ES2802174T3 - Compuestos - Google Patents
Compuestos Download PDFInfo
- Publication number
- ES2802174T3 ES2802174T3 ES15743797T ES15743797T ES2802174T3 ES 2802174 T3 ES2802174 T3 ES 2802174T3 ES 15743797 T ES15743797 T ES 15743797T ES 15743797 T ES15743797 T ES 15743797T ES 2802174 T3 ES2802174 T3 ES 2802174T3
- Authority
- ES
- Spain
- Prior art keywords
- mmol
- lcms
- methyl
- pyrazol
- mixture
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 473
- 125000001424 substituent group Chemical group 0.000 claims abstract description 75
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 59
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 33
- 125000003566 oxetanyl group Chemical group 0.000 claims abstract description 31
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 24
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 12
- -1 tetrahydro-2 H-pyran-3-yl Chemical group 0.000 claims description 129
- 229910052799 carbon Inorganic materials 0.000 claims description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 239000003814 drug Substances 0.000 claims description 21
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 18
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 9
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 claims 15
- RGLFLHRKZUNPAL-CQSZACIVSA-N N-[5-chloro-1-[(4R)-3,3-difluoro-1-(oxetan-3-yl)piperidin-4-yl]pyrazol-4-yl]-4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound ClC1=C(C=NN1[C@H]1C(CN(CC1)C1COC1)(F)F)NC=1N=C(C2=C(N=1)NC=C2)OCC RGLFLHRKZUNPAL-CQSZACIVSA-N 0.000 claims 3
- 230000001419 dependent effect Effects 0.000 claims 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 165
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract description 6
- 229910052701 rubidium Inorganic materials 0.000 abstract description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 475
- 239000000243 solution Substances 0.000 description 336
- 239000000203 mixture Substances 0.000 description 279
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 268
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 202
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 177
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
- 239000012043 crude product Substances 0.000 description 141
- 238000005160 1H NMR spectroscopy Methods 0.000 description 133
- 238000010898 silica gel chromatography Methods 0.000 description 130
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 114
- 239000007787 solid Substances 0.000 description 110
- 239000003921 oil Substances 0.000 description 107
- 239000012044 organic layer Substances 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
- 238000006243 chemical reaction Methods 0.000 description 99
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 94
- 239000011541 reaction mixture Substances 0.000 description 89
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 82
- 229910052938 sodium sulfate Inorganic materials 0.000 description 82
- 235000011152 sodium sulphate Nutrition 0.000 description 82
- 239000007832 Na2SO4 Substances 0.000 description 81
- 235000019439 ethyl acetate Nutrition 0.000 description 76
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 74
- 239000000460 chlorine Substances 0.000 description 67
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 64
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 62
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 61
- 125000005843 halogen group Chemical group 0.000 description 58
- 239000002904 solvent Substances 0.000 description 57
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 56
- 239000000706 filtrate Substances 0.000 description 56
- 208000018737 Parkinson disease Diseases 0.000 description 53
- 201000010099 disease Diseases 0.000 description 49
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 46
- 238000011282 treatment Methods 0.000 description 46
- 239000000543 intermediate Substances 0.000 description 44
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 41
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- 230000035772 mutation Effects 0.000 description 36
- 238000000034 method Methods 0.000 description 35
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 34
- 239000012267 brine Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 239000011734 sodium Substances 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 29
- 125000003545 alkoxy group Chemical group 0.000 description 29
- 239000012230 colorless oil Substances 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 28
- 101150003085 Pdcl gene Proteins 0.000 description 28
- 229910000029 sodium carbonate Inorganic materials 0.000 description 27
- 235000017550 sodium carbonate Nutrition 0.000 description 27
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 23
- 239000000546 pharmaceutical excipient Substances 0.000 description 23
- XORHNJQEWQGXCN-UHFFFAOYSA-N 4-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C=1C=NNC=1 XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 21
- 108091000080 Phosphotransferase Proteins 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- 102000020233 phosphotransferase Human genes 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 20
- 235000019270 ammonium chloride Nutrition 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 19
- 235000011181 potassium carbonates Nutrition 0.000 description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 17
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 17
- 208000024827 Alzheimer disease Diseases 0.000 description 16
- 201000011240 Frontotemporal dementia Diseases 0.000 description 16
- 229940124786 LRRK2 inhibitor Drugs 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 102200092160 rs34637584 Human genes 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- 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 16
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- PMULDKJKKUDRAI-UHFFFAOYSA-N 2-chloro-4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N=1)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1)OCC PMULDKJKKUDRAI-UHFFFAOYSA-N 0.000 description 13
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 13
- 206010012289 Dementia Diseases 0.000 description 13
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 13
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 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 13
- 239000002253 acid Substances 0.000 description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 229910052742 iron Inorganic materials 0.000 description 11
- 238000002953 preparative HPLC Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012453 solvate Substances 0.000 description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000004296 chiral HPLC Methods 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 8
- 208000027089 Parkinsonian disease Diseases 0.000 description 8
- 206010034010 Parkinsonism Diseases 0.000 description 8
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 8
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 208000032382 Ischaemic stroke Diseases 0.000 description 7
- 208000030886 Traumatic Brain injury Diseases 0.000 description 7
- 208000010877 cognitive disease Diseases 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 7
- 208000032839 leukemia Diseases 0.000 description 7
- 208000027061 mild cognitive impairment Diseases 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 208000020431 spinal cord injury Diseases 0.000 description 7
- 230000009529 traumatic brain injury Effects 0.000 description 7
- CROCDXCMEKSYHU-UHFFFAOYSA-N 2-chloro-4-ethoxy-7H-pyrrolo[2,3-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N=1)NC=C2)OCC CROCDXCMEKSYHU-UHFFFAOYSA-N 0.000 description 6
- WTZYTQJELOHMMJ-UHFFFAOYSA-N 5-methyl-4-nitro-1h-pyrazole Chemical compound CC=1NN=CC=1[N+]([O-])=O WTZYTQJELOHMMJ-UHFFFAOYSA-N 0.000 description 6
- 208000011231 Crohn disease Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 208000015872 Gaucher disease Diseases 0.000 description 6
- 102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 description 6
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 description 6
- 208000015439 Lysosomal storage disease Diseases 0.000 description 6
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 6
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 210000000481 breast Anatomy 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000002636 symptomatic treatment Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N DBU Substances C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 201000004810 Vascular dementia Diseases 0.000 description 5
- 206010000496 acne Diseases 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 230000007074 memory dysfunction Effects 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- XMHFZVYKNRRPMO-UHFFFAOYSA-N (2-cyano-2-methylpropyl) methanesulfonate Chemical compound N#CC(C)(C)COS(C)(=O)=O XMHFZVYKNRRPMO-UHFFFAOYSA-N 0.000 description 4
- MXGZZCOXTWCXGG-UHFFFAOYSA-N (3-phenylmethoxycyclobutyl) methanesulfonate Chemical compound C1C(OS(=O)(=O)C)CC1OCC1=CC=CC=C1 MXGZZCOXTWCXGG-UHFFFAOYSA-N 0.000 description 4
- YSZYFGMARJFMJK-UHFFFAOYSA-N 1,3,5-trimethyl-4-nitropyrazole Chemical compound CC1=NN(C)C(C)=C1[N+]([O-])=O YSZYFGMARJFMJK-UHFFFAOYSA-N 0.000 description 4
- YGIPIARFNXHZEM-UHFFFAOYSA-N 1-(3,5-dimethyl-4-nitropyrazol-1-yl)-2-methylpropan-2-ol Chemical compound CC1=NN(CC(C)(C)O)C(C)=C1[N+]([O-])=O YGIPIARFNXHZEM-UHFFFAOYSA-N 0.000 description 4
- QYTMYJJUQCPZNG-UHFFFAOYSA-N 1-cyclopent-3-en-1-yl-4-nitropyrazole Chemical compound C1(CC=CC1)N1N=CC(=C1)[N+](=O)[O-] QYTMYJJUQCPZNG-UHFFFAOYSA-N 0.000 description 4
- OZYUCHWXACEUFK-UHFFFAOYSA-N 1-cyclopent-3-en-1-yl-5-cyclopropyl-4-nitropyrazole Chemical compound C1(CC=CC1)N1N=CC(=C1C1CC1)[N+](=O)[O-] OZYUCHWXACEUFK-UHFFFAOYSA-N 0.000 description 4
- ZIQWKVFQOWQUTM-UHFFFAOYSA-N 2,2-dimethyl-3-(5-methyl-4-nitropyrazol-1-yl)propanenitrile Chemical compound CC(C#N)(CN1N=CC(=C1C)[N+](=O)[O-])C ZIQWKVFQOWQUTM-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- PIHWQCPRNIEHKQ-UHFFFAOYSA-N 2-methyl-2-(5-methyl-4-nitropyrazol-1-yl)propan-1-ol Chemical compound CC(CO)(C)N1N=CC(=C1C)[N+](=O)[O-] PIHWQCPRNIEHKQ-UHFFFAOYSA-N 0.000 description 4
- HWXRLDVYSJMSOX-UHFFFAOYSA-N 3-(4-amino-5-methylpyrazol-1-yl)-2,2-dimethylpropanenitrile Chemical compound CC1=C(N)C=NN1CC(C)(C)C#N HWXRLDVYSJMSOX-UHFFFAOYSA-N 0.000 description 4
- LXZATPVTGFTLDI-UHFFFAOYSA-N 3-(4-nitropyrazol-1-yl)cyclopentan-1-ol Chemical compound C1C(O)CCC1N1N=CC([N+]([O-])=O)=C1 LXZATPVTGFTLDI-UHFFFAOYSA-N 0.000 description 4
- PVRHLOANYBBVSY-UHFFFAOYSA-N 3-(5-chloro-4-nitropyrazol-1-yl)cyclopentan-1-ol Chemical compound ClC1=C(C=NN1C1CC(CC1)O)[N+](=O)[O-] PVRHLOANYBBVSY-UHFFFAOYSA-N 0.000 description 4
- WWIBVAFBQGFVIO-UHFFFAOYSA-N 3-(5-methyl-4-nitropyrazol-1-yl)cyclopentan-1-ol Chemical compound CC1=C(C=NN1C1CC(CC1)O)[N+](=O)[O-] WWIBVAFBQGFVIO-UHFFFAOYSA-N 0.000 description 4
- WFYMRSZBLIBYHB-UHFFFAOYSA-N 3-[2-(5-methyl-4-nitropyrazol-1-yl)ethyl]-3-azabicyclo[3.1.0]hexane Chemical compound CC1=C(C=NN1CCN1CC2CC2C1)[N+](=O)[O-] WFYMRSZBLIBYHB-UHFFFAOYSA-N 0.000 description 4
- ARHABUPWWWNNCO-UHFFFAOYSA-N 4-(4-amino-5-methylpyrazol-1-yl)cyclohexan-1-ol Chemical compound NC=1C=NN(C=1C)C1CCC(CC1)O ARHABUPWWWNNCO-UHFFFAOYSA-N 0.000 description 4
- JENSEZAAXBIKRB-UHFFFAOYSA-N 4-nitro-1-(3-phenylmethoxycyclobutyl)pyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)N1N=CC(=C1)[N+](=O)[O-] JENSEZAAXBIKRB-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- WPSFLXZCUFGLOL-UHFFFAOYSA-N 5-chloro-1-cyclopent-3-en-1-yl-4-nitropyrazole Chemical compound ClC1=C(C=NN1C1CC=CC1)[N+](=O)[O-] WPSFLXZCUFGLOL-UHFFFAOYSA-N 0.000 description 4
- YPEPPLVPISNWCL-UHFFFAOYSA-N 5-chloro-4-nitro-1-(3-phenylmethoxycyclobutyl)pyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)N1N=CC(=C1Cl)[N+](=O)[O-] YPEPPLVPISNWCL-UHFFFAOYSA-N 0.000 description 4
- QPVGWCMIXFOUCV-UHFFFAOYSA-N 5-methoxy-4-nitro-1-(oxan-4-yl)pyrazole Chemical compound COC1=C(C=NN1C1CCOCC1)[N+](=O)[O-] QPVGWCMIXFOUCV-UHFFFAOYSA-N 0.000 description 4
- AIPARNBTXMMWCG-UHFFFAOYSA-N 5-methyl-1-(2-methyloxan-4-yl)-4-nitropyrazole Chemical compound CC1=C(C=NN1C1CC(OCC1)C)[N+](=O)[O-] AIPARNBTXMMWCG-UHFFFAOYSA-N 0.000 description 4
- PEWKIXHIFXCBNA-UHFFFAOYSA-N 5-methyl-1-(2-methyloxan-4-yl)pyrazol-4-amine Chemical compound CC1=C(C=NN1C1CC(OCC1)C)N PEWKIXHIFXCBNA-UHFFFAOYSA-N 0.000 description 4
- ODEKXJZVYKJWLW-UHFFFAOYSA-N 5-methyl-1-(2-morpholin-4-ylethyl)pyrazol-4-amine Chemical compound CC1=C(C=NN1CCN1CCOCC1)N ODEKXJZVYKJWLW-UHFFFAOYSA-N 0.000 description 4
- FAKWNAOPZQHESB-UHFFFAOYSA-N 5-methyl-4-nitro-1-(3-phenylmethoxycyclobutyl)pyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)N1N=CC(=C1C)[N+](=O)[O-] FAKWNAOPZQHESB-UHFFFAOYSA-N 0.000 description 4
- KTOSNVUXQMGFAE-UHFFFAOYSA-N 5-methyl-4-nitro-1-(oxetan-3-ylmethyl)pyrazole Chemical compound CC1=C(C=NN1CC1COC1)[N+](=O)[O-] KTOSNVUXQMGFAE-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- UOXUKFJFFUNPGG-UHFFFAOYSA-N CC(COCOCC[Si](C)(C)C)(C)N1N=CC(=C1)[N+](=O)[O-] Chemical compound CC(COCOCC[Si](C)(C)C)(C)N1N=CC(=C1)[N+](=O)[O-] UOXUKFJFFUNPGG-UHFFFAOYSA-N 0.000 description 4
- GWPDIEVFPBIKMA-UHFFFAOYSA-N ClC1=C(C=NN1C(COCOCC[Si](C)(C)C)(C)C)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1C(COCOCC[Si](C)(C)C)(C)C)[N+](=O)[O-] GWPDIEVFPBIKMA-UHFFFAOYSA-N 0.000 description 4
- 208000012661 Dyskinesia Diseases 0.000 description 4
- 208000004332 Evans syndrome Diseases 0.000 description 4
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 4
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 4
- 208000009829 Lewy Body Disease Diseases 0.000 description 4
- 201000002832 Lewy body dementia Diseases 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 201000002481 Myositis Diseases 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 208000003670 Pure Red-Cell Aplasia Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 206010047115 Vasculitis Diseases 0.000 description 4
- GBSUZLCJIUDZPL-UHFFFAOYSA-N [5-tert-butyl-3-chloro-1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl] carbamate Chemical compound C(N)(OC=1C(=NN(C=1C(C)(C)C)CC(C)(C)O)Cl)=O GBSUZLCJIUDZPL-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000003281 allosteric effect Effects 0.000 description 4
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- YLFMPILRUAGGFE-UHFFFAOYSA-N chloro methanesulfonate Chemical compound CS(=O)(=O)OCl YLFMPILRUAGGFE-UHFFFAOYSA-N 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 208000008795 neuromyelitis optica Diseases 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 102200092223 rs33939927 Human genes 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 4
- FANBQIYELKQGIS-UHFFFAOYSA-N tert-butyl n-(5-chloro-1h-pyrazol-4-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CNN=C1Cl FANBQIYELKQGIS-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 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 3
- XHZILAWLZPODAL-UHFFFAOYSA-N (2-methyloxan-4-yl)methanesulfonic acid Chemical compound CC1CC(CS(O)(=O)=O)CCO1 XHZILAWLZPODAL-UHFFFAOYSA-N 0.000 description 3
- SSDGMKHZMNTWLS-UHFFFAOYSA-N 1,3,5-trimethylpyrazol-4-amine Chemical compound CC1=NN(C)C(C)=C1N SSDGMKHZMNTWLS-UHFFFAOYSA-N 0.000 description 3
- SMSKBRKFDJEVQD-UHFFFAOYSA-N 1-(2-fluoroethyl)-5-methyl-4-nitropyrazole Chemical compound FCCN1N=CC(=C1C)[N+](=O)[O-] SMSKBRKFDJEVQD-UHFFFAOYSA-N 0.000 description 3
- YGDLHUYSWSROIF-UHFFFAOYSA-N 1-(4-fluoro-1-methylpyrrolidin-3-yl)-5-methylpyrazol-4-amine Chemical compound FC1C(CN(C1)C)N1N=CC(=C1C)N YGDLHUYSWSROIF-UHFFFAOYSA-N 0.000 description 3
- IBYMPEZOJUQOGD-UHFFFAOYSA-N 1-[2-(3-azabicyclo[3.1.0]hexan-3-yl)ethyl]-5-methylpyrazol-4-amine Chemical compound C12CN(CC2C1)CCN1N=CC(=C1C)N IBYMPEZOJUQOGD-UHFFFAOYSA-N 0.000 description 3
- JHENTNSXZVTNDX-UHFFFAOYSA-N 1-[5-chloro-4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]pyrazol-1-yl]-2-methylpropan-2-ol Chemical compound ClC1=C(C=NN1CC(C)(O)C)NC=1N=C(C2=C(N=1)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1)OCC JHENTNSXZVTNDX-UHFFFAOYSA-N 0.000 description 3
- LPVDNSGYLNNZSB-UHFFFAOYSA-N 2-(4-amino-5-methylpyrazol-1-yl)-2-methylpropan-1-ol Chemical compound NC=1C=NN(C=1C)C(CO)(C)C LPVDNSGYLNNZSB-UHFFFAOYSA-N 0.000 description 3
- WPHRZHRRRLDGDT-UHFFFAOYSA-N 2-[4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]-5-methylpyrazol-1-yl]ethanol Chemical compound C(C)OC=1C2=C(N=C(N=1)NC=1C=NN(C=1C)CCO)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 WPHRZHRRRLDGDT-UHFFFAOYSA-N 0.000 description 3
- VVKKSKQZLBRBBO-UHFFFAOYSA-N 2-chloro-4-ethoxy-5-iodo-7H-pyrrolo[2,3-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N=1)NC=C2I)OCC VVKKSKQZLBRBBO-UHFFFAOYSA-N 0.000 description 3
- CSXHYQCXIKBLLX-UHFFFAOYSA-N 2-chloro-4-ethoxy-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile Chemical compound ClC=1N=C(C2=C(N=1)NC=C2C#N)OCC CSXHYQCXIKBLLX-UHFFFAOYSA-N 0.000 description 3
- SYKXWOMUKHBREY-UHFFFAOYSA-N 3-(4-amino-5-methylpyrazol-1-yl)cyclobutan-1-ol Chemical compound NC=1C=NN(C=1C)C1CC(C1)O SYKXWOMUKHBREY-UHFFFAOYSA-N 0.000 description 3
- CGWZRAAMBRLSFT-UHFFFAOYSA-N 3-methyl-4-nitro-1-(oxan-3-yl)pyrazole Chemical compound CC1=NN(C=C1[N+](=O)[O-])C1COCCC1 CGWZRAAMBRLSFT-UHFFFAOYSA-N 0.000 description 3
- APVWGKPWVISBDW-UHFFFAOYSA-N 4-[4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]-5-methylpyrazol-1-yl]cyclohexan-1-ol Chemical compound C(C)OC=1C2=C(N=C(N=1)NC=1C=NN(C=1C)C1CCC(CC1)O)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 APVWGKPWVISBDW-UHFFFAOYSA-N 0.000 description 3
- QNCKLWTXSIETAA-UHFFFAOYSA-N 5-chloro-1-(oxetan-3-ylmethyl)pyrazol-4-amine Chemical compound ClC1=C(C=NN1CC1COC1)N QNCKLWTXSIETAA-UHFFFAOYSA-N 0.000 description 3
- UGGANOBMWCETQF-UHFFFAOYSA-N 5-cyclopropyl-1-(oxan-4-yl)pyrazol-4-amine Chemical compound C1(CC1)C1=C(C=NN1C1CCOCC1)N UGGANOBMWCETQF-UHFFFAOYSA-N 0.000 description 3
- OROVLQJHGFKEOJ-UHFFFAOYSA-N 5-cyclopropyl-4-nitro-1-(oxan-4-yl)pyrazole Chemical compound C1(CC1)C1=C(C=NN1C1CCOCC1)[N+](=O)[O-] OROVLQJHGFKEOJ-UHFFFAOYSA-N 0.000 description 3
- FEUMEIPWCKWJPC-UHFFFAOYSA-N 5-methoxy-1-(oxan-4-yl)pyrazol-4-amine Chemical compound COC1=C(C=NN1C1CCOCC1)N FEUMEIPWCKWJPC-UHFFFAOYSA-N 0.000 description 3
- OOZZZYXZNSPSQU-UHFFFAOYSA-N 5-methyl-1-(oxetan-3-ylmethyl)pyrazol-4-amine Chemical compound CC1=C(C=NN1CC1COC1)N OOZZZYXZNSPSQU-UHFFFAOYSA-N 0.000 description 3
- YPEVQYRKCFHAKX-UHFFFAOYSA-N 5-methyl-4-nitro-1-(oxan-3-yl)pyrazole Chemical compound CC1=C(C=NN1C1COCCC1)[N+](=O)[O-] YPEVQYRKCFHAKX-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 3
- ANBUDEVYRRYFSI-PSASIEDQSA-N C1(CC1)C1=C(C=NN1[C@@H]1CC=C[C@H]1O)[N+](=O)[O-] Chemical compound C1(CC1)C1=C(C=NN1[C@@H]1CC=C[C@H]1O)[N+](=O)[O-] ANBUDEVYRRYFSI-PSASIEDQSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229910010084 LiAlH4 Inorganic materials 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- KFYFXTKYQKTDCC-UHFFFAOYSA-N N-(1,3-dimethylpyrazol-4-yl)-4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-amine Chemical compound CN1N=C(C(=C1)NC=1N=C(C2=C(N=1)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1)OCC)C KFYFXTKYQKTDCC-UHFFFAOYSA-N 0.000 description 3
- OXZTWGAAFBRILN-UHFFFAOYSA-N N-(5-chloro-1-methylpyrazol-4-yl)-4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-amine Chemical compound ClC1=C(C=NN1C)NC=1N=C(C2=C(N=1)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1)OCC OXZTWGAAFBRILN-UHFFFAOYSA-N 0.000 description 3
- URTPMRGXMWWTNJ-UHFFFAOYSA-N NC=1C(=NN(C1C)CC(C)(O)C)C Chemical compound NC=1C(=NN(C1C)CC(C)(O)C)C URTPMRGXMWWTNJ-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 102000001253 Protein Kinase Human genes 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000002393 azetidinyl group Chemical group 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 3
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 206010013663 drug dependence Diseases 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 3
- 238000002600 positron emission tomography Methods 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- WEBMFFAOYTXXND-UHFFFAOYSA-N stl415302 Chemical compound CC1=NN(CCF)C=C1[N+]([O-])=O WEBMFFAOYTXXND-UHFFFAOYSA-N 0.000 description 3
- PGDDDJHGRPWKOC-UHFFFAOYSA-N stl415352 Chemical compound CC1=C([N+]([O-])=O)C=NN1CCO PGDDDJHGRPWKOC-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000011117 substance-related disease Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- PYXHFKXRSWCUNF-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-methylpyrazol-4-amine Chemical compound CC1=NN(CCF)C=C1N PYXHFKXRSWCUNF-UHFFFAOYSA-N 0.000 description 2
- VHZKZRPIQRLFEX-UHFFFAOYSA-N 1-(2-fluoroethyl)-5-methylpyrazol-4-amine Chemical compound CC1=C(N)C=NN1CCF VHZKZRPIQRLFEX-UHFFFAOYSA-N 0.000 description 2
- ZVCDDXQSDMXKRX-UHFFFAOYSA-N 1-(3-fluoro-1-methylpiperidin-4-yl)-5-methylpyrazol-4-amine Chemical compound FC1CN(CCC1N1N=CC(=C1C)N)C ZVCDDXQSDMXKRX-UHFFFAOYSA-N 0.000 description 2
- FFMZZHPTWDFXRU-UHFFFAOYSA-N 1-(3-fluoro-1-methylpiperidin-4-yl)pyrazol-4-amine Chemical compound CN1CCC(C(F)C1)n1cc(N)cn1 FFMZZHPTWDFXRU-UHFFFAOYSA-N 0.000 description 2
- IUNGMCFYEUSBQT-UHFFFAOYSA-N 1-(4-amino-3-chloropyrazol-1-yl)-2-methylpropan-2-ol Chemical compound CC(C)(O)CN1C=C(N)C(Cl)=N1 IUNGMCFYEUSBQT-UHFFFAOYSA-N 0.000 description 2
- SSDPAWWGDOYPOU-UHFFFAOYSA-N 1-[3,3-difluoro-1-(oxetan-3-yl)piperidin-4-yl]-5-methylpyrazol-4-amine Chemical compound FC1(CN(CCC1N1N=CC(=C1C)N)C1COC1)F SSDPAWWGDOYPOU-UHFFFAOYSA-N 0.000 description 2
- ZUBSOOAAXYCXMN-UHFFFAOYSA-N 2,2-difluoroethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCC(F)F)C=C1 ZUBSOOAAXYCXMN-UHFFFAOYSA-N 0.000 description 2
- DPGSPRJLAZGUBQ-UHFFFAOYSA-N 2-ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(C=C)OC1(C)C DPGSPRJLAZGUBQ-UHFFFAOYSA-N 0.000 description 2
- NWIBZURWGLOVKZ-UHFFFAOYSA-N 3,3-difluoro-4-(5-methyl-4-nitropyrazol-1-yl)-1-(oxetan-3-yl)piperidine Chemical compound FC1(CN(CCC1N1N=CC(=C1C)[N+](=O)[O-])C1COC1)F NWIBZURWGLOVKZ-UHFFFAOYSA-N 0.000 description 2
- OFQCJVVJRNPSET-UHFFFAOYSA-N 3,5-dimethyl-4-nitro-1h-pyrazole Chemical compound CC1=NNC(C)=C1[N+]([O-])=O OFQCJVVJRNPSET-UHFFFAOYSA-N 0.000 description 2
- BTUXGPKTAOQBPD-UHFFFAOYSA-N 3-(5-chloro-4-nitropyrazol-1-yl)-4,4-difluoro-1-(oxetan-3-yl)piperidine Chemical compound ClC1=C(C=NN1C1CN(CCC1(F)F)C1COC1)[N+](=O)[O-] BTUXGPKTAOQBPD-UHFFFAOYSA-N 0.000 description 2
- YTHLPBJUMOXMGW-UHFFFAOYSA-N 3-fluoro-1-methyl-4-(4-nitropyrazol-1-yl)piperidine Chemical compound FC1CN(CCC1N1N=CC(=C1)[N+](=O)[O-])C YTHLPBJUMOXMGW-UHFFFAOYSA-N 0.000 description 2
- CLIAXYPZANDZOI-UHFFFAOYSA-N 3-fluoro-1-methyl-4-(5-methyl-4-nitropyrazol-1-yl)piperidine Chemical compound FC1CN(CCC1N1N=CC(=C1C)[N+](=O)[O-])C CLIAXYPZANDZOI-UHFFFAOYSA-N 0.000 description 2
- DCHLTMUIWMYRGJ-UHFFFAOYSA-N 3-fluoro-4-(4-nitropyrazol-1-yl)piperidine Chemical compound FC1CNCCC1N1N=CC(=C1)[N+](=O)[O-] DCHLTMUIWMYRGJ-UHFFFAOYSA-N 0.000 description 2
- MLQSKWOMDPZZRD-UHFFFAOYSA-N 3-fluoro-4-(5-methyl-4-nitropyrazol-1-yl)piperidine Chemical compound FC1CNCCC1N1N=CC(=C1C)[N+](=O)[O-] MLQSKWOMDPZZRD-UHFFFAOYSA-N 0.000 description 2
- UTUPESZTMCQTJC-UHFFFAOYSA-N 3-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CCCN(C(O)=O)C1 UTUPESZTMCQTJC-UHFFFAOYSA-N 0.000 description 2
- RNTIGIXLWOXCMU-UHFFFAOYSA-N 3-methyl-1-(oxan-3-yl)pyrazol-4-amine Chemical compound C1=C(N)C(C)=NN1C1COCCC1 RNTIGIXLWOXCMU-UHFFFAOYSA-N 0.000 description 2
- OSYBYLDBOIJXMZ-UHFFFAOYSA-N 4-(5-chloro-4-nitropyrazol-1-yl)-3,3-difluoro-1-(oxetan-3-yl)piperidine Chemical compound ClC1=C(C=NN1C1C(CN(CC1)C1COC1)(F)F)[N+](=O)[O-] OSYBYLDBOIJXMZ-UHFFFAOYSA-N 0.000 description 2
- NSRGYONJPAZGKU-UHFFFAOYSA-N 4-(5-methyl-4-nitropyrazol-1-yl)cyclohexan-1-ol Chemical compound CC1=C(C=NN1C1CCC(CC1)O)[N+](=O)[O-] NSRGYONJPAZGKU-UHFFFAOYSA-N 0.000 description 2
- RNLQYAUPWKQLIP-UHFFFAOYSA-N 5-chloro-1-[3,3-difluoro-1-(oxetan-3-yl)piperidin-4-yl]pyrazol-4-amine Chemical compound ClC1=C(C=NN1C1C(CN(CC1)C1COC1)(F)F)N RNLQYAUPWKQLIP-UHFFFAOYSA-N 0.000 description 2
- ZLYMLCZXYCLGEB-UHFFFAOYSA-N 5-chloro-1-[4,4-difluoro-1-(oxetan-3-yl)piperidin-3-yl]pyrazol-4-amine Chemical compound ClC1=C(C=NN1C1CN(CCC1(F)F)C1COC1)N ZLYMLCZXYCLGEB-UHFFFAOYSA-N 0.000 description 2
- OLLBZJSOAWVDJA-UHFFFAOYSA-N 5-chloro-4-nitro-1-(oxan-4-yl)pyrazole Chemical compound ClC1=C([N+](=O)[O-])C=NN1C1CCOCC1 OLLBZJSOAWVDJA-UHFFFAOYSA-N 0.000 description 2
- KYALKMBPVIHJLL-UHFFFAOYSA-N 5-chloro-4-nitro-1-(oxetan-3-ylmethyl)pyrazole Chemical compound ClC1=C([N+](=O)[O-])C=NN1CC1COC1 KYALKMBPVIHJLL-UHFFFAOYSA-N 0.000 description 2
- ZVZRTCDXHCBQNV-UHFFFAOYSA-N 5-methyl-1-(oxan-3-yl)pyrazol-4-amine Chemical compound Cc1c(N)cnn1C1CCCOC1 ZVZRTCDXHCBQNV-UHFFFAOYSA-N 0.000 description 2
- NZVJTZOGQCEZNG-UHFFFAOYSA-N 6-chloro-4-(cyclopropylmethoxy)-1h-pyrazolo[3,4-d]pyrimidine Chemical compound C=12C=NNC2=NC(Cl)=NC=1OCC1CC1 NZVJTZOGQCEZNG-UHFFFAOYSA-N 0.000 description 2
- DUMZNUKZTTUQQA-UHFFFAOYSA-N 6-chloro-4-ethoxy-3-methyl-2h-pyrazolo[3,4-d]pyrimidine Chemical compound CCOC1=NC(Cl)=NC2=NNC(C)=C12 DUMZNUKZTTUQQA-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- PPALJANFDIDXDN-UHFFFAOYSA-N CC(C)(CO)n1cc(cn1)[N+]([O-])=O Chemical compound CC(C)(CO)n1cc(cn1)[N+]([O-])=O PPALJANFDIDXDN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 2
- 108091006109 GTPases Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
- 101100021877 Homo sapiens LRRK2 gene Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 101150081013 LRRK2 gene Proteins 0.000 description 2
- 206010024230 Leprous infections Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 108091062154 Mir-205 Proteins 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 102000003802 alpha-Synuclein Human genes 0.000 description 2
- 108090000185 alpha-Synuclein Proteins 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 125000005620 boronic acid group Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000006951 hyperphosphorylation Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000002314 neuroinflammatory effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 102200092222 rs33939927 Human genes 0.000 description 2
- 102200092216 rs34995376 Human genes 0.000 description 2
- 102200092167 rs35801418 Human genes 0.000 description 2
- 102200092155 rs35870237 Human genes 0.000 description 2
- 102220010566 rs74163686 Human genes 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 229940100445 wheat starch Drugs 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- GMMDMYGCQBKABZ-HTQZYQBOSA-N (1R,2R)-2-(4-nitropyrazol-1-yl)cyclopentan-1-ol Chemical compound [N+](=O)([O-])C=1C=NN(C=1)[C@H]1[C@@H](CCC1)O GMMDMYGCQBKABZ-HTQZYQBOSA-N 0.000 description 1
- UCSBTNAVQFHNMF-UHFFFAOYSA-N (2-methyl-2-morpholin-4-ylpropyl) methanesulfonate Chemical compound CS(=O)(=O)OCC(C)(N1CCOCC1)C UCSBTNAVQFHNMF-UHFFFAOYSA-N 0.000 description 1
- QPWMGMCPSFBYOU-UHFFFAOYSA-N (3-hydroxycyclopentyl) methanesulfonate Chemical compound CS(=O)(=O)OC1CCC(O)C1 QPWMGMCPSFBYOU-UHFFFAOYSA-N 0.000 description 1
- YVYSXVZMZGTRFP-RKDXNWHRSA-N (3R,4R)-4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoro-1-(oxetan-3-yl)piperidine Chemical compound ClC1=C(C=NN1[C@H]1[C@@H](CN(CC1)C1COC1)F)[N+](=O)[O-] YVYSXVZMZGTRFP-RKDXNWHRSA-N 0.000 description 1
- RQNUOFAKLTYGLH-PHDIDXHHSA-N (3R,4R)-4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoropiperidine Chemical compound ClC1=C(C=NN1[C@H]1[C@@H](CNCC1)F)[N+](=O)[O-] RQNUOFAKLTYGLH-PHDIDXHHSA-N 0.000 description 1
- YVYSXVZMZGTRFP-IUCAKERBSA-N (3S,4S)-4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoro-1-(oxetan-3-yl)piperidine Chemical compound ClC1=C(C=NN1[C@@H]1[C@H](CN(CC1)C1COC1)F)[N+](=O)[O-] YVYSXVZMZGTRFP-IUCAKERBSA-N 0.000 description 1
- RQNUOFAKLTYGLH-WDSKDSINSA-N (3S,4S)-4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoropiperidine Chemical compound ClC1=C(C=NN1[C@@H]1[C@H](CNCC1)F)[N+](=O)[O-] RQNUOFAKLTYGLH-WDSKDSINSA-N 0.000 description 1
- CDDGNGVFPQRJJM-SCSAIBSYSA-N (3r)-3-fluoropyrrolidine Chemical compound F[C@@H]1CCNC1 CDDGNGVFPQRJJM-SCSAIBSYSA-N 0.000 description 1
- CDDGNGVFPQRJJM-BYPYZUCNSA-N (3s)-3-fluoropyrrolidine Chemical compound F[C@H]1CCNC1 CDDGNGVFPQRJJM-BYPYZUCNSA-N 0.000 description 1
- VOEWECZIRRCJID-UHFFFAOYSA-N (4-methylsulfonyloxycyclohexyl) methanesulfonate Chemical compound CS(=O)(=O)OC1CCC(OS(C)(=O)=O)CC1 VOEWECZIRRCJID-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- AXLKRXWNAFFPDB-UHFFFAOYSA-N 1,3-dimethylpyrazol-4-amine Chemical compound CC1=NN(C)C=C1N AXLKRXWNAFFPDB-UHFFFAOYSA-N 0.000 description 1
- VMVMLAPJMPSWAT-UHFFFAOYSA-N 1-(2-methoxyethyl)-3-methylpyrazol-4-amine Chemical compound COCCN1C=C(N)C(C)=N1 VMVMLAPJMPSWAT-UHFFFAOYSA-N 0.000 description 1
- AEWUNVWGFWYRGV-UHFFFAOYSA-N 1-(3-fluorooxan-4-yl)-4-nitropyrazole Chemical compound FC1COCCC1N1N=CC(=C1)[N+](=O)[O-] AEWUNVWGFWYRGV-UHFFFAOYSA-N 0.000 description 1
- RFWJSZUVFMYDPO-UHFFFAOYSA-N 1-(3-fluorooxan-4-yl)-5-methyl-4-nitropyrazole Chemical compound FC1COCCC1N1N=CC(=C1C)[N+](=O)[O-] RFWJSZUVFMYDPO-UHFFFAOYSA-N 0.000 description 1
- ACHYTQKICOKOAR-UHFFFAOYSA-N 1-(3-fluorooxan-4-yl)-5-methylpyrazol-4-amine Chemical compound FC1COCCC1N1N=CC(=C1C)N ACHYTQKICOKOAR-UHFFFAOYSA-N 0.000 description 1
- IBJQREYEHQBRQJ-UHFFFAOYSA-N 1-(4-amino-5-chloropyrazol-1-yl)-2-methylpropan-2-ol Chemical compound CC(C)(O)CN1N=CC(N)=C1Cl IBJQREYEHQBRQJ-UHFFFAOYSA-N 0.000 description 1
- LOCRXNKSDRSSLC-UHFFFAOYSA-N 1-(4-nitropyrazol-1-yl)propan-2-ol Chemical compound CC(O)CN1C=C([N+]([O-])=O)C=N1 LOCRXNKSDRSSLC-UHFFFAOYSA-N 0.000 description 1
- XYXJSXYKDKOEBW-UHFFFAOYSA-N 1-(5,8-dioxaspiro[3.4]octan-2-yl)-4-nitropyrazole Chemical compound [N+](=O)([O-])C=1C=NN(C=1)C1CC2(C1)OCCO2 XYXJSXYKDKOEBW-UHFFFAOYSA-N 0.000 description 1
- ZQCPQYQTUGHDMW-UHFFFAOYSA-N 1-(5,8-dioxaspiro[3.4]octan-2-yl)-5-methyl-4-nitropyrazole Chemical compound CC1=C(C=NN1C1CC2(C1)OCCO2)[N+](=O)[O-] ZQCPQYQTUGHDMW-UHFFFAOYSA-N 0.000 description 1
- VSUGRNXKGSCLOG-UHFFFAOYSA-N 1-(5,8-dioxaspiro[3.4]octan-2-yl)-5-methylpyrazol-4-amine Chemical compound CC1=C(C=NN1C1CC2(C1)OCCO2)N VSUGRNXKGSCLOG-UHFFFAOYSA-N 0.000 description 1
- JVEONYFNDUKWEB-ZETCQYMHSA-N 1-[(3S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]-4-nitropyrazole Chemical compound FC(CN1C[C@H](CC1)N1N=CC(=C1)[N+](=O)[O-])F JVEONYFNDUKWEB-ZETCQYMHSA-N 0.000 description 1
- RJLJKKRLTNZGIJ-QMMMGPOBSA-N 1-[(3S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]-5-methyl-4-nitropyrazole Chemical compound FC(CN1C[C@H](CC1)N1N=CC(=C1C)[N+](=O)[O-])F RJLJKKRLTNZGIJ-QMMMGPOBSA-N 0.000 description 1
- KHQFMDKPFVMTCL-QMMMGPOBSA-N 1-[(3S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]-5-methylpyrazol-4-amine Chemical compound FC(CN1C[C@H](CC1)N1N=CC(=C1C)N)F KHQFMDKPFVMTCL-QMMMGPOBSA-N 0.000 description 1
- FERDGCXQAYQGIO-UHFFFAOYSA-N 1-[2-(3,3-difluoroazetidin-1-yl)ethyl]-5-methyl-4-nitropyrazole Chemical compound FC1(CN(C1)CCN1N=CC(=C1C)[N+](=O)[O-])F FERDGCXQAYQGIO-UHFFFAOYSA-N 0.000 description 1
- DKPNWSUAEQTDTI-UHFFFAOYSA-N 1-[2-(3,3-difluoroazetidin-1-yl)ethyl]-5-methylpyrazol-4-amine Chemical compound FC1(CN(C1)CCN1N=CC(=C1C)N)F DKPNWSUAEQTDTI-UHFFFAOYSA-N 0.000 description 1
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XMDQJXIEKHMDMG-UHFFFAOYSA-N 1-methyl-6-oxabicyclo[3.1.0]hexane Chemical compound C1CCC2OC21C XMDQJXIEKHMDMG-UHFFFAOYSA-N 0.000 description 1
- HJXHERPOBSPVEX-UHFFFAOYSA-N 1-tert-butyl-5-methyl-4-nitropyrazole Chemical compound CC1=C(C=NN1C(C)(C)C)[N+]([O-])=O HJXHERPOBSPVEX-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- KYFXPHPBTUJULU-UHFFFAOYSA-N 2-(2-methoxyanilino)-2-(2-phenylmethoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1NC(C#N)C1=CC=CC=C1OCC1=CC=CC=C1 KYFXPHPBTUJULU-UHFFFAOYSA-N 0.000 description 1
- DOSGEBYQRMBTGS-UHFFFAOYSA-N 2-(3,6-dihydro-2h-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CCOCC1 DOSGEBYQRMBTGS-UHFFFAOYSA-N 0.000 description 1
- ZMZUKEHUOKTMOC-UHFFFAOYSA-N 2-(4-amino-5-methylpyrazol-1-yl)-2-methylpropanamide Chemical compound NC=1C=NN(C=1C)C(C(=O)N)(C)C ZMZUKEHUOKTMOC-UHFFFAOYSA-N 0.000 description 1
- UTELQZJJGIPZJC-UHFFFAOYSA-N 2-(4-amino-5-methylpyrazol-1-yl)ethanol Chemical compound CC1=C(N)C=NN1CCO UTELQZJJGIPZJC-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- JDOZKYSYUBXTKU-UHFFFAOYSA-N 2-[4-[(4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino]-5-methylpyrazol-1-yl]-2-methylpropanamide Chemical compound C(C)OC=1C2=C(N=C(N=1)NC=1C=NN(C=1C)C(C(=O)N)(C)C)NC=C2 JDOZKYSYUBXTKU-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- UNCAROXZKKXJOK-UHFFFAOYSA-N 2-methyl-2-(5-methyl-4-nitropyrazol-1-yl)propanoic acid Chemical compound CC(C(=O)O)(C)N1N=CC(=C1C)[N+](=O)[O-] UNCAROXZKKXJOK-UHFFFAOYSA-N 0.000 description 1
- FCCWRGFCAKZCBF-UHFFFAOYSA-N 2-methyl-2-morpholin-4-ylpropan-1-ol Chemical compound OCC(C)(C)N1CCOCC1 FCCWRGFCAKZCBF-UHFFFAOYSA-N 0.000 description 1
- ZHPKAPJNEIKPGV-UHFFFAOYSA-N 2-methyloxan-4-ol Chemical compound CC1CC(O)CCO1 ZHPKAPJNEIKPGV-UHFFFAOYSA-N 0.000 description 1
- UUZRTCRGFJOCCZ-UHFFFAOYSA-N 2-phenylmethoxy-5,8-dioxaspiro[3.4]octane Chemical compound C(C1=CC=CC=C1)OC1CC2(C1)OCCO2 UUZRTCRGFJOCCZ-UHFFFAOYSA-N 0.000 description 1
- QUHVRXKSQHIZNV-UHFFFAOYSA-N 3,3-difluoroazetidine Chemical compound FC1(F)CNC1 QUHVRXKSQHIZNV-UHFFFAOYSA-N 0.000 description 1
- IIKQVMCRXZZIQX-UHFFFAOYSA-N 3-(4-amino-5-chloropyrazol-1-yl)cyclopentan-1-ol Chemical compound NC=1C=NN(C=1Cl)C1CC(CC1)O IIKQVMCRXZZIQX-UHFFFAOYSA-N 0.000 description 1
- KYGROKBXZYXRAE-UHFFFAOYSA-N 3-(4-nitropyrazol-1-yl)-4-oxopiperidine-1-carboxylic acid Chemical compound [N+](=O)([O-])C=1C=NN(C1)C1CN(CCC1=O)C(=O)O KYGROKBXZYXRAE-UHFFFAOYSA-N 0.000 description 1
- WHLQRAUHORHKIU-UHFFFAOYSA-N 3-(5-chloro-4-nitropyrazol-1-yl)-4,4-difluoropiperidine Chemical compound ClC1=C(C=NN1C1CNCCC1(F)F)[N+](=O)[O-] WHLQRAUHORHKIU-UHFFFAOYSA-N 0.000 description 1
- DDWSNCDBESIXHN-UHFFFAOYSA-N 3-[4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]-5-methylpyrazol-1-yl]cyclobutan-1-ol Chemical compound C(C)OC=1C2=C(N=C(N=1)NC=1C=NN(C=1C)C1CC(C1)O)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 DDWSNCDBESIXHN-UHFFFAOYSA-N 0.000 description 1
- LNAHYVJSWTWTMJ-UHFFFAOYSA-N 3-[4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]-5-methylpyrazol-1-yl]cyclobutan-1-one Chemical compound C(C)OC=1C2=C(N=C(N=1)NC=1C=NN(C=1C)C1CC(C1)=O)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 LNAHYVJSWTWTMJ-UHFFFAOYSA-N 0.000 description 1
- HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 1
- JIDICTVNYOIKDK-UHFFFAOYSA-N 3-chloro-1-methylpyrazol-4-amine Chemical compound CN1C=C(N)C(Cl)=N1 JIDICTVNYOIKDK-UHFFFAOYSA-N 0.000 description 1
- WWXFHHXOVMQARV-UHFFFAOYSA-N 3-hydroxy-2,2-dimethylpropanenitrile Chemical compound OCC(C)(C)C#N WWXFHHXOVMQARV-UHFFFAOYSA-N 0.000 description 1
- XIEFKWWOPVXTIQ-UHFFFAOYSA-N 3-methyl-1-(1-methylpiperidin-4-yl)pyrazol-4-amine Chemical compound C1CN(C)CCC1N1N=C(C)C(N)=C1 XIEFKWWOPVXTIQ-UHFFFAOYSA-N 0.000 description 1
- PGPWMORFOPRGCA-UHFFFAOYSA-N 3-methyloxan-4-one Chemical compound CC1COCCC1=O PGPWMORFOPRGCA-UHFFFAOYSA-N 0.000 description 1
- ZGSDRBWWICYJBU-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-ol Chemical compound C1C(O)CC1OCC1=CC=CC=C1 ZGSDRBWWICYJBU-UHFFFAOYSA-N 0.000 description 1
- GPPSQLLIFNWNSB-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-one Chemical compound C1C(=O)CC1OCC1=CC=CC=C1 GPPSQLLIFNWNSB-UHFFFAOYSA-N 0.000 description 1
- CNTCGTICJJAASZ-UHFFFAOYSA-N 4-(4-nitropyrazol-1-yl)oxan-3-ol Chemical compound [N+](=O)([O-])C=1C=NN(C=1)C1C(COCC1)O CNTCGTICJJAASZ-UHFFFAOYSA-N 0.000 description 1
- MEGBPGXORRMYNW-UHFFFAOYSA-N 4-(5-chloro-4-nitropyrazol-1-yl)-3,3-difluoropiperidine Chemical compound ClC1=C(C=NN1C1C(CNCC1)(F)F)[N+](=O)[O-] MEGBPGXORRMYNW-UHFFFAOYSA-N 0.000 description 1
- JIGQEXMNBWDZEW-UHFFFAOYSA-N 4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoropiperidine-1-carboxylic acid Chemical compound C1CN(CC(C1N2C(=C(C=N2)[N+](=O)[O-])Cl)F)C(=O)O JIGQEXMNBWDZEW-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
- FJXJAAFKONAPKR-UHFFFAOYSA-N 4-methoxy-2-nitrobenzo[e][1]benzofuran Chemical compound COC1=CC2=CC=CC=C2C2=C1OC([N+]([O-])=O)=C2 FJXJAAFKONAPKR-UHFFFAOYSA-N 0.000 description 1
- JSTHZKWDZSLMQO-LURJTMIESA-N 4-nitro-1-[(3S)-pyrrolidin-3-yl]pyrazole Chemical compound [N+](=O)([O-])C=1C=NN(C=1)[C@@H]1CNCC1 JSTHZKWDZSLMQO-LURJTMIESA-N 0.000 description 1
- NYIVWTWKIQOBKO-UHFFFAOYSA-N 4-phenanthren-3-ylbutanoic acid Chemical compound C1=CC=C2C3=CC(CCCC(=O)O)=CC=C3C=CC2=C1 NYIVWTWKIQOBKO-UHFFFAOYSA-N 0.000 description 1
- IDQGQAPNOMZNFC-UHFFFAOYSA-N 5,8-dioxaspiro[3.4]octan-2-ol Chemical compound C1C(CC11OCCO1)O IDQGQAPNOMZNFC-UHFFFAOYSA-N 0.000 description 1
- MBWFQLACRRNIEM-UHFFFAOYSA-N 5,8-dioxaspiro[3.4]octan-2-yl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OC1CC2(C1)OCCO2 MBWFQLACRRNIEM-UHFFFAOYSA-N 0.000 description 1
- 108091005482 5-HT4 receptors Proteins 0.000 description 1
- 108091005435 5-HT6 receptors Proteins 0.000 description 1
- QDDQSSZZYNCVHC-UHFFFAOYSA-N 5-[(4-tert-butylphenoxy)carbonylamino]-2-hydroxybenzoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1OC(=O)NC1=CC=C(O)C(C(O)=O)=C1 QDDQSSZZYNCVHC-UHFFFAOYSA-N 0.000 description 1
- OWKNRAFOFWTEJG-UHFFFAOYSA-N 5-chloro-1-(3-fluorooxan-4-yl)-4-nitropyrazole Chemical compound ClC1=C(C=NN1C1C(COCC1)F)[N+](=O)[O-] OWKNRAFOFWTEJG-UHFFFAOYSA-N 0.000 description 1
- FHOZPMWHFAQZCX-UHFFFAOYSA-N 5-chloro-1-(5,8-dioxaspiro[3.4]octan-2-yl)-4-nitropyrazole Chemical compound ClC1=C(C=NN1C1CC2(C1)OCCO2)[N+](=O)[O-] FHOZPMWHFAQZCX-UHFFFAOYSA-N 0.000 description 1
- MFNVTIHUVCIQBQ-LURJTMIESA-N 5-chloro-1-[(3S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]-4-nitropyrazole Chemical compound ClC1=C(C=NN1[C@@H]1CN(CC1)CC(F)F)[N+](=O)[O-] MFNVTIHUVCIQBQ-LURJTMIESA-N 0.000 description 1
- HAVZARVPJOGOSJ-WPRPVWTQSA-N 5-chloro-1-[(3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl]pyrazol-4-amine Chemical compound ClC1=C(C=NN1[C@@H]1[C@H](CN(CC1)C1COC1)F)N HAVZARVPJOGOSJ-WPRPVWTQSA-N 0.000 description 1
- CHWZUWDRNLWSPU-UHFFFAOYSA-N 5-chloro-1h-pyrazol-4-amine Chemical compound NC=1C=NNC=1Cl CHWZUWDRNLWSPU-UHFFFAOYSA-N 0.000 description 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- SMFCMJXDYRFFQL-UHFFFAOYSA-N 5-methyl-1-(1-methylpiperidin-4-yl)pyrazol-4-amine Chemical compound C1CN(C)CCC1N1C(C)=C(N)C=N1 SMFCMJXDYRFFQL-UHFFFAOYSA-N 0.000 description 1
- IWGYPRPQUKNACD-UHFFFAOYSA-N 5-methyl-1-(2-methyl-1-morpholin-4-ylpropan-2-yl)pyrazol-4-amine Chemical compound CC1=C(C=NN1C(CN1CCOCC1)(C)C)N IWGYPRPQUKNACD-UHFFFAOYSA-N 0.000 description 1
- LOBKMEHOWUESGJ-UHFFFAOYSA-N 5-methyl-1-(2-morpholin-4-ylpropyl)pyrazol-4-amine Chemical compound CC1=C(C=NN1CC(C)N1CCOCC1)N LOBKMEHOWUESGJ-UHFFFAOYSA-N 0.000 description 1
- GVTKUZYODXQACG-VIFPVBQESA-N 5-methyl-1-[2-[(2S)-2-methylmorpholin-4-yl]ethyl]pyrazol-4-amine Chemical compound CC1=C(C=NN1CCN1C[C@@H](OCC1)C)N GVTKUZYODXQACG-VIFPVBQESA-N 0.000 description 1
- DEYMUPCSDCGFNN-VIFPVBQESA-N 5-methyl-1-[2-[(3S)-3-methylmorpholin-4-yl]ethyl]pyrazol-4-amine Chemical compound CC1=C(C=NN1CCN1[C@H](COCC1)C)N DEYMUPCSDCGFNN-VIFPVBQESA-N 0.000 description 1
- GJEZBVHHZQAEDB-UHFFFAOYSA-N 6-oxabicyclo[3.1.0]hexane Chemical compound C1CCC2OC21 GJEZBVHHZQAEDB-UHFFFAOYSA-N 0.000 description 1
- YBGOLOJQJWLUQP-UHFFFAOYSA-O 7-(dimethylamino)-4-hydroxy-3-oxophenoxazin-10-ium-1-carboxylic acid Chemical compound OC(=O)C1=CC(=O)C(O)=C2OC3=CC(N(C)C)=CC=C3[NH+]=C21 YBGOLOJQJWLUQP-UHFFFAOYSA-O 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 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 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- VFCPWLMLVYJTHV-UHFFFAOYSA-N CC(C)(COS(C)(=O)=O)n1cc(cn1)[N+]([O-])=O Chemical compound CC(C)(COS(C)(=O)=O)n1cc(cn1)[N+]([O-])=O VFCPWLMLVYJTHV-UHFFFAOYSA-N 0.000 description 1
- FTTDWZGYDFFSGO-UHFFFAOYSA-N CC1=C(C=NN1C(COCOCC[Si](C)(C)C)(C)C)[N+](=O)[O-] Chemical compound CC1=C(C=NN1C(COCOCC[Si](C)(C)C)(C)C)[N+](=O)[O-] FTTDWZGYDFFSGO-UHFFFAOYSA-N 0.000 description 1
- DINSCDJCYUHGRY-UHFFFAOYSA-N CC1=C(C=NN1C1CN(CC1)C)N Chemical compound CC1=C(C=NN1C1CN(CC1)C)N DINSCDJCYUHGRY-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- SLDLGCPLKINAJC-VXNVDRBHSA-N F[C@@H]1CNCC[C@H]1N1N=CC(=C1C=C)[N+](=O)[O-] Chemical compound F[C@@H]1CNCC[C@H]1N1N=CC(=C1C=C)[N+](=O)[O-] SLDLGCPLKINAJC-VXNVDRBHSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 102000007207 Muscarinic M1 Receptor Human genes 0.000 description 1
- 108010008406 Muscarinic M1 Receptor Proteins 0.000 description 1
- ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000002192 Parkinson disease 3 Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 208000034799 Tauopathies Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- XPIMCIQJVLACNX-UHFFFAOYSA-N [N].CC[Zn]CC Chemical compound [N].CC[Zn]CC XPIMCIQJVLACNX-UHFFFAOYSA-N 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940048053 acrylate Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 201000002783 amyotrophic lateral sclerosis type 12 Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000004642 autophagic pathway Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229950004221 besilate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000004915 chaperone-mediated autophagy Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 150000001975 deuterium Chemical group 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 1
- 229960003135 donepezil hydrochloride Drugs 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
- SRZCNFCBCVDIHX-UHFFFAOYSA-N ethyl 2-methyl-2-(4-nitropyrazol-1-yl)propanoate Chemical compound CCOC(=O)C(C)(C)N1C=C([N+]([O-])=O)C=N1 SRZCNFCBCVDIHX-UHFFFAOYSA-N 0.000 description 1
- YBAUKWDRWDHULW-UHFFFAOYSA-N ethyl 2-methyl-2-morpholin-4-ylpropanoate Chemical compound CCOC(=O)C(C)(C)N1CCOCC1 YBAUKWDRWDHULW-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 238000005227 gel permeation chromatography Methods 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
- 230000014509 gene expression Effects 0.000 description 1
- 230000008571 general function Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 229940116871 l-lactate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 230000006655 lysosomal degradation pathway Effects 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 230000004142 macroautophagy Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 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
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000006676 mitochondrial damage Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 238000001964 muscle biopsy Methods 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 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
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- ZKFXSGOGYHXYDT-UHFFFAOYSA-N oxan-3-yl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCOC1 ZKFXSGOGYHXYDT-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000007112 pro inflammatory response Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000007111 proteostasis Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- 229940080817 rotenone Drugs 0.000 description 1
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
- 102200092154 rs34778348 Human genes 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JJXOIFHXNBFRNV-UHFFFAOYSA-N tert-butyl (2-methylpropan-2-yl)oxycarbonyl carbonate Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C.CC(C)(C)OC(=O)OC(=O)OC(C)(C)C JJXOIFHXNBFRNV-UHFFFAOYSA-N 0.000 description 1
- XRNLYXKYODGLMI-YUMQZZPRSA-N tert-butyl (3s,4s)-3-fluoro-4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](O)[C@@H](F)C1 XRNLYXKYODGLMI-YUMQZZPRSA-N 0.000 description 1
- RGWGRRBHQUREDE-UHFFFAOYSA-N tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C(Br)C1 RGWGRRBHQUREDE-UHFFFAOYSA-N 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- MMPWHAJQEZIIEH-UHFFFAOYSA-N tert-butyl 7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2OC21 MMPWHAJQEZIIEH-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Substances [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2014000139 | 2014-01-29 | ||
| PCT/CN2015/000055 WO2015113452A1 (en) | 2014-01-29 | 2015-01-28 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2802174T3 true ES2802174T3 (es) | 2021-01-15 |
Family
ID=53756224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15743797T Active ES2802174T3 (es) | 2014-01-29 | 2015-01-28 | Compuestos |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US10087186B2 (enExample) |
| EP (1) | EP3099695B1 (enExample) |
| JP (1) | JP6422986B2 (enExample) |
| KR (1) | KR20160106622A (enExample) |
| CN (1) | CN105940004B (enExample) |
| AU (2) | AU2015210593A1 (enExample) |
| CA (1) | CA2937431A1 (enExample) |
| CL (1) | CL2016001895A1 (enExample) |
| CR (1) | CR20160348A (enExample) |
| DO (2) | DOP2016000195A (enExample) |
| EA (1) | EA029774B1 (enExample) |
| ES (1) | ES2802174T3 (enExample) |
| IL (1) | IL246579B (enExample) |
| MA (1) | MA39219B1 (enExample) |
| MX (1) | MX367370B (enExample) |
| PE (1) | PE20161443A1 (enExample) |
| PH (1) | PH12016501307A1 (enExample) |
| SG (1) | SG11201605342UA (enExample) |
| UA (1) | UA118369C2 (enExample) |
| WO (1) | WO2015113452A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10339791B2 (en) | 2007-06-12 | 2019-07-02 | Icontrol Networks, Inc. | Security network integrated with premise security system |
| US9815841B2 (en) | 2014-01-29 | 2017-11-14 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
| KR20160106622A (ko) | 2014-01-29 | 2016-09-12 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 화합물 |
| CN105153131B (zh) * | 2015-09-21 | 2017-10-17 | 马彦丽 | 一种在护理上治疗人神经胶质瘤的药物组合物 |
| CN105348270B (zh) * | 2015-11-09 | 2018-01-09 | 吕显艳 | 一种防治牙体牙髓感染的药物组合物 |
| WO2017087905A1 (en) * | 2015-11-20 | 2017-05-26 | Denali Therapeutics Inc. | Compound, compositions, and methods |
| CN108934162A (zh) | 2015-12-16 | 2018-12-04 | 南方研究所 | 吡咯并嘧啶化合物、作为激酶lrrk2抑制剂的用途及其制备方法 |
| CN105418616B (zh) * | 2015-12-26 | 2018-01-12 | 山东大学 | 一种含有 4‑氨基吡唑结构的jak 激酶抑制剂及其制备方法和应用 |
| US11028080B2 (en) | 2016-03-11 | 2021-06-08 | Denali Therapeutics Inc. | Substituted pyrimidines as LRKK2 inhibitors |
| IL299415B2 (en) | 2016-06-16 | 2025-09-01 | Denali Therapeutics Inc | Pyrimidine-2-ylamino-1H-pyrazoles as LRRK2 inhibitors for use in the treatment of neurodegenerative disorders |
| CA3050156A1 (en) * | 2017-01-25 | 2018-08-02 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
| WO2018155916A2 (ko) * | 2017-02-22 | 2018-08-30 | 재단법인 대구경북첨단의료산업진흥재단 | 피롤로-피리미딘 유도체 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| AU2018239798B2 (en) * | 2017-03-23 | 2020-08-27 | Daegu Gyeongbuk Institute Of Science And Technology | Pyrrolo-pyridine derivative compound, method for preparing same, and pharmaceutical composition containing same as active ingredient for prevention or treatment of protein kinase-related diseases |
| MX2020005866A (es) * | 2017-12-05 | 2020-09-09 | Oscotec Inc | Derivado de pirrolo(pirazolo)pirimidina como inhibidor de lrrk2. |
| CN108715834B (zh) * | 2018-06-01 | 2021-09-14 | 天晴干细胞股份有限公司 | 一种富含cd41+、cd81+微囊的血小板裂解液制备方法 |
| WO2020036437A1 (ko) * | 2018-08-16 | 2020-02-20 | 재단법인 대구경북첨단의료산업진흥재단 | 치환된 헤테로아릴 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| EP3856188B1 (en) * | 2018-09-25 | 2023-06-21 | Cardurion Pharmaceuticals, Inc. | Aminopyrimidine compound |
| CA3168211A1 (en) | 2019-01-18 | 2020-07-23 | Voronoi Co., Ltd. | Pyrrolopyridine derivative and use thereof for preventing or treating protein kinase related disease |
| CZ308800B6 (cs) * | 2019-02-12 | 2021-05-26 | Univerzita Palackého v Olomouci | Heterocyklické dusíkaté deriváty purinu, farmaceutické přípravky obsahující tyto deriváty a jejich použití při neuroprotekci |
| CN114426542B (zh) * | 2020-10-29 | 2023-06-30 | 苏州亚宝药物研发有限公司 | 取代的二芳基胺化合物及其药物组合物、制备方法和用途 |
| CA3195193A1 (en) | 2020-10-29 | 2022-05-05 | Peter H. Fuller | N-linked isoquinoline amides as lrrk2 inhibitors, pharmaceutical compositions, and uses thereof |
| KR20220081631A (ko) | 2020-12-09 | 2022-06-16 | 보로노이 주식회사 | 염증성 질환의 예방 및/또는 치료를 위한 피롤로-피리딘 유도체 화합물의 신규 용도 |
| WO2023073013A1 (en) | 2021-10-27 | 2023-05-04 | H. Lundbeck A/S | Lrrk2 inhibitors |
| WO2023076404A1 (en) | 2021-10-27 | 2023-05-04 | Aria Pharmaceuticals, Inc. | Methods for treating systemic lupus erythematosus |
| AR130483A1 (es) | 2022-09-15 | 2024-12-11 | H Lundbeck As | Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2) |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005028480A2 (en) | 2003-09-03 | 2005-03-31 | Neurogen Corporation | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| EP2316927B1 (en) | 2004-10-21 | 2014-11-05 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Kaspp (lrrk2) gene, its production and use for the detection and treatment of neurodegenerative disorders |
| US7855205B2 (en) | 2004-10-29 | 2010-12-21 | Janssen Pharmaceutica Nv | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
| NO323175B1 (no) | 2004-12-23 | 2007-01-15 | Jan O Aasly | Framgangsmate for a pavise en mutasjon som forarsaker arvelig parkinsonisme |
| US20080004295A1 (en) | 2005-10-13 | 2008-01-03 | Gore Paul M | Novel compounds |
| CA2651072A1 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| WO2009036066A1 (en) | 2007-09-10 | 2009-03-19 | Curis, Inc. | Vegfr inhibitors containing a zinc binding moiety |
| US9315449B2 (en) | 2008-05-15 | 2016-04-19 | Duke University | Substituted pyrazoles as heat shock transcription factor activators |
| US8158636B2 (en) | 2008-05-19 | 2012-04-17 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US20090325964A1 (en) | 2008-05-23 | 2009-12-31 | Wyeth | Piperazine Metabotropic Glutamate Receptor 5 (MGLUR5) Negative Allosteric Modulators For Anxiety/Depression |
| JP5918693B2 (ja) | 2009-05-05 | 2016-05-18 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | Ｅｇｆｒ阻害剤及び疾患の治療方法 |
| SG179120A1 (en) * | 2009-09-29 | 2012-05-30 | Glaxo Group Ltd | Novel compounds |
| WO2011153553A2 (en) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| WO2012009258A2 (en) | 2010-07-13 | 2012-01-19 | Edward Roberts | Peptidomimetic galanin receptor modulators |
| WO2012045195A1 (en) | 2010-10-09 | 2012-04-12 | Abbott Laboratories | Pyrrolopyrimidines as fak and alk inhibiters for treatment of cancers and other diseases |
| JP2013545749A (ja) | 2010-11-10 | 2013-12-26 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環化合物及びその使用 |
| SI2638031T1 (en) * | 2010-11-10 | 2018-02-28 | Genentech, Inc. | Pyrazole aminopyrimidine derivatives as LRRK2 modulators |
| US20140031547A1 (en) | 2010-12-14 | 2014-01-30 | Electrophoretics Limited | CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODE-GENERATIVE DISEASES SUCH AS TAUOPATHIES |
| AU2012244550C1 (en) * | 2011-04-21 | 2017-06-22 | Origenis Gmbh | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
| ES2575710T3 (es) * | 2011-09-22 | 2016-06-30 | Pfizer Inc | Derivados de pirrolopirimidina y purina |
| BR112014012822A8 (pt) * | 2011-11-30 | 2017-07-11 | Hoffmann La Roche | Radioligantes rotulados com flúor-18 e carbono-11 para imagiologia por tomografia por emissão de pósitrons (pet) para lrrk2 |
| GB201204985D0 (en) * | 2012-03-21 | 2012-05-02 | Genentech Inc | Compounds |
| WO2013164321A1 (en) | 2012-05-03 | 2013-11-07 | F. Hoffmann-La Roche Ag | Pyrazole aminopyrimidine derivatives as lrrk2 modulators |
| BR112014027117B1 (pt) | 2012-05-03 | 2022-09-06 | Genentech, Inc | Derivados de pirazol aminopirimidina como moduladores de lrrk2, seus usos, e composição |
| MD20140130A2 (ro) | 2012-06-29 | 2015-04-30 | Pfizer Inc. | 4-(amino-substituite)-7H-pirolo[2,3-d]pirimidine noi ca inhibitori de LRRK2 |
| KR20160106622A (ko) | 2014-01-29 | 2016-09-12 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 화합물 |
| US9815841B2 (en) | 2014-01-29 | 2017-11-14 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
-
2015
- 2015-01-28 KR KR1020167020367A patent/KR20160106622A/ko not_active Ceased
- 2015-01-28 US US15/114,858 patent/US10087186B2/en not_active Expired - Fee Related
- 2015-01-28 PE PE2016001250A patent/PE20161443A1/es unknown
- 2015-01-28 EP EP15743797.1A patent/EP3099695B1/en active Active
- 2015-01-28 AU AU2015210593A patent/AU2015210593A1/en not_active Abandoned
- 2015-01-28 CN CN201580006361.XA patent/CN105940004B/zh not_active Expired - Fee Related
- 2015-01-28 EA EA201691514A patent/EA029774B1/ru not_active IP Right Cessation
- 2015-01-28 SG SG11201605342UA patent/SG11201605342UA/en unknown
- 2015-01-28 MX MX2016009893A patent/MX367370B/es active IP Right Grant
- 2015-01-28 CR CR20160348A patent/CR20160348A/es unknown
- 2015-01-28 UA UAA201609099A patent/UA118369C2/uk unknown
- 2015-01-28 MA MA39219A patent/MA39219B1/fr unknown
- 2015-01-28 JP JP2016549028A patent/JP6422986B2/ja not_active Expired - Fee Related
- 2015-01-28 CA CA2937431A patent/CA2937431A1/en not_active Abandoned
- 2015-01-28 WO PCT/CN2015/000055 patent/WO2015113452A1/en not_active Ceased
- 2015-01-28 ES ES15743797T patent/ES2802174T3/es active Active
-
2016
- 2016-06-30 PH PH12016501307A patent/PH12016501307A1/en unknown
- 2016-07-03 IL IL246579A patent/IL246579B/en not_active IP Right Cessation
- 2016-07-26 CL CL2016001895A patent/CL2016001895A1/es unknown
- 2016-07-29 DO DO2016000195A patent/DOP2016000195A/es unknown
-
2018
- 2018-01-12 AU AU2018200277A patent/AU2018200277B2/en not_active Ceased
- 2018-08-02 US US16/052,791 patent/US10618901B2/en not_active Expired - Fee Related
-
2019
- 2019-01-15 DO DO2019000010A patent/DOP2019000010A/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10618901B2 (en) | LRRK2 inhibitors for the treatment of Parkinson's disease | |
| ES2862188T3 (es) | Compuestos heterocíclicos, particularmente compuestos pirimidinilindazol para el tratamiento de la enfermedad de Parkinson | |
| ES3031704T3 (en) | Nlrp3 inhibitors | |
| KR102717616B1 (ko) | PI3Kδ 관련 장애의 치료를 위한 피라졸로피리미딘 유도체의 용도 | |
| US10858367B2 (en) | Compounds | |
| WO2019012093A1 (en) | INHIBITORS OF REACTION KINASE 2 RICH IN LEUCINE | |
| CN118084866A (zh) | 稠环化合物 | |
| US20210130339A1 (en) | Compounds | |
| CA3050021A1 (en) | Compounds | |
| HK1230172B (en) | Compounds |