RU2724899C2 - Новые бициклические соединения в качестве дуальных ингибиторов atx/ca - Google Patents

Info

Publication number

RU2724899C2

RU2724899C2 RU2018112237A RU2018112237A RU2724899C2 RU 2724899 C2 RU2724899 C2 RU 2724899C2 RU 2018112237 A RU2018112237 A RU 2018112237A RU 2018112237 A RU2018112237 A RU 2018112237A RU 2724899 C2 RU2724899 C2 RU 2724899C2

Authority

RU

Russia

Prior art keywords

alkyl

substituted

pyrrole

methyl

tetrahydropyrrolo

Prior art date

2015-09-24

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title claims abstract description 8
• 125000002619 bicyclic group Chemical group 0.000 title description 4
• 230000009977 dual effect Effects 0.000 title description 3
• -1 aminosulphonyl Chemical group 0.000 claims abstract description 183
• 150000001875 compounds Chemical class 0.000 claims abstract description 167
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 49
• 150000003839 salts Chemical class 0.000 claims abstract description 46
• 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 claims abstract description 41
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 40
• 150000002367 halogens Chemical class 0.000 claims abstract description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
• 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 claims abstract description 36
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 26
• 238000000034 method Methods 0.000 claims abstract description 22
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 21
• 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
• 230000000694 effects Effects 0.000 claims abstract description 14
• 102000003846 Carbonic anhydrases Human genes 0.000 claims abstract description 13
• 108090000209 Carbonic anhydrases Proteins 0.000 claims abstract description 13
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 10
• 239000003814 drug Substances 0.000 claims abstract description 9
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 68
• 125000003545 alkoxy group Chemical group 0.000 claims description 35
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 12
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
• 230000005764 inhibitory process Effects 0.000 claims description 8
• KDEHVTPVUXGJMD-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C=C1)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C=C1)S(N)(=O)=O)C(F)(F)F KDEHVTPVUXGJMD-UHFFFAOYSA-N 0.000 claims description 5
• PMMLAGCGRWXTKW-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(Cl)=C(C=C1)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(Cl)=C(C=C1)S(N)(=O)=O)C(F)(F)F PMMLAGCGRWXTKW-UHFFFAOYSA-N 0.000 claims description 5
• SATKYBKQMZMOTQ-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(F)=C(C=C1)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(F)=C(C=C1)S(N)(=O)=O)C(F)(F)F SATKYBKQMZMOTQ-UHFFFAOYSA-N 0.000 claims description 5
• 239000013543 active substance Substances 0.000 claims description 4
• 229940079593 drug Drugs 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• IKKKOADRDQAIRV-UHFFFAOYSA-N C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C(=C(C=C1)S(=O)(=O)N)F)F)OCC1CCN(CC1)C Chemical compound C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C(=C(C=C1)S(=O)(=O)N)F)F)OCC1CCN(CC1)C IKKKOADRDQAIRV-UHFFFAOYSA-N 0.000 claims description 3
• SEVKTBQHKXKOGU-UHFFFAOYSA-N C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)OCC1CCOCC1 Chemical compound C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)OCC1CCOCC1 SEVKTBQHKXKOGU-UHFFFAOYSA-N 0.000 claims description 3
• UZTXHXYLFOLAIC-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C(F)=C(C=C1)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C(F)=C(C=C1)S(N)(=O)=O)C(F)(F)F UZTXHXYLFOLAIC-UHFFFAOYSA-N 0.000 claims description 3
• JWMMUGJLKFEDKE-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C(F)=C1)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C(F)=C1)S(N)(=O)=O)C(F)(F)F JWMMUGJLKFEDKE-UHFFFAOYSA-N 0.000 claims description 3
• GORMEHYDOGSCDJ-UHFFFAOYSA-N CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C=C1F)S(N)(=O)=O)C(F)(F)F Chemical compound CC(C)(C)C(=O)NC1=CC(=CN=C1COC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(F)C=C(C=C1F)S(N)(=O)=O)C(F)(F)F GORMEHYDOGSCDJ-UHFFFAOYSA-N 0.000 claims description 3
• KAEUZYKVGXFROT-UHFFFAOYSA-N CC(C)(C)C(NC(C(C(C)(C(CNC1)=C1C1)N1C(C(C=C1)=CC(F)=C1S(N)(=O)=O)=O)=N1)=CC=C1Cl)=O Chemical compound CC(C)(C)C(NC(C(C(C)(C(CNC1)=C1C1)N1C(C(C=C1)=CC(F)=C1S(N)(=O)=O)=O)=N1)=CC=C1Cl)=O KAEUZYKVGXFROT-UHFFFAOYSA-N 0.000 claims description 3
• CDAGLKQWPICOKI-UHFFFAOYSA-N CC(C)(C)C(NC(C(C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=N1)=CC=C1Cl)=O Chemical compound CC(C)(C)C(NC(C(C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=N1)=CC=C1Cl)=O CDAGLKQWPICOKI-UHFFFAOYSA-N 0.000 claims description 3
• ASAQAJDODUUIDG-UHFFFAOYSA-N CC(C)(C)C(NC(C=C1C#N)=C(C(C)(C(CNC2)=C2C2)N2C(C(C=C2)=NC=C2S(N)(=O)=O)=O)C=C1Cl)=O Chemical compound CC(C)(C)C(NC(C=C1C#N)=C(C(C)(C(CNC2)=C2C2)N2C(C(C=C2)=NC=C2S(N)(=O)=O)=O)C=C1Cl)=O ASAQAJDODUUIDG-UHFFFAOYSA-N 0.000 claims description 3
• LHDDLTRFNHEHNW-UHFFFAOYSA-N CC(C)(C)C(NC1=CC(C#N)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=O Chemical compound CC(C)(C)C(NC1=CC(C#N)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=O LHDDLTRFNHEHNW-UHFFFAOYSA-N 0.000 claims description 3
• RRBYTWMNJAEWNP-UHFFFAOYSA-N CC(C)(C)C(NC1=CC(Cl)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=C1)=CC(F)=C1S(N)(=O)=O)=O)=O Chemical compound CC(C)(C)C(NC1=CC(Cl)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=C1)=CC(F)=C1S(N)(=O)=O)=O)=O RRBYTWMNJAEWNP-UHFFFAOYSA-N 0.000 claims description 3
• MRXDYCXDZDWVJE-UHFFFAOYSA-N CC(C)(C)C(NC1=CC(Cl)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=O Chemical compound CC(C)(C)C(NC1=CC(Cl)=CN=C1C(C)(C(CNC1)=C1C1)N1C(C(C=CC(S(N)(=O)=O)=C1)=C1F)=O)=O MRXDYCXDZDWVJE-UHFFFAOYSA-N 0.000 claims description 3
• TXNWJJSZEDRKCK-UHFFFAOYSA-N CC1=NN(CC2=CC(=CN=C2CCC(=O)N2CC3=C(C2)CN(C3)C(=O)C2=C(F)C=C(C=C2)S(N)(=O)=O)C(F)(F)F)N=N1 Chemical compound CC1=NN(CC2=CC(=CN=C2CCC(=O)N2CC3=C(C2)CN(C3)C(=O)C2=C(F)C=C(C=C2)S(N)(=O)=O)C(F)(F)F)N=N1 TXNWJJSZEDRKCK-UHFFFAOYSA-N 0.000 claims description 3
• XSYCFADWFZWFQI-UHFFFAOYSA-N ClC1=CC(=C(C=C1)CCC(=O)N1CC=2CN(CC=2C1)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)CN1N=C(N=N1)C Chemical compound ClC1=CC(=C(C=C1)CCC(=O)N1CC=2CN(CC=2C1)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)CN1N=C(N=N1)C XSYCFADWFZWFQI-UHFFFAOYSA-N 0.000 claims description 3
• QZEJPCSNGFLHEW-UHFFFAOYSA-N FC1=C(C(=O)N2CC=3CCN(CC=3CC2)C(=O)OCC2=CC=C(C=C2)OC(F)(F)F)C=CC(=C1)S(N)(=O)=O Chemical compound FC1=C(C(=O)N2CC=3CCN(CC=3CC2)C(=O)OCC2=CC=C(C=C2)OC(F)(F)F)C=CC(=C1)S(N)(=O)=O QZEJPCSNGFLHEW-UHFFFAOYSA-N 0.000 claims description 3
• MVPFYSLLQCAIQD-UHFFFAOYSA-N FC1=C(C(=O)N2CC=3CN(CC=3C2)C(=O)OCC2=CC=C(C=C2)OC(F)(F)F)C=CC(=C1)S(N)(=O)=O Chemical compound FC1=C(C(=O)N2CC=3CN(CC=3C2)C(=O)OCC2=CC=C(C=C2)OC(F)(F)F)C=CC(=C1)S(N)(=O)=O MVPFYSLLQCAIQD-UHFFFAOYSA-N 0.000 claims description 3
• ANABDZJHSXTWSW-UHFFFAOYSA-N FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(CCC1=C(C=C(C=C1)C(F)(F)F)CN1N=CC(=N1)C)=O)S(=O)(=O)N Chemical compound FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(CCC1=C(C=C(C=C1)C(F)(F)F)CN1N=CC(=N1)C)=O)S(=O)(=O)N ANABDZJHSXTWSW-UHFFFAOYSA-N 0.000 claims description 3
• APBVJBBITMBTRY-UHFFFAOYSA-N FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(CCC1=C(C=C(C=C1)C(F)(F)F)CN1N=NC(=C1)C)=O)S(=O)(=O)N Chemical compound FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(CCC1=C(C=C(C=C1)C(F)(F)F)CN1N=NC(=C1)C)=O)S(=O)(=O)N APBVJBBITMBTRY-UHFFFAOYSA-N 0.000 claims description 3
• FINNZCKERLGVEU-UHFFFAOYSA-N FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(COC1=CC=C(C=C1)OC(F)(F)F)=O)S(=O)(=O)N Chemical compound FC=1C=C(C=CC=1C(=O)N1CC2=C(C1)CN(C2)C(COC1=CC=C(C=C1)OC(F)(F)F)=O)S(=O)(=O)N FINNZCKERLGVEU-UHFFFAOYSA-N 0.000 claims description 3
• HYLZLYCVBDHFAF-UHFFFAOYSA-N NS(=O)(=O)C1=CC(F)=C(C=C1)C(=O)N1CC2=C(CN(C2)C(=O)CCC2=CC=C(OC(F)(F)F)C=C2)C1 Chemical compound NS(=O)(=O)C1=CC(F)=C(C=C1)C(=O)N1CC2=C(CN(C2)C(=O)CCC2=CC=C(OC(F)(F)F)C=C2)C1 HYLZLYCVBDHFAF-UHFFFAOYSA-N 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• DKTYCIYTZNUZKB-UHFFFAOYSA-N C(#N)C1=CC(=C(C=C1)CCC(=O)N1CC=2CN(CC=2C1)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)CN1N=C(N=N1)C Chemical compound C(#N)C1=CC(=C(C=C1)CCC(=O)N1CC=2CN(CC=2C1)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)CN1N=C(N=N1)C DKTYCIYTZNUZKB-UHFFFAOYSA-N 0.000 claims description 2
• UNYZRWFYQCMKRL-FPYGCLRLSA-N NS(=O)(=O)C1=CC=C(N=C1)C(=O)N1CC2=C(CN(C2)C(=O)\C=C\C2=CC=C(OC(F)(F)F)C=C2)C1 Chemical compound NS(=O)(=O)C1=CC=C(N=C1)C(=O)N1CC2=C(CN(C2)C(=O)\C=C\C2=CC=C(OC(F)(F)F)C=C2)C1 UNYZRWFYQCMKRL-FPYGCLRLSA-N 0.000 claims description 2
• 229910052757 nitrogen Inorganic materials 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims 2
• 125000000304 alkynyl group Chemical group 0.000 claims 2
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
• 229940125436 dual inhibitor Drugs 0.000 claims 1
• NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 21
• 201000010099 disease Diseases 0.000 abstract description 17
• 125000005843 halogen group Chemical group 0.000 abstract description 11
• 208000035475 disorder Diseases 0.000 abstract description 4
• 239000000126 substance Substances 0.000 abstract description 4
• 230000004071 biological effect Effects 0.000 abstract description 3
• WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 abstract 2
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 abstract 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
• 239000000543 intermediate Substances 0.000 description 138
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
• 239000000243 solution Substances 0.000 description 86
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• 150000001412 amines Chemical class 0.000 description 63
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 239000000203 mixture Substances 0.000 description 37
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 30
• RCMQDKXOHFOYQE-UHFFFAOYSA-N 2-fluoro-4-sulfamoylbenzoic acid Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C(F)=C1 RCMQDKXOHFOYQE-UHFFFAOYSA-N 0.000 description 29
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 27
• 239000002244 precipitate Substances 0.000 description 27
• 239000002904 solvent Substances 0.000 description 27
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 26
• 238000006243 chemical reaction Methods 0.000 description 26
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
• 235000019341 magnesium sulphate Nutrition 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• JJRPXOQSXGBENW-UHFFFAOYSA-N tert-butyl 2,3,4,6-tetrahydro-1h-pyrrolo[3,4-c]pyrrole-5-carboxylate;hydrochloride Chemical compound Cl.C1N(C(=O)OC(C)(C)C)CC2=C1CNC2 JJRPXOQSXGBENW-UHFFFAOYSA-N 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• 238000004587 chromatography analysis Methods 0.000 description 21
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• OKRROXQXGNEUSS-UHFFFAOYSA-N 1h-imidazol-1-ium-1-carboxylate Chemical compound OC(=O)N1C=CN=C1 OKRROXQXGNEUSS-UHFFFAOYSA-N 0.000 description 18
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 150000002148 esters Chemical class 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 235000019270 ammonium chloride Nutrition 0.000 description 13
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 12
• 239000000758 substrate Substances 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
• 239000003153 chemical reaction reagent Substances 0.000 description 11
• 208000030533 eye disease Diseases 0.000 description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
• 125000001544 thienyl group Chemical group 0.000 description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 10
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 238000004458 analytical method Methods 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 230000009897 systematic effect Effects 0.000 description 9
• TXJHPBWTPBYLFP-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Br)C(CBr)=C1 TXJHPBWTPBYLFP-UHFFFAOYSA-N 0.000 description 8
• 206010028980 Neoplasm Diseases 0.000 description 8
• ZLSOZAOCYJDPKX-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]methanol Chemical compound OCC1=CC=C(OC(F)(F)F)C=C1 ZLSOZAOCYJDPKX-UHFFFAOYSA-N 0.000 description 8
• 238000009835 boiling Methods 0.000 description 8
• 230000001684 chronic effect Effects 0.000 description 8
• 229960004592 isopropanol Drugs 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 235000011181 potassium carbonates Nutrition 0.000 description 8
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical class CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 8
• 238000011282 treatment Methods 0.000 description 8
• GBIUSRIYIIMTFL-UHFFFAOYSA-N FC1=C(C(=O)O)C=CC(=C1F)S(N)(=O)=O Chemical compound FC1=C(C(=O)O)C=CC(=C1F)S(N)(=O)=O GBIUSRIYIIMTFL-UHFFFAOYSA-N 0.000 description 7
• 239000002671 adjuvant Substances 0.000 description 7
• 201000011510 cancer Diseases 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000006260 foam Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 230000002792 vascular Effects 0.000 description 7
• YBADLXQNJCMBKR-UHFFFAOYSA-M (4-nitrophenyl)acetate Chemical compound [O-]C(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-M 0.000 description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 6
• RNYVTJANWYBGPW-ZZXKWVIFSA-N (e)-3-[4-(trifluoromethoxy)phenyl]prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(OC(F)(F)F)C=C1 RNYVTJANWYBGPW-ZZXKWVIFSA-N 0.000 description 6
• VVFLFTAOLYCDDT-UHFFFAOYSA-N 3-fluoro-4-sulfamoylbenzoic acid Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C=C1F VVFLFTAOLYCDDT-UHFFFAOYSA-N 0.000 description 6
• XZGLNCKSNVGDNX-UHFFFAOYSA-N 5-methyl-2h-tetrazole Chemical compound CC=1N=NNN=1 XZGLNCKSNVGDNX-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 208000010412 Glaucoma Diseases 0.000 description 6
• DGPZHVYBVJJQTN-UHFFFAOYSA-N OCC1=NC=C(C=C1NC(C(C)(C)C)=O)C(F)(F)F Chemical compound OCC1=NC=C(C=C1NC(C(C)(C)C)=O)C(F)(F)F DGPZHVYBVJJQTN-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 5
• OCHMCRMKYVESAO-UHFFFAOYSA-N 2,6-difluoro-4-sulfamoylbenzoic acid Chemical compound FC1=C(C(=O)O)C(=CC(=C1)S(N)(=O)=O)F OCHMCRMKYVESAO-UHFFFAOYSA-N 0.000 description 5
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
• QEYUHTHXJXUUNE-UHFFFAOYSA-N 5-sulfamoylpyridine-2-carboxylic acid Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)N=C1 QEYUHTHXJXUUNE-UHFFFAOYSA-N 0.000 description 5
• DZJMNWUXVKLXPX-UHFFFAOYSA-N C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CNC2)OCC1CCOCC1 Chemical compound C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CNC2)OCC1CCOCC1 DZJMNWUXVKLXPX-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• RPVJAVUZDKOFAA-UHFFFAOYSA-N Cc1nnn(Cc2cc(ccc2CCC(O)=O)C(F)(F)F)n1 Chemical compound Cc1nnn(Cc2cc(ccc2CCC(O)=O)C(F)(F)F)n1 RPVJAVUZDKOFAA-UHFFFAOYSA-N 0.000 description 5
• DBFXPWGQZNTEND-UHFFFAOYSA-N FC1=C(C(=O)O)C=C(C(=C1)S(N)(=O)=O)F Chemical compound FC1=C(C(=O)O)C=C(C(=C1)S(N)(=O)=O)F DBFXPWGQZNTEND-UHFFFAOYSA-N 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 239000000010 aprotic solvent Substances 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
• UCAGLBKTLXCODC-UHFFFAOYSA-N carzenide Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C=C1 UCAGLBKTLXCODC-UHFFFAOYSA-N 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 125000000000 cycloalkoxy group Chemical group 0.000 description 5
• 206010012601 diabetes mellitus Diseases 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 208000030159 metabolic disease Diseases 0.000 description 5
• 239000000825 pharmaceutical preparation Substances 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 230000011664 signaling Effects 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 208000019553 vascular disease Diseases 0.000 description 5
• LHOIAFAJRRSRRQ-UHFFFAOYSA-N 1,1-dimethyl-2-pyridin-4-ylhydrazine Chemical compound CN(C)NC1=CC=NC=C1 LHOIAFAJRRSRRQ-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• QHSBEEUEIRDHCD-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(OC(F)(F)F)C=C1 QHSBEEUEIRDHCD-UHFFFAOYSA-N 0.000 description 4
• RRPISZJLUXOOCL-UHFFFAOYSA-N 3-[4-(trifluoromethoxy)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=C(OC(F)(F)F)C=C1 RRPISZJLUXOOCL-UHFFFAOYSA-N 0.000 description 4
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 4
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 4
• WWPQWLDWJORWGP-UHFFFAOYSA-N ClC1=CC(=C(C=C1C#N)NC(C(C)(C)C)=O)CO Chemical compound ClC1=CC(=C(C=C1C#N)NC(C(C)(C)C)=O)CO WWPQWLDWJORWGP-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• PYQBJNZHOVNBED-UHFFFAOYSA-N FC=1C(=NC=C(C=1)S(N)(=O)=O)C(=O)O Chemical compound FC=1C(=NC=C(C=1)S(N)(=O)=O)C(=O)O PYQBJNZHOVNBED-UHFFFAOYSA-N 0.000 description 4
• 206010016654 Fibrosis Diseases 0.000 description 4
• 239000001828 Gelatine Substances 0.000 description 4
• 101000760643 Homo sapiens Carbonic anhydrase 2 Proteins 0.000 description 4
• 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• IJVKUZNUIAICEH-UHFFFAOYSA-N [5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2,3,4,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrole-5-carboxylate hydrochloride Chemical compound Cl.CC(C)(C)C(=O)Nc1cc(Cl)c(Cl)nc1COC(=O)N1CC2=C(CNC2)C1 IJVKUZNUIAICEH-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 230000004761 fibrosis Effects 0.000 description 4
• 230000003176 fibrotic effect Effects 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 102000057327 human CA2 Human genes 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 239000002198 insoluble material Substances 0.000 description 4
• MVUXWLVSWKZDLJ-UHFFFAOYSA-N methyl 2-amino-4-bromo-5-chlorobenzoate Chemical compound COC(=O)C1=CC(Cl)=C(Br)C=C1N MVUXWLVSWKZDLJ-UHFFFAOYSA-N 0.000 description 4
• RPBPQAHDCODVNJ-UHFFFAOYSA-N methyl 3-amino-5-(trifluoromethyl)pyridine-2-carboxylate Chemical compound COC(=O)C1=NC=C(C(F)(F)F)C=C1N RPBPQAHDCODVNJ-UHFFFAOYSA-N 0.000 description 4
• 210000000653 nervous system Anatomy 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• 229920005862 polyol Polymers 0.000 description 4
• 150000003077 polyols Chemical class 0.000 description 4
• 239000011736 potassium bicarbonate Substances 0.000 description 4
• 235000015497 potassium bicarbonate Nutrition 0.000 description 4
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
• 229940086066 potassium hydrogencarbonate Drugs 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
• SRFWIYLEHUULCU-UHFFFAOYSA-N 2-cyclopropyl-6-oxo-1h-pyridine-4-carboxylic acid Chemical compound N1C(=O)C=C(C(=O)O)C=C1C1CC1 SRFWIYLEHUULCU-UHFFFAOYSA-N 0.000 description 3
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 3
• GNJGXWDZPDLQFE-UHFFFAOYSA-N CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)O Chemical compound CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)O GNJGXWDZPDLQFE-UHFFFAOYSA-N 0.000 description 3
• YKNMQNLQUMRUIL-UHFFFAOYSA-N CC=1N=NN(N=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)N1CC2=C(C1)CNC2 Chemical compound CC=1N=NN(N=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)N1CC2=C(C1)CNC2 YKNMQNLQUMRUIL-UHFFFAOYSA-N 0.000 description 3
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• LNEMUIXQNJTKHK-UHFFFAOYSA-N ClC=1C=C(C(=NC=1)CO)CN1N=C(N=N1)C Chemical compound ClC=1C=C(C(=NC=1)CO)CN1N=C(N=N1)C LNEMUIXQNJTKHK-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• CINQIYLBFJSMTI-UHFFFAOYSA-N FC=1C(=NC=C(C=1)S(N)(=O)=O)C(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C Chemical compound FC=1C(=NC=C(C=1)S(N)(=O)=O)C(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C CINQIYLBFJSMTI-UHFFFAOYSA-N 0.000 description 3
• 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 3
• 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 description 3
• 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 208000008589 Obesity Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 208000003251 Pruritus Diseases 0.000 description 3
• 206010052779 Transplant rejections Diseases 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 239000002168 alkylating agent Substances 0.000 description 3
• 229940100198 alkylating agent Drugs 0.000 description 3
• 108010022198 alkylglycerophosphoethanolamine phosphodiesterase Proteins 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 230000001587 cholestatic effect Effects 0.000 description 3
• 239000008120 corn starch Substances 0.000 description 3
• 239000008298 dragée Substances 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 230000004968 inflammatory condition Effects 0.000 description 3
• 230000007803 itching Effects 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 235000020824 obesity Nutrition 0.000 description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 description 3
• 210000002345 respiratory system Anatomy 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000011550 stock solution Substances 0.000 description 3
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 3
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 2
• RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 2
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
• CJRJJFDNVYKZIX-UHFFFAOYSA-N 2,5-difluoro-4-methylbenzenesulfonamide Chemical compound CC1=CC(F)=C(S(N)(=O)=O)C=C1F CJRJJFDNVYKZIX-UHFFFAOYSA-N 0.000 description 2
• FWLXUXKNSGRPDX-UHFFFAOYSA-N 2-fluoro-4-sulfamoylbenzenesulfonyl chloride Chemical compound NS(=O)(=O)C1=CC=C(S(Cl)(=O)=O)C(F)=C1 FWLXUXKNSGRPDX-UHFFFAOYSA-N 0.000 description 2
• DSDDAPCNVDJNKS-UHFFFAOYSA-N 3-[2-[(4-methyltriazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propanoic acid Chemical compound CC1=NN(N=C1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)O DSDDAPCNVDJNKS-UHFFFAOYSA-N 0.000 description 2
• LPWSSZKXKQCTCS-UHFFFAOYSA-N 4-(bromomethyl)-1-methylpiperidine;hydrobromide Chemical compound Br.CN1CCC(CBr)CC1 LPWSSZKXKQCTCS-UHFFFAOYSA-N 0.000 description 2
• MQLFSPBSNWUXSO-UHFFFAOYSA-N 4-(iodomethyl)oxane Chemical compound ICC1CCOCC1 MQLFSPBSNWUXSO-UHFFFAOYSA-N 0.000 description 2
• BKIRKJMXYUWQBI-UHFFFAOYSA-N 5-O-tert-butyl 2-O-[[3-(2,2-dimethylpropanoylamino)quinolin-2-yl]methyl] 1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2,5-dicarboxylate Chemical compound C1N(CC2=C1CN(C2)C(=O)OC(C)(C)C)C(=O)OCC1=NC2=CC=CC=C2C=C1NC(C(C)(C)C)=O BKIRKJMXYUWQBI-UHFFFAOYSA-N 0.000 description 2
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
• HDWDTSUSZZDKGG-UHFFFAOYSA-N 6-chloro-5-fluoropyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CN=C(Cl)C(F)=C1 HDWDTSUSZZDKGG-UHFFFAOYSA-N 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• AERBKKBOKOEBSJ-UHFFFAOYSA-N C(#N)C=1C=C(C(=NC=1)CO)NC(C(C)(C)C)=O Chemical compound C(#N)C=1C=C(C(=NC=1)CO)NC(C(C)(C)C)=O AERBKKBOKOEBSJ-UHFFFAOYSA-N 0.000 description 2
• 102100021935 C-C motif chemokine 26 Human genes 0.000 description 2
• KJTSUDNAUXPLHU-UHFFFAOYSA-N C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C(=C(C=C1)S(=O)(=O)N)F)F)OCC1CCOCC1 Chemical compound C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CN(C2)C(=O)C1=C(C(=C(C=C1)S(=O)(=O)N)F)F)OCC1CCOCC1 KJTSUDNAUXPLHU-UHFFFAOYSA-N 0.000 description 2
• FAIWQORMJZRWIS-UHFFFAOYSA-N C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CNC2)OCC1CCN(CC1)C Chemical compound C1(CC1)C1=NC(=CC(=C1)C(=O)N1CC2=C(C1)CNC2)OCC1CCN(CC1)C FAIWQORMJZRWIS-UHFFFAOYSA-N 0.000 description 2
• LJPVKRSBXNRQOL-UHFFFAOYSA-N C1(CC1)C=1C=C(C(=O)N2CC3=C(C2)CN(C3)C(=O)OC(C)(C)C)C=C(N=1)OCC1CCOCC1 Chemical compound C1(CC1)C=1C=C(C(=O)N2CC3=C(C2)CN(C3)C(=O)OC(C)(C)C)C=C(N=1)OCC1CCOCC1 LJPVKRSBXNRQOL-UHFFFAOYSA-N 0.000 description 2
• WYSFFGDVLBLEIH-UHFFFAOYSA-N C1N(CC2=C1CN(C2)C(=O)OCC1=NC=C(C=C1NC(C(C)(C)C)=O)C(F)(F)F)C(=O)OC(C)(C)C Chemical compound C1N(CC2=C1CN(C2)C(=O)OCC1=NC=C(C=C1NC(C(C)(C)C)=O)C(F)(F)F)C(=O)OC(C)(C)C WYSFFGDVLBLEIH-UHFFFAOYSA-N 0.000 description 2
• ITPYMRYMAIEALE-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(=O)NC(=C1)C1CC1 Chemical compound CC(C)(C)OC(=O)N1CC2=C(C1)CN(C2)C(=O)C1=CC(=O)NC(=C1)C1CC1 ITPYMRYMAIEALE-UHFFFAOYSA-N 0.000 description 2
• WHVAVBFXIUELHE-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CC2=C(CN(C2)C(=O)OCC2=CC=C(OC(F)(F)F)C=C2)C1 Chemical compound CC(C)(C)OC(=O)N1CC2=C(CN(C2)C(=O)OCC2=CC=C(OC(F)(F)F)C=C2)C1 WHVAVBFXIUELHE-UHFFFAOYSA-N 0.000 description 2
• NPPDVDOJVQJGMK-UHFFFAOYSA-N CC1=CN(CC2=C(Br)C=CC(=C2)C(F)(F)F)N=N1 Chemical compound CC1=CN(CC2=C(Br)C=CC(=C2)C(F)(F)F)N=N1 NPPDVDOJVQJGMK-UHFFFAOYSA-N 0.000 description 2
• QZPYMLZSXYRGGQ-FNORWQNLSA-N CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)/C=C/C(=O)OCC Chemical compound CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)/C=C/C(=O)OCC QZPYMLZSXYRGGQ-FNORWQNLSA-N 0.000 description 2
• GUFJDXLRKAYASD-UHFFFAOYSA-N CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)OCC Chemical compound CC=1N=NN(C=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)OCC GUFJDXLRKAYASD-UHFFFAOYSA-N 0.000 description 2
• WJWAKXPCRONRAW-UHFFFAOYSA-N CC=1N=NN(N=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C Chemical compound CC=1N=NN(N=1)CC1=C(C=CC(=C1)C(F)(F)F)CCC(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C WJWAKXPCRONRAW-UHFFFAOYSA-N 0.000 description 2
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• VDGCFTQOYQKIFX-UHFFFAOYSA-N Cc1nnn(Cc2cc(ccc2Br)C(F)(F)F)n1 Chemical compound Cc1nnn(Cc2cc(ccc2Br)C(F)(F)F)n1 VDGCFTQOYQKIFX-UHFFFAOYSA-N 0.000 description 2
• ARNKBTBTDCTGHJ-UHFFFAOYSA-N ClC(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C Chemical compound ClC(=O)N1CC2=C(C1)CN(C2)C(=O)OC(C)(C)C ARNKBTBTDCTGHJ-UHFFFAOYSA-N 0.000 description 2
• VZOFWPJUBLCSEE-UHFFFAOYSA-N ClC1=C(C=C(C=N1)S(=O)(=O)N=CN(C)C)F Chemical compound ClC1=C(C=C(C=N1)S(=O)(=O)N=CN(C)C)F VZOFWPJUBLCSEE-UHFFFAOYSA-N 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• HUANQPOEGJLYSQ-UHFFFAOYSA-N FC1=C(C(=O)N2CC3=C(C2)CN(C3)C(=O)OC(C)(C)C)C=CC(=C1)S(N)(=O)=O Chemical compound FC1=C(C(=O)N2CC3=C(C2)CN(C3)C(=O)OC(C)(C)C)C=CC(=C1)S(N)(=O)=O HUANQPOEGJLYSQ-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
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 2
• 101000897035 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 2
• 101001038006 Homo sapiens Lysophosphatidic acid receptor 3 Proteins 0.000 description 2
• 101001038043 Homo sapiens Lysophosphatidic acid receptor 4 Proteins 0.000 description 2
• 101001038037 Homo sapiens Lysophosphatidic acid receptor 5 Proteins 0.000 description 2
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 102100040388 Lysophosphatidic acid receptor 3 Human genes 0.000 description 2
• 102100040405 Lysophosphatidic acid receptor 4 Human genes 0.000 description 2
• 102100040404 Lysophosphatidic acid receptor 5 Human genes 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• HTLDXXPJSOZPOI-UHFFFAOYSA-N N(=[N+]=[N-])CC1=C(C=CC(=C1)C(F)(F)F)Br Chemical compound N(=[N+]=[N-])CC1=C(C=CC(=C1)C(F)(F)F)Br HTLDXXPJSOZPOI-UHFFFAOYSA-N 0.000 description 2
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
• 208000012902 Nervous system disease Diseases 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• 206010064930 age-related macular degeneration Diseases 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 150000001805 chlorine compounds Chemical class 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 239000012228 culture supernatant Substances 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• USRMOSOONWAMRT-FNORWQNLSA-N ethyl (E)-3-[2-[(5-methyltetrazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]prop-2-enoate Chemical compound CCOC(=O)\C=C\c1ccc(C(F)(F)F)cc1Cn1nnc(C)n1 USRMOSOONWAMRT-FNORWQNLSA-N 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 210000004072 lung Anatomy 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
• 230000000873 masking effect Effects 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
• NSQWRUQCYYRTMX-UHFFFAOYSA-N methyl 3-(bromomethyl)-5-chloropyridine-2-carboxylate Chemical compound COC(=O)C1=NC=C(Cl)C=C1CBr NSQWRUQCYYRTMX-UHFFFAOYSA-N 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000013049 sediment Substances 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000012224 working solution Substances 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
• VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 1
• RVGDPMLTBMXTFM-UHFFFAOYSA-N 3-[3-[(5-methyltetrazol-2-yl)methyl]-5-(trifluoromethyl)pyridin-2-yl]propanoic acid Chemical compound CC=1N=NN(N=1)CC=1C(=NC=C(C=1)C(F)(F)F)CCC(=O)O RVGDPMLTBMXTFM-UHFFFAOYSA-N 0.000 description 1
• SYJHGBJUJGQBFT-UHFFFAOYSA-N 3-[4-chloro-2-[(5-methyltetrazol-2-yl)methyl]phenyl]propanoic acid Chemical compound ClC1=CC(=C(C=C1)CCC(=O)O)CN1N=C(N=N1)C SYJHGBJUJGQBFT-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• VOISTTGQLIPIHV-UHFFFAOYSA-N 3-chloro-4-sulfamoylbenzoic acid Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C=C1Cl VOISTTGQLIPIHV-UHFFFAOYSA-N 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• UTICIZWBNOHDIF-UHFFFAOYSA-N 4-[4-[3-[2-[(5-methyltetrazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propanoyl]piperazine-1-carbonyl]benzenesulfonamide Chemical compound Cc1nnn(Cc2cc(ccc2CCC(=O)N2CCN(CC2)C(=O)c2ccc(cc2)S(N)(=O)=O)C(F)(F)F)n1 UTICIZWBNOHDIF-UHFFFAOYSA-N 0.000 description 1
• GVSNQMFKEPBIOY-UHFFFAOYSA-N 4-methyl-2h-triazole Chemical compound CC=1C=NNN=1 GVSNQMFKEPBIOY-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
• 206010001881 Alveolar proteinosis Diseases 0.000 description 1
• 206010001889 Alveolitis Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010003658 Atrial Fibrillation Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• CGVRHGJKNQYLHX-UHFFFAOYSA-N C(#N)C1=CC(=C(C=C1)CCC(=O)O)CN1N=C(N=N1)C Chemical compound C(#N)C1=CC(=C(C=C1)CCC(=O)O)CN1N=C(N=N1)C CGVRHGJKNQYLHX-UHFFFAOYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• ABBHJBNLSHMFHP-UHFFFAOYSA-N ClC1=CC=C(C(=N1)CO)NC(C(C)(C)C)=O Chemical compound ClC1=CC=C(C(=N1)CO)NC(C(C)(C)C)=O ABBHJBNLSHMFHP-UHFFFAOYSA-N 0.000 description 1
• 208000027932 Collagen disease Diseases 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 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
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 102000036530 EDG receptors Human genes 0.000 description 1
• 108091007263 EDG receptors Proteins 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018341 Gliosis Diseases 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
• 206010018691 Granuloma Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101001038001 Homo sapiens Lysophosphatidic acid receptor 2 Proteins 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 241000976924 Inca Species 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000029523 Interstitial Lung disease Diseases 0.000 description 1
• 206010023421 Kidney fibrosis Diseases 0.000 description 1
• 239000005909 Kieselgur Substances 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 206010049459 Lymphangioleiomyomatosis Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102100040387 Lysophosphatidic acid receptor 2 Human genes 0.000 description 1
• 239000007993 MOPS buffer Substances 0.000 description 1
• 208000001344 Macular Edema Diseases 0.000 description 1
• 206010025415 Macular oedema Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000024556 Mendelian disease Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• 101000966781 Mus musculus Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
• FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
• DVSVKXDIHRRYMJ-UHFFFAOYSA-N N-[2-(hydroxymethyl)-6-methylpyridin-3-yl]-2,2-dimethylpropanamide Chemical compound OCC1=NC(=CC=C1NC(C(C)(C)C)=O)C DVSVKXDIHRRYMJ-UHFFFAOYSA-N 0.000 description 1
• XNZGARRXWLZVJO-UHFFFAOYSA-N N-[2-(hydroxymethyl)pyridin-3-yl]-2,2-dimethylpropanamide Chemical compound OCC1=NC=CC=C1NC(C(C)(C)C)=O XNZGARRXWLZVJO-UHFFFAOYSA-N 0.000 description 1
• LYLXQFYIOJXSJU-UHFFFAOYSA-N N-[5,6-dichloro-2-(hydroxymethyl)pyridin-3-yl]-2,2-dimethylpropanamide Chemical compound ClC=1C=C(C(=NC=1Cl)CO)NC(C(C)(C)C)=O LYLXQFYIOJXSJU-UHFFFAOYSA-N 0.000 description 1
• VNGXSWPXLYKOPU-UHFFFAOYSA-N N-[5-chloro-2-(hydroxymethyl)pyridin-3-yl]-2,2-dimethylpropanamide Chemical compound ClC=1C=C(C(=NC=1)CO)NC(C(C)(C)C)=O VNGXSWPXLYKOPU-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• QHBTXNFNGTXRJL-LOYHVIPDSA-N NCCOCCOCCOCCOCCC(=O)NCCOP(=O)(O)OC[C@@H](COC[C@H](COP(=O)(OCCNC(CCOCCOCCOCCOCCN)=O)O)O)O Chemical compound NCCOCCOCCOCCOCCC(=O)NCCOP(=O)(O)OC[C@@H](COC[C@H](COP(=O)(OCCNC(CCOCCOCCOCCOCCN)=O)O)O)O QHBTXNFNGTXRJL-LOYHVIPDSA-N 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 208000036110 Neuroinflammatory disease Diseases 0.000 description 1
• 241000080590 Niso Species 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• MCWGHWKIQFXAPZ-UHFFFAOYSA-N OCC1=NC2=CC=CC=C2C=C1NC(C(C)(C)C)=O Chemical compound OCC1=NC2=CC=CC=C2C=C1NC(C(C)(C)C)=O MCWGHWKIQFXAPZ-UHFFFAOYSA-N 0.000 description 1
• 208000031964 Other metabolic disease Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 108010080192 Purinergic Receptors Proteins 0.000 description 1
• 102000000033 Purinergic Receptors Human genes 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 101000995838 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Nucleotide pyrophosphatase Proteins 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 201000010001 Silicosis Diseases 0.000 description 1
• 206010050207 Skin fibrosis Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 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
• 229930006000 Sucrose Natural products 0.000 description 1
• 239000012505 Superdex™ Substances 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 206010058990 Venous occlusion Diseases 0.000 description 1
• 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
• RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
• 150000001266 acyl halides Chemical class 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
• 210000001742 aqueous humor Anatomy 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 208000037849 arterial hypertension Diseases 0.000 description 1
• 208000021328 arterial occlusion Diseases 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 239000010425 asbestos Substances 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 208000037875 astrocytosis Diseases 0.000 description 1
• 230000007341 astrogliosis Effects 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000002567 autonomic effect Effects 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 239000007998 bicine buffer Substances 0.000 description 1
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
• 229940045348 brown mixture Drugs 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000011575 calcium Chemical class 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
• JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
• 230000037198 cardiovascular physiology Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000034196 cell chemotaxis Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 210000004240 ciliary body Anatomy 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 239000013065 commercial product Substances 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 230000000536 complexating effect Effects 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 208000011325 dry age related macular degeneration Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 230000009762 endothelial cell differentiation Effects 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
• 238000000855 fermentation Methods 0.000 description 1
• 230000004151 fermentation Effects 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
• 230000000642 iatrogenic effect Effects 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 230000004410 intraocular pressure Effects 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 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
• 125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 201000010230 macular retinal edema Diseases 0.000 description 1
• 239000011777 magnesium Chemical class 0.000 description 1
• 229910052749 magnesium Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• DWRSWUPHDNTLKJ-UHFFFAOYSA-N methyl 3-amino-5-bromopyridine-2-carboxylate Chemical compound COC(=O)C1=NC=C(Br)C=C1N DWRSWUPHDNTLKJ-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000001333 moisturizer Effects 0.000 description 1
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 230000003959 neuroinflammation Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000004963 pathophysiological condition Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 206010034674 peritonitis Diseases 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 230000010118 platelet activation Effects 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229960003975 potassium Drugs 0.000 description 1
• 239000011591 potassium Chemical class 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 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 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000033458 reproduction Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000004644 retinal vein occlusion Diseases 0.000 description 1
• 229910052895 riebeckite Inorganic materials 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 230000016160 smooth muscle contraction Effects 0.000 description 1
• MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ZDKJSVXJJJRAQS-UHFFFAOYSA-N tert-butyl 3,4,5,6,7,8-hexahydro-1h-2,6-naphthyridine-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1CCNC2 ZDKJSVXJJJRAQS-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 208000009999 tuberous sclerosis Diseases 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• 230000006459 vascular development Effects 0.000 description 1
• 231100000216 vascular lesion Toxicity 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
• UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
• 229940007718 zinc hydroxide Drugs 0.000 description 1
• 229910021511 zinc hydroxide Inorganic materials 0.000 description 1