TW201802103A - 一種奧貝膽酸及其中間體的製備方法 - Google Patents

一種奧貝膽酸及其中間體的製備方法 Download PDF

Info

Publication number: TW201802103A
Authority: TW; Taiwan
Prior art keywords: compound; formula; group; preparation; production method
Prior art date: 2016-07-13

Application number

TW106123325A

Other languages

English (en)

Chinese (zh)

Inventor

張順吉

王生

劉路

田偉偉

Original Assignee

江蘇恆瑞醫藥股份有限公司

Priority date (The priority date 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 date listed.)

2016-07-13

Filing date

2017-07-12

Publication date

2018-01-16

2017-07-12 Application filed by 江蘇恆瑞醫藥股份有限公司 filed Critical 江蘇恆瑞醫藥股份有限公司

2018-01-16 Publication of TW201802103A publication Critical patent/TW201802103A/zh

Links

238000002360 preparation method Methods 0.000 title claims abstract description 25
239000000543 intermediate Substances 0.000 title abstract description 5
ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 title abstract 3
229960001601 obeticholic acid Drugs 0.000 title abstract 3
150000001875 compounds Chemical class 0.000 claims abstract description 87
238000000034 method Methods 0.000 claims abstract description 22
230000002378 acidificating effect Effects 0.000 claims abstract description 16
239000003054 catalyst Substances 0.000 claims abstract description 14
239000000126 substance Substances 0.000 claims abstract description 12
238000005984 hydrogenation reaction Methods 0.000 claims abstract description 7
238000010438 heat treatment Methods 0.000 claims description 25
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 22
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 22
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 22
239000005642 Oleic acid Substances 0.000 claims description 22
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 22
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 22
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
125000006239 protecting group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
239000012279 sodium borohydride Substances 0.000 claims description 11
229910000033 sodium borohydride Inorganic materials 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 9
239000003638 chemical reducing agent Substances 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 8
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical group C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
235000019253 formic acid Nutrition 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
239000000047 product Substances 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
239000007795 chemical reaction product Substances 0.000 claims description 3
230000009467 reduction Effects 0.000 claims description 3
239000007868 Raney catalyst Substances 0.000 claims description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
229910000564 Raney nickel Inorganic materials 0.000 claims description 2
239000000463 material Substances 0.000 claims description 2
150000007522 mineralic acids Chemical class 0.000 claims description 2
150000007524 organic acids Chemical class 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 12
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
235000005985 organic acids Nutrition 0.000 claims 1
238000006243 chemical reaction Methods 0.000 abstract description 16
239000006227 byproduct Substances 0.000 abstract description 2
238000011031 large-scale manufacturing process Methods 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000003786 synthesis reaction Methods 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 7
-1 enol compound Chemical class 0.000 description 7
235000019439 ethyl acetate Nutrition 0.000 description 7
239000000243 solution Substances 0.000 description 7
0 C[C@](CCC(O*)=O)[C@@](CC1)[C@@](C)(CC[C@@]2[C@@](C)(CC[C@@](*)C3)[C@@]3C3*)[C@]1[C@]2C3=O Chemical compound C[C@](CCC(O*)=O)[C@@](CC1)[C@@](C)(CC[C@@]2[C@@](C)(CC[C@@](*)C3)[C@@]3C3*)[C@]1[C@]2C3=O 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 5
239000000203 mixture Substances 0.000 description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
230000003321 amplification Effects 0.000 description 4
239000003613 bile acid Substances 0.000 description 4
239000012535 impurity Substances 0.000 description 4
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 4
238000003199 nucleic acid amplification method Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000007787 solid Substances 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
125000006244 carboxylic acid protecting group Chemical group 0.000 description 3
239000012467 final product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
102100038495 Bile acid receptor Human genes 0.000 description 2
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
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 2
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 2
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
238000009776 industrial production Methods 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl 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
208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
108020005497 Nuclear hormone receptor Proteins 0.000 description 1
208000012654 Primary biliary cholangitis Diseases 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000004104 aryloxy group Chemical group 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
JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000002844 chenodeoxycholic acid derivative Substances 0.000 description 1
150000001801 chenodeoxycholic acids Chemical class 0.000 description 1
230000003098 cholesteric effect Effects 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
239000003925 fat Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 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
125000000623 heterocyclic group Chemical group 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 1
102000006255 nuclear receptors Human genes 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
208000007232 portal hypertension Diseases 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

TW106123325A 2016-07-13 2017-07-12 一種奧貝膽酸及其中間體的製備方法 TW201802103A (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
??201610551378.X		2016-07-13
CN201610551378		2016-07-13

Publications (1)

Publication Number	Publication Date
TW201802103A true TW201802103A (zh)	2018-01-16

Family

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TW106123325A TW201802103A (zh)	2016-07-13	2017-07-12	一種奧貝膽酸及其中間體的製備方法

Country Status (4)

Country	Link
CN (1)	CN108602850B (fr)
CA (1)	CA3027761A1 (fr)
TW (1)	TW201802103A (fr)
WO (1)	WO2018010651A1 (fr)

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Publication number	Priority date	Publication date	Assignee	Title
WO2019145977A1 (fr) *	2018-01-25	2019-08-01	Msn Laboratories Private Limited, R&D Center	PROCÉDÉ DE PRÉPARATION DE L'ACIDE 3α,7α-DIHYDROXY6α-ÉTHYL-5β-CHOLAN-24-OÏQUE
CN116178473B (zh) *	2018-12-10	2025-03-04	江西科睿药业有限公司	一种奥贝胆酸的制备方法
CN112898369B (zh) *	2019-12-04	2024-09-17	博瑞生物医药（苏州）股份有限公司	用于制备奥贝胆酸的方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1568706A1 (fr) *	2004-02-26	2005-08-31	Intercept Pharmaceuticals, Inc.	Nouveau agonist steroidal pour FXR
ITMI20050912A1 (it) *	2005-05-19	2006-11-20	Erregierre Spa	Processo di preparazione di acidi 3-a-ya(b)-diidrossi-6-a(b)-alchil-5b-colanici
WO2016045480A1 (fr) *	2014-09-28	2016-03-31	上海源力生物技术有限公司	Procédé de préparation d'acide obéticholique
CN105669811B (zh) *	2014-11-17	2020-09-04	正大天晴药业集团股份有限公司	新的7-酮-6β-烷基胆烷酸衍生物在制备奥贝胆酸以及其在医药领域的用途
CN104672290B (zh) *	2015-01-05	2017-06-06	北京普禄德医药科技有限公司	一种用于预防或治疗fxr‑介导的疾病的药物及其制备方法和用途
WO2016173493A1 (fr) *	2015-04-28	2016-11-03	Shanghai De Novo Pharmatech Co. Ltd.	Dérivé sulfonylaminocarbonyle, composition pharmaceutique et utilisations associées
TW201704251A (zh) *	2015-04-29	2017-02-01	正大天晴藥業集團股份有限公司	鵝去氧膽酸衍生物
CN106008639B (zh) *	2016-03-11	2019-01-08	深圳市塔吉瑞生物医药有限公司	用于预防或治疗fxr-介导疾病的胆烷酸化合物

2017
- 2017-07-12 WO PCT/CN2017/092554 patent/WO2018010651A1/fr not_active Ceased
- 2017-07-12 CN CN201780004218.6A patent/CN108602850B/zh active Active
- 2017-07-12 TW TW106123325A patent/TW201802103A/zh unknown
- 2017-07-12 CA CA3027761A patent/CA3027761A1/fr not_active Abandoned

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Publication number	Publication date
CN108602850A (zh)	2018-09-28
WO2018010651A1 (fr)	2018-01-18
CA3027761A1 (fr)	2018-01-18
CN108602850B (zh)	2021-04-06

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