JP7418227B2 - 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 - Google Patents
痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 Download PDFInfo
- Publication number
- JP7418227B2 JP7418227B2 JP2020014109A JP2020014109A JP7418227B2 JP 7418227 B2 JP7418227 B2 JP 7418227B2 JP 2020014109 A JP2020014109 A JP 2020014109A JP 2020014109 A JP2020014109 A JP 2020014109A JP 7418227 B2 JP7418227 B2 JP 7418227B2
- Authority
- JP
- Japan
- Prior art keywords
- deuterium
- compounds
- alkyl
- contemplated
- aryl
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims description 171
- 239000000203 mixture Substances 0.000 title description 83
- 238000000034 method Methods 0.000 title description 45
- 201000001431 Hyperuricemia Diseases 0.000 title description 33
- 201000005569 Gout Diseases 0.000 title description 28
- 208000024891 symptom Diseases 0.000 title description 3
- ZYHWDBVIUWBPCO-QFFDRWTDSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)O)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)O)Br)O ZYHWDBVIUWBPCO-QFFDRWTDSA-N 0.000 claims description 2
- 229910052805 deuterium Inorganic materials 0.000 description 129
- -1 substituted Chemical class 0.000 description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
- 125000000217 alkyl group Chemical group 0.000 description 47
- 201000010099 disease Diseases 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 41
- 125000004093 cyano group Chemical group *C#N 0.000 description 41
- 229910052736 halogen Inorganic materials 0.000 description 40
- 150000002367 halogens Chemical class 0.000 description 40
- 150000003839 salts Chemical class 0.000 description 35
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 34
- 125000005842 heteroatom Chemical group 0.000 description 31
- 229910052760 oxygen Inorganic materials 0.000 description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 25
- 125000003118 aryl group Chemical group 0.000 description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 23
- 239000001301 oxygen Substances 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 125000001624 naphthyl group Chemical group 0.000 description 21
- 125000000547 substituted alkyl group Chemical group 0.000 description 20
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 18
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 18
- 229940116269 uric acid Drugs 0.000 description 18
- 238000009472 formulation Methods 0.000 description 17
- 229910052739 hydrogen Inorganic materials 0.000 description 17
- 239000001257 hydrogen Substances 0.000 description 16
- 125000003545 alkoxy group Chemical group 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 description 12
- 239000003937 drug carrier Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 101000821903 Homo sapiens Solute carrier family 22 member 12 Proteins 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 229960002529 benzbromarone Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 102000002269 Cytochrome P-450 CYP2C9 Human genes 0.000 description 8
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 8
- 102100021495 Solute carrier family 22 member 12 Human genes 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 239000003064 xanthine oxidase inhibitor Substances 0.000 description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
- 125000000304 alkynyl group Chemical group 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 108010078791 Carrier Proteins Proteins 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000009103 reabsorption Effects 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 210000005239 tubule Anatomy 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- 206010019851 Hepatotoxicity Diseases 0.000 description 5
- 229910006069 SO3H Inorganic materials 0.000 description 5
- 229940123769 Xanthine oxidase inhibitor Drugs 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000001188 haloalkyl group Chemical group 0.000 description 5
- 231100000304 hepatotoxicity Toxicity 0.000 description 5
- 230000007686 hepatotoxicity Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 229960003459 allopurinol Drugs 0.000 description 4
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 description 4
- 229960005101 febuxostat Drugs 0.000 description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- UBVZQGOVTLIHLH-UHFFFAOYSA-N 4-[5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl]-pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC(C=2N=C(NN=2)C=2C=CN=CC=2)=C1 UBVZQGOVTLIHLH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 230000036983 biotransformation Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 3
- 229960000367 inositol Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- HXNFUBHNUDHIGC-UHFFFAOYSA-N oxypurinol Chemical compound O=C1NC(=O)N=C2NNC=C21 HXNFUBHNUDHIGC-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229950004176 topiroxostat Drugs 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000821902 Homo sapiens Solute carrier family 22 member 11 Proteins 0.000 description 2
- 101001094053 Homo sapiens Solute carrier family 22 member 9 Proteins 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229930194542 Keto Natural products 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 108091006269 SLC5A2 Proteins 0.000 description 2
- 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 description 2
- 102100021493 Solute carrier family 22 member 11 Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000005956 quaternization reaction Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000008060 renal absorption Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- ZYHWDBVIUWBPCO-PBNXXWCMSA-N (3,5-dibromo-4-hydroxyphenyl)-[5,6-dideuterio-2-(1-hydroxyethyl)-1-benzofuran-3-yl]methanone Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C(=C2)[2H])[2H])C(C)O)Br)O ZYHWDBVIUWBPCO-PBNXXWCMSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- XRTXLIRHGDFBEQ-QFFDRWTDSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-QFFDRWTDSA-N 0.000 description 1
- COHDBVLSNGVRJQ-QFFDRWTDSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)Cl)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)Cl)Br)O COHDBVLSNGVRJQ-QFFDRWTDSA-N 0.000 description 1
- CAZPNZXKOATUQQ-QFFDRWTDSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C(=C(C(=C2[2H])[2H])[2H])[2H])C(C)F)Br)O CAZPNZXKOATUQQ-QFFDRWTDSA-N 0.000 description 1
- XRTXLIRHGDFBEQ-PBNXXWCMSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C(=C2)[2H])[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C(=C2)[2H])[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-PBNXXWCMSA-N 0.000 description 1
- CAZPNZXKOATUQQ-PBNXXWCMSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C(=C2)[2H])[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C(=C2)[2H])[2H])C(C)F)Br)O CAZPNZXKOATUQQ-PBNXXWCMSA-N 0.000 description 1
- MKVQLZIDEZSXFQ-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)F)C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)F)C(C)F)Br)O MKVQLZIDEZSXFQ-UHFFFAOYSA-N 0.000 description 1
- FRXNVYBVVWBUGP-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)F)C(C)O)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)F)C(C)O)Br)O FRXNVYBVVWBUGP-UHFFFAOYSA-N 0.000 description 1
- XRTXLIRHGDFBEQ-VMNATFBRSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-VMNATFBRSA-N 0.000 description 1
- CAZPNZXKOATUQQ-VMNATFBRSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2)[2H])C(C)F)Br)O CAZPNZXKOATUQQ-VMNATFBRSA-N 0.000 description 1
- XRTXLIRHGDFBEQ-GSUVGXDCSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2[2H])[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2[2H])[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-GSUVGXDCSA-N 0.000 description 1
- CAZPNZXKOATUQQ-GSUVGXDCSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2[2H])[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=C(C=C2[2H])[2H])C(C)F)Br)O CAZPNZXKOATUQQ-GSUVGXDCSA-N 0.000 description 1
- XRTXLIRHGDFBEQ-WFVSFCRTSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-WFVSFCRTSA-N 0.000 description 1
- COHDBVLSNGVRJQ-WFVSFCRTSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)Cl)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)Cl)Br)O COHDBVLSNGVRJQ-WFVSFCRTSA-N 0.000 description 1
- CAZPNZXKOATUQQ-WFVSFCRTSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC(=C2)[2H])C(C)F)Br)O CAZPNZXKOATUQQ-WFVSFCRTSA-N 0.000 description 1
- CAZPNZXKOATUQQ-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC=C2)C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC2=C1C=CC=C2)C(C)F)Br)O CAZPNZXKOATUQQ-UHFFFAOYSA-N 0.000 description 1
- FRXNVYBVVWBUGP-WQNTXASMSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C(=C(C=2[2H])[2H])F)[2H])C(C)O)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C(=C(C=2[2H])[2H])F)[2H])C(C)O)Br)O FRXNVYBVVWBUGP-WQNTXASMSA-N 0.000 description 1
- XRTXLIRHGDFBEQ-NMQOAUCRSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)(F)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)(F)F)Br)O XRTXLIRHGDFBEQ-NMQOAUCRSA-N 0.000 description 1
- CAZPNZXKOATUQQ-NMQOAUCRSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)F)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)F)Br)O CAZPNZXKOATUQQ-NMQOAUCRSA-N 0.000 description 1
- ZYHWDBVIUWBPCO-NMQOAUCRSA-N BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)O)Br)O Chemical compound BrC1=C(C(=CC(=C1)C(=O)C1=C(OC=2C1=C(C=C(C=2)[2H])[2H])C(C)O)Br)O ZYHWDBVIUWBPCO-NMQOAUCRSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000005487 Cytochrome P-450 CYP2C9 Inhibitors Diseases 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000002355 alkine group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 125000003406 indolizinyl group Chemical class C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000007794 irritation Effects 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
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-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
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Furan Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本明細書は以下の発明の開示を包含する。
[1]式1の化合物、あるいはその薬学的に許容可能な塩であって、
-R1、-R2、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、ならびに、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは、XがOC(O)R、ハロゲン、または-OHであるとき、-重水素である、化合物。
[2]Xは-OHであり、および、-R1、-R2、-R3、および-R4のそれぞれは-重水素であり、-R5は-Hである、[1]に記載の化合物。
[3]Xは-OHであり、-R1、-R2、および-R4の少なくとも1つは-重水素であり、-R3はハロゲンであり、および、-R5は-Hである、[1]に記載の化合物。
[4]-R3は-Fである、[3]に記載の化合物。
[5]Xは-Fであり、-R1、-R2、-R3、および-R4のそれぞれは-重水素であり、および、R5は-Hである、[1]に記載の化合物。
[6]Xは-Fであり、-R3はハロゲンであり、-R1、-R2、および-R4の少なくとも2つは-Hであり、-R1、-R2、および-R4の少なくとも1つは-重水素であり、および、-R5は-Hである、[1]に記載の化合物。
[7]-R3は-Fである、[6]に記載の化合物。
[8]-Xは-Fまたは-OHであり、-R2と-R4のそれぞれは-重水素であり、および、-R1、-R3、および-R5のそれぞれは-Hである、[1]に記載の化合物。
[9]-Xは-Fまたは-OHであり、-R2と-R3のそれぞれは-重水素であり、ならびに、-R1、-R4、および-R5のそれぞれは-Hである、[1]に記載の化合物。
[10]高尿酸血症または痛風に関連する疾病の処置のための組成物であって、前記組成物は、
薬学的に許容可能な担体、
式1の化合物、あるいはその薬学的に許容可能な塩を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、
-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素であり、ならびに、
式1の化合物は、高尿酸血症または痛風に関連する疾病を処置するのに治療上有効な量で存在する、組成物。
[11]-R2は重水素である、[10]に記載の組成物。
[12]-Xは-Fまたは-OHであり、-R1、-R2、および-R4は重水素であり、および、-R5は-Hである、[11]に記載の組成物。
[13]-R3は-重水素である、[12]に記載の組成物。
[14]-Xは-Fであり、-R2と-R3のそれぞれは重水素であり、ならびに、-R1、-R4、および-R5のそれぞれは-Hである、[10]に記載の組成物。
[15]-Xと-R5のそれぞれは-Fであり、ならびに、-R1、-R2、-R3、および-R4のそれぞれは重水素である、[10]に記載の組成物。
[16]-Xは-Fまたは-OHであり、-R1、-R2、-R4、および-R5の3つ以下は-Hであり、-R1、-R2、-R4、および-R5の少なくとも1つは-重水素であり、および、-R3はハロゲンである、[10]に記載の組成物。
[17]-R3は-Fである、[16]に記載の組成物。
[18]疾病は、高尿酸血症、痛風、高血圧、および糖尿病の少なくとも1つである、[10]に記載の組成物。
[19]キサンチンオキシダーゼ阻害剤をさらに含む、[10]に記載の組成物。
[20]キサンチンオキシダーゼ阻害剤は、アロプリノール、オキシプリノール、フェブキソスタット、トピロキソスタット、あるいはイノシトールである、[19]に記載の組成物。
[21]高尿酸血症または痛風に関連する疾病を処置する方法であって、前記方法は、
薬学的に許容可能な担体、および式1の化合物、あるいはその薬学的に許容可能な塩を含む有効な量の組成物を投与する工程を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
ならびに、-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素である、方法。
[22]-Xは-Fまたは-OHであり、-R1、-R2、R3、および-R4のそれぞれは-重水素であり、および、-R5は-Hである、[21]に記載の方法。
[23]-Xは-Fまたは-OHであり、-R3はハロゲンであり、-R1、-R2、-R3、および-R5の3つ以下は-Hであり、ならびに、-R1、-R2、-R3、および-R5の少なくとも1つは重水素である、[21]に記載の方法。
[24]-R3は-Fである、[23]に記載の化合物。
[25]-Xと-R5のそれぞれは-Fであり、-R2は重水素であり、および、-R1、-R3、および-R4のそれぞれは-Hである、[21]に記載の方法。
[26]-Xと-R5のそれぞれは-Fであり、ならびに、-R1、-R2、-R3、および-R4のそれぞれは重水素である、[21]に記載の方法。
[27]50-300mgの式1の化合物が組成物中に存在し、組成物は単回投与として投与される、[21]に記載の方法。
[28]疾病は、高尿酸血症、痛風、高血圧、および糖尿病の少なくとも1つである、[21]に記載の方法。
[29]組成物はキサンチンオキシダーゼ阻害剤をさらに含む、[21]に記載の方法。
[30]キサンチンオキシダーゼ阻害剤は、アロプリノール、オキシプリノール、フェブキソスタット、トピロキソスタット、あるいはイノシトールである、[29]に記載の方法。
[31]高尿酸血症または痛風に関連する疾病を処置するための医薬組成物を製造する方法であって、前記方法は、
薬学的に許容可能な担体、および式1の化合物、あるいはその薬学的に許容可能な塩を含む経口製剤を製剤化する工程を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素であり、ならびに、
式1の化合物は、高尿酸血症に関連する疾病を処置するのに治療上有効な量で存在する、方法。
[32]高尿酸血症または痛風に関連する疾病を処置するための液体医薬組成物を製造する方法であって、前記方法は、
薬学的に許容可能な担体、および式1の化合物、あるいはその薬学的に許容可能な塩を含む液体製剤を製剤化する工程を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素であり、ならびに、
式1の化合物は、高尿酸血症に関連する疾病を処置するのに治療上有効な量で存在する、方法。
[33]尿細管中の尿酸再吸収に関与する少なくとも1つの腎臓輸送体を阻害する方法であって、前記方法は、
治療上有効な量の式1の化合物、あるいはその薬学的に許容可能な塩を投与する工程を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素である、方法。
[34]尿酸の腎再吸収の媒介はURAT1活性を調節することを含む、[33]に記載の方法。
[35]尿細管中の尿酸再吸収に関与する少なくとも1つの腎臓輸送体によって媒介される疾病、障害、あるいは疾患を処置する方法であって、前記方法は、
薬学的に許容可能な担体、および式1の化合物、あるいはその薬学的に許容可能な塩を含む有効な量の組成物を投与する工程を含み、
-Xは-OH、-OR、-OC(O)R、-NH3+、-NO2、-SO2R、-CN、-SO3H、-CHO、-COOH、-COCl、-CONH2、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素あるいは-Hであり、
-R1、-R3、-R4、および-R5はそれぞれ、-H、-重水素、-F、-Cl、-Br、-I、-CN、-C1-C6-アルキル、C6-C14-アリール、置換された-C6-C14-アリール、C1-C14-アルコキシ、-ヒドロキシル、-カルボキシル、-C1-C6-アルキルスルホニル、-トリフルオロメチル、-C1-C6-アルカノイルオキシ、-C1-C6-アルキルチオ、-C1-C6-アルキルスルホニル、-C2-C6-アルコキシカルボニル、-C2-C6-アルカノイルアミノ、-O-R6、-S2R6、-SO2-R6、-NHSO2R6、および-NHCO2R6からなる群から独立して選択され、-R6が、-C1-C6-アルキル、-C6-C10-アリール、-C1-C6-アルコキシ、およびハロゲン、ならびに-C4-C20-ヒドロキシヘテロアリールから選択される1または3の基で随意に置換されるフェニルまたはナフチルであり、および、-C4-C20-ヒドロキシヘテロアリール中のヘテロ原子が窒素と酸素からなる群から選択され、
-R1、-R2、-R3、-R4、および-R5の少なくとも1つは重水素である、方法。
[36]式1の化合物、あるいはその薬学的に許容可能な塩であって、
-Xは、-OH、-OR、-F、-Cl、-Br、または-Iであり、-Rは-H、-C1-C10アルキル、あるいは-C1-C10置換アルキルであり、
-R2は-重水素であり、
-R3は-Fであり、ならびに、
-R1、-R4、および-R5のそれぞれは、-Hと-重水素からなる群から選択される、化合物。
[37]薬物の製造における[36]の化合物の使用。
[38]高尿酸血症または痛風に関連する疾病を処置するための[36]の化合物の使用。
[39]ヒトにおいてURAT1活性を調節するための[36]の化合物の使用。
[40]URAT1活性によって媒介される障害または疾患を処置または予防するための[36の化合物の使用。
[41]高尿酸血症、痛風、あるいは糖尿病に関連する疾病を処置するための、キサンチンオキシダーゼ阻害剤と組み合わせた[36]の化合物の使用。
[42]組成物はエナンチオマー富化した組成物である、[10]に記載の組成物。
[43]組成物は単一のエナンチオマー組成物である、[10]に記載の組成物。
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022144720A JP2022188052A (ja) | 2016-07-18 | 2022-09-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662363473P | 2016-07-18 | 2016-07-18 | |
US62/363,473 | 2016-07-18 | ||
JP2019502791A JP2019524747A (ja) | 2016-07-18 | 2017-07-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019502791A Division JP2019524747A (ja) | 2016-07-18 | 2017-07-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022144720A Division JP2022188052A (ja) | 2016-07-18 | 2022-09-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020143044A JP2020143044A (ja) | 2020-09-10 |
JP7418227B2 true JP7418227B2 (ja) | 2024-01-19 |
Family
ID=60992707
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019502791A Pending JP2019524747A (ja) | 2016-07-18 | 2017-07-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
JP2020014109A Active JP7418227B2 (ja) | 2016-07-18 | 2020-01-30 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
JP2022144720A Pending JP2022188052A (ja) | 2016-07-18 | 2022-09-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019502791A Pending JP2019524747A (ja) | 2016-07-18 | 2017-07-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022144720A Pending JP2022188052A (ja) | 2016-07-18 | 2022-09-12 | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 |
Country Status (15)
Country | Link |
---|---|
US (7) | US10239854B2 (ja) |
EP (2) | EP3484862B1 (ja) |
JP (3) | JP2019524747A (ja) |
KR (1) | KR102610573B1 (ja) |
CN (3) | CN116332886A (ja) |
AU (1) | AU2017298142B2 (ja) |
CA (1) | CA3030821A1 (ja) |
DK (1) | DK3484862T3 (ja) |
EA (1) | EA201990333A1 (ja) |
ES (2) | ES2897968T3 (ja) |
IL (1) | IL264268B (ja) |
PL (1) | PL3484862T3 (ja) |
PT (1) | PT3484862T (ja) |
SG (1) | SG11201900405XA (ja) |
WO (1) | WO2018017368A1 (ja) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2016274633B2 (en) | 2015-06-09 | 2022-04-21 | Gammadelta Therapeutics Ltd | Methods for the production of TCR gamma delta+ T cells |
ES2897968T3 (es) | 2016-07-18 | 2022-03-03 | Arthrosi Therapeutics Inc | Compuestos, composiciones y métodos para tratar o prevenir un síntoma asociado a la gota o a la hiperuricemia |
WO2020118113A1 (en) * | 2018-12-06 | 2020-06-11 | Arthrosi Therapeutics, Inc. | Crystalline forms of a compound for treating or preventing gout or hyperuricemia |
JP7528080B2 (ja) * | 2018-12-06 | 2024-08-05 | アースローシ セラピューティクス,インク. | 痛風または高尿酸血症を処置または予防するための方法 |
CA3140412A1 (en) * | 2019-05-14 | 2020-11-19 | Arthrosi Therapeutics, Inc. | Compound for treating gout or hyperuricemia |
JP2022537291A (ja) * | 2019-06-17 | 2022-08-25 | フォチョン・ファーマシューティカルズ・リミテッド | ヘテロ環式誘導体及びその使用 |
MX2022015678A (es) * | 2020-06-10 | 2023-03-14 | Arthrosi Therapeutics Inc | Metodos para tratar o prevenir la enfermedad renal cronica. |
WO2022169974A1 (en) | 2021-02-05 | 2022-08-11 | Nexys Therapeutics, Inc. | Inhibitors of urat1 and pharmaceutical uses thereof |
WO2023098872A1 (en) * | 2021-12-02 | 2023-06-08 | Arthrosi Therapeutics, Inc. | Crystalline forms of a compound for treating or preventing gout or hyperuricemia |
WO2023125667A1 (en) * | 2021-12-30 | 2023-07-06 | Arthrosi Therapeutics, Inc. | Preparation of a compound for the treatment of gout or hyperuricemia |
WO2023149549A1 (ja) * | 2022-02-03 | 2023-08-10 | 国立大学法人富山大学 | 新規医薬組成物 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010525081A (ja) | 2007-04-26 | 2010-07-22 | オースペックス・ファーマシューティカルズ・インコーポレイテッド | 重水素標識ケタミン |
JP2013539757A (ja) | 2010-10-06 | 2013-10-28 | ジェイファーマ株式会社 | 強力な尿酸トランスポーター阻害剤の開発:それらの尿酸排泄効果のために設計された化合物 |
WO2014113407A2 (en) | 2013-01-16 | 2014-07-24 | Children's Hospital Medical Center | Use of small molecule inhibitors targeting eya tyrosine phosphatase |
WO2015134467A1 (en) | 2014-03-05 | 2015-09-11 | The Trustees Of Princeton University | Methods and compositions for direct radioactive labeling of bio-active molecules and building blocks |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1023985A (en) | 1911-05-29 | 1912-04-23 | Louis Emile Beaulieu | Fish-plate bolt. |
US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
US4624848A (en) | 1984-05-10 | 1986-11-25 | Ciba-Geigy Corporation | Active agent containing hydrogel devices wherein the active agent concentration profile contains a sigmoidal concentration gradient for improved constant release, their manufacture and use |
US4968509A (en) | 1987-07-27 | 1990-11-06 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Hydrogel-operated release devices |
WO1992018106A1 (en) | 1991-04-16 | 1992-10-29 | Nippon Shinyaku Co., Ltd. | Method of manufacturing solid dispersion |
HU227530B1 (en) | 1991-11-22 | 2011-07-28 | Warner Chilcott Company | Delayed-release compositions containing risedronate and process for their production |
US5461140A (en) | 1992-04-30 | 1995-10-24 | Pharmaceutical Delivery Systems | Bioerodible polymers for solid controlled release pharmaceutical compositions |
US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
EP0665010B1 (en) | 1992-10-16 | 2002-09-11 | Nippon Shinyaku Company, Limited | Method of manufacturing wax matrices |
US5686105A (en) | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
CA2220451A1 (en) | 1995-05-17 | 1996-11-21 | Cedars-Sinai Medical Center | Methods and compositions for improving digestion and absorption in the small intestine |
DE19624292A1 (de) * | 1996-06-18 | 1998-01-02 | Merckle Gmbh | Verfahren und Zwischenprodukte zur Herstellung von 1'-Hydroxybenzbromaron |
US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
US6465014B1 (en) | 2001-03-21 | 2002-10-15 | Isp Investments Inc. | pH-dependent sustained release, drug-delivery composition |
WO2005121112A1 (ja) * | 2004-06-10 | 2005-12-22 | Torii Pharmaceutical Co., Ltd. | 6-ヒドロキシベンズブロマロン又はその塩からなる医薬組成物 |
US20080305169A1 (en) * | 2006-05-26 | 2008-12-11 | Japan Tobacco Inc. | Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds |
JP5325065B2 (ja) * | 2009-09-30 | 2013-10-23 | 株式会社富士薬品 | 新規フェノール誘導体 |
GB2484298A (en) | 2010-10-05 | 2012-04-11 | Plexus Ocean Syst Ltd | Subsea wellhead with adjustable hanger forming an annular seal |
US20150031768A1 (en) | 2011-08-19 | 2015-01-29 | The Trustees Of Princeton University | C-halogen bond formation |
US9962362B2 (en) | 2012-03-29 | 2018-05-08 | Children's Hospital Medical Center | Use of small molecule inhibitors targeting EYA tyrosine phosphatase |
CN105579037A (zh) * | 2013-05-31 | 2016-05-11 | 武田制药美国有限公司 | 用黄嘌呤氧化酶抑制剂治疗的方法和含黄嘌呤氧化酶抑制剂的组合物 |
AR101395A1 (es) | 2014-07-31 | 2016-12-14 | Merck Patent Gmbh | Derivados de indolizina y su uso en enfermedades neurodegenerativas |
CN104311516B (zh) | 2014-09-16 | 2017-01-11 | 东北制药集团股份有限公司 | 一种苯溴马隆晶型b及其制备方法 |
CN104262305B (zh) | 2014-09-16 | 2016-06-08 | 东北制药集团股份有限公司 | 一种苯溴马隆晶型a及其制备方法 |
ES2897968T3 (es) | 2016-07-18 | 2022-03-03 | Arthrosi Therapeutics Inc | Compuestos, composiciones y métodos para tratar o prevenir un síntoma asociado a la gota o a la hiperuricemia |
WO2020118113A1 (en) | 2018-12-06 | 2020-06-11 | Arthrosi Therapeutics, Inc. | Crystalline forms of a compound for treating or preventing gout or hyperuricemia |
JP7528080B2 (ja) | 2018-12-06 | 2024-08-05 | アースローシ セラピューティクス,インク. | 痛風または高尿酸血症を処置または予防するための方法 |
-
2017
- 2017-07-12 ES ES17831578T patent/ES2897968T3/es active Active
- 2017-07-12 KR KR1020197004544A patent/KR102610573B1/ko active IP Right Grant
- 2017-07-12 SG SG11201900405XA patent/SG11201900405XA/en unknown
- 2017-07-12 EP EP17831578.4A patent/EP3484862B1/en active Active
- 2017-07-12 CA CA3030821A patent/CA3030821A1/en active Pending
- 2017-07-12 CN CN202211434030.4A patent/CN116332886A/zh active Pending
- 2017-07-12 WO PCT/US2017/041763 patent/WO2018017368A1/en unknown
- 2017-07-12 DK DK17831578.4T patent/DK3484862T3/da active
- 2017-07-12 EA EA201990333A patent/EA201990333A1/ru unknown
- 2017-07-12 AU AU2017298142A patent/AU2017298142B2/en active Active
- 2017-07-12 EP EP21185425.2A patent/EP3957629B1/en active Active
- 2017-07-12 PT PT178315784T patent/PT3484862T/pt unknown
- 2017-07-12 CN CN202110361823.7A patent/CN113214198B/zh active Active
- 2017-07-12 CN CN201780057295.8A patent/CN109790135B/zh active Active
- 2017-07-12 IL IL264268A patent/IL264268B/en unknown
- 2017-07-12 JP JP2019502791A patent/JP2019524747A/ja active Pending
- 2017-07-12 PL PL17831578T patent/PL3484862T3/pl unknown
- 2017-07-12 ES ES21185425T patent/ES2964344T3/es active Active
-
2018
- 2018-10-04 US US16/151,641 patent/US10239854B2/en active Active
-
2019
- 2019-02-05 US US16/268,367 patent/US10508093B2/en active Active
- 2019-11-14 US US16/684,046 patent/US11236058B2/en active Active
-
2020
- 2020-01-30 JP JP2020014109A patent/JP7418227B2/ja active Active
-
2021
- 2021-12-21 US US17/558,370 patent/US20220112171A1/en not_active Abandoned
-
2022
- 2022-08-04 US US17/817,440 patent/US20220396558A1/en not_active Abandoned
- 2022-09-12 JP JP2022144720A patent/JP2022188052A/ja active Pending
-
2023
- 2023-03-23 US US18/189,024 patent/US20230227419A1/en not_active Abandoned
- 2023-11-13 US US18/507,999 patent/US20240116888A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010525081A (ja) | 2007-04-26 | 2010-07-22 | オースペックス・ファーマシューティカルズ・インコーポレイテッド | 重水素標識ケタミン |
JP2013539757A (ja) | 2010-10-06 | 2013-10-28 | ジェイファーマ株式会社 | 強力な尿酸トランスポーター阻害剤の開発:それらの尿酸排泄効果のために設計された化合物 |
WO2014113407A2 (en) | 2013-01-16 | 2014-07-24 | Children's Hospital Medical Center | Use of small molecule inhibitors targeting eya tyrosine phosphatase |
WO2015134467A1 (en) | 2014-03-05 | 2015-09-11 | The Trustees Of Princeton University | Methods and compositions for direct radioactive labeling of bio-active molecules and building blocks |
Non-Patent Citations (4)
Title |
---|
Journal of Chromatography B、(2012)、911、pp.122-132 |
JOURNAL OF HIGH TECHNOLOGY LAW、(2009)、Vol.X、No.1、pp.22-74 |
Journal of Pharmaceutical Sciences、(1975)、Vol.64、No.3、pp.367-391 |
Wako Organic Square、(2010)、September、No.33、pp.2-3 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7418227B2 (ja) | 痛風または高尿酸血症に関連する症状を処置または予防するための化合物、組成物、および方法 | |
JP5966014B2 (ja) | 新規トリフルオロメチル−オキサジアゾール誘導体および疾患の処置におけるその使用 | |
DK2185515T3 (en) | DERIVATIVES OF 1-PHENYL-2-PYRIDINYLALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS | |
TWI804743B (zh) | 治療特發性肺纖維化的方法 | |
US20170119795A1 (en) | Fused triterpene compounds and uses thereof | |
US20220024935A1 (en) | Triazolopyridines And Triazolopyrimidines That Lower Stress-Induced P-Tau | |
JP2009535374A (ja) | ピリジルメチルピペラジンおよび−ピペリジン誘導体のn−オキサイド | |
EA041729B1 (ru) | Соединение, композиция и применение для лечения гиперурикемии или подагры |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AA31 | Notification that no translation was submitted |
Free format text: JAPANESE INTERMEDIATE CODE: A243631 Effective date: 20200401 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200707 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200707 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210726 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211020 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211220 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220125 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220511 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20220729 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20220808 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220729 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220912 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20220912 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220912 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20221003 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20221004 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20221104 |
|
C211 | Notice of termination of reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C211 Effective date: 20221108 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20230904 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240109 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7418227 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |