZ-UHFFFAOYSA-N 2h-triazol-4-amine Chemical compound NC1=CNN=N1 JSIAIROWMJGMQZ-UHFFFAOYSA-N 0.000 description 1
- KGUHUVQIJHGHLX-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridin-5-amine Chemical compound NC1=CC=C2NN=NC2=N1 KGUHUVQIJHGHLX-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- BSSPNISMQJMZBJ-UHFFFAOYSA-N 3-(2,2,2-trifluoroethoxy)pyridin-2-amine Chemical compound NC1=NC=CC=C1OCC(F)(F)F BSSPNISMQJMZBJ-UHFFFAOYSA-N 0.000 description 1
- WWZMVWNUORBHBH-UHFFFAOYSA-N 3-(3,3,3-trifluoropropoxy)pyridin-2-amine Chemical compound NC1=NC=CC=C1OCCC(F)(F)F WWZMVWNUORBHBH-UHFFFAOYSA-N 0.000 description 1
- WCRYAXUZQGCSAO-UHFFFAOYSA-N 3-(trifluoromethoxy)pyridin-2-amine Chemical compound NC1=NC=CC=C1OC(F)(F)F WCRYAXUZQGCSAO-UHFFFAOYSA-N 0.000 description 1
- TULNIAUGCUPXKX-UHFFFAOYSA-N 3-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=CN=C1 TULNIAUGCUPXKX-UHFFFAOYSA-N 0.000 description 1
- DEJSNICBKCZCRF-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound C12CN(CC(CC1)C2)C(=O)O DEJSNICBKCZCRF-UHFFFAOYSA-N 0.000 description 1
- UWGGGYYCKDCTGN-UHFFFAOYSA-N 3-bromo-5-chloropyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1Br UWGGGYYCKDCTGN-UHFFFAOYSA-N 0.000 description 1
- PNTYGOBZCMESJG-UHFFFAOYSA-N 3-bromo-6-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC(C(F)(F)F)=CC=C1Br PNTYGOBZCMESJG-UHFFFAOYSA-N 0.000 description 1
- HNAYRVKSWGSQTP-UHFFFAOYSA-N 3-methoxypyridin-2-amine Chemical compound COC1=CC=CN=C1N HNAYRVKSWGSQTP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NNSNDHTUFCXSAS-UHFFFAOYSA-N 4-bromo-3-fluoropyridine;hydrochloride Chemical compound Cl.FC1=CN=CC=C1Br NNSNDHTUFCXSAS-UHFFFAOYSA-N 0.000 description 1
- MENOXSCJWFSFHL-UHFFFAOYSA-N 4-bromo-5-fluoro-2-methylpyridine Chemical compound CC1=CC(Br)=C(F)C=N1 MENOXSCJWFSFHL-UHFFFAOYSA-N 0.000 description 1
- WDTVJRYCMIZPMX-UHFFFAOYSA-N 4-chloro-2-methylpyrimidine Chemical compound CC1=NC=CC(Cl)=N1 WDTVJRYCMIZPMX-UHFFFAOYSA-N 0.000 description 1
- GHMKXPYBLNJQIK-UHFFFAOYSA-N 4-chloro-5-fluoro-6-methylpyrimidine Chemical compound CC1=NC=NC(Cl)=C1F GHMKXPYBLNJQIK-UHFFFAOYSA-N 0.000 description 1
- TYSPDLZOMUDHQZ-UHFFFAOYSA-N 4-chloro-6-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC(Cl)=NC=N1 TYSPDLZOMUDHQZ-UHFFFAOYSA-N 0.000 description 1
- DLAFWIYXXOBITQ-UHFFFAOYSA-N 4-chloro-6-fluoropyrimidine Chemical compound FC1=CC(Cl)=NC=N1 DLAFWIYXXOBITQ-UHFFFAOYSA-N 0.000 description 1
- MVAXKFAQKTWRAH-UHFFFAOYSA-N 4-chloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC=N1 MVAXKFAQKTWRAH-UHFFFAOYSA-N 0.000 description 1
- HBZJVDNETONGIS-UHFFFAOYSA-N 4-chloropyrimidine;hydrochloride Chemical compound Cl.ClC1=CC=NC=N1 HBZJVDNETONGIS-UHFFFAOYSA-N 0.000 description 1
- OYQSAEIWDLIZHC-UHFFFAOYSA-N 4-iodo-2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(I)=CC=N1 OYQSAEIWDLIZHC-UHFFFAOYSA-N 0.000 description 1
- QDBUDQCGLQIPKI-UHFFFAOYSA-N 4-iodo-6-methoxypyrimidine Chemical compound COC1=CC(I)=NC=N1 QDBUDQCGLQIPKI-UHFFFAOYSA-N 0.000 description 1
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
- MMERROPKZFZEAL-UHFFFAOYSA-N 5-(trifluoromethyl)-8-(1,1,1-trifluoropropan-2-yloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound FC(F)(F)C1=CC=C(C=2N1N=C(N=2)N)OC(C(F)(F)F)C MMERROPKZFZEAL-UHFFFAOYSA-N 0.000 description 1
- IBCAQAOIUROZCQ-UHFFFAOYSA-N 5-(trifluoromethyl)-8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(OCC1(CC1)C(F)(F)F)=CC=C2C(F)(F)F IBCAQAOIUROZCQ-UHFFFAOYSA-N 0.000 description 1
- ILTLLMVRPBXCSX-UHFFFAOYSA-N 5-chloro-3-methyl-1,2,4-thiadiazole Chemical compound CC1=NSC(Cl)=N1 ILTLLMVRPBXCSX-UHFFFAOYSA-N 0.000 description 1
- HDEPDCIKNFFYSO-UHFFFAOYSA-N 5-fluoro-3-methoxypyridin-2-amine Chemical compound COC1=CC(F)=CN=C1N HDEPDCIKNFFYSO-UHFFFAOYSA-N 0.000 description 1
- FESHDHSFWWFFFN-UHFFFAOYSA-N 5-methyl-2-nitropyridin-3-ol Chemical compound CC1=CN=C([N+]([O-])=O)C(O)=C1 FESHDHSFWWFFFN-UHFFFAOYSA-N 0.000 description 1
- QOIXGDNEWDXUMJ-UHFFFAOYSA-N 6-fluoro-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound COC1=CC(F)=CN2N=C(N)N=C12 QOIXGDNEWDXUMJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SZOMCZNEKMLQAD-UHFFFAOYSA-N 8-(2-fluoroethoxy)-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C(=N1)C(OCCF)=CC=C2C(F)(F)F SZOMCZNEKMLQAD-UHFFFAOYSA-N 0.000 description 1
- ORQLGWUTFBIBOW-UHFFFAOYSA-N 8-bromo-6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound NC1=NN2C=C(Cl)C=C(Br)C2=N1 ORQLGWUTFBIBOW-UHFFFAOYSA-N 0.000 description 1
- JKWVYDCURGHICU-UHFFFAOYSA-N 8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound COC1=CC=CN2N=C(N)N=C12 JKWVYDCURGHICU-UHFFFAOYSA-N 0.000 description 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101000898643 Candida albicans Vacuolar aspartic protease Proteins 0.000 description 1
- 101000898783 Candida tropicalis Candidapepsin Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101000898784 Cryphonectria parasitica Endothiapepsin Proteins 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 1
- FUMNGYNBOMTTBW-UHFFFAOYSA-N N=C=S.[Ar] Chemical compound N=C=S.[Ar] FUMNGYNBOMTTBW-UHFFFAOYSA-N 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 101000579647 Penaeus vannamei Penaeidin-2a Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 101000933133 Rhizopus niveus Rhizopuspepsin-1 Proteins 0.000 description 1
- 101000910082 Rhizopus niveus Rhizopuspepsin-2 Proteins 0.000 description 1
- 101000910079 Rhizopus niveus Rhizopuspepsin-3 Proteins 0.000 description 1
- 101000910086 Rhizopus niveus Rhizopuspepsin-4 Proteins 0.000 description 1
- 101000910088 Rhizopus niveus Rhizopuspepsin-5 Proteins 0.000 description 1
- 101000898773 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Saccharopepsin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- PHTMVIAGTMTVSK-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC=CN2N=C(N)N=C21 PHTMVIAGTMTVSK-UHFFFAOYSA-N 0.000 description 1
- YYWSKSKIJXVNTH-UHFFFAOYSA-N [1-(trifluoromethyl)cyclopropyl]methanol Chemical compound OCC1(C(F)(F)F)CC1 YYWSKSKIJXVNTH-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 101150089041 aph-1 gene Proteins 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- RRJZEMAFCNWPQO-UHFFFAOYSA-N butylamino carbamate Chemical compound C(N)(=O)ONCCCC RRJZEMAFCNWPQO-UHFFFAOYSA-N 0.000 description 1
- 210000004900 c-terminal fragment Anatomy 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- HCSHUEPPBIJJCB-UHFFFAOYSA-N carbamic acid;2,2,2-trifluoroacetic acid Chemical compound NC(O)=O.OC(=O)C(F)(F)F HCSHUEPPBIJJCB-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- FULSCKQLKRBVJV-UHFFFAOYSA-N carbonyl diisothiocyanate Chemical compound S=C=NC(=O)N=C=S FULSCKQLKRBVJV-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- WDVGNXKCFBOKDF-UHFFFAOYSA-N dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 WDVGNXKCFBOKDF-UHFFFAOYSA-N 0.000 description 1
- SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- FHNBUHPOKAPPAC-UHFFFAOYSA-N ethylamino formate Chemical compound CCNOC=O FHNBUHPOKAPPAC-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000006419 fluorocyclopropyl group Chemical group 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- MHSPLKBWKCJRFJ-UHFFFAOYSA-N methyl 2-amino-8-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylate Chemical compound COC(=O)C1=CC=C(OCC(F)(F)F)C2=NC(N)=NN12 MHSPLKBWKCJRFJ-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VIRYRCBSAQHUND-UHFFFAOYSA-N n-bromopyridin-2-amine Chemical class BrNC1=CC=CC=N1 VIRYRCBSAQHUND-UHFFFAOYSA-N 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 102000046701 nicastrin Human genes 0.000 description 1
- 108700022821 nicastrin Proteins 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 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
- 238000005580 one pot reaction Methods 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
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- JGTNAGYHADQMCM-UHFFFAOYSA-N perfluorobutanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JGTNAGYHADQMCM-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ROVTUJRZGCDHDL-UHFFFAOYSA-N tert-butyl 2-ethylheptanoate Chemical compound CCCCCC(CC)C(=O)OC(C)(C)C ROVTUJRZGCDHDL-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- WFNSSRVVNZGTTR-UHFFFAOYSA-N tert-butyl n-octylcarbamate Chemical compound CCCCCCCCNC(=O)OC(C)(C)C WFNSSRVVNZGTTR-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical group C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ??15199260.9 | 2015-12-10 | ||
| EP15199260 | 2015-12-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201725209A TW201725209A (zh) | 2017-07-16 |
| TWI629278B true TWI629278B (zh) | 2018-07-11 |
Family
ID=54848457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW105140951A TWI629278B (zh) | 2015-12-10 | 2016-12-09 | 橋聯哌啶衍生物 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US10562903B2 (enExample) |
| EP (1) | EP3386978B1 (enExample) |
| JP (1) | JP6872550B2 (enExample) |
| CN (1) | CN108137579B (enExample) |
| AR (1) | AR107010A1 (enExample) |
| TW (1) | TWI629278B (enExample) |
| WO (1) | WO2017097728A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA43028B1 (fr) | 2015-10-02 | 2021-09-30 | Hoffmann La Roche | Anticorps bispécifiques pour pd1 et tim3 |
| CA3119019C (en) | 2015-12-10 | 2024-06-11 | Ptc Therapeutics, Inc. | Compounds and methods for treating huntington's disease |
| CN109311878B (zh) * | 2016-06-27 | 2022-05-24 | 豪夫迈·罗氏有限公司 | 作为γ-分泌酶调节剂的三唑并吡啶类化合物 |
| AR109829A1 (es) * | 2016-09-29 | 2019-01-30 | Hoffmann La Roche | Derivados de piperidina puenteados |
| EP3535266B1 (en) * | 2016-11-01 | 2021-12-29 | F. Hoffmann-La Roche AG | Bicyclic heteroaryl derivatives |
| KR102461885B1 (ko) | 2017-04-03 | 2022-11-03 | 에프. 호프만-라 로슈 아게 | 항-pd-1 항체와 돌연변이 il-2 또는 il-15의 면역접합체 |
| CA3052532A1 (en) | 2017-04-05 | 2018-10-11 | F. Hoffmann-La Roche Ag | Bispecific antibodies specifically binding to pd1 and lag3 |
| EP4151627A1 (en) | 2017-06-05 | 2023-03-22 | PTC Therapeutics, Inc. | Compounds for treating huntington's disease |
| CN111182898B (zh) | 2017-06-28 | 2024-04-16 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| CN111163838B (zh) | 2017-06-28 | 2023-03-28 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| BR112020019373A2 (pt) | 2018-03-27 | 2020-12-29 | Ptc Therapeutics, Inc. | Compostos para o tratamento da doença de hutington |
| KR20210038845A (ko) | 2018-06-27 | 2021-04-08 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료를 위한 헤테로아릴 화합물 |
| IL279688B2 (en) | 2018-06-27 | 2025-01-01 | Ptc Therapeutics Inc | Heterocyclic and heteroaryl compounds for the treatment of Huntington's disease |
| MX2021002087A (es) | 2018-09-03 | 2021-04-28 | Hoffmann La Roche | Derivados de heteroarilo biciclicos. |
| AU2019395774B2 (en) * | 2018-12-13 | 2024-12-12 | F. Hoffmann-La Roche Ag | 7-phenoxy-N-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds as gamma-secretase modulators for the treatment of Alzheimer's disease |
| AU2019412747B8 (en) | 2018-12-27 | 2025-04-24 | F. Hoffmann-La Roche Ag | Process for the preparation exo-tert-butyl N-(3-azabicyclo[3.2.1]octan-8-yl)carbamate |
| CA3139821A1 (en) | 2019-05-13 | 2020-11-19 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| EP4337323A4 (en) * | 2021-05-14 | 2025-07-09 | Bm Pharma Consulting Pty Ltd | BICYCLIC HETEROCYCLIC COMPOUNDS FOR THE PROPHYLAXIS AND TREATMENT OF VIRAL INFECTIONS |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012116965A1 (en) * | 2011-03-02 | 2012-09-07 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1383409A (en) | 1972-09-09 | 1974-02-12 | Pfizer Ltd | Derivatives of 2-amino- and 4-amino-quinazoline and pharmaceutical compositions containing them |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| CA2551178C (en) | 2003-12-24 | 2012-11-06 | Biota Scientific Management Pty Ltd | Polycyclic agents for the treatment of respiratory syncytial virus infections |
| EP1932844B1 (en) * | 2005-10-06 | 2015-09-02 | Nippon Soda Co., Ltd. | Cross-linked cyclic amine compounds and agents for pest control |
| FR2914188B1 (fr) | 2007-03-28 | 2012-06-22 | Trophos | Nouvelle composition a base d'oxime de cholest-4-en-3-one |
| US8633019B2 (en) | 2008-05-27 | 2014-01-21 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| JP2011529722A (ja) | 2008-08-14 | 2011-12-15 | カーディアック ペースメイカーズ， インコーポレイテッド | 音響通信リンクの性能評価および適合 |
| US8486967B2 (en) * | 2010-02-17 | 2013-07-16 | Hoffmann-La Roche Inc. | Heteroaryl substituted piperidines |
| US8871756B2 (en) | 2011-08-11 | 2014-10-28 | Hoffmann-La Roche Inc. | Compounds for the treatment and prophylaxis of Respiratory Syncytial Virus disease |
| GB201119538D0 (en) | 2011-11-10 | 2011-12-21 | Viral Ltd | Pharmaceutical compounds |
| MX352861B (es) | 2011-12-30 | 2017-12-13 | Ptc Therapeutics Inc | Compuestos para tratar la atrofia muscular espinal. |
| MX357834B (es) | 2012-01-26 | 2018-07-26 | Ptc Therapeutics Inc | Compuestos de tipo isocumarina sustituidos para tratar la atrofia muscular espinal. |
| EP3406252B1 (en) | 2012-02-10 | 2020-05-13 | PTC Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| US9212209B2 (en) | 2012-07-13 | 2015-12-15 | Indiana University Research And Technology Corporation | Screening methods for spinal muscular atrophy |
| JP2016518421A (ja) | 2013-05-14 | 2016-06-23 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 呼吸器合胞体ウイルス感染症の処置および予防のためのアザ−オキソ−インドール |
| CA2913785C (en) | 2013-06-25 | 2021-08-31 | F. Hoffmann-La Roche Ag | Compounds for treating spinal muscular atrophy |
| AR099134A1 (es) | 2014-01-24 | 2016-06-29 | Hoffmann La Roche | Procedimiento para la preparación de n-[(3-aminooxetán-3-il)metil]-2-(1,1-dioxo-3,5-dihidro-1,4-benzotiazepín-4-il)-6-metil-quinazolín-4-amina |
| AU2015261046C1 (en) | 2014-05-15 | 2019-07-25 | F. Hoffmann-La Roche Ag | Compounds for treating spinal muscular atrophy |
| AU2016353961B2 (en) | 2015-11-12 | 2019-08-29 | F. Hoffmann-La Roche Ag | Compositions for treating spinal muscular atrophy |
-
2016
- 2016-12-06 EP EP16805853.5A patent/EP3386978B1/en active Active
- 2016-12-06 JP JP2018529006A patent/JP6872550B2/ja active Active
- 2016-12-06 CN CN201680057010.6A patent/CN108137579B/zh active Active
- 2016-12-06 WO PCT/EP2016/079816 patent/WO2017097728A1/en not_active Ceased
- 2016-12-07 AR ARP160103753A patent/AR107010A1/es unknown
- 2016-12-09 TW TW105140951A patent/TWI629278B/zh not_active IP Right Cessation
-
2018
- 2018-06-08 US US16/004,145 patent/US10562903B2/en active Active
-
2020
- 2020-02-13 US US16/790,629 patent/US20200291034A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012116965A1 (en) * | 2011-03-02 | 2012-09-07 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| AR107010A1 (es) | 2018-03-14 |
| CN108137579A (zh) | 2018-06-08 |
| US20200291034A1 (en) | 2020-09-17 |
| EP3386978A1 (en) | 2018-10-17 |
| JP2018536671A (ja) | 2018-12-13 |
| TW201725209A (zh) | 2017-07-16 |
| US10562903B2 (en) | 2020-02-18 |
| CN108137579B (zh) | 2022-01-07 |
| US20190010156A1 (en) | 2019-01-10 |
| JP6872550B2 (ja) | 2021-05-19 |
| WO2017097728A1 (en) | 2017-06-15 |
| EP3386978B1 (en) | 2021-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6872550B2 (ja) | 架橋されたピペリジン誘導体 | |
| AU2012250958B2 (en) | Amino-pyridine-containing Spleen Tyrosine Kinase (Syk) inhibitors | |
| TWI716446B (zh) | 橋聯哌啶衍生物 | |
| AU2017376624A1 (en) | Aminothiazole compounds as c-Kit inhibitors | |
| TW201927778A (zh) | 作為lpa拮抗劑之環己基酸三唑唑類 | |
| JP2024056755A (ja) | ホスファチジルイノシトールリン酸キナーゼ阻害剤としてのアミノピリジン誘導体 | |
| JP7111704B2 (ja) | 二環式ヘテロアリール誘導体 | |
| MX2013009031A (es) | Derivados de piperidina puenteada. | |
| AU2019395774B2 (en) | 7-phenoxy-N-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds as gamma-secretase modulators for the treatment of Alzheimer's disease | |
| AU2014248763A1 (en) | Substituted piperidine compounds and their use as orexin receptor modulators | |
| TW201815792A (zh) | 橋聯哌啶衍生物 | |
| JP7012715B2 (ja) | γ－セクレターゼモジュレーターとしてのトリアゾロピリジン | |
| CN109476670B (zh) | 二环杂芳基衍生物 | |
| WO2014153280A1 (en) | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors | |
| JP2025520081A (ja) | Ｔｒｐｍ３媒介性障害を治療するためのインドリジン誘導体 | |
| HK1262827A1 (en) | Triazolopyridines as gamma-secretase modulators | |
| HK1262827B (en) | Triazolopyridines as gamma-secretase modulators | |
| HK1254787A1 (en) | Bridged piperidine derivatives | |
| HK1254787B (en) | Bridged piperidine derivatives | |
| HK1262487A1 (en) | Bicyclic heteroaryl derivatives | |
| HK1262487B (en) | Bicyclic heteroaryl derivatives | |
| HK40002985B (zh) | 二环杂芳基衍生物 | |
| HK40002502B (en) | Bridged piperidine derivatives | |
| HK40002502A (en) | Bridged piperidine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |