CN114206893A - (杂)芳基-甲基-硫代-β-D-吡喃半乳糖苷衍生物 - Google Patents
(杂)芳基-甲基-硫代-β-D-吡喃半乳糖苷衍生物 Download PDFInfo
- Publication number
- CN114206893A CN114206893A CN202080056681.7A CN202080056681A CN114206893A CN 114206893 A CN114206893 A CN 114206893A CN 202080056681 A CN202080056681 A CN 202080056681A CN 114206893 A CN114206893 A CN 114206893A
- Authority
- CN
- China
- Prior art keywords
- pyran
- methyl
- triazol
- thio
- tetrahydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000005842 heteroatom Chemical group 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 342
- -1 tetrahydro-2H-pyran-4, 4-diyl Chemical group 0.000 claims description 289
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 43
- 238000011282 treatment Methods 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 208000020832 chronic kidney disease Diseases 0.000 claims description 26
- 206010016654 Fibrosis Diseases 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 25
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 230000004761 fibrosis Effects 0.000 claims description 19
- 208000037765 diseases and disorders Diseases 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- 230000002265 prevention Effects 0.000 claims description 17
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 14
- 208000022873 Ocular disease Diseases 0.000 claims description 14
- 208000016222 Pancreatic disease Diseases 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 208000019423 liver disease Diseases 0.000 claims description 13
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 210000000056 organ Anatomy 0.000 claims description 12
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 8
- 208000033626 Renal failure acute Diseases 0.000 claims description 8
- 206010052779 Transplant rejections Diseases 0.000 claims description 8
- 230000002159 abnormal effect Effects 0.000 claims description 8
- 201000011040 acute kidney failure Diseases 0.000 claims description 8
- 230000033115 angiogenesis Effects 0.000 claims description 8
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 8
- 230000002062 proliferating effect Effects 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 208000019693 Lung disease Diseases 0.000 claims description 7
- 210000004556 brain Anatomy 0.000 claims description 7
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 208000024691 pancreas disease Diseases 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- MYKUIDQPHNNALF-XATIALBVSA-N OC([C@@H](C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C MYKUIDQPHNNALF-XATIALBVSA-N 0.000 claims description 4
- CVZRNBYTUIGJTN-WTGKAQRQSA-N OC[C@@H](C1=CC=CC=C1)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound OC[C@@H](C1=CC=CC=C1)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO CVZRNBYTUIGJTN-WTGKAQRQSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims description 4
- VCUAXODKLDNVTA-CCUOSZMHSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(1R)-2-hydroxy-2-methyl-1-[2-(2-methylpropyl)phenyl]propyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC([C@@H](C1=C(C=CC=C1)CC(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C VCUAXODKLDNVTA-CCUOSZMHSA-N 0.000 claims description 3
- URNHDQNEVNGJOB-CCUOSZMHSA-N (2S,3R,4S,5R,6R)-2-[(R)-(1-hydroxycyclohexyl)-(2-methylphenyl)methyl]sulfanyl-6-(hydroxymethyl)-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC1(CCCCC1)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C URNHDQNEVNGJOB-CCUOSZMHSA-N 0.000 claims description 3
- KYJFFRQAMGUMCP-WIBPYNGWSA-N C1(=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=CC=CC=C1 Chemical compound C1(=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=CC=CC=C1 KYJFFRQAMGUMCP-WIBPYNGWSA-N 0.000 claims description 3
- GHGRZEIXQFGNPY-WWJMMCNDSA-N C1(CC1)C1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound C1(CC1)C1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO GHGRZEIXQFGNPY-WWJMMCNDSA-N 0.000 claims description 3
- WAOHGZBWWLZECQ-DYRNCQFLSA-N CC=1SC(=C(N=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C Chemical compound CC=1SC(=C(N=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C WAOHGZBWWLZECQ-DYRNCQFLSA-N 0.000 claims description 3
- ZVOPHSHOWOEIHG-XATIALBVSA-N FC=1C(=C(C=CC=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C Chemical compound FC=1C(=C(C=CC=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C ZVOPHSHOWOEIHG-XATIALBVSA-N 0.000 claims description 3
- PAVDSVBSVHEIBU-HCRCWBKNSA-N OC([C@@H](C1=C(C=CC=C1)CCO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)CCO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C PAVDSVBSVHEIBU-HCRCWBKNSA-N 0.000 claims description 3
- JSMROVHTKDYUEP-CCUOSZMHSA-N OC([C@@H](C1=CC=CC2=CC=CC=C12)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=CC=CC2=CC=CC=C12)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C JSMROVHTKDYUEP-CCUOSZMHSA-N 0.000 claims description 3
- FKLPGGSLYWUHAY-WWJMMCNDSA-N OC1(CCCC1)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C Chemical compound OC1(CCCC1)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C FKLPGGSLYWUHAY-WWJMMCNDSA-N 0.000 claims description 3
- DOEAVJNELYUBKI-PIYILYQRSA-N OC1(CCCCC1)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=NOC=C1C Chemical compound OC1(CCCCC1)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=NOC=C1C DOEAVJNELYUBKI-PIYILYQRSA-N 0.000 claims description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- IHFJDOKDEMDMPK-QKEDNXFGSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(1R)-2-hydroxy-2-methyl-1-(4-methylthiophen-3-yl)propyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC([C@@H](C1=CSC=C1C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C IHFJDOKDEMDMPK-QKEDNXFGSA-N 0.000 claims description 2
- ZVTTYXUKQGMTDA-TUFAUPKWSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(1R,2S)-2-hydroxy-1-[2-(trifluoromethyl)phenyl]butyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound O[C@H]([C@@H](C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)CC ZVTTYXUKQGMTDA-TUFAUPKWSA-N 0.000 claims description 2
- IXFHANIKWLCTHH-DYRNCQFLSA-N (2S,3R,4S,5R,6R)-2-[(1R)-1-(3,5-dimethyl-1,2-oxazol-4-yl)-2-hydroxy-2-methylpropyl]sulfanyl-6-(hydroxymethyl)-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound CC1=NOC(=C1[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C IXFHANIKWLCTHH-DYRNCQFLSA-N 0.000 claims description 2
- JJZPDIJDTAPLKD-WWJMMCNDSA-N (2S,3R,4S,5R,6R)-2-[(R)-(1-hydroxy-3,3-dimethylcyclobutyl)-(2-methylphenyl)methyl]sulfanyl-6-(hydroxymethyl)-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC1(CC(C1)(C)C)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C JJZPDIJDTAPLKD-WWJMMCNDSA-N 0.000 claims description 2
- XYAZFHUFNFFRDL-WTGKAQRQSA-N BrC1=C(C=CC=C1)[C@H](CO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound BrC1=C(C=CC=C1)[C@H](CO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO XYAZFHUFNFFRDL-WTGKAQRQSA-N 0.000 claims description 2
- YEQKHJOSZVGPDE-ARQYYYJSSA-N C(C)C([C@@H](C=1C(=NOC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(CC)O Chemical compound C(C)C([C@@H](C=1C(=NOC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(CC)O YEQKHJOSZVGPDE-ARQYYYJSSA-N 0.000 claims description 2
- DHEABPUFHXGQJB-HCRCWBKNSA-N C(C)C1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound C(C)C1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO DHEABPUFHXGQJB-HCRCWBKNSA-N 0.000 claims description 2
- FAVVWDQUIBYZSF-DYRNCQFLSA-N CC=1OC(=C(N=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C Chemical compound CC=1OC(=C(N=1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C FAVVWDQUIBYZSF-DYRNCQFLSA-N 0.000 claims description 2
- NXIYXHXCPKFIBH-ARQYYYJSSA-N ClC1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound ClC1=C(C=CC=C1)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO NXIYXHXCPKFIBH-ARQYYYJSSA-N 0.000 claims description 2
- RWNIGAFTMQYPPS-IKADZPNNSA-N ClC1=C(C=CC=C1Cl)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound ClC1=C(C=CC=C1Cl)[C@H](C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO RWNIGAFTMQYPPS-IKADZPNNSA-N 0.000 claims description 2
- 239000004593 Epoxy Substances 0.000 claims description 2
- ZDUNTUNDBSQXQO-MSXPJASTSA-N OC([C@@H](C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC2=CC=CC=C2C=C1)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC2=CC=CC=C2C=C1)O)CO)(C)C ZDUNTUNDBSQXQO-MSXPJASTSA-N 0.000 claims description 2
- RTDBVNIEYVGLJM-WWJMMCNDSA-N OC([C@@H](C1=C(C=CC=C1)CCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)CCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C RTDBVNIEYVGLJM-WWJMMCNDSA-N 0.000 claims description 2
- RAXIHXUNDYGLLH-ZPYPPCPKSA-N OC([C@@H](C1=C(C=CC=C1)CCCCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)CCCCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C RAXIHXUNDYGLLH-ZPYPPCPKSA-N 0.000 claims description 2
- OEMQPUOZMXHHMQ-ARQYYYJSSA-N OC([C@@H](C=1C(=NC=CC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C=1C(=NC=CC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C OEMQPUOZMXHHMQ-ARQYYYJSSA-N 0.000 claims description 2
- OVADRJQRWINEEV-ARQYYYJSSA-N OC([C@@H](C=1C=NC=CC=1C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C=1C=NC=CC=1C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C OVADRJQRWINEEV-ARQYYYJSSA-N 0.000 claims description 2
- YROIJMNDEZGDSH-WYRSWYAISA-N OC1(CC(C1)C)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C Chemical compound OC1(CC(C1)C)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C YROIJMNDEZGDSH-WYRSWYAISA-N 0.000 claims description 2
- HPPLNBOOFRJQGH-MNQQAKMZSA-N OC1(CCC1)[C@H](CC1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C Chemical compound OC1(CCC1)[C@H](CC1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C HPPLNBOOFRJQGH-MNQQAKMZSA-N 0.000 claims description 2
- GCHUPPIDKVSURV-GUQVHUPFSA-N OC[C@@H](C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound OC[C@@H](C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO GCHUPPIDKVSURV-GUQVHUPFSA-N 0.000 claims description 2
- ZVTTYXUKQGMTDA-CVTZZESPSA-N O[C@@H]([C@@H](C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)CC Chemical compound O[C@@H]([C@@H](C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)CC ZVTTYXUKQGMTDA-CVTZZESPSA-N 0.000 claims description 2
- UOWHCAKKYIRMSX-UHFFFAOYSA-N [N].C1CNC1 Chemical compound [N].C1CNC1 UOWHCAKKYIRMSX-UHFFFAOYSA-N 0.000 claims description 2
- IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 claims description 2
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims 1
- XSDHLCGOYZWTFR-UHFFFAOYSA-N OCC1OCC(C(C1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O Chemical compound OCC1OCC(C(C1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O XSDHLCGOYZWTFR-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 108010001517 Galectin 3 Proteins 0.000 abstract description 46
- 239000003112 inhibitor Substances 0.000 abstract description 10
- 102000000802 Galectin 3 Human genes 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 170
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 153
- 239000000543 intermediate Substances 0.000 description 101
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 98
- 239000011541 reaction mixture Substances 0.000 description 74
- 239000007787 solid Substances 0.000 description 71
- 239000000243 solution Substances 0.000 description 65
- 238000002953 preparative HPLC Methods 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 239000010410 layer Substances 0.000 description 57
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 50
- 239000012044 organic layer Substances 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 43
- 102100039558 Galectin-3 Human genes 0.000 description 37
- 239000003921 oil Substances 0.000 description 36
- 235000019198 oils Nutrition 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
- 239000012267 brine Substances 0.000 description 29
- 230000005764 inhibitory process Effects 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 25
- 239000003480 eluent Substances 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- 239000007864 aqueous solution Substances 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 22
- 239000013058 crude material Substances 0.000 description 22
- 238000001914 filtration Methods 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 238000001035 drying Methods 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
- 125000006239 protecting group Chemical group 0.000 description 19
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 18
- 206010012601 diabetes mellitus Diseases 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 238000001514 detection method Methods 0.000 description 15
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- 208000019425 cirrhosis of liver Diseases 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
- 102000007563 Galectins Human genes 0.000 description 11
- 108010046569 Galectins Proteins 0.000 description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 11
- 238000011321 prophylaxis Methods 0.000 description 11
- 125000004076 pyridyl group Chemical group 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 10
- 206010020772 Hypertension Diseases 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 230000001684 chronic effect Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 206010019280 Heart failures Diseases 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 201000009594 Systemic Scleroderma Diseases 0.000 description 9
- 206010042953 Systemic sclerosis Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 208000005069 pulmonary fibrosis Diseases 0.000 description 9
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 125000000842 isoxazolyl group Chemical group 0.000 description 8
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 description 7
- 206010018364 Glomerulonephritis Diseases 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- TXVVVEUSVBLDED-UHFFFAOYSA-N 1-(bromomethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CBr TXVVVEUSVBLDED-UHFFFAOYSA-N 0.000 description 6
- KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical compound C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 208000017169 kidney disease Diseases 0.000 description 6
- 125000002971 oxazolyl group Chemical group 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 6
- 125000001425 triazolyl group Chemical group 0.000 description 6
- 208000035150 Hypercholesterolemia Diseases 0.000 description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- 230000007882 cirrhosis Effects 0.000 description 5
- 208000033679 diabetic kidney disease Diseases 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000012286 potassium permanganate Substances 0.000 description 5
- 230000037390 scarring Effects 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- YYAAUTBQSOQTGX-UHFFFAOYSA-N FC(C1=C(CSC2=NC3=CC=CC=C3C=C2)C=CC=C1)(F)F Chemical compound FC(C1=C(CSC2=NC3=CC=CC=C3C=C2)C=CC=C1)(F)F YYAAUTBQSOQTGX-UHFFFAOYSA-N 0.000 description 4
- 206010072877 Intestinal fibrosis Diseases 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- 229930182475 S-glycoside Natural products 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 210000003128 head Anatomy 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000001117 keloid Anatomy 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 150000003569 thioglycosides Chemical class 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- BRZLGIOBJYQVAV-UHFFFAOYSA-N CC1=NC(=C(N=C1C)C)CSC1OCCCC1 Chemical compound CC1=NC(=C(N=C1C)C)CSC1OCCCC1 BRZLGIOBJYQVAV-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 3
- CYOUFQZNRBTWNQ-UHFFFAOYSA-N FC1(CC(C1)(O)C(C1=C(C=CC=C1)C(F)(F)F)S)F Chemical compound FC1(CC(C1)(O)C(C1=C(C=CC=C1)C(F)(F)F)S)F CYOUFQZNRBTWNQ-UHFFFAOYSA-N 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 208000002260 Keloid Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- OEJUAWSHVYACLO-UHFFFAOYSA-N O=C1CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C Chemical compound O=C1CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C OEJUAWSHVYACLO-UHFFFAOYSA-N 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000009787 cardiac fibrosis Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- HYBCDSDGTPUCMQ-LLVKDONJSA-N ethyl (2R)-2-(dimethylcarbamothioylsulfanyl)-2-phenylacetate Chemical compound CN(C(=S)S[C@@H](C(=O)OCC)C1=CC=CC=C1)C HYBCDSDGTPUCMQ-LLVKDONJSA-N 0.000 description 3
- 230000003176 fibrotic effect Effects 0.000 description 3
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 208000019622 heart disease Diseases 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 230000001969 hypertrophic effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 201000006334 interstitial nephritis Diseases 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- NTMHWRHEGDRTPD-UHFFFAOYSA-N n-(4-azidosulfonylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S(=O)(=O)N=[N+]=[N-])C=C1 NTMHWRHEGDRTPD-UHFFFAOYSA-N 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 208000005987 polymyositis Diseases 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000005493 quinolyl group Chemical group 0.000 description 3
- 201000002793 renal fibrosis Diseases 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- NFLSYCABOYZAMW-UHFFFAOYSA-N s-(oxan-2-yl) ethanethioate Chemical compound CC(=O)SC1CCCCO1 NFLSYCABOYZAMW-UHFFFAOYSA-N 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- OOHIPDLPISIYKN-JOCHJYFZSA-N (1,1,1-trichloro-2-methylpropan-2-yl) 4-hydroxy-4-[(R)-quinolin-2-ylsulfanyl-[2-(trifluoromethyl)phenyl]methyl]piperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C)[C@@H](C1=C(C=CC=C1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1 OOHIPDLPISIYKN-JOCHJYFZSA-N 0.000 description 2
- PWSRRKRPSCYOKC-CYBMUJFWSA-N (1,1,1-trichloro-2-methylpropan-2-yl) 4-hydroxy-4-[(R)-sulfanyl-[2-(trifluoromethyl)phenyl]methyl]piperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C)[C@@H](C1=C(C=CC=C1)C(F)(F)F)S PWSRRKRPSCYOKC-CYBMUJFWSA-N 0.000 description 2
- QZRDHEFNEPDVOO-CHUNWDLHSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-5-methoxy-6-methylsulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxan-3-ol Chemical compound OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)OC)SC QZRDHEFNEPDVOO-CHUNWDLHSA-N 0.000 description 2
- XUNFMWZPSLEDHJ-NZNQWUEYSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-methylsulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)SC XUNFMWZPSLEDHJ-NZNQWUEYSA-N 0.000 description 2
- AOLXADMIUZJXSN-CLFJVBSWSA-N (2S,3R,4S,5R,6R)-4-azido-2-[(4,4-difluoro-1-hydroxycyclohexyl)-(3-methylpyridin-2-yl)methyl]sulfanyl-6-(hydroxymethyl)oxane-3,5-diol Chemical compound N(=[N+]=[N-])[C@@H]1[C@H]([C@@H](O[C@@H]([C@@H]1O)CO)SC(C1=NC=CC=C1C)C1(CCC(CC1)(F)F)O)O AOLXADMIUZJXSN-CLFJVBSWSA-N 0.000 description 2
- NKWPBDOGGJDHOD-UHFFFAOYSA-N 2,2,2-trichloroethyl piperidine-1-carboxylate Chemical compound ClC(Cl)(Cl)COC(=O)N1CCCCC1 NKWPBDOGGJDHOD-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- PPOWHBFTXPMELN-UHFFFAOYSA-N 2-methyl-1-sulfanyl-1-[2-(trifluoromethyl)phenyl]propan-2-ol Chemical compound SC(C(C)(O)C)C1=C(C=CC=C1)C(F)(F)F PPOWHBFTXPMELN-UHFFFAOYSA-N 0.000 description 2
- DOVLQPYYSCACJX-UHFFFAOYSA-N 3,3-difluorocyclobutan-1-one Chemical compound FC1(F)CC(=O)C1 DOVLQPYYSCACJX-UHFFFAOYSA-N 0.000 description 2
- YPBVPJBVLWXKLN-UHFFFAOYSA-N 3-(bromomethyl)-2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=NC=CC=C1CBr YPBVPJBVLWXKLN-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- BZXWRVPVZZZAKB-UHFFFAOYSA-N 5-ethynyl-1,2,3-trifluorobenzene Chemical group FC1=CC(C#C)=CC(F)=C1F BZXWRVPVZZZAKB-UHFFFAOYSA-N 0.000 description 2
- 206010000050 Abdominal adhesions Diseases 0.000 description 2
- 208000024985 Alport syndrome Diseases 0.000 description 2
- 206010001889 Alveolitis Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
- YDZIPYONNZIJHJ-UHFFFAOYSA-N BrC1=C(C=CC=C1)C(C(=O)OCC)=[N+]=[N-] Chemical compound BrC1=C(C=CC=C1)C(C(=O)OCC)=[N+]=[N-] YDZIPYONNZIJHJ-UHFFFAOYSA-N 0.000 description 2
- YPSRDSZDAGEVQP-YENDSXDJSA-N BrC1=C(C=CC=C1)C(CO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=CC=C1)F)O)CO Chemical compound BrC1=C(C=CC=C1)C(CO)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=CC=C1)F)O)CO YPSRDSZDAGEVQP-YENDSXDJSA-N 0.000 description 2
- VKAQSANHDTWELN-QGZVFWFLSA-N CC([C@@H](C=1C(=NC=CC=1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)(C)O Chemical compound CC([C@@H](C=1C(=NC=CC=1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)(C)O VKAQSANHDTWELN-QGZVFWFLSA-N 0.000 description 2
- 208000025721 COVID-19 Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 101000608757 Homo sapiens Galectin-3 Proteins 0.000 description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010023421 Kidney fibrosis Diseases 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 2
- MYKUIDQPHNNALF-PCVYKCHKSA-N OC(C(C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC(C(C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C MYKUIDQPHNNALF-PCVYKCHKSA-N 0.000 description 2
- DCVSXLYUTSYAOQ-WWJMMCNDSA-N OC([C@@H](C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C DCVSXLYUTSYAOQ-WWJMMCNDSA-N 0.000 description 2
- GCHUPPIDKVSURV-CDRLGBIPSA-N OCC(C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound OCC(C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO GCHUPPIDKVSURV-CDRLGBIPSA-N 0.000 description 2
- MWQPPBAGYPLFPF-MFFRZBKQSA-N OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)SC(C1=C(C=CC=C1)C(F)(F)F)C1(CCNCC1)O Chemical compound OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)SC(C1=C(C=CC=C1)C(F)(F)F)C1(CCNCC1)O MWQPPBAGYPLFPF-MFFRZBKQSA-N 0.000 description 2
- IMHSXZCRTIGSBE-YFWNVBJASA-N OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)SC(COC)C1=CC=CC=C1 Chemical compound OC[C@H]1O[C@H]([C@@H]([C@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)SC(COC)C1=CC=CC=C1 IMHSXZCRTIGSBE-YFWNVBJASA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- DFFQUVDTXIVORG-MRVPVSSYSA-N S[C@@H](C(C)(O)C)C=1C(=NC=CC=1)C(F)(F)F Chemical compound S[C@@H](C(C)(O)C)C=1C(=NC=CC=1)C(F)(F)F DFFQUVDTXIVORG-MRVPVSSYSA-N 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 206010050207 Skin fibrosis Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 239000005870 Ziram Substances 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical group NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 201000000159 corneal neovascularization Diseases 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000003997 cyclic ketones Chemical class 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 208000003215 hereditary nephritis Diseases 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- DBBRJAWSDTYYBM-UHFFFAOYSA-N isocyanatocyclopropane Chemical compound O=C=NC1CC1 DBBRJAWSDTYYBM-UHFFFAOYSA-N 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 229910052760 oxygen Chemical group 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Substances OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 208000030613 peripheral artery disease Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 208000030761 polycystic kidney disease Diseases 0.000 description 2
- 208000007232 portal hypertension Diseases 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 238000001238 wet grinding Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- DUBNHZYBDBBJHD-UHFFFAOYSA-L ziram Chemical compound [Zn+2].CN(C)C([S-])=S.CN(C)C([S-])=S DUBNHZYBDBBJHD-UHFFFAOYSA-L 0.000 description 2
- GMELMFSDPDSXOZ-UHFFFAOYSA-N (1,1,1-trichloro-2-methylpropan-2-yl) carbonochloridate Chemical compound ClC(Cl)(Cl)C(C)(C)OC(Cl)=O GMELMFSDPDSXOZ-UHFFFAOYSA-N 0.000 description 1
- DIXJXZFTHSBZMM-UHFFFAOYSA-N (1,1,1-trichloro-2-methylpropan-2-yl) piperidine-1-carboxylate Chemical compound ClC(C(C)(C)OC(=O)N1CCCCC1)(Cl)Cl DIXJXZFTHSBZMM-UHFFFAOYSA-N 0.000 description 1
- SQQXWIORNCMVFC-QAZYLWTASA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(4-hydroxy-1-methylpiperidin-4-yl)-(2-methylphenyl)methyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC1(CCN(CC1)C)C(S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C SQQXWIORNCMVFC-QAZYLWTASA-N 0.000 description 1
- SQQXWIORNCMVFC-CCUOSZMHSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(R)-(4-hydroxy-1-methylpiperidin-4-yl)-(2-methylphenyl)methyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC1(CCN(CC1)C)[C@H](S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)C1=C(C=CC=C1)C SQQXWIORNCMVFC-CCUOSZMHSA-N 0.000 description 1
- RQBCKNGCMZQWDJ-QMMMGPOBSA-N (2r)-2-phenyl-2-sulfanylethanol Chemical compound OC[C@H](S)C1=CC=CC=C1 RQBCKNGCMZQWDJ-QMMMGPOBSA-N 0.000 description 1
- KEJGAYKWRDILTF-JDDHQFAOSA-N (3ar,5s,6s,6ar)-5-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol Chemical compound O1C(C)(C)OC[C@@H]1[C@@H]1[C@H](O)[C@H]2OC(C)(C)O[C@H]2O1 KEJGAYKWRDILTF-JDDHQFAOSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- 125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
- WGVYCXYGPNNUQA-UHFFFAOYSA-N 1-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CBr WGVYCXYGPNNUQA-UHFFFAOYSA-N 0.000 description 1
- IQKOWJUUQAATOR-XNJHUCFUSA-N 1-[(4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-6-methylsulfanyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl]-4-(3,4,5-trifluorophenyl)triazole Chemical compound CO[C@@H]1[C@H]([C@H]2OC(OC[C@H]2O[C@H]1SC)(C)C)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F IQKOWJUUQAATOR-XNJHUCFUSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- JZUMPNUYDJBTNO-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 JZUMPNUYDJBTNO-UHFFFAOYSA-N 0.000 description 1
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
- YBNMJUAXERDNRJ-UHFFFAOYSA-N 2-(2-bromophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1Br YBNMJUAXERDNRJ-UHFFFAOYSA-N 0.000 description 1
- HOPVUIZLMIEGMJ-UHFFFAOYSA-N 2-(bromomethyl)-3,5,6-trimethylpyrazine Chemical compound CC1=NC(C)=C(CBr)N=C1C HOPVUIZLMIEGMJ-UHFFFAOYSA-N 0.000 description 1
- XGEGMUFLOUPCSL-UHFFFAOYSA-N 2-(bromomethyl)-3-methylpyridine Chemical compound CC1=CC=CN=C1CBr XGEGMUFLOUPCSL-UHFFFAOYSA-N 0.000 description 1
- MAYLZBMEJMCYHL-UHFFFAOYSA-N 2-[(2-methylphenyl)methylsulfanyl]quinoline Chemical compound CC1=CC=CC=C1CSC1=CC=C(C=CC=C2)C2=N1 MAYLZBMEJMCYHL-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- KMJOANZKMSCULR-UHFFFAOYSA-N 2-methoxy-1-phenylethanethiol Chemical compound COCC(S)C1=CC=CC=C1 KMJOANZKMSCULR-UHFFFAOYSA-N 0.000 description 1
- GAYWRLYTWOAYSI-UHFFFAOYSA-N 2-methyl-1-(2-methylphenyl)-1-sulfanylpropan-2-ol Chemical compound SC(C(C)(O)C)C1=C(C=CC=C1)C GAYWRLYTWOAYSI-UHFFFAOYSA-N 0.000 description 1
- GHJGKUKNRIYXKL-UHFFFAOYSA-N 2-methyl-1-phenyl-1-quinolin-2-ylsulfanylpropan-2-ol Chemical compound C=1C=C2C=CC=CC2=NC=1SC(C(C)(O)C)C1=CC=CC=C1 GHJGKUKNRIYXKL-UHFFFAOYSA-N 0.000 description 1
- GXMIUQCGLBGCAY-UHFFFAOYSA-N 2-methyl-1-phenyl-1-sulfanylpropan-2-ol Chemical compound CC(C)(O)C(S)C1=CC=CC=C1 GXMIUQCGLBGCAY-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- HQFLTUZKIRYQSP-UHFFFAOYSA-N 3-ethyl-2h-1,3-benzothiazole-6-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2N(CC)CSC2=C1 HQFLTUZKIRYQSP-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- SVSUYEJKNSMKKW-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-prop-1-en-2-yl-1,3,2-dioxaborolane Chemical compound CC(=C)B1OC(C)(C)C(C)(C)O1 SVSUYEJKNSMKKW-UHFFFAOYSA-N 0.000 description 1
- FLCLKJQSYHBTIP-UHFFFAOYSA-N 4-[quinolin-2-ylsulfanyl-[2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol Chemical compound OC1(CCNCC1)C(C1=C(C(F)(F)F)C=CC=C1)SC1=NC2=CC=CC=C2C=C1 FLCLKJQSYHBTIP-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- XFPAOXIWRDDQGG-UHFFFAOYSA-N 4-ethynyl-1,2-difluorobenzene Chemical compound FC1=CC=C(C#C)C=C1F XFPAOXIWRDDQGG-UHFFFAOYSA-N 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 206010002889 Aortic aneurysms and dissections Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 206010054793 Arterial fibrosis Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 206010005042 Bladder fibrosis Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000007257 Budd-Chiari syndrome Diseases 0.000 description 1
- DHEABPUFHXGQJB-MFFRZBKQSA-N C(C)C1=C(C=CC=C1)C(C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound C(C)C1=C(C=CC=C1)C(C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO DHEABPUFHXGQJB-MFFRZBKQSA-N 0.000 description 1
- GHGRZEIXQFGNPY-BJHKXESGSA-N C1(CC1)C1=C(C=CC=C1)C(C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO Chemical compound C1(CC1)C1=C(C=CC=C1)C(C(C)(C)O)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO GHGRZEIXQFGNPY-BJHKXESGSA-N 0.000 description 1
- GGRHIVHIURADPX-UHFFFAOYSA-N CC(C(C1=C(C=CC=C1)C)SC1=NC2=CC=CC=C2C=C1)(C)O Chemical compound CC(C(C1=C(C=CC=C1)C)SC1=NC2=CC=CC=C2C=C1)(C)O GGRHIVHIURADPX-UHFFFAOYSA-N 0.000 description 1
- VKAQSANHDTWELN-UHFFFAOYSA-N CC(C(C=1C(=NC=CC=1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)(C)O Chemical compound CC(C(C=1C(=NC=CC=1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)(C)O VKAQSANHDTWELN-UHFFFAOYSA-N 0.000 description 1
- PYLXYYJMCFRPRT-MNLARUNXSA-N CC1(OC[C@@H]2[C@H](O1)[C@@H]([C@H]([C@@H](O2)SC)O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)C Chemical compound CC1(OC[C@@H]2[C@H](O1)[C@@H]([C@H]([C@@H](O2)SC)O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)C PYLXYYJMCFRPRT-MNLARUNXSA-N 0.000 description 1
- FLGBRMAZIYXVBV-UHFFFAOYSA-N CN1CCC(CC1)(O)C(C1=NC(=C(N=C1C)C)C)SC1OCCCC1 Chemical compound CN1CCC(CC1)(O)C(C1=NC(=C(N=C1C)C)C)SC1OCCCC1 FLGBRMAZIYXVBV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 208000004990 Cardiorenal syndrome Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- XUDCFCUAJZTLJL-UHFFFAOYSA-N ClC1=C(C(=NC=C1)C(C1(CCC(CC1)(F)F)O)S)C Chemical compound ClC1=C(C(=NC=C1)C(C1(CCC(CC1)(F)F)O)S)C XUDCFCUAJZTLJL-UHFFFAOYSA-N 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 208000029147 Collagen-vascular disease Diseases 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 206010055665 Corneal neovascularisation Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- AVVWPBAENSWJCB-YIDFTEPTSA-N D-gulofuranose Chemical compound OC[C@@H](O)[C@@H]1OC(O)[C@H](O)[C@@H]1O AVVWPBAENSWJCB-YIDFTEPTSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- ZBGTVDSRPIQUKQ-UHFFFAOYSA-N FC1(CC(C1)(O)C(C1=C(C=CC=C1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)F Chemical compound FC1(CC(C1)(O)C(C1=C(C=CC=C1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1)F ZBGTVDSRPIQUKQ-UHFFFAOYSA-N 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010001498 Galectin 1 Proteins 0.000 description 1
- 102100021736 Galectin-1 Human genes 0.000 description 1
- 102100025614 Galectin-related protein Human genes 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001042451 Homo sapiens Galectin-1 Proteins 0.000 description 1
- 101001004750 Homo sapiens Galectin-related protein Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020852 Hypertonia Diseases 0.000 description 1
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000001826 Marfan syndrome Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000012192 Mucous membrane pemphigoid Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- DXDCAOPZRZBUEF-NIFOPYEASA-N N(=[N+]=[N-])[C@@H]1[C@H]([C@@H](O[C@H]2[C@@H]1OC(OC2)(C)C)SC(C1=NC=CC=C1C)C1(CCC(CC1)(F)F)O)O Chemical compound N(=[N+]=[N-])[C@@H]1[C@H]([C@@H](O[C@H]2[C@@H]1OC(OC2)(C)C)SC(C1=NC=CC=C1C)C1(CCC(CC1)(F)F)O)O DXDCAOPZRZBUEF-NIFOPYEASA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- PRNBTYXNGNXQTB-UHFFFAOYSA-N O=C1CN(C1)C(=O)OC(C(Cl)(Cl)Cl)(C)C Chemical compound O=C1CN(C1)C(=O)OC(C(Cl)(Cl)Cl)(C)C PRNBTYXNGNXQTB-UHFFFAOYSA-N 0.000 description 1
- DCVSXLYUTSYAOQ-BJHKXESGSA-N OC(C(C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC(C(C1=C(C=CC=C1)C(C)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C DCVSXLYUTSYAOQ-BJHKXESGSA-N 0.000 description 1
- ZVTTYXUKQGMTDA-ZWAZJMGPSA-N OC(C(C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)CC Chemical compound OC(C(C1=C(C=CC=C1)C(F)(F)F)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)CC ZVTTYXUKQGMTDA-ZWAZJMGPSA-N 0.000 description 1
- RTDBVNIEYVGLJM-BJHKXESGSA-N OC(C(C1=C(C=CC=C1)CCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC(C(C1=C(C=CC=C1)CCC)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C RTDBVNIEYVGLJM-BJHKXESGSA-N 0.000 description 1
- OEMQPUOZMXHHMQ-DQUCWBKNSA-N OC(C(C=1C(=NC=CC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC(C(C=1C(=NC=CC=1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C OEMQPUOZMXHHMQ-DQUCWBKNSA-N 0.000 description 1
- VJEQHAFPJKBDOK-UHFFFAOYSA-N OC(CC1)(CCN1C(O)=O)C(C1=CC=CC=C1)S Chemical compound OC(CC1)(CCN1C(O)=O)C(C1=CC=CC=C1)S VJEQHAFPJKBDOK-UHFFFAOYSA-N 0.000 description 1
- YFYAFCZQHGJKFI-GZBSGOROSA-N OC([C@@H](C1=NOC=C1C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@@H](C1=NOC=C1C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C YFYAFCZQHGJKFI-GZBSGOROSA-N 0.000 description 1
- MYKUIDQPHNNALF-QJKCBQBNSA-N OC([C@H](C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C Chemical compound OC([C@H](C1=C(C=CC=C1)C)S[C@@H]1O[C@@H]([C@@H]([C@@H]([C@H]1O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)O)CO)(C)C MYKUIDQPHNNALF-QJKCBQBNSA-N 0.000 description 1
- OOHIPDLPISIYKN-UHFFFAOYSA-N OC1(CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C)C(C1=C(C=CC=C1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1 Chemical compound OC1(CCN(CC1)C(=O)OC(C(Cl)(Cl)Cl)(C)C)C(C1=C(C=CC=C1)C(F)(F)F)SC1=NC2=CC=CC=C2C=C1 OOHIPDLPISIYKN-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 102000008080 Pancreatitis-Associated Proteins Human genes 0.000 description 1
- 108010074467 Pancreatitis-Associated Proteins Proteins 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 206010061336 Pelvic neoplasm Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 208000004362 Penile Induration Diseases 0.000 description 1
- 208000020758 Peyronie disease Diseases 0.000 description 1
- 206010035600 Pleural fibrosis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010037688 Q fever Diseases 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- DREFPIQFSWMLFB-UHFFFAOYSA-N SC(C1(CCN(CC1)C)O)C1=NC(=C(N=C1C)C)C Chemical compound SC(C1(CCN(CC1)C)O)C1=NC(=C(N=C1C)C)C DREFPIQFSWMLFB-UHFFFAOYSA-N 0.000 description 1
- DFFQUVDTXIVORG-QMMMGPOBSA-N S[C@H](C(C)(O)C)C=1C(=NC=CC=1)C(F)(F)F Chemical compound S[C@H](C(C)(O)C)C=1C(=NC=CC=1)C(F)(F)F DFFQUVDTXIVORG-QMMMGPOBSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039580 Scar Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010040867 Skin hypertrophy Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- QFIRONPERRUJAN-UHFFFAOYSA-N [NH2-].[Na+].C[Si](N[Si](C)(C)C)(C)C Chemical compound [NH2-].[Na+].C[Si](N[Si](C)(C)C)(C)C QFIRONPERRUJAN-UHFFFAOYSA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 206010002906 aortic stenosis Diseases 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 108010044715 asialofetuin Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000007213 cerebrovascular event Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 230000001587 cholestatic effect Effects 0.000 description 1
- 230000007881 chronic fibrosis Effects 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 201000010002 cicatricial pemphigoid Diseases 0.000 description 1
- 238000011220 combination immunotherapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- MZGNSEAPZQGJRB-UHFFFAOYSA-N dimethyldithiocarbamic acid Chemical compound CN(C)C(S)=S MZGNSEAPZQGJRB-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000012990 dithiocarbamate Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004406 elevated intraocular pressure Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- SCABWMJQWXPFJD-UHFFFAOYSA-N ethyl 2-(2-bromophenyl)-2-hydroxyacetate Chemical compound CCOC(=O)C(O)C1=CC=CC=C1Br SCABWMJQWXPFJD-UHFFFAOYSA-N 0.000 description 1
- MZQXAVZPEZUJIJ-UHFFFAOYSA-N ethyl 2-(2-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC=C1Br MZQXAVZPEZUJIJ-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000009795 fibrotic process Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 1
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000008195 galaktosides Chemical class 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000012912 hepatic vascular disease Diseases 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- AMVCFIFDMKEIRE-UHFFFAOYSA-N methyl 2-(2-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1Br AMVCFIFDMKEIRE-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- FGNGTWFJQFTFGN-UHFFFAOYSA-N n,n,n',n'-tetramethylethane-1,2-diamine Chemical compound CN(C)CCN(C)C.CN(C)CCN(C)C FGNGTWFJQFTFGN-UHFFFAOYSA-N 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- UJJUEJRWNWVHCM-UHFFFAOYSA-N n-methylsulfamoyl chloride Chemical compound CNS(Cl)(=O)=O UJJUEJRWNWVHCM-UHFFFAOYSA-N 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 201000002674 obstructive nephropathy Diseases 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007110 pathogen host interaction Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000004124 rheumatic heart disease Diseases 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- RVEZZJVBDQCTEF-UHFFFAOYSA-N sulfenic acid Chemical compound SO RVEZZJVBDQCTEF-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000031068 symbiosis, encompassing mutualism through parasitism Effects 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1
- 210000002105 tongue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- JDYCDPFQWXHUDL-UHFFFAOYSA-N trimethyl(methylsulfanyl)silane Chemical compound CS[Si](C)(C)C JDYCDPFQWXHUDL-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 201000011531 vascular cancer Diseases 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 206010055031 vascular neoplasm Diseases 0.000 description 1
- 201000002498 viral encephalitis Diseases 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/056—Triazole or tetrazole radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Transplantation (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2019/071416 | 2019-08-09 | ||
| EP2019071416 | 2019-08-09 | ||
| PCT/EP2020/072238 WO2021028336A1 (en) | 2019-08-09 | 2020-08-07 | (hetero)aryl-methyl-thio-beta-d-galactopyranoside derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114206893A true CN114206893A (zh) | 2022-03-18 |
Family
ID=71948599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080056681.7A Pending CN114206893A (zh) | 2019-08-09 | 2020-08-07 | (杂)芳基-甲基-硫代-β-D-吡喃半乳糖苷衍生物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US12404295B2 (https=) |
| EP (1) | EP4010076B1 (https=) |
| JP (1) | JP7612662B2 (https=) |
| KR (1) | KR102854071B1 (https=) |
| CN (1) | CN114206893A (https=) |
| CA (1) | CA3147082A1 (https=) |
| ES (1) | ES2972509T3 (https=) |
| TW (1) | TWI873165B (https=) |
| WO (1) | WO2021028336A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4010348B1 (en) | 2019-08-09 | 2023-12-20 | Idorsia Pharmaceuticals Ltd | (2-acetamidyl)thio-beta-d-galactopyranoside derivatives |
| JP7604457B2 (ja) | 2019-08-15 | 2024-12-23 | イドルシア・ファーマシューティカルズ・リミテッド | 2-ヒドロキシシクロアルカン-1-カルバモイル誘導体 |
| CA3148365A1 (en) | 2019-08-29 | 2021-03-04 | Martin Bolli | Alpha-d-galactopyranoside derivatives |
| ES3014851T3 (en) | 2020-10-06 | 2025-04-25 | Idorsia Pharmaceuticals Ltd | Spiro derivatives of alpha-d-galactopyranosides |
| KR20230104190A (ko) | 2020-11-02 | 2023-07-07 | 이도르시아 파마슈티컬스 리미티드 | 갈렉틴-3 억제 2-히드록시시클로알칸-1-카르바모일 유도체 |
| KR20230145111A (ko) | 2021-02-09 | 2023-10-17 | 이도르시아 파마슈티컬스 리미티드 | 히드록시헤테로시클로알칸-카르바모일 유도체 |
| PL4301748T3 (pl) | 2021-03-03 | 2025-09-08 | Idorsia Pharmaceuticals Ltd | Triazolilo-metylo podstawione pochodne alfa-d-galaktopiranozydu |
| WO2022189459A2 (en) * | 2021-03-10 | 2022-09-15 | Galecto Biotech Ab | Novel galactoside inhibitor of galectins |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0100172D0 (sv) | 2001-01-22 | 2001-01-22 | Ulf Nilsson | New inhibitors against galectins |
| SE0401300D0 (sv) | 2004-05-21 | 2004-05-21 | Forskarpatent I Syd Ab | Novel Galactoside Inhibitors of Galectins |
| SE0401301D0 (sv) | 2004-05-21 | 2004-05-21 | Forskarpatent I Syd Ab | Novel 3-triazolyl-galactoside inhibitors of galectins |
| US8828971B2 (en) | 2012-10-10 | 2014-09-09 | Galectin Therapeutics, Inc. | Galactose-pronged carbohydrate compounds for the treatment of diabetic nephropathy and associated disorders |
| JP2015535233A (ja) | 2012-10-31 | 2015-12-10 | ガレクト・バイオテック・エイビイ | ガレクチン−3のガラクトシド阻害剤及び肺線維症のためのその使用 |
| WO2014078655A1 (en) | 2012-11-15 | 2014-05-22 | Tufts University | Methods, compositions and kits for treating, modulating, or preventing ocular angiogenesis or fibrosis in a subject using a galectin protein inhibitor |
| JP6904906B2 (ja) | 2015-01-30 | 2021-07-21 | ガレクト・バイオテック・エイビイ | ガレクチンの新規なガラクトシド阻害剤 |
| KR101974793B1 (ko) | 2015-07-06 | 2019-05-02 | 길리애드 사이언시즈, 인코포레이티드 | Cot 조정제 및 그의 사용 방법 |
| JP7086008B2 (ja) * | 2016-03-04 | 2022-06-17 | ガレクティン・サイエンシーズ・リミテッド・ライアビリティ・カンパニー | ガレクチンに関連する疾患を予防および処置するためのセレノガラクトシド化合物およびその使用 |
| CA3025867A1 (en) | 2016-07-12 | 2018-01-18 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| CA3062648A1 (en) | 2017-05-12 | 2018-11-15 | Galectin Sciences, Llc | Compounds for the prevention and treatment of diseases and the use thereof |
| US20200061095A1 (en) | 2017-05-12 | 2020-02-27 | Galectin Sciences, Llc | Compounds for the Treatment of Systemic Insulin Resistance Disorders and the Use Thereof |
| WO2019067702A1 (en) | 2017-09-27 | 2019-04-04 | Bristol-Myers Squibb Company | INHIBITORS WITH SMALL MOLECULES OF GALECTIN-3 |
| WO2019075045A1 (en) | 2017-10-11 | 2019-04-18 | Bristol-Myers Squibb Company | INHIBITORS WITH SMALL MOLECULES OF GALECTIN-3 |
| AU2018361991A1 (en) | 2017-10-31 | 2020-05-14 | Galectin Sciences, Llc | Selenogalactoside compounds for the treatment of systemic insulin resistance disorders and the use thereof |
| JP2022508719A (ja) | 2018-10-15 | 2022-01-19 | ガレクト バイオテック エービー | ガレクチンのガラクトシド阻害剤のプロドラッグ |
| CN113366007A (zh) | 2018-10-15 | 2021-09-07 | 格莱克特生物技术公司 | 半乳糖凝集素的半乳糖苷抑制剂 |
| JP7486484B2 (ja) | 2018-11-21 | 2024-05-17 | ガレクト バイオテック エービー | ガレクチンのα-D-ガラクトシド阻害剤 |
| EP3953349A1 (en) | 2019-04-10 | 2022-02-16 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| CA3141436A1 (en) | 2019-07-03 | 2021-01-07 | Fredrik Zetterberg | Novel galactoside inhibitor of galectins |
| CN114450282A (zh) | 2019-07-05 | 2022-05-06 | 格莱克特生物技术公司 | 半乳糖凝集素的新型半乳糖苷抑制剂 |
| EP4010348B1 (en) | 2019-08-09 | 2023-12-20 | Idorsia Pharmaceuticals Ltd | (2-acetamidyl)thio-beta-d-galactopyranoside derivatives |
| JP7604457B2 (ja) | 2019-08-15 | 2024-12-23 | イドルシア・ファーマシューティカルズ・リミテッド | 2-ヒドロキシシクロアルカン-1-カルバモイル誘導体 |
| CA3148365A1 (en) | 2019-08-29 | 2021-03-04 | Martin Bolli | Alpha-d-galactopyranoside derivatives |
| ES3014851T3 (en) | 2020-10-06 | 2025-04-25 | Idorsia Pharmaceuticals Ltd | Spiro derivatives of alpha-d-galactopyranosides |
| KR20230104190A (ko) | 2020-11-02 | 2023-07-07 | 이도르시아 파마슈티컬스 리미티드 | 갈렉틴-3 억제 2-히드록시시클로알칸-1-카르바모일 유도체 |
| KR20230145111A (ko) | 2021-02-09 | 2023-10-17 | 이도르시아 파마슈티컬스 리미티드 | 히드록시헤테로시클로알칸-카르바모일 유도체 |
| PL4301748T3 (pl) | 2021-03-03 | 2025-09-08 | Idorsia Pharmaceuticals Ltd | Triazolilo-metylo podstawione pochodne alfa-d-galaktopiranozydu |
-
2020
- 2020-08-07 CN CN202080056681.7A patent/CN114206893A/zh active Pending
- 2020-08-07 US US17/633,895 patent/US12404295B2/en active Active
- 2020-08-07 WO PCT/EP2020/072238 patent/WO2021028336A1/en not_active Ceased
- 2020-08-07 EP EP20751158.5A patent/EP4010076B1/en active Active
- 2020-08-07 ES ES20751158T patent/ES2972509T3/es active Active
- 2020-08-07 CA CA3147082A patent/CA3147082A1/en active Pending
- 2020-08-07 JP JP2022507725A patent/JP7612662B2/ja active Active
- 2020-08-07 KR KR1020227007509A patent/KR102854071B1/ko active Active
- 2020-08-07 TW TW109126972A patent/TWI873165B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| US20220315619A1 (en) | 2022-10-06 |
| TWI873165B (zh) | 2025-02-21 |
| KR102854071B1 (ko) | 2025-09-02 |
| EP4010076B1 (en) | 2024-01-17 |
| JP2022543666A (ja) | 2022-10-13 |
| CA3147082A1 (en) | 2021-02-18 |
| EP4010076C0 (en) | 2024-01-17 |
| US12404295B2 (en) | 2025-09-02 |
| JP7612662B2 (ja) | 2025-01-14 |
| WO2021028336A1 (en) | 2021-02-18 |
| KR20220044785A (ko) | 2022-04-11 |
| TW202120102A (zh) | 2021-06-01 |
| ES2972509T3 (es) | 2024-06-13 |
| EP4010076A1 (en) | 2022-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114206893A (zh) | (杂)芳基-甲基-硫代-β-D-吡喃半乳糖苷衍生物 | |
| TWI864071B (zh) | 2-羥環烷-1-胺甲醯基衍生物 | |
| JP7612663B2 (ja) | (2-アセタミジル)チオ-ベータ-d-ガラクトピラノシド誘導体 | |
| US12291520B2 (en) | Galectin-3 inhibiting 2-hydroxycycloalkane-1-carbamoyl derivatives | |
| KR20230145111A (ko) | 히드록시헤테로시클로알칸-카르바모일 유도체 | |
| KR20230083301A (ko) | 알파-d-갈락토피라노사이드의 스피로 유도체 | |
| EA048291B1 (ru) | 2-гидроксициклоалкан-1-карбамоильные производные | |
| CN116745282A (zh) | 抑制2-羟环烷-1-氨甲酰基衍生物的半乳糖凝集素-3 | |
| EA050798B1 (ru) | 2-гидроксициклоалкан-1-карбамоильные производные, ингибирующие галектин-3 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |