JP2020143044A - 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
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- JP2020143044A JP2020143044A JP2020014109A JP2020014109A JP2020143044A JP 2020143044 A JP2020143044 A JP 2020143044A JP 2020014109 A JP2020014109 A JP 2020014109A JP 2020014109 A JP2020014109 A JP 2020014109A JP 2020143044 A JP2020143044 A JP 2020143044A
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- deuterium
- alkyl
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- compound
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- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 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
- 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
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 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
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000011707 mineral Chemical class 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
- 125000006608 n-octyloxy group Chemical group 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
- 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
- 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
- 230000001575 pathological 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
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 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
- 125000005547 pivalate group Chemical group 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 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
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 208000018320 severe joint pain Diseases 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
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 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
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 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
- 150000003567 thiocyanates Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class 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
- 238000012800 visualization Methods 0.000 description 1
- 230000002747 voluntary effect Effects 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
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- 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
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- 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
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Abstract
Description
Claims (43)
- 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。 - 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、請求項1に記載の化合物。
- 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、請求項1に記載の化合物。
- −R3は−Fである、請求項3に記載の化合物。
- 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、請求項1に記載の化合物。
- 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、請求項1に記載の化合物。
- −R3は−Fである、請求項6に記載の化合物。
- −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、請求項1に記載の化合物。
- −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、請求項1に記載の化合物。
- 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。 - −R2は重水素である、請求項10に記載の組成物。
- −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、請求項11に記載の組成物。
- −R3は−重水素である、請求項12に記載の組成物。
- −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、請求項10に記載の組成物。
- −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、請求項10に記載の組成物。
- −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、請求項10に記載の組成物。
- −R3は−Fである、請求項16に記載の組成物。
- 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、請求項10に記載の組成物。
- キサンチンオキシダーゼ阻害剤をさらに含む、請求項10に記載の組成物。
- 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、請求項19に記載の組成物。
- 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。 - −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、請求項21に記載の方法。
- −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、請求項21に記載の方法。
- −R3は−Fである、請求項23に記載の化合物。
- −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、請求項21に記載の方法。
- −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、請求項21に記載の方法。
- 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、請求項21に記載の方法。
- 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、請求項21に記載の方法。
- 組成物はキサンチンオキシダーゼ阻害剤をさらに含む、請求項21に記載の方法。
- 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、請求項29に記載の方法。
- 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。 - 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。 - 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。 - 尿酸の腎再吸収の媒介はURAT1活性を調節することを含む、請求項33に記載の方法。
- 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。 - 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。 - 薬物の製造における請求項36の化合物の使用。
- 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請求項36の化合物の使用。
- ヒトにおいてURAT1活性を調節するための請求項36の化合物の使用。
- 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請求項36の化合物の使用。
- 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請求項36の化合物の使用。
- 組成物はエナンチオマー富化した組成物である、請求項10に記載の組成物。
- 組成物は単一のエナンチオマー組成物である、請求項10に記載の組成物。
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