CN112479850A - Compound and application thereof - Google Patents
Compound and application thereof Download PDFInfo
- Publication number
- CN112479850A CN112479850A CN202011481182.0A CN202011481182A CN112479850A CN 112479850 A CN112479850 A CN 112479850A CN 202011481182 A CN202011481182 A CN 202011481182A CN 112479850 A CN112479850 A CN 112479850A
- Authority
- CN
- China
- Prior art keywords
- compound
- medicaments
- compound according
- dichloromethane
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 21
- 210000004369 blood Anatomy 0.000 claims abstract description 17
- 239000008280 blood Substances 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 208000010706 fatty liver disease Diseases 0.000 claims abstract description 6
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 4
- 102000002072 Non-Receptor Type 1 Protein Tyrosine Phosphatase Human genes 0.000 claims abstract 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000003524 antilipemic agent Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 230000004580 weight loss Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 241000699670 Mus sp. Species 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241001205401 Aspergillus cristatus Species 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000004930 Fatty Liver Diseases 0.000 description 3
- 206010019708 Hepatic steatosis Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000012000 cholesterol Nutrition 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
- -1 digluconate Chemical compound 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- 235000013616 tea Nutrition 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241001122767 Theaceae Species 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000004185 liver Anatomy 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
- 238000000034 method Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000012360 testing method Methods 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
- RQXXCWHCUOJQGR-UHFFFAOYSA-N 1,1-dichlorohexane Chemical compound CCCCCC(Cl)Cl RQXXCWHCUOJQGR-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 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
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 101100299622 Mus musculus Ptpn1 gene Proteins 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 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
- 150000001350 alkyl halides Chemical class 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000014590 basal diet Nutrition 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
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
- 239000003833 bile salt Substances 0.000 description 1
- 230000017531 blood circulation Effects 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000012258 culturing Methods 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
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical compound CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical compound CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water 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
- 230000035622 drinking Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([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
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000021590 normal diet Nutrition 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
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940049954 penicillin Drugs 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
- 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
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 229940103117 simvastatin 10 mg Drugs 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
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/56—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing hydroxy groups
- C07C47/565—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing hydroxy groups all hydroxy groups bound to the ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the technical field of compound medicine application. The invention discloses a compound and application thereof in preparation of preparations with protein tyrosine phosphatase 1B inhibitory activity, medicaments for treating type II diabetes, medicaments for reducing blood sugar, medicaments for reducing blood fat, medicaments for losing weight and medicaments for treating fatty liver diseases.
Description
Technical Field
The invention belongs to the technical field of compound medicine application.
Background
Microorganisms play an important role in drug and food development, such as penicillin, streptomycin, statin drugs and the like, and make great contribution to the health industry of human beings.
The invention belongs to the technical field of medical food, and particularly relates to a compound prepared by fermenting eurotium cristatum in different culture media and extracting and separating. The compounds and their analogs, derivatives, prodrugs, metabolites and active salts thereof (representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, isothionate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmitate, pectate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, acetate, thiocyanate, fumarate, acetate, propionate, acetate, P-toluenesulfonate and undecanoate. Likewise, basic nitrogen-containing groups may be quaternized with: lower alkyl halides such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkyl sulfates such as dimethyl sulfate, diethyl sulfate, dibutyl sulfate, and diamyl sulfate; long chain halides such as decyl, dodecyl, tetradecyl and octadecyl chlorides, bromides and iodides; arylalkyl halides such as benzyl bromide and phenethyl bromide and others. Thus obtaining a product that is soluble or dispersible in water or oil. Examples of acids which can be used to form pharmaceutically acceptable acid addition salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, and organic acids such as oxalic acid, maleic acid, succinic acid and citric acid), and their use in the preparation of pharmaceuticals, health foods and functional foods for regulating blood lipids, improving blood circulation, alleviating fatty liver, and reducing weight.
Disclosure of Invention
The invention aims to provide a compound, which has the following structural formula;
the compound provided by the invention is applied to preparation of preparations with protein tyrosine phosphatase 1B inhibitory activity, medicines for treating type II diabetes, medicines for reducing blood sugar, medicines for reducing blood fat, medicines for losing weight and medicines for treating fatty liver diseases.
Drawings
FIG. 1 is a reverse phase high performance liquid chromatogram of a compound.
FIG. 2 is a graph of the results of a blood glucose test for a compound.
FIG. 3 is a graph of the results of a compound fatty liver experiment.
FIG. 4 is a graph showing the results of the compound cholesterol, triglyceride, low density lipoprotein and body weight experiments.
Detailed Description
Example 1
1. Isolation of fungi
Eurotium cristatum was isolated from Jingwei Fuzhuan tea (Xianyangjing Fu tea Co., Ltd.) according to the methods of the literature (Yangjuan, Wangqianmei, Penwen, Ji Ainshen, Zwenjie, Yangliang, isolation and identification of microorganisms among 8 commercially available "Jinhua" teas, tropical agriculture, 2019,39(10), 81-88).
2. Fermentation culture of fungi
Preparing activated Eurotium cristatum into spore suspension, inoculating to sterilized tea culture medium, standing at 25-32 deg.C, fermenting and culturing for 10-30 days.
2. Preparation of active compounds
Extracting the fermented product with methanol, ethanol, ethyl acetate, acetone, dichloromethane, diethyl ether, or supercritical extraction (but not limited to the above method) to obtain extract.
Dissolving the extract into a mixed solvent of dichloromethane and methanol, mixing the crude fermentation extract with column chromatography silica gel (100-200 mesh) at a weight ratio of 1:1.5, and performing reduced pressure column chromatography separation.
The column chromatography is eluted by organic solvent systems of n-hexane and dichloromethane with different proportions, wherein the volume ratios of the n-hexane to the dichloromethane are 100%, 1:99 (the n-hexane: the dichloromethane to obtain the sample A), 2:98 (the n-hexane: the dichloromethane to obtain the sample B), 3:97 (the n-hexane: the dichloromethane to obtain the sample C), 4:96 (the n-hexane: the dichloromethane to obtain the sample D), 5:95 (the n-hexane: the dichloromethane to obtain the sample E), 6:94 (the n-hexane: the dichloromethane to obtain the sample F), 8:92 (the n-hexane: the dichloromethane to obtain the sample G) and 10:90 (the n-hexane: the dichloromethane to obtain the sample H), and 8 fractions with the polarity from small to large are.
And (3) separating the sample B by using gel Sephadex LH-20 column chromatography, wherein an eluent is n-hexane to dichlorohexane (the volume ratio is 2:1), collecting 1 fraction per 10ml, and combining according to the analysis result of the high performance liquid chromatography to obtain 5 fractions.
Wherein fraction 3 is purified by reversed-phase high performance liquid chromatography using Agilent reversed-phase C18 column and mobile phase of 40% acetonitrile in water-100% acetonitrile (20 min) to obtain the target compound (shown in FIG. 1).
3. Structural identification of compounds
Performing purity identification on the prepared target compound by HPLC, performing structure identification on a sample with the purity of more than 98% by mass spectrometry and nuclear magnetic resonance technology, and measuring the nuclear magnetic resonance by a Bruker AVANCE DRX-500 nuclear magnetic resonance instrument; mass spectra were determined using an Agilent 6520Q-TOF mass spectrometer.
Nuclear magnetic resonance hydrogen spectrum data delta of the target compoundH(Pyridine-d5)：12.45(s)，10.57(s)，7.37(s)，6.16(dd,J＝14.5,10.5Hz)，6.08(dd,J＝14.5,10.5Hz)，5.78(dt,J＝14.5,7.0Hz)，5.56,(dq,J＝14.5,7.5Hz)，5.41(brt,J＝7.5Hz)，3.48(d,J＝7.5Hz)，3.36(t,J＝7.5Hz)，2.60(dt,J＝7.5,7.5Hz)，1.64(s)，1.63(d,J＝7.5Hz)，1.59(s)；
Nuclear magnetic resonance carbon spectrum data delta of the target compoundC(Pyridine-d5)：197.4，155.2，148.8，133.7，132.6，132.2，131.4，129.2，128.7，127.9，126.6，122.7，118.9，35.2，27.9，26.1，24.8，18.4，18.0；
High-resolution ESI mass spectrum [ M + Na ] of target compound]+m/z 323.1621，C19H24NaO3Calculated value 323.1621).
The molecular structural formula of the target compound is determined as follows:
4. inhibitory activity of compound on protein tyrosine phosphatase 1B:
protein tyrosine phosphatase 1B (PTP 1B) is an important target for screening and treating type II diabetes.
(a) Recombinant PTP1B protein (Recombinant mouse PTP1B proteinab42574(ab42574)) was purchased from Abcam corporation.
(b) The screening adopts a transparent Beckman96 pore plate, the reaction system is 80 mu L, the temperature is 37 ℃, and the substrate concentration, the enzyme concentration, the reaction time and the like are optimized on the basis.
Finally, the enzyme reaction system is determined to have the following composition: 10mmol/L Tris HCl, pH 7.6, 10mmol/L PNPP, 2% DMSO, 50. mu.g/mL PTP 1B.
The reaction system was mixed well and left at 37 ℃ for 30 min. The reaction was terminated by adding 1M NaOH, and the absorbance (A) at a wavelength of 405nm was measured on a microplate reader, and the enzyme activity was calculated by subtracting the background value from the measurement result.
Computing IC5011.86. mu.M.
5. Hypoglycemic effect of compound on ob/ob mice
Grouping experiments: average grouping of ob/ob mice according to blood glucose values and body weights: (1) c57 mice fed with normal feed were used as a blank control group; (2) model control group (ob/ob); (3) 100mg/kg of metformin; (4) administration group (Compound 5.0mg/kg) 10 of them were administered to each group for 5 weeks.
Blank, model, dosing group, and positive control group blood glucose levels (fig. 2).
TABLE 1 Effect of Compounds on blood glucose in ob/ob diabetic mice (fasting blood glucose)
6. The compound pair can relieve the blood lipid index of a C57 mouse high fat feeding model and reduce the body weight
(1) Experimental Material
Experimental animals: c57 mouse, weight 20-25g, male, supplied by Beijing Huafukang Biotech GmbH.
② high-fat feed: beijing Huafukang Biotechnology GmbH.
③ testing the tested product: the compound is administered at a daily dose of 5mg/kg body weight;
fourthly, positive contrast medicine: simvastatin, 10mg/kg body weight, manufactured by Hangzhou Moshadong pharmaceuticals, Inc.
(2) The test method comprises the following steps:
40C 57 mice were taken, weighing 20-25g, and were male. The groups were randomly divided into 2 groups, 10 of which were blank control groups and the remaining 30 were high lipid models. The blank control group was fed with normal diet, and the other 30 animals were fed with high fat diet (formula: 78.6% basal diet, 10% lard, 10% egg yolk powder, 1% cholesterol, 0.4% bile salt), and had free access to water. After 8 weeks, after all animals are fasted for 12 hours, blood is collected from fundus venous plexus, and TC and TG contents in serum are measured to confirm molding conditions.
The molded animals were then randomly grouped into groups of 8 animals each, and fed as before. (1) C57 mice fed with normal feed were used as a blank control group; (2) feeding high fat feed all the time as model high fat control; (3) simvastatin 10 mg/kg; (4) group to be administered (Compound 5.0 mg/kg).
The administration is carried out by intragastric administration once a day for 8 weeks.
Both the blank control group and the model high-fat control group were given the same volume of distilled water.
After 8 weeks of administration and 12h of fasting, blood is collected from the fundus venous plexus after the last administration, and analysis is carried out by using a semi-automatic biochemical analyzer according to the test method of the serum cholesterol and triglyceride kit specification.
The analyzer detects the contents of two indexes in the serum and weighs the body weight.
And dissecting the mouse, taking a liver section, and observing the occurrence condition of the fatty liver under a microscope.
A significant reduction in fat particles was seen in the group administered (figure 3).
The results showed that cholesterol, triglyceride levels, low density lipoprotein levels in the blood of the administered group, and body weight were significantly reduced compared to the control group (fig. 4).
TABLE 2 Effect of Compounds on blood lipid-related indices in C57 mice
During the experiment, the behavior and activity of the C57 mice were observed in real time, the body weight and death were recorded, and blood samples and liver samples were collected after eight weeks of administration. Within sixteen weeks of the experiment, none of the tested animals died, and the food intake, water drinking and feces were normal.
TABLE 3 Effect of Compounds on body weight in C57 mice
Claims (7)
1. A compound of the formula:
2. use of a compound according to claim 1 for the preparation of a formulation having an inhibitory activity on protein tyrosine phosphatase 1B.
3. The use of a compound according to claim 1 for the manufacture of a medicament for the treatment of type II diabetes.
4. Use of a compound according to claim 1 for the preparation of a medicament for lowering blood glucose.
5. The use of a compound according to claim 1 for the preparation of a hypolipidemic agent.
6. Use of a compound according to claim 1 for the manufacture of a medicament for weight loss.
7. The use of a compound according to claim 1 in a medicament for the treatment of fatty liver disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011481182.0A CN112479850A (en) | 2020-12-15 | 2020-12-15 | Compound and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011481182.0A CN112479850A (en) | 2020-12-15 | 2020-12-15 | Compound and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112479850A true CN112479850A (en) | 2021-03-12 |
Family
ID=74917185
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011481182.0A Pending CN112479850A (en) | 2020-12-15 | 2020-12-15 | Compound and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112479850A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411781A (en) * | 2008-11-21 | 2009-04-22 | 普洱市人民政府茶产业发展办公室科技服务中心 | Use of pu'er tea in preparing medicament for treating or preventing diabetes |
| CN103860529A (en) * | 2014-03-25 | 2014-06-18 | 华北制药集团新药研究开发有限责任公司 | Novel application of auroglaucin compounds |
-
2020
- 2020-12-15 CN CN202011481182.0A patent/CN112479850A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411781A (en) * | 2008-11-21 | 2009-04-22 | 普洱市人民政府茶产业发展办公室科技服务中心 | Use of pu'er tea in preparing medicament for treating or preventing diabetes |
| CN103860529A (en) * | 2014-03-25 | 2014-06-18 | 华北制药集团新药研究开发有限责任公司 | Novel application of auroglaucin compounds |
Non-Patent Citations (1)
| Title |
|---|
| PANPAN ZHANG等: "Anti-inflammatory prenylbenzaldehyde derivatives isolated from Eurotium cristatum", 《PHYTOCHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101221973B1 (en) | Composition for Preventing or Treating of Obesity, Hyperlipidemia, Fatty Liver or Diabetes Comprising Indole-3-carbinol Derivatives as Active Ingredients | |
| KR100896700B1 (en) | A.tuberosum Rottl. extract having an activity of activating choline acetyltransferase in brain nerve cells | |
| CN106994131A (en) | A kind of application for adjusting lipid metaboli and fat compound PAQG in pharmacy | |
| KR20180043342A (en) | Improved methods for producing fucoxanthin and / or polysaccharides from microalgae | |
| CN110898053B (en) | Application of monascin C in preparation of fat-reducing product | |
| CN112479850A (en) | Compound and application thereof | |
| CN112608224A (en) | Compound and application thereof | |
| CN112479849A (en) | Compound and application thereof | |
| CN112521260A (en) | Compound and application thereof | |
| CN106456594A (en) | Ppar gamma activating agent | |
| CN108017600A (en) | Six kinds from terpenoid of Common Sage Herb and its preparation method and application | |
| CN108310226B (en) | Composition with effect of preventing and treating diabetes as well as preparation method and application thereof | |
| JP4939761B2 (en) | Ingredients of stone lotus flowers and their uses | |
| LU503166B1 (en) | A compound and its applications | |
| TWI577382B (en) | Plant extract | |
| CN112047910B (en) | Aromatic farnesyl compound and application thereof | |
| CN111544440A (en) | Application of diosmin and composition in preparation of anti-obesity product | |
| CN116730961B (en) | Bisabolane sesquiterpenoids and application thereof as MptpB inhibitor | |
| TWI484973B (en) | Mixture from fermentation of anoectochilus formosanus hayata by microorganism and use thereof | |
| CN111304093A (en) | Monascus for preparing monascin C and method for preparing monascin C by using monascin C | |
| JP7330575B2 (en) | Use of monascinol in the preparation of fat-reduced products | |
| CN112206229A (en) | Composition for treating fatty liver, hepatitis and hepatic fibrosis and its preparation method | |
| CN114569613B (en) | Application of dauricine alkaloid compound in treatment of metabolic diseases | |
| TWI825706B (en) | Lactobacillus paracasei fermented turmeric for mediating metabolic diseases | |
| KR101466381B1 (en) | Food and pharmaceutical composition for preventing or improving obesitiy comprising specific compound isolated from Eisenia bicyclis as effective component |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210312 |
|
| RJ01 | Rejection of invention patent application after publication |