SK9372000A3 - Substituted beta-alanines - Google Patents

Info

Publication number

SK9372000A3

SK9372000A3 SK937-2000A SK9372000A SK9372000A3 SK 9372000 A3 SK9372000 A3 SK 9372000A3 SK 9372000 A SK9372000 A SK 9372000A SK 9372000 A3 SK9372000 A3 SK 9372000A3

Authority

SK

Slovakia

Prior art keywords

compound

group

alkyl

acetyl

amino

Prior art date

1997-12-23

Links

• Espacenet
• Global Dossier
• Discuss

• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 564
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 94
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 60
• 150000003839 salts Chemical class 0.000 claims abstract description 58
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 53
• 239000000651 prodrug Substances 0.000 claims abstract description 35
• 229940002612 prodrug Drugs 0.000 claims abstract description 35
• 239000001257 hydrogen Substances 0.000 claims abstract description 21
• 239000012453 solvate Substances 0.000 claims abstract description 21
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
• 150000002367 halogens Chemical class 0.000 claims abstract description 16
• 150000002431 hydrogen Chemical class 0.000 claims abstract 7
• -1 cyclic amine Chemical class 0.000 claims description 352
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 264
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 163
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 129
• 235000019260 propionic acid Nutrition 0.000 claims description 127
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 110
• 125000004432 carbon atom Chemical group C* 0.000 claims description 73
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 65
• 239000011347 resin Substances 0.000 claims description 64
• 229920005989 resin Polymers 0.000 claims description 64
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 239000000203 mixture Substances 0.000 claims description 44
• 125000001072 heteroaryl group Chemical group 0.000 claims description 39
• 238000000034 method Methods 0.000 claims description 39
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 23
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 21
• 230000002378 acidificating effect Effects 0.000 claims description 18
• 238000011282 treatment Methods 0.000 claims description 18
• 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 14
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
• 125000002947 alkylene group Chemical group 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 229910005965 SO 2 Inorganic materials 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 12
• 239000003112 inhibitor Substances 0.000 claims description 12
• 230000021164 cell adhesion Effects 0.000 claims description 11
• 150000004677 hydrates Chemical class 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000000524 functional group Chemical group 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
• 125000000304 alkynyl group Chemical group 0.000 claims description 7
• 125000004043 oxo group Chemical group O=* 0.000 claims description 7
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 6
• 229940126062 Compound A Drugs 0.000 claims description 5
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 230000001668 ameliorated effect Effects 0.000 claims description 5
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 4
• 125000002252 acyl group Chemical group 0.000 claims description 4
• 125000004450 alkenylene group Chemical group 0.000 claims description 4
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
• 125000000732 arylene group Chemical group 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
• PRZMGAZLBSVGFD-UHFFFAOYSA-N 3-[(3,4-dimethoxyphenyl)methyl-[2-[[2-[3-methoxy-4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]-methylamino]acetyl]amino]propanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1CN(CCC(O)=O)C(=O)CN(C)C(=O)CC(C=C1OC)=CC=C1NC(=O)NC1=CC=CC=C1C PRZMGAZLBSVGFD-UHFFFAOYSA-N 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 125000005518 carboxamido group Chemical group 0.000 claims description 3
• 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 3
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 208000027866 inflammatory disease Diseases 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 11
• 238000004519 manufacturing process Methods 0.000 claims 2
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
• 108010067306 Fibronectins Proteins 0.000 abstract description 14
• 102000016359 Fibronectins Human genes 0.000 abstract description 14
• 108010008212 Integrin alpha4beta1 Proteins 0.000 abstract description 10
• 230000003993 interaction Effects 0.000 abstract description 8
• 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 abstract 1
• 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 abstract 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 235
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
• 230000000052 comparative effect Effects 0.000 description 51
• 239000002253 acid Substances 0.000 description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• 239000000243 solution Substances 0.000 description 44
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 41
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• 238000001819 mass spectrum Methods 0.000 description 28
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 239000007787 solid Substances 0.000 description 27
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
• 210000004027 cell Anatomy 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 22
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 20
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
• 239000002585 base Substances 0.000 description 17
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• 108010044426 integrins Proteins 0.000 description 16
• 102000006495 integrins Human genes 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000000921 elemental analysis Methods 0.000 description 15
• 239000011734 sodium Substances 0.000 description 15
• 125000003373 pyrazinyl group Chemical group 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 12
• 239000011541 reaction mixture Substances 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 238000010828 elution Methods 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• BEYOHIUUBRQWQF-UHFFFAOYSA-N ethyl 3-[(3,4-dimethoxyphenyl)methylamino]propanoate Chemical compound CCOC(=O)CCNCC1=CC=C(OC)C(OC)=C1 BEYOHIUUBRQWQF-UHFFFAOYSA-N 0.000 description 9
• 239000006260 foam Substances 0.000 description 9
• 239000012458 free base Substances 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• 241000699670 Mus sp. Species 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 241000700159 Rattus Species 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• 239000003446 ligand Substances 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 125000001931 aliphatic group Chemical group 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 125000002883 imidazolyl group Chemical group 0.000 description 7
• 238000003018 immunoassay Methods 0.000 description 7
• 125000004076 pyridyl group Chemical group 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 125000004442 acylamino group Chemical group 0.000 description 6
• 239000000427 antigen Substances 0.000 description 6
• 102000036639 antigens Human genes 0.000 description 6
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• 206010003246 arthritis Diseases 0.000 description 6
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• 239000012267 brine Substances 0.000 description 6
• 125000004494 ethyl ester group Chemical group 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 238000005897 peptide coupling reaction Methods 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 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 5
• 239000000284 extract Substances 0.000 description 5
• 125000002541 furyl group Chemical group 0.000 description 5
• 125000001041 indolyl group Chemical group 0.000 description 5
• 210000004072 lung Anatomy 0.000 description 5
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• 125000006239 protecting group Chemical group 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
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• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
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• 210000001744 T-lymphocyte Anatomy 0.000 description 4
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• 125000003435 aroyl group Chemical group 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
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• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 3
• LQAWZBVFPYYFGB-UHFFFAOYSA-N 2-[3-methoxy-4-[(2-methylphenyl)carbamoylamino]phenyl]acetic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1NC(=O)NC1=CC=CC=C1C LQAWZBVFPYYFGB-UHFFFAOYSA-N 0.000 description 3
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 3
• 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
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• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
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• NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
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• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
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• 125000004414 alkyl thio group Chemical group 0.000 description 3
• 125000004419 alkynylene group Chemical group 0.000 description 3
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 125000004659 aryl alkyl thio group Chemical group 0.000 description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 3
• 125000005110 aryl thio group Chemical group 0.000 description 3
• 125000004104 aryloxy group Chemical group 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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• 210000002889 endothelial cell Anatomy 0.000 description 3
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• 238000002474 experimental method Methods 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000005114 heteroarylalkoxy group Chemical group 0.000 description 3
• 125000005553 heteroaryloxy group Chemical group 0.000 description 3
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