TW200413362A - Novel oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors - Google Patents

Info

Publication number

TW200413362A

TW200413362A TW092125637A TW92125637A TW200413362A TW 200413362 A TW200413362 A TW 200413362A TW 092125637 A TW092125637 A TW 092125637A TW 92125637 A TW92125637 A TW 92125637A TW 200413362 A TW200413362 A TW 200413362A

Authority

TW

Taiwan

Prior art keywords

alkyl

cvc6

group

phenyl

methyl

Prior art date

2002-09-18

Links

• Espacenet
• Global Dossier
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• 102000009618 Transforming Growth Factors Human genes 0.000 title abstract description 23
• 108010009583 Transforming Growth Factors Proteins 0.000 title abstract description 23
• 239000003112 inhibitor Substances 0.000 title abstract description 9
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 title abstract description 7
• 150000003557 thiazoles Chemical class 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 183
• -1 derivatives thereof Chemical class 0.000 claims abstract description 92
• 201000010099 disease Diseases 0.000 claims abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
• 201000011510 cancer Diseases 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 92
• 150000003839 salts Chemical class 0.000 claims description 41
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 28
• 239000002253 acid Substances 0.000 claims description 25
• 150000001412 amines Chemical class 0.000 claims description 24
• 125000001072 heteroaryl group Chemical group 0.000 claims description 23
• 239000000651 prodrug Substances 0.000 claims description 22
• 229940002612 prodrug Drugs 0.000 claims description 22
• 125000000623 heterocyclic group Chemical group 0.000 claims description 18
• 125000003277 amino group Chemical group 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 125000004122 cyclic group Chemical group 0.000 claims description 14
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 125000003282 alkyl amino group Chemical group 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• 229920006395 saturated elastomer Polymers 0.000 claims description 12
• 241001465754 Metazoa Species 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 150000002148 esters Chemical class 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000002619 bicyclic group Chemical group 0.000 claims description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• 150000004677 hydrates Chemical class 0.000 claims description 5
• 239000012453 solvate Substances 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 3
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 206010016654 Fibrosis Diseases 0.000 claims description 3
• 150000001335 aliphatic alkanes Chemical group 0.000 claims description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
• 125000004104 aryloxy group Chemical group 0.000 claims description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
• 125000003367 polycyclic group Chemical group 0.000 claims description 3
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 206010039710 Scleroderma Diseases 0.000 claims description 2
• 230000007882 cirrhosis Effects 0.000 claims description 2
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
• 206010020718 hyperplasia Diseases 0.000 claims description 2
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 241000234282 Allium Species 0.000 claims 1
• 235000002732 Allium cepa var. cepa Nutrition 0.000 claims 1
• 125000001980 alanyl group Chemical group 0.000 claims 1
• 125000004043 oxo group Chemical group O=* 0.000 claims 1
• 125000003884 phenylalkyl group Chemical group 0.000 claims 1
• 238000010186 staining Methods 0.000 claims 1
• 150000003573 thiols Chemical class 0.000 claims 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
• 229920002554 vinyl polymer Polymers 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 63
• 239000000543 intermediate Substances 0.000 abstract description 9
• 230000019491 signal transduction Effects 0.000 abstract description 8
• 230000003389 potentiating effect Effects 0.000 abstract description 3
• 230000003176 fibrotic effect Effects 0.000 abstract description 2
• 238000000034 method Methods 0.000 description 78
• 238000006243 chemical reaction Methods 0.000 description 56
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 45
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 239000000243 solution Substances 0.000 description 32
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 31
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
• 239000002585 base Substances 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
• 239000000203 mixture Substances 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• 239000002904 solvent Substances 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 238000007792 addition Methods 0.000 description 13
• 239000003814 drug Substances 0.000 description 12
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 12
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 239000000443 aerosol Substances 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
• 239000000460 chlorine Chemical group 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 229910052801 chlorine Inorganic materials 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• 241000282412 Homo Species 0.000 description 5
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 5
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
• 125000000539 amino acid group Chemical group 0.000 description 5
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 5
• 239000012964 benzotriazole Substances 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 239000002798 polar solvent Substances 0.000 description 5
• 239000003586 protic polar solvent Substances 0.000 description 5
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 4
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
• MAQAGRJURDEYDQ-UHFFFAOYSA-N 6-methylpyridine Chemical compound CC1=C=CC=C[N]1 MAQAGRJURDEYDQ-UHFFFAOYSA-N 0.000 description 4
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 150000001409 amidines Chemical class 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 125000005605 benzo group Chemical group 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 150000001768 cations Chemical class 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
• 229940011051 isopropyl acetate Drugs 0.000 description 4
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 4
• 238000000021 kinase assay Methods 0.000 description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000007921 spray Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
• ACTKAGSPIFDCMF-UHFFFAOYSA-N 1,3-oxazol-2-amine Chemical compound NC1=NC=CO1 ACTKAGSPIFDCMF-UHFFFAOYSA-N 0.000 description 3
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• 239000005695 Ammonium acetate Substances 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 244000025254 Cannabis sativa Species 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
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• 102000047918 Myelin Basic Human genes 0.000 description 3
• 101710107068 Myelin basic protein Proteins 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
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• 150000001450 anions Chemical class 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
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• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
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• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
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• 150000002576 ketones Chemical class 0.000 description 3
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• 239000000047 product Substances 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• 238000004007 reversed phase HPLC Methods 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
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