ES2972509T3 - Derivados de (hetero)aril-metil-tio-beta-D-galactopiranósidos - Google Patents

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Publication number

ES2972509T3

ES2972509T3 ES20751158T ES20751158T ES2972509T3 ES 2972509 T3 ES2972509 T3 ES 2972509T3 ES 20751158 T ES20751158 T ES 20751158T ES 20751158 T ES20751158 T ES 20751158T ES 2972509 T3 ES2972509 T3 ES 2972509T3

Authority

ES

Spain

Prior art keywords

pyran

thio

methyl

tetrahydro

triazol

Prior art date

2019-08-09

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.)

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• 125000005842 heteroatom Chemical group 0.000 title description 10
• 150000001875 compounds Chemical class 0.000 claims abstract description 242
• 150000003839 salts Chemical class 0.000 claims abstract description 30
• 238000002360 preparation method Methods 0.000 claims abstract description 10
• 239000003814 drug Substances 0.000 claims abstract description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 312
• -1 tetrahydro-2H-pyran-4,4-diyl Chemical group 0.000 claims description 269
• BHDLTOUYJMTTTM-UHFFFAOYSA-N oxan-3-ol Chemical compound OC1CCCOC1 BHDLTOUYJMTTTM-UHFFFAOYSA-N 0.000 claims description 75
• 125000001424 substituent group Chemical group 0.000 claims description 74
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 73
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 67
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 33
• 150000002367 halogens Chemical class 0.000 claims description 32
• 238000011282 treatment Methods 0.000 claims description 29
• 125000004432 carbon atom Chemical group C* 0.000 claims description 25
• 206010016654 Fibrosis Diseases 0.000 claims description 23
• 230000002265 prevention Effects 0.000 claims description 23
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 21
• 208000037765 diseases and disorders Diseases 0.000 claims description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 20
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 20
• 206010028980 Neoplasm Diseases 0.000 claims description 19
• 208000020832 chronic kidney disease Diseases 0.000 claims description 19
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 17
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• 230000004761 fibrosis Effects 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
• 230000002757 inflammatory effect Effects 0.000 claims description 13
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 12
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
• 208000027866 inflammatory disease Diseases 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• 208000016222 Pancreatic disease Diseases 0.000 claims description 10
• 125000002947 alkylene group Chemical group 0.000 claims description 10
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 10
• 210000000056 organ Anatomy 0.000 claims description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims description 9
• 208000029523 Interstitial Lung disease Diseases 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 208000019423 liver disease Diseases 0.000 claims description 9
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 7
• 208000019693 Lung disease Diseases 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 7
• 208000009304 Acute Kidney Injury Diseases 0.000 claims description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
• 208000033626 Renal failure acute Diseases 0.000 claims description 6
• 206010052779 Transplant rejections Diseases 0.000 claims description 6
• 230000002159 abnormal effect Effects 0.000 claims description 6
• 201000011040 acute kidney failure Diseases 0.000 claims description 6
• 230000033115 angiogenesis Effects 0.000 claims description 6
• 210000004556 brain Anatomy 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
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• 230000002062 proliferating effect Effects 0.000 claims description 6
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 5
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
• 208000004296 neuralgia Diseases 0.000 claims description 5
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• 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
• 208000024691 pancreas disease Diseases 0.000 claims description 5
• 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
• WLBAWQXOIADRMI-AEDKVNNLSA-N 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=NC(=C(N=C1C)C)C 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=NC(=C(N=C1C)C)C WLBAWQXOIADRMI-AEDKVNNLSA-N 0.000 claims description 4
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• 208000030533 eye disease Diseases 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims description 4
• 229940124530 sulfonamide Drugs 0.000 claims description 4
• RWVAINKLJZNRAP-PIYILYQRSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(1R)-2-hydroxy-2-methyl-1-(3,5,6-trimethylpyrazin-2-yl)propyl]sulfanyl-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol Chemical compound OC([C@@H](C1=NC(=C(N=C1C)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 RWVAINKLJZNRAP-PIYILYQRSA-N 0.000 claims description 3
• 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
• NYISZEOSLITVEQ-WWJMMCNDSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(R)-(4-hydroxy-1-methylpiperidin-4-yl)-[2-(trifluoromethyl)phenyl]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(F)(F)F NYISZEOSLITVEQ-WWJMMCNDSA-N 0.000 claims description 3
• BMWSZQJBMXPYMP-SUVLSFNQSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(R)-(4-hydroxyoxan-4-yl)-(3-methylpyridin-2-yl)methyl]sulfanyl-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)S[C@H](C1=NC=CC=C1C)C1(CCOCC1)O BMWSZQJBMXPYMP-SUVLSFNQSA-N 0.000 claims description 3
• VGMCONQPUXNWOJ-PIYILYQRSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(R)-(4-hydroxyoxan-4-yl)-(4-methyl-1,2-oxazol-3-yl)methyl]sulfanyl-5-methoxy-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)S[C@H](C1=NOC=C1C)C1(CCOCC1)O VGMCONQPUXNWOJ-PIYILYQRSA-N 0.000 claims description 3
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• KCOWHCDRLIWHMC-PIYILYQRSA-N (2R,3R,4S,5R,6S)-6-[(R)-(4,4-difluoro-1-hydroxycyclohexyl)-(4-methyl-1,2-oxazol-3-yl)methyl]sulfanyl-2-(hydroxymethyl)-5-methoxy-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxan-3-ol Chemical compound FC1(CCC(CC1)(O)[C@H](S[C@H]1[C@@H]([C@H]([C@H]([C@H](O1)CO)O)N1N=NC(=C1)C1=CC(=C(C(=C1)F)F)F)OC)C1=NOC=C1C)F KCOWHCDRLIWHMC-PIYILYQRSA-N 0.000 claims description 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
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