EA029774B1 - Соединения - Google Patents

Info

Publication number

EA029774B1

EA029774B1 EA201691514A EA201691514A EA029774B1 EA 029774 B1 EA029774 B1 EA 029774B1 EA 201691514 A EA201691514 A EA 201691514A EA 201691514 A EA201691514 A EA 201691514A EA 029774 B1 EA029774 B1 EA 029774B1

Authority

EA

Eurasian Patent Office

Prior art keywords

mmol

pharmaceutically acceptable

methyl

compound

lcms

Prior art date

2014-01-29

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 599
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 53
• 238000000034 method Methods 0.000 claims abstract description 49
• 238000011282 treatment Methods 0.000 claims abstract description 46
• 230000000694 effects Effects 0.000 claims abstract description 21
• 150000003839 salts Chemical class 0.000 claims description 188
• -1 tetrahydro-2H-pyranyl Chemical group 0.000 claims description 141
• 229910052736 halogen Inorganic materials 0.000 claims description 71
• 150000002367 halogens Chemical class 0.000 claims description 70
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 62
• 125000000623 heterocyclic group Chemical group 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 43
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• 125000003566 oxetanyl group Chemical group 0.000 claims description 30
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 26
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims description 24
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 24
• 239000003814 drug Substances 0.000 claims description 20
• 125000002757 morpholinyl group Chemical group 0.000 claims description 20
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 14
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 13
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims description 7
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
• 102000001253 Protein Kinase Human genes 0.000 claims description 6
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
• 108060006633 protein kinase Proteins 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 125000002393 azetidinyl group Chemical group 0.000 claims description 4
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 1
• 229910052760 oxygen Inorganic materials 0.000 claims 1
• 229910052717 sulfur Inorganic materials 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 358
• 208000024827 Alzheimer disease Diseases 0.000 abstract description 22
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract description 15
• 238000002360 preparation method Methods 0.000 abstract description 10
• 230000008569 process Effects 0.000 abstract description 5
• 102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 abstract 2
• 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 abstract 2
• 230000006806 disease prevention Effects 0.000 abstract 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 565
• 239000000243 solution Substances 0.000 description 381
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 299
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 272
• 239000011541 reaction mixture Substances 0.000 description 234
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 204
• 238000005481 NMR spectroscopy Methods 0.000 description 195
• 238000010898 silica gel chromatography Methods 0.000 description 161
• 239000013058 crude material Substances 0.000 description 152
• 239000012044 organic layer Substances 0.000 description 138
• 239000007787 solid Substances 0.000 description 129
• 239000003921 oil Substances 0.000 description 121
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 111
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 76
• 239000012298 atmosphere Substances 0.000 description 75
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 69
• 239000000706 filtrate Substances 0.000 description 69
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 62
• 239000002904 solvent Substances 0.000 description 57
• 239000011734 sodium Substances 0.000 description 55
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
• 239000007864 aqueous solution Substances 0.000 description 51
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 50
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 50
• 239000012267 brine Substances 0.000 description 46
• 201000010099 disease Diseases 0.000 description 45
• 239000000543 intermediate Substances 0.000 description 45
• XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 43
• 239000012299 nitrogen atmosphere Substances 0.000 description 41
• 239000012230 colorless oil Substances 0.000 description 39
• 230000035772 mutation Effects 0.000 description 36
• 239000001257 hydrogen Substances 0.000 description 30
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 28
• 239000000284 extract Substances 0.000 description 28
• 239000000047 product Substances 0.000 description 28
• 238000004440 column chromatography Methods 0.000 description 27
• 238000003756 stirring Methods 0.000 description 27
• XORHNJQEWQGXCN-UHFFFAOYSA-N 4-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C=1C=NNC=1 XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 26
• 239000000460 chlorine Substances 0.000 description 26
• VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 26
• 229910000027 potassium carbonate Inorganic materials 0.000 description 25
• 239000012047 saturated solution Substances 0.000 description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 24
• 235000011181 potassium carbonates Nutrition 0.000 description 23
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
• 239000010410 layer Substances 0.000 description 22
• 239000000741 silica gel Substances 0.000 description 22
• 229910002027 silica gel Inorganic materials 0.000 description 22
• 239000003112 inhibitor Substances 0.000 description 21
• KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 20
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• 108091000080 Phosphotransferase Proteins 0.000 description 19
• 102000020233 phosphotransferase Human genes 0.000 description 19
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 206010012289 Dementia Diseases 0.000 description 17
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
• 229920006395 saturated elastomer Polymers 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 16
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• 239000000126 substance Substances 0.000 description 15
• ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• 238000003818 flash chromatography Methods 0.000 description 14
• 229910052742 iron Inorganic materials 0.000 description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• 125000004432 carbon atom Chemical group C* 0.000 description 13
• 238000006243 chemical reaction Methods 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
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 238000002953 preparative HPLC Methods 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• 239000012453 solvate Substances 0.000 description 12
• 208000032382 Ischaemic stroke Diseases 0.000 description 11
• 208000030886 Traumatic Brain injury Diseases 0.000 description 11
• 238000004296 chiral HPLC Methods 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• 230000009529 traumatic brain injury Effects 0.000 description 11
• 125000004429 atom Chemical group 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 9
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 9
• 208000032839 leukemia Diseases 0.000 description 9
• 102000004169 proteins and genes Human genes 0.000 description 9
• 201000011240 Frontotemporal dementia Diseases 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
• 230000003902 lesion Effects 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 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 8
• NGTQEBZGQDLEGD-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)hexanenitrile Chemical compound C1=NC=NN1C(C#N)(CCCC)C1=CC=C(Cl)C=C1 NGTQEBZGQDLEGD-UHFFFAOYSA-N 0.000 description 7
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
• WTZYTQJELOHMMJ-UHFFFAOYSA-N 5-methyl-4-nitro-1h-pyrazole Chemical compound CC=1NN=CC=1[N+]([O-])=O WTZYTQJELOHMMJ-UHFFFAOYSA-N 0.000 description 7
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
• 208000008839 Kidney Neoplasms Diseases 0.000 description 7
• 208000010877 cognitive disease Diseases 0.000 description 7
• 125000000753 cycloalkyl group Chemical group 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 201000006417 multiple sclerosis Diseases 0.000 description 7
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
• 206010051290 Central nervous system lesion Diseases 0.000 description 6
• 208000011990 Corticobasal Degeneration Diseases 0.000 description 6
• 208000015872 Gaucher disease Diseases 0.000 description 6
• 239000005909 Kieselgur Substances 0.000 description 6
• 208000015439 Lysosomal storage disease Diseases 0.000 description 6
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
• 208000027089 Parkinsonian disease Diseases 0.000 description 6
• 206010034010 Parkinsonism Diseases 0.000 description 6
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 6
• 230000001594 aberrant effect Effects 0.000 description 6
• 230000037396 body weight Effects 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 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 6
• 210000004072 lung Anatomy 0.000 description 6
• 208000027061 mild cognitive impairment Diseases 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
• 210000002307 prostate Anatomy 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 238000002636 symptomatic treatment Methods 0.000 description 6
• NHPBIVOKGCZPIF-UHFFFAOYSA-N tert-butyl 3-(4-amino-5-chloropyrazol-1-yl)-4,4-difluoropiperidine-1-carboxylate Chemical compound NC=1C=NN(C=1Cl)C1CN(CCC1(F)F)C(=O)OC(C)(C)C NHPBIVOKGCZPIF-UHFFFAOYSA-N 0.000 description 6
• 229940124597 therapeutic agent Drugs 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
• 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 5
• 208000011231 Crohn disease Diseases 0.000 description 5
• 208000026139 Memory disease Diseases 0.000 description 5
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 5
• 201000004810 Vascular dementia Diseases 0.000 description 5
• 235000019270 ammonium chloride Nutrition 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 210000000481 breast Anatomy 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 210000000349 chromosome Anatomy 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000012458 free base Substances 0.000 description 5
• 150000004677 hydrates Chemical class 0.000 description 5
• 208000015122 neurodegenerative disease Diseases 0.000 description 5
• 230000001717 pathogenic effect Effects 0.000 description 5
• 229910052700 potassium Inorganic materials 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 238000011321 prophylaxis Methods 0.000 description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 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 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• MRNOEZUTGICYDY-UHFFFAOYSA-N 4-[2-methyl-1-(5-methyl-4-nitropyrazol-1-yl)propan-2-yl]morpholine Chemical compound CC(CN1N=CC(=C1C)[N+](=O)[O-])(C)N1CCOCC1 MRNOEZUTGICYDY-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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
• 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
• 201000002832 Lewy body dementia Diseases 0.000 description 4
• 206010025323 Lymphomas Diseases 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• 201000002481 Myositis 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
• 206010038389 Renal cancer Diseases 0.000 description 4
• 208000024770 Thyroid neoplasm Diseases 0.000 description 4
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 210000003169 central nervous system Anatomy 0.000 description 4
• 239000006184 cosolvent Substances 0.000 description 4
• 230000007547 defect Effects 0.000 description 4
• 230000002068 genetic effect Effects 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 150000002431 hydrogen Chemical class 0.000 description 4
• WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
• 201000010982 kidney cancer Diseases 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 4
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
• 239000002798 polar solvent Substances 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 208000017520 skin disease Diseases 0.000 description 4
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 4
• SAWXCBOXTZVTHE-UHFFFAOYSA-N tert-butyl 3-(5-chloro-4-nitropyrazol-1-yl)-4,4-difluoropiperidine-1-carboxylate Chemical compound ClC1=C(C=NN1C1CN(CCC1(F)F)C(=O)OC(C)(C)C)[N+](=O)[O-] SAWXCBOXTZVTHE-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
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 3
• OQINCYOODKLWDH-UHFFFAOYSA-N 4-[2-(5-methyl-4-nitropyrazol-1-yl)ethyl]morpholine Chemical compound CC1=C([N+]([O-])=O)C=NN1CCN1CCOCC1 OQINCYOODKLWDH-UHFFFAOYSA-N 0.000 description 3
• 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 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
• 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 3
• 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 3
• 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 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
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 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 3
• VQRDCJAPAZJUMN-VXNVDRBHSA-N CC1=C(C=NN1[C@H]1[C@@H](CCC1)O)[N+](=O)[O-] Chemical compound CC1=C(C=NN1[C@H]1[C@@H](CCC1)O)[N+](=O)[O-] VQRDCJAPAZJUMN-VXNVDRBHSA-N 0.000 description 3
• IJGQVURVGFDTRY-UWVGGRQHSA-N ClC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)N Chemical compound ClC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)N IJGQVURVGFDTRY-UWVGGRQHSA-N 0.000 description 3
• ZOSHNGODIFQKNX-BDAKNGLRSA-N ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)F)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)F)[N+](=O)[O-] ZOSHNGODIFQKNX-BDAKNGLRSA-N 0.000 description 3
• HAVZARVPJOGOSJ-SCZZXKLOSA-N ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C1COC1)F)N Chemical compound ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C1COC1)F)N HAVZARVPJOGOSJ-SCZZXKLOSA-N 0.000 description 3
• VWDYBOHBVWZQFH-IYSWYEEDSA-N ClC1=C(C=NN1[C@H]1[C@@H](CCC1)O)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@H]1[C@@H](CCC1)O)[N+](=O)[O-] VWDYBOHBVWZQFH-IYSWYEEDSA-N 0.000 description 3
• 206010012335 Dependence Diseases 0.000 description 3
• 239000004398 Ethyl lauroyl arginate Substances 0.000 description 3
• PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 3
• RIDQEJIIPMJYGG-ZYHUDNBSSA-N F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C=C)[N+](=O)[O-])C1COC1 Chemical compound F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C=C)[N+](=O)[O-])C1COC1 RIDQEJIIPMJYGG-ZYHUDNBSSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 3
• FQSLPTBXOGKWLC-RNFRBKRXSA-N NC=1C=NN(C=1Cl)[C@H]1[C@@H](CCC1)O Chemical compound NC=1C=NN(C=1Cl)[C@H]1[C@@H](CCC1)O FQSLPTBXOGKWLC-RNFRBKRXSA-N 0.000 description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
• 208000021386 Sjogren Syndrome Diseases 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• 206010047115 Vasculitis Diseases 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
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 125000005620 boronic acid group Chemical class 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• 239000010949 copper Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000004316 dimethyl dicarbonate Substances 0.000 description 3
• 239000003937 drug carrier Substances 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
• 238000001914 filtration Methods 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 239000004312 hexamethylene tetramine Substances 0.000 description 3
• QNVRIHYSUZMSGM-UHFFFAOYSA-N hexan-2-ol Chemical compound CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 208000020816 lung neoplasm Diseases 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 239000012046 mixed solvent Substances 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000008795 neuromyelitis optica Diseases 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 239000008184 oral solid dosage form Substances 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 230000002018 overexpression Effects 0.000 description 3
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 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
• ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 3
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 210000000278 spinal cord Anatomy 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 229940032147 starch Drugs 0.000 description 3
• 235000019698 starch Nutrition 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
• 239000003826 tablet Substances 0.000 description 3
• YJMPGVYEIDNJBY-UHFFFAOYSA-N tert-butyl 4-(5-chloro-4-nitropyrazol-1-yl)-3,3-difluoropiperidine-1-carboxylate Chemical compound ClC1=C(C=NN1C1C(CN(CC1)C(=O)OC(C)(C)C)(F)F)[N+](=O)[O-] YJMPGVYEIDNJBY-UHFFFAOYSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 201000002510 thyroid cancer Diseases 0.000 description 3
• 238000011830 transgenic mouse model Methods 0.000 description 3
• CNKCYDXVSPVHLH-RKDXNWHRSA-N (1R,2R)-2-(4-amino-5-methylpyrazol-1-yl)cyclopentan-1-ol Chemical compound NC=1C=NN(C=1C)[C@H]1[C@@H](CCC1)O CNKCYDXVSPVHLH-RKDXNWHRSA-N 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 2
• MXGZZCOXTWCXGG-UHFFFAOYSA-N (3-phenylmethoxycyclobutyl) methanesulfonate Chemical compound C1C(OS(=O)(=O)C)CC1OCC1=CC=CC=C1 MXGZZCOXTWCXGG-UHFFFAOYSA-N 0.000 description 2
• YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 2
• 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 2
• SMSKBRKFDJEVQD-UHFFFAOYSA-N 1-(2-fluoroethyl)-5-methyl-4-nitropyrazole Chemical compound FCCN1N=CC(=C1C)[N+](=O)[O-] SMSKBRKFDJEVQD-UHFFFAOYSA-N 0.000 description 2
• 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 2
• IBKBZEOJYQRYBO-UHFFFAOYSA-N 1-(3,6-dihydro-2H-pyran-4-yl)-4-nitropyrazole Chemical compound O1CCC(=CC1)N1N=CC(=C1)[N+](=O)[O-] IBKBZEOJYQRYBO-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
• 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 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
• 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 2
• FCCWRGFCAKZCBF-UHFFFAOYSA-N 2-methyl-2-morpholin-4-ylpropan-1-ol Chemical compound OCC(C)(C)N1CCOCC1 FCCWRGFCAKZCBF-UHFFFAOYSA-N 0.000 description 2
• 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 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
• 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 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
• 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 2
• 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 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
• 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 2
• GPPSQLLIFNWNSB-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-one Chemical compound C1C(=O)CC1OCC1=CC=CC=C1 GPPSQLLIFNWNSB-UHFFFAOYSA-N 0.000 description 2
• KDJIYPXAVQGDRT-UHFFFAOYSA-N 4,4-difluoro-3-(4-nitropyrazol-1-yl)cyclohexan-1-one Chemical compound FC1(C(CC(CC1)=O)N1N=CC(=C1)[N+](=O)[O-])F KDJIYPXAVQGDRT-UHFFFAOYSA-N 0.000 description 2
• 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 2
• ILOJWRNMZBFSHS-UHFFFAOYSA-N 4-(4-nitropyrazol-1-yl)cyclohexan-1-one Chemical compound [N+](=O)([O-])C=1C=NN(C=1)C1CCC(CC1)=O ILOJWRNMZBFSHS-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
• QWXUJEIKEHCZCU-UHFFFAOYSA-N 4-[2-methyl-2-(4-nitropyrazol-1-yl)propyl]morpholine Chemical compound CC(CN1CCOCC1)(C)N1N=CC(=C1)[N+](=O)[O-] QWXUJEIKEHCZCU-UHFFFAOYSA-N 0.000 description 2
• 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 2
• IDQGQAPNOMZNFC-UHFFFAOYSA-N 5,8-dioxaspiro[3.4]octan-2-ol Chemical compound C1C(CC11OCCO1)O IDQGQAPNOMZNFC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• QQDKYRWMCPEFHO-UHFFFAOYSA-N 5-chloro-1-(1-methyl-3-phenylmethoxycyclobutyl)-4-nitropyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)(C)N1N=CC(=C1Cl)[N+](=O)[O-] QQDKYRWMCPEFHO-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
• 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 2
• 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 2
• 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 2
• HFVJWYGYAGGHPI-UHFFFAOYSA-N 5-methyl-1-(1-methyl-3-phenylmethoxycyclobutyl)-4-nitropyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)(C)N1N=CC(=C1C)[N+](=O)[O-] HFVJWYGYAGGHPI-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 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 2
• 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 2
• 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 2
• 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 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• HIKGQFIYBYTIPS-CABCVRRESA-N C(C1=CC=CC=C1)O[C@@H]1CCC([C@H](C1)N1N=CC(=C1)[N+](=O)[O-])(F)F Chemical compound C(C1=CC=CC=C1)O[C@@H]1CCC([C@H](C1)N1N=CC(=C1)[N+](=O)[O-])(F)F HIKGQFIYBYTIPS-CABCVRRESA-N 0.000 description 2
• 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 2
• 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 2
• 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 2
• WCQZFMFXVYJCAP-XCBNKYQSSA-N CC1=C(C=NN1[C@@H]1[C@@H](COCC1)C)N Chemical compound CC1=C(C=NN1[C@@H]1[C@@H](COCC1)C)N WCQZFMFXVYJCAP-XCBNKYQSSA-N 0.000 description 2
• CURPKCALQZJJDL-VXNVDRBHSA-N CC1=C(C=NN1[C@H]1[C@@H](COCC1)C)[N+](=O)[O-] Chemical compound CC1=C(C=NN1[C@H]1[C@@H](COCC1)C)[N+](=O)[O-] CURPKCALQZJJDL-VXNVDRBHSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282693 Cercopithecidae Species 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
• ZNZMVZVFBFNPSO-UWVGGRQHSA-N ClC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] ZNZMVZVFBFNPSO-UWVGGRQHSA-N 0.000 description 2
• RQNUOFAKLTYGLH-RITPCOANSA-N ClC1=C(C=NN1[C@@H]1[C@@H](CNCC1)F)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@@H]1[C@@H](CNCC1)F)[N+](=O)[O-] RQNUOFAKLTYGLH-RITPCOANSA-N 0.000 description 2
• ZNZMVZVFBFNPSO-VHSXEESVSA-N ClC1=C(C=NN1[C@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] ZNZMVZVFBFNPSO-VHSXEESVSA-N 0.000 description 2
• GYYZQIWGJSEHHU-ONGXEEELSA-N ClC1=C(C=NN1[C@H]1C[C@H](CCC1(F)F)N1CCOCC1)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@H]1C[C@H](CCC1(F)F)N1CCOCC1)[N+](=O)[O-] GYYZQIWGJSEHHU-ONGXEEELSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 206010067889 Dementia with Lewy bodies Diseases 0.000 description 2
• 206010061818 Disease progression Diseases 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
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• 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 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 206010024230 Leprous infections Diseases 0.000 description 2
• 208000009829 Lewy Body Disease Diseases 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
• 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
• 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
• GNRBHHQSSWTKAN-SFYZADRCSA-N NC=1C=NN(C=1C)[C@H]1C[C@H](CC1)O Chemical compound NC=1C=NN(C=1C)[C@H]1C[C@H](CC1)O GNRBHHQSSWTKAN-SFYZADRCSA-N 0.000 description 2
• 206010028980 Neoplasm Diseases 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
• 101150059547 PRKCI gene Proteins 0.000 description 2
• 206010033799 Paralysis Diseases 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
• ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 239000001361 adipic acid Substances 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
• 150000001412 amines Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 238000004458 analytical method Methods 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
• 230000008901 benefit Effects 0.000 description 2
• 229940077388 benzenesulfonate Drugs 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000004281 calcium formate Substances 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
• 230000003197 catalytic effect Effects 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 230000001413 cellular effect 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
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 238000004140 cleaning Methods 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
• XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
• 230000005750 disease progression Effects 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
• 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
• 239000000945 filler Substances 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 230000006951 hyperphosphorylation Effects 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 229910052744 lithium Inorganic materials 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
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 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
• 238000013508 migration Methods 0.000 description 2
• 230000002314 neuroinflammatory effect Effects 0.000 description 2
• 230000003961 neuronal insult Effects 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 2
• IRWXYFWBGITFAG-UHFFFAOYSA-N piperidin-4-yl methanesulfonate Chemical compound CS(=O)(=O)OC1CCNCC1 IRWXYFWBGITFAG-UHFFFAOYSA-N 0.000 description 2
• 239000004175 ponceau 4R Substances 0.000 description 2
• 235000012731 ponceau 4R Nutrition 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 235000015320 potassium carbonate Nutrition 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 201000001514 prostate carcinoma Diseases 0.000 description 2
• 239000011241 protective layer Substances 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 238000011084 recovery Methods 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
• 150000003384 small molecules Chemical class 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• PGDDDJHGRPWKOC-UHFFFAOYSA-N stl415352 Chemical compound CC1=C([N+]([O-])=O)C=NN1CCO PGDDDJHGRPWKOC-UHFFFAOYSA-N 0.000 description 2
• 229940095064 tartrate Drugs 0.000 description 2
• MKIOAKIICSYKOC-UHFFFAOYSA-N tert-butyl 2-hydroxymorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(O)C1 MKIOAKIICSYKOC-UHFFFAOYSA-N 0.000 description 2
• XRNLYXKYODGLMI-UHFFFAOYSA-N tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)C(F)C1 XRNLYXKYODGLMI-UHFFFAOYSA-N 0.000 description 2
• APCBTRDHCDOPNY-UHFFFAOYSA-N tert-butyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)C1 APCBTRDHCDOPNY-UHFFFAOYSA-N 0.000 description 2
• ZOSHNGODIFQKNX-UHFFFAOYSA-N tert-butyl 4-(5-chloro-4-nitropyrazol-1-yl)-3-fluoropiperidine-1-carboxylate Chemical compound ClC1=C(C=NN1C1C(CN(CC1)C(=O)OC(C)(C)C)F)[N+](=O)[O-] ZOSHNGODIFQKNX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• XMHFZVYKNRRPMO-UHFFFAOYSA-N (2-cyano-2-methylpropyl) methanesulfonate Chemical compound N#CC(C)(C)COS(C)(=O)=O XMHFZVYKNRRPMO-UHFFFAOYSA-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
• MADASEHUCLKZHJ-UHFFFAOYSA-N (2-methyloxan-4-yl) methanesulfonate Chemical compound CC1CC(CCO1)OS(C)(=O)=O MADASEHUCLKZHJ-UHFFFAOYSA-N 0.000 description 1
• XHZILAWLZPODAL-UHFFFAOYSA-N (2-methyloxan-4-yl)methanesulfonic acid Chemical compound CC1CC(CS(O)(=O)=O)CCO1 XHZILAWLZPODAL-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
• VOEWECZIRRCJID-UHFFFAOYSA-N (4-methylsulfonyloxycyclohexyl) methanesulfonate Chemical compound CS(=O)(=O)OC1CCC(OS(C)(=O)=O)CC1 VOEWECZIRRCJID-UHFFFAOYSA-N 0.000 description 1
• WEWGLPTVNYPYLB-UHFFFAOYSA-N (4-nitropyrazol-1-yl) 2-methylpropane-1-sulfonate Chemical compound CC(C)CS(=O)(=O)On1cc(cn1)[N+]([O-])=O WEWGLPTVNYPYLB-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
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• SSDGMKHZMNTWLS-UHFFFAOYSA-N 1,3,5-trimethylpyrazol-4-amine Chemical compound CC1=NN(C)C(C)=C1N SSDGMKHZMNTWLS-UHFFFAOYSA-N 0.000 description 1
• ZDOGXPGAEYKUJK-UHFFFAOYSA-N 1,3-dimethylpyrazol-4-amine;hydrochloride Chemical compound Cl.CC1=NN(C)C=C1N ZDOGXPGAEYKUJK-UHFFFAOYSA-N 0.000 description 1
• HKQTYQDNCKMNHZ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)CCC21OCCO2 HKQTYQDNCKMNHZ-UHFFFAOYSA-N 0.000 description 1
• NPQKISWLDHUTRY-UHFFFAOYSA-N 1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-nitropyrazole Chemical compound [O-][N+](=O)C1=CN(N=C1)C1CCC2(CC1)OCCO2 NPQKISWLDHUTRY-UHFFFAOYSA-N 0.000 description 1
• OWKKAOIAXKWVJW-UHFFFAOYSA-N 1-(1-methyl-3-phenylmethoxycyclobutyl)-4-nitropyrazole Chemical compound C(C1=CC=CC=C1)OC1CC(C1)(C)N1N=CC(=C1)[N+](=O)[O-] OWKKAOIAXKWVJW-UHFFFAOYSA-N 0.000 description 1
• PYXHFKXRSWCUNF-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-methylpyrazol-4-amine Chemical compound CC1=NN(CCF)C=C1N PYXHFKXRSWCUNF-UHFFFAOYSA-N 0.000 description 1
• VHZKZRPIQRLFEX-UHFFFAOYSA-N 1-(2-fluoroethyl)-5-methylpyrazol-4-amine Chemical compound CC1=C(N)C=NN1CCF VHZKZRPIQRLFEX-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
• LAGHHXLVBWVVQH-UHFFFAOYSA-N 1-(2-methoxyethyl)-5-methylpyrazol-4-amine Chemical compound COCCN1N=CC(N)=C1C LAGHHXLVBWVVQH-UHFFFAOYSA-N 0.000 description 1
• 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 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
• 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 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
• 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
• 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 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
• RMUMFNPDDLMEPT-UHFFFAOYSA-N 1-methyl-3-phenylmethoxycyclobutan-1-ol Chemical compound C(C1=CC=CC=C1)OC1CC(C1)(O)C RMUMFNPDDLMEPT-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
• 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
• 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 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
• MVQYAILQOUZHAD-UHFFFAOYSA-N 2-(5-chloro-4-nitropyrazol-1-yl)-4-(oxetan-3-yl)morpholine Chemical compound ClC1=C(C=NN1C1CN(CCO1)C1COC1)[N+](=O)[O-] MVQYAILQOUZHAD-UHFFFAOYSA-N 0.000 description 1
• MZAOLZADSMIGKP-UHFFFAOYSA-N 2-(5-chloro-4-nitropyrazol-1-yl)morpholine Chemical compound ClC1=C(C=NN1C1CNCCO1)[N+](=O)[O-] MZAOLZADSMIGKP-UHFFFAOYSA-N 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
• ZHPKAPJNEIKPGV-UHFFFAOYSA-N 2-methyloxan-4-ol Chemical compound CC1CC(O)CCO1 ZHPKAPJNEIKPGV-UHFFFAOYSA-N 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• QUHVRXKSQHIZNV-UHFFFAOYSA-N 3,3-difluoroazetidine Chemical compound FC1(F)CNC1 QUHVRXKSQHIZNV-UHFFFAOYSA-N 0.000 description 1
• XLSAQENNLCJRAX-UHFFFAOYSA-N 3-(4-amino-5-methylpyrazol-1-yl)-3-methylcyclobutan-1-ol Chemical compound NC=1C=NN(C=1C)C1(CC(C1)O)C XLSAQENNLCJRAX-UHFFFAOYSA-N 0.000 description 1
• 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 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
• 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
• 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 1
• ZGSDRBWWICYJBU-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-ol Chemical compound C1C(O)CC1OCC1=CC=CC=C1 ZGSDRBWWICYJBU-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
• 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 1
• LVCSPKBOBUPZDT-UHFFFAOYSA-N 4-[1-(4-nitropyrazol-1-yl)propan-2-yl]morpholine Chemical compound [N+](=O)([O-])C=1C=NN(C=1)CC(C)N1CCOCC1 LVCSPKBOBUPZDT-UHFFFAOYSA-N 0.000 description 1
• DQZIMXITEZWNIG-UHFFFAOYSA-N 4-[1-(5-chloro-4-nitropyrazol-1-yl)-2-methylpropan-2-yl]morpholine Chemical compound ClC1=C(C=NN1CC(C)(C)N1CCOCC1)[N+](=O)[O-] DQZIMXITEZWNIG-UHFFFAOYSA-N 0.000 description 1
• GXCLNJRQGFQRDP-UHFFFAOYSA-N 4-[1-(5-chloro-4-nitropyrazol-1-yl)propan-2-yl]morpholine Chemical compound ClC1=C(C=NN1CC(C)N1CCOCC1)[N+](=O)[O-] GXCLNJRQGFQRDP-UHFFFAOYSA-N 0.000 description 1
• IMEMAOHCEBTVAL-UHFFFAOYSA-N 4-[1-(5-methyl-4-nitropyrazol-1-yl)propan-2-yl]morpholine Chemical compound CC1=C(C=NN1CC(C)N1CCOCC1)[N+](=O)[O-] IMEMAOHCEBTVAL-UHFFFAOYSA-N 0.000 description 1
• ZACPOTMSEFVJSF-UHFFFAOYSA-N 4-[2-methyl-1-(4-nitropyrazol-1-yl)propan-2-yl]morpholine Chemical compound CC(CN1N=CC(=C1)[N+](=O)[O-])(C)N1CCOCC1 ZACPOTMSEFVJSF-UHFFFAOYSA-N 0.000 description 1
• YMPWZXYNINJNIF-UHFFFAOYSA-N 4-[2-methyl-2-(5-methyl-4-nitropyrazol-1-yl)propyl]morpholine Chemical compound CC(CN1CCOCC1)(C)N1N=CC(=C1C)[N+](=O)[O-] YMPWZXYNINJNIF-UHFFFAOYSA-N 0.000 description 1
• UXQGHPDAXLWNCU-UHFFFAOYSA-N 4-[4-(5-chloro-4-nitropyrazol-1-yl)cyclohexyl]morpholine Chemical compound ClC1=C(C=NN1C1CCC(CC1)N1CCOCC1)[N+](=O)[O-] UXQGHPDAXLWNCU-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-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-M 4-aminosalicylate(1-) Chemical compound NC1=CC=C(C([O-])=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-M 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• FFGVIYUANJAFJS-UHFFFAOYSA-N 4-phenylmethoxycyclohexan-1-one Chemical compound C1CC(=O)CCC1OCC1=CC=CC=C1 FFGVIYUANJAFJS-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
• WISWIQBWXICGCC-UHFFFAOYSA-N 5-chloro-1-(4-morpholin-4-ylcyclohexyl)pyrazol-4-amine Chemical compound ClC1=C(C=NN1C1CCC(CC1)N1CCOCC1)N WISWIQBWXICGCC-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
• 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 1
• DTWLPPNHKXQXRL-UHFFFAOYSA-N 5-chloro-1-[4-(oxetan-3-yl)morpholin-2-yl]pyrazol-4-amine Chemical compound ClC1=C(C=NN1C1CN(CCO1)C1COC1)N DTWLPPNHKXQXRL-UHFFFAOYSA-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
• 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 1
• 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 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
• ZVZRTCDXHCBQNV-UHFFFAOYSA-N 5-methyl-1-(oxan-3-yl)pyrazol-4-amine Chemical compound Cc1c(N)cnn1C1CCCOC1 ZVZRTCDXHCBQNV-UHFFFAOYSA-N 0.000 description 1
• GJEZBVHHZQAEDB-UHFFFAOYSA-N 6-oxabicyclo[3.1.0]hexane Chemical compound C1CCC2OC21 GJEZBVHHZQAEDB-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 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
• 102100039182 Ankyrin repeat and protein kinase domain-containing protein 1 Human genes 0.000 description 1
• 235000005749 Anthriscus sylvestris Nutrition 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
• 206010006187 Breast cancer Diseases 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
• DHCIETCURKSTIE-ZWNOBZJWSA-N C(C)C1=C(C=NN1[C@H]1[C@@H](CN(CC1)C1COC1)F)N Chemical compound C(C)C1=C(C=NN1[C@H]1[C@@H](CN(CC1)C1COC1)F)N DHCIETCURKSTIE-ZWNOBZJWSA-N 0.000 description 1
• BYULBDFJKNBSDV-NEPJUHHUSA-N C(C1=CC=CC=C1)O[C@H]1C[C@@H](C(CC1)=O)Br Chemical compound C(C1=CC=CC=C1)O[C@H]1C[C@@H](C(CC1)=O)Br BYULBDFJKNBSDV-NEPJUHHUSA-N 0.000 description 1
• GBSFOJLCGOXOFV-CABCVRRESA-N C(C1=CC=CC=C1)O[C@H]1C[C@@H](C(CC1)=O)N1N=CC(=C1)[N+](=O)[O-] Chemical compound C(C1=CC=CC=C1)O[C@H]1C[C@@H](C(CC1)=O)N1N=CC(=C1)[N+](=O)[O-] GBSFOJLCGOXOFV-CABCVRRESA-N 0.000 description 1
• XVQSJUOGWXZEFZ-UHFFFAOYSA-N CC(C)(CCS(=O)(=O)O)C#N Chemical compound CC(C)(CCS(=O)(=O)O)C#N XVQSJUOGWXZEFZ-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
• FWRZMWZPAIFWTH-RYUDHWBXSA-N CC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)N Chemical compound CC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)N FWRZMWZPAIFWTH-RYUDHWBXSA-N 0.000 description 1
• DIILDUJQDBRMOR-RYUDHWBXSA-N CC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] Chemical compound CC1=C(C=NN1[C@@H]1C[C@H](CC1)N1CCOCC1)[N+](=O)[O-] DIILDUJQDBRMOR-RYUDHWBXSA-N 0.000 description 1
• WCQZFMFXVYJCAP-GMSGAONNSA-N CC1=C(C=NN1[C@H]1[C@@H](COCC1)C)N Chemical compound CC1=C(C=NN1[C@H]1[C@@H](COCC1)C)N WCQZFMFXVYJCAP-GMSGAONNSA-N 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 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
• 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 1
• IUPVTCGAKOLIBJ-ONGXEEELSA-N ClC1=C(C=NN1[C@@H]1C(CC[C@@H](C1)N1CCOCC1)(F)F)N Chemical compound ClC1=C(C=NN1[C@@H]1C(CC[C@@H](C1)N1CCOCC1)(F)F)N IUPVTCGAKOLIBJ-ONGXEEELSA-N 0.000 description 1
• IUPVTCGAKOLIBJ-KOLCDFICSA-N ClC1=C(C=NN1[C@@H]1C(CC[C@H](C1)N1CCOCC1)(F)F)N Chemical compound ClC1=C(C=NN1[C@@H]1C(CC[C@H](C1)N1CCOCC1)(F)F)N IUPVTCGAKOLIBJ-KOLCDFICSA-N 0.000 description 1
• IJGQVURVGFDTRY-ZJUUUORDSA-N ClC1=C(C=NN1[C@@H]1C[C@@H](CC1)N1CCOCC1)N Chemical compound ClC1=C(C=NN1[C@@H]1C[C@@H](CC1)N1CCOCC1)N IJGQVURVGFDTRY-ZJUUUORDSA-N 0.000 description 1
• GYYZQIWGJSEHHU-GXSJLCMTSA-N ClC1=C(C=NN1[C@@H]1C[C@H](CCC1(F)F)N1CCOCC1)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@@H]1C[C@H](CCC1(F)F)N1CCOCC1)[N+](=O)[O-] GYYZQIWGJSEHHU-GXSJLCMTSA-N 0.000 description 1
• YVYSXVZMZGTRFP-BDAKNGLRSA-N ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C1COC1)F)[N+](=O)[O-] Chemical compound ClC1=C(C=NN1[C@@H]1[C@@H](CN(CC1)C1COC1)F)[N+](=O)[O-] YVYSXVZMZGTRFP-BDAKNGLRSA-N 0.000 description 1
• 208000028698 Cognitive impairment Diseases 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
• 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
• GQHTUMJGOHRCHB-UHFFFAOYSA-N DBU Substances C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [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
• 241000402754 Erythranthe moschata 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
• 241001124123 Evania Species 0.000 description 1
• JKBQLGDMVDOSGQ-CMPLNLGQSA-N FC1([C@@H](C[C@H](CC1)N1CCOCC1)N1N=CC(=C1)[N+](=O)[O-])F Chemical compound FC1([C@@H](C[C@H](CC1)N1CCOCC1)N1N=CC(=C1)[N+](=O)[O-])F JKBQLGDMVDOSGQ-CMPLNLGQSA-N 0.000 description 1
• VDPYEYHOZPMMAV-JGVFFNPUSA-N FC1([C@@H](C[C@H](CC1)O)N1N=CC(=C1)[N+](=O)[O-])F Chemical compound FC1([C@@H](C[C@H](CC1)O)N1N=CC(=C1)[N+](=O)[O-])F VDPYEYHOZPMMAV-JGVFFNPUSA-N 0.000 description 1
• JKBQLGDMVDOSGQ-JQWIXIFHSA-N FC1([C@H](C[C@H](CC1)N1CCOCC1)N1N=CC(=C1)[N+](=O)[O-])F Chemical compound FC1([C@H](C[C@H](CC1)N1CCOCC1)N1N=CC(=C1)[N+](=O)[O-])F JKBQLGDMVDOSGQ-JQWIXIFHSA-N 0.000 description 1
• FCRINDMVGKIGEV-ZYHUDNBSSA-N F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C)N)C1COC1 Chemical compound F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C)N)C1COC1 FCRINDMVGKIGEV-ZYHUDNBSSA-N 0.000 description 1
• RMKBCMIGJXCXCC-GHMZBOCLSA-N F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C)[N+](=O)[O-])C1COC1 Chemical compound F[C@@H]1CN(CC[C@H]1N1N=CC(=C1C)[N+](=O)[O-])C1COC1 RMKBCMIGJXCXCC-GHMZBOCLSA-N 0.000 description 1
• MLQSKWOMDPZZRD-SFYZADRCSA-N F[C@@H]1CNCC[C@@H]1N1N=CC(=C1C)[N+](=O)[O-] Chemical compound F[C@@H]1CNCC[C@@H]1N1N=CC(=C1C)[N+](=O)[O-] MLQSKWOMDPZZRD-SFYZADRCSA-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
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
• 229920000084 Gum arabic Polymers 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101100491147 Homo sapiens ANKK1 gene Proteins 0.000 description 1
• 101001115732 Homo sapiens MOB kinase activator 2 Proteins 0.000 description 1
• 101000759453 Homo sapiens YY1-associated protein 1 Proteins 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
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 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
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 108091022875 Microtubule Proteins 0.000 description 1
• 102000029749 Microtubule Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• 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 1
• GNRBHHQSSWTKAN-YUMQZZPRSA-N NC=1C=NN(C=1C)[C@@H]1C[C@H](CC1)O Chemical compound NC=1C=NN(C=1C)[C@@H]1C[C@H](CC1)O GNRBHHQSSWTKAN-YUMQZZPRSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 101100526762 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) rpl-28 gene Proteins 0.000 description 1
• 208000014060 Niemann-Pick disease Diseases 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
• 241001494479 Pecora Species 0.000 description 1
• 241001417527 Pempheridae Species 0.000 description 1
• 239000004237 Ponceau 6R Substances 0.000 description 1
• 239000004236 Ponceau SX Substances 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 102100037580 Sesquipedalian-1 Human genes 0.000 description 1
• 101710169844 Sesquipedalian-1 Proteins 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 239000004280 Sodium formate Substances 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
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• 208000034799 Tauopathies Diseases 0.000 description 1
• 208000024799 Thyroid disease Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 244000274883 Urtica dioica Species 0.000 description 1
• 235000009108 Urtica dioica Nutrition 0.000 description 1
• 102100023267 YY1-associated protein 1 Human genes 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XQAXGZLFSSPBMK-UHFFFAOYSA-M [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate Chemical compound O.O.O.[Cl-].C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21 XQAXGZLFSSPBMK-UHFFFAOYSA-M 0.000 description 1
• PQISXNOCRYOLLR-QWRGUYRKSA-N [N+](=O)([O-])C=1C=NN(C=1)[C@@H]1C[C@H](CC1)N1CCOCC1 Chemical compound [N+](=O)([O-])C=1C=NN(C=1)[C@@H]1C[C@H](CC1)N1CCOCC1 PQISXNOCRYOLLR-QWRGUYRKSA-N 0.000 description 1
• PQISXNOCRYOLLR-WDEREUQCSA-N [N+](=O)([O-])C=1C=NN(C=1)[C@H]1C[C@H](CC1)N1CCOCC1 Chemical compound [N+](=O)([O-])C=1C=NN(C=1)[C@H]1C[C@H](CC1)N1CCOCC1 PQISXNOCRYOLLR-WDEREUQCSA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 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
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 229940048053 acrylate Drugs 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 239000004178 amaranth Substances 0.000 description 1
• 235000012735 amaranth Nutrition 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 201000007201 aphasia Diseases 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 239000004176 azorubin Substances 0.000 description 1
• 235000012733 azorubine Nutrition 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 239000002439 beta secretase inhibitor Substances 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
• 230000033228 biological regulation Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 208000029028 brain injury Diseases 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
• 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
• 244000309466 calf Species 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000012292 cell migration Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 238000002659 cell therapy Methods 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 230000008859 change Effects 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
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 238000005352 clarification Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000011970 concomitant therapy Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
• SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• FIOVMKKOHJJECB-UHFFFAOYSA-N cyclobutyl methanesulfonate Chemical compound CS(=O)(=O)OC1CCC1 FIOVMKKOHJJECB-UHFFFAOYSA-N 0.000 description 1
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
• FJWFZRXGXZLAGU-UHFFFAOYSA-N cyclopent-3-en-1-yl methanesulfonate Chemical compound CS(=O)(=O)OC1CC=CC1 FJWFZRXGXZLAGU-UHFFFAOYSA-N 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
• SHALBPKEGDBVKK-VOTSOKGWSA-N danishefsky's diene Chemical compound CO\C=C\C(=C)O[Si](C)(C)C SHALBPKEGDBVKK-VOTSOKGWSA-N 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 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
• 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
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
• HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-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
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-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
• 239000007884 disintegrant Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 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
• 239000000975 dye Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 229950000206 estolate Drugs 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
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000005021 gait Effects 0.000 description 1
• 239000003540 gamma secretase inhibitor Substances 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 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
• 230000012010 growth Effects 0.000 description 1
• 235000010417 guar gum Nutrition 0.000 description 1
• 239000000665 guar gum Substances 0.000 description 1
• 229960002154 guar gum Drugs 0.000 description 1
• 208000019622 heart disease Diseases 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
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 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
• 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
• 230000001900 immune effect Effects 0.000 description 1
• 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 208000014674 injury Diseases 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
• 238000000752 ionisation method 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
• 208000017169 kidney disease Diseases 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 230000006655 lysosomal degradation pathway 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
• 206010025482 malaise Diseases 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
• 210000005075 mammary gland Anatomy 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 238000001819 mass spectrum Methods 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
• 239000001369 metatartaric acid Substances 0.000 description 1
• IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 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
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 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
• 230000005012 migration Effects 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
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• BNTZPYZTYZBPSC-UHFFFAOYSA-N morpholin-2-ol;hydrochloride Chemical compound Cl.OC1CNCCO1 BNTZPYZTYZBPSC-UHFFFAOYSA-N 0.000 description 1
• 238000001964 muscle biopsy Methods 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
• 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
• 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
• 230000001537 neural effect Effects 0.000 description 1
• 210000002241 neurite Anatomy 0.000 description 1
• 230000000926 neurological effect 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
• 231100000862 numbness Toxicity 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
• 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
• 239000007800 oxidant agent Substances 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
• 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
• 239000002304 perfume Substances 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000003208 petroleum Substances 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
• 235000019238 ponceau 6R Nutrition 0.000 description 1
• 235000019237 ponceau SX Nutrition 0.000 description 1
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
• 239000001608 potassium adipate Substances 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates 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
• 230000035755 proliferation 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
• 230000007111 proteostasis Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 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
• 108020003175 receptors Proteins 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007363 ring formation reaction 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
• 229960001860 salicylate Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 239000001601 sodium adipate 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
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000011182 sodium carbonates Nutrition 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000014347 soups Nutrition 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010561 standard procedure Methods 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
• 239000000758 substrate Substances 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
• 229910021653 sulphate ion 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
• 208000037100 susceptibility to 1 spondyloarthropathy Diseases 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
• 238000001308 synthesis method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 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
• 230000002123 temporal effect Effects 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
• GNJVAMYHVWGBGS-UHFFFAOYSA-N tert-butyl 1-methyl-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound CC12CN(CCC2O1)C(=O)OC(C)(C)C GNJVAMYHVWGBGS-UHFFFAOYSA-N 0.000 description 1
• FJYBLMJHXRWDAQ-UHFFFAOYSA-N tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC(CO)C1 FJYBLMJHXRWDAQ-UHFFFAOYSA-N 0.000 description 1
• PXNPGAPJCXDNLK-UHFFFAOYSA-N tert-butyl 3-(4-amino-5-methylpyrazol-1-yl)-4,4-difluoropiperidine-1-carboxylate Chemical compound NC=1C=NN(C=1C)C1CN(CCC1(F)F)C(=O)OC(C)(C)C PXNPGAPJCXDNLK-UHFFFAOYSA-N 0.000 description 1
• VYHFLIFNGPQXEV-UHFFFAOYSA-N tert-butyl 3-(4-nitropyrazol-1-yl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1N1N=CC([N+]([O-])=O)=C1 VYHFLIFNGPQXEV-UHFFFAOYSA-N 0.000 description 1
• UIJXHKXIOCDSEB-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1 UIJXHKXIOCDSEB-UHFFFAOYSA-N 0.000 description 1
• CGTRFKXCKHZQAV-UHFFFAOYSA-N tert-butyl 5-methyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC1=CCCN(C(=O)OC(C)(C)C)C1 CGTRFKXCKHZQAV-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
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Substances [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical group [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-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
• 230000003582 thrombocytopenic effect Effects 0.000 description 1
• 208000021510 thyroid gland disease Diseases 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 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
• 230000008733 trauma Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
• 235000019798 tripotassium phosphate Nutrition 0.000 description 1
• 210000004881 tumor cell Anatomy 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
• 239000003981 vehicle Substances 0.000 description 1
• 238000001851 vibrational circular dichroism spectroscopy Methods 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