JPH0197A - 16-membered ring macrolide compound - Google Patents
16-membered ring macrolide compoundInfo
- Publication number
- JPH0197A JPH0197A JP62-154826A JP15482687A JPH0197A JP H0197 A JPH0197 A JP H0197A JP 15482687 A JP15482687 A JP 15482687A JP H0197 A JPH0197 A JP H0197A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- acid
- formula
- membered ring
- coc
- 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 description 46
- 239000003120 macrolide antibiotic agent Substances 0.000 title 1
- 239000000126 substance Substances 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 230000000844 anti-bacterial effect Effects 0.000 description 9
- 239000003242 anti bacterial agent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 229930194936 Tylosin Natural products 0.000 description 5
- 239000004182 Tylosin Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 5
- 229960004059 tylosin Drugs 0.000 description 5
- 235000019375 tylosin Nutrition 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- XJSFLOJWULLJQS-NGVXBBESSA-N josamycin Chemical compound CO[C@H]1[C@H](OC(C)=O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 XJSFLOJWULLJQS-NGVXBBESSA-N 0.000 description 4
- 229960004144 josamycin Drugs 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical compound OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000000434 field desorption mass spectrometry Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- YRMCBQLZVBXOSJ-PCFSSPOYSA-N (e)-3-[(6r,6as)-4-hydroxy-6-methoxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide Chemical compound CO[C@H]1NC2=C(O)C(C)=CC=C2C(=O)N2C=C(\C=C\C(N)=O)C[C@@H]12 YRMCBQLZVBXOSJ-PCFSSPOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- CFPHMAVQAJGVPV-UHFFFAOYSA-N 2-sulfanylbutanoic acid Chemical compound CCC(S)C(O)=O CFPHMAVQAJGVPV-UHFFFAOYSA-N 0.000 description 1
- RQPNXPWEGVCPCX-UHFFFAOYSA-N 3-sulfanylbutanoic acid Chemical compound CC(S)CC(O)=O RQPNXPWEGVCPCX-UHFFFAOYSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 102000009338 Gastric Mucins Human genes 0.000 description 1
- 108010009066 Gastric Mucins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- IEMDOFXTVAPVLX-YWQHLDGFSA-N Leucomycin A1 Chemical compound CO[C@H]1[C@H](O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 IEMDOFXTVAPVLX-YWQHLDGFSA-N 0.000 description 1
- PQMWYJDJHJQZDE-UHFFFAOYSA-M Methantheline bromide Chemical compound [Br-].C1=CC=C2C(C(=O)OCC[N+](C)(CC)CC)C3=CC=CC=C3OC2=C1 PQMWYJDJHJQZDE-UHFFFAOYSA-M 0.000 description 1
- DMUAPQTXSSNEDD-QALJCMCCSA-N Midecamycin Chemical compound C1[C@](O)(C)[C@@H](OC(=O)CC)[C@H](C)O[C@H]1O[C@H]1[C@H](N(C)C)[C@@H](O)[C@H](O[C@@H]2[C@H]([C@H](OC(=O)CC)CC(=O)O[C@H](C)C/C=C/C=C/[C@H](O)[C@H](C)C[C@@H]2CC=O)OC)O[C@@H]1C DMUAPQTXSSNEDD-QALJCMCCSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [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
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 229960002757 midecamycin Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- MXHTZQSKTCCMFG-UHFFFAOYSA-N n,n-dibenzyl-1-phenylmethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CC1=CC=CC=C1 MXHTZQSKTCCMFG-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
〔発明の前景〕
技術分野
本発明は、新規な16員環マクロラード系化合物に関す
るものである。さらに詳しくは、本発明は、抗生物質と
して既知の16i(環マクロラード系化合物の、新規で
且つ生体内抗菌活性に優れた誘導体に関するものである
。DETAILED DESCRIPTION OF THE INVENTION [Foreground of the Invention] Technical Field The present invention relates to a novel 16-membered ring macrolade compound. More specifically, the present invention relates to a novel derivative of 16i (ring macrolade compound), which is known as an antibiotic, and has excellent in vivo antibacterial activity.
先行技術
16員環マクロラード系化合物は、抗生物質の一つとし
て既に知られている物質である。Prior Art A 16-membered ring macrolade compound is a substance already known as an antibiotic.
既知の16員環マクロラード系化合物として、式([1
で示される化合物がある。As a known 16-membered ring macrolade compound, the formula ([1
There is a compound shown by
(式中、AはHO−10−あるいは
RはOCH又はCHを表わし、R2はHRはCHを表わ
し、R3はH%CH3、
CH20Hあるいは
RはCH3又はC2H5を表わし、R5はH1C0CH
又はCOC2H5を表わし、R6はH又はCOC2H5
を表わし、R7はHlCOCHCOC2H5、C0C3
H7又は3ゝ
C0CHCH(CH3) 2を表わす)この式(n)で
表わされる化合物からなる抗生物質としては、例えば次
のものが挙げられる。(In the formula, A is HO-10- or R represents OCH or CH, R2 is HR represents CH, R3 is H%CH3, CH20H or R is CH3 or C2H5, R5 is H1C0CH
or represents COC2H5, R6 is H or COC2H5
, R7 is HlCOCHCOC2H5, C0C3
Examples of antibiotics comprising the compound represented by formula (n) (representing H7 or 3'C0CHCH(CH3) 2) include the following.
2,7/
抗生物質 A Rt R2R3ジヨ
サマイシン HO−OCH3HHロイコマイシ
ンA HO−0CR3HHTMS−19−Q
HO−OCH3HHミデカマイシン
HO−0CR3HHC
)CH3
RR6R7
R45
CH3HHC0C3H7
CH3HC0C2H3COC3H7
CHCOCHHCOC2H5
CH3I HH
CHHHH
これらは、既に抗菌剤として、広くヒトや動物に用いら
れている。従って、マクロラード系化合物は、医薬品(
抗菌剤)として重要な位置を占めていると言える。一般
に、化学物質の生理活性は、その化学構造に依存すると
ころが大きく、マクロラード系化合物についても、その
アグリコン部分および糖部分の種類または置換基におい
て、既存のものと異なる化合物に対して不断の希求があ
る。2,7/ Antibiotic A Rt R2R3 Diyosamycin HO-OCH3HH Leucomycin A HO-0CR3HHTMS-19-Q
HO-OCH3HH midecamycin
HO-0CR3HHC )CH3 RR6R7 R45 CH3HHC0C3H7 CH3HC0C2H3COC3H7 CHCOCHHCOC2H5 CH3I HH CHHHH These are already widely used as antibacterial agents in humans and animals. Therefore, macrolade-based compounds can be used as pharmaceuticals (
It can be said that it occupies an important position as an antibacterial agent. In general, the physiological activity of a chemical substance largely depends on its chemical structure, and there is a constant demand for macrolade compounds that differ from existing ones in the type or substituents of their aglycone moieties and sugar moieties. There is.
要旨
本発明者等は、16M環マクロラード系化合物の18位
のアルデヒド部分に着目して、生体内抗菌活性に優れた
誘導体を提供すべく検討を重ねた結果、Sを含む5又は
6B環ラクトンを形成させた誘導体が、出発抗生物質に
比して、経口投与において極めて高い感染治療効果(生
体内抗菌活性)を示すことを見出して、本発明を完成し
た。Summary The present inventors focused on the aldehyde moiety at position 18 of 16M-ring macrolade compounds, and as a result of repeated studies to provide a derivative with excellent in vivo antibacterial activity, the present inventors discovered that a 5- or 6-B ring lactone containing S The present invention was completed based on the discovery that a derivative in which the compound has been formed exhibits an extremely high infection treatment effect (in vivo antibacterial activity) when administered orally, compared to the starting antibiotic.
すなわち、本発明による16員環マクロラード系化合物
は、下記の式〔I〕で示されるもの又はその酸付加塩で
ある。That is, the 16-membered ring macrolade compound according to the present invention is represented by the following formula [I] or an acid addition salt thereof.
(式中、nは0又は1であり、RoはH又は直鎖もしく
は分枝アルキル基を表わし、AはHO−1RはOCH又
はCH3を表わし、
R2はH又はCH3を表わし、R3はH%CH3、H2
0H
RはCH3又はC2H5を表わし、R5はH2C0CH
又はCOC2H5を表わし、R6はH又はCOCHを表
わし、R7はH1
COCHCOCHC0C3H7又は
3ゝ 2 5ゝ
C0CHCH(CH3) 2を表わす)効果
上記のように、本発明による16員環マクロラード系化
合物は、その親化合物に比べて経口投与での生体内抗菌
活性が大きい。(In the formula, n is 0 or 1, Ro represents H or a linear or branched alkyl group, A represents HO-1R represents OCH or CH3, R2 represents H or CH3, R3 represents H% CH3, H2
0H R represents CH3 or C2H5, R5 is H2C0CH
or COC2H5, R6 represents H or COCH, and R7 represents H1 COCHCOCHC0C3H7 or 3ゝ 2 5ゝC0CHCH(CH3) 2) Effect As described above, the 16-membered ring macrolade compound according to the present invention has the following effects: It has greater in vivo antibacterial activity upon oral administration than the parent compound.
化合物
本発明により提供される化合物は、上記の式〔I〕で示
される。nは、0であることが好ましい。また、Rは、
低級アルキル(01〜C6程度)であることが好ましい
。Meはメチル基である。Compound The compound provided by the present invention is represented by the above formula [I]. It is preferable that n is 0. Also, R is
Lower alkyl (about 01 to C6) is preferred. Me is a methyl group.
式(13で表わされる本発明化合物の一例を示せば、下
記の通りである。An example of the compound of the present invention represented by formula (13) is as follows.
ト
(m) (JM−2MP)
(IVI (TL−2MP)
これらの化合物は、分子中に塩基性のアミノ基をNuて
いるので、酸付加塩の形で存在し、うる。(m) (JM-2MP) (IVI (TL-2MP) These compounds have a basic amino group in their molecules, so they exist in the form of acid addition salts.
このような酸付加塩を形成するのに用いうる酸としては
、例えば、塩酸、硫酸、リン酸等の無機酸、あるいは酢
酸、酒石酸、プロピオン酸、クエン酸、コハク酸等の有
機酸が包含される。Acids that can be used to form such acid addition salts include, for example, inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, or organic acids such as acetic acid, tartaric acid, propionic acid, citric acid, and succinic acid. Ru.
化合物の製造
前記式〔l〕の化合物は、その置換基の導入および結合
鎖の形成に合目的的な任意の方法によって製造すること
ができる。代表的な方法は、公知の式(II)の化合物
の17−位に結合しているホルミル基を含硫ラクトン環
に変換することからなるものである。具体的には、たと
えば、前記式(II)の化合物とメルカプトカルボン酸
とを縮合させることにより式CI)の本発明化合物を製
造することができる。即ち、化合物(n)を活性水素原
子を持たない有機溶媒中で、1.3−ジシクロへキシル
カルボジイミド(以下DCCと略す)および必要に応じ
て塩基の存在下、
H
R−CH(CH2)、C0OH(式中n1Roは前記と
同義である)で表わされるメルカプトカルボン酸と、−
25〜60℃で1〜6旧間反応させる。ここで、活性水
素原子を持たない有機溶媒としては、クロロホルム、ジ
クロロメタン、ジクロロエタン、ベンゼン、トルエン、
アセトン、酢酸エチル、テトラヒドロフラン、ジメチル
ホルムアミド、ピリジン等を挙げることができるが、そ
の中でもクロロホルムまたはジクロロメタンが好ましい
。塩基としては、三級アミン、たとえばピリジン、ジメ
チルアミノピリジン、キノリン、トリエチルアミン、ト
リベンジルアミン、および無機塩基、たとえば炭酸ナト
リウム、炭酸カリウム、水酸化ナトリウム、水酸化カリ
ウム等を挙げることができるが、その巾でもジメチルア
ミノピリジンが最も好ましい。メルカプトカルボン酸の
例としては、メルカプト酢酸、2−メルカプトプロピオ
ン酸、3−メルカプトプロピオン酸、2−メルカプトブ
タン酸、3−メルカプトブタン酸等を挙げることができ
る。反応生成物は、シリカゲルカラムクロマトグラフィ
ーを用いて精製することができる。Preparation of Compound The compound of formula [1] above can be prepared by any method suitable for introducing the substituent and forming a bonded chain. A typical method consists of converting the formyl group attached to the 17-position of the known compound of formula (II) into a sulfur-containing lactone ring. Specifically, for example, the compound of formula (CI) of the present invention can be produced by condensing the compound of formula (II) with a mercaptocarboxylic acid. That is, compound (n) is prepared in an organic solvent having no active hydrogen atom in the presence of 1,3-dicyclohexylcarbodiimide (hereinafter abbreviated as DCC) and optionally a base, H R-CH(CH2), A mercaptocarboxylic acid represented by C0OH (in the formula, n1Ro has the same meaning as above), and -
React at 25-60°C for 1-6 hours. Here, examples of organic solvents without active hydrogen atoms include chloroform, dichloromethane, dichloroethane, benzene, toluene,
Examples include acetone, ethyl acetate, tetrahydrofuran, dimethylformamide, and pyridine, among which chloroform or dichloromethane is preferred. Bases include tertiary amines such as pyridine, dimethylaminopyridine, quinoline, triethylamine, tribenzylamine, and inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, etc. Dimethylaminopyridine is most preferable in terms of width. Examples of mercaptocarboxylic acids include mercaptoacetic acid, 2-mercaptopropionic acid, 3-mercaptopropionic acid, 2-mercaptobutanoic acid, 3-mercaptobutanoic acid, and the like. The reaction product can be purified using silica gel column chromatography.
以上のようにして製造される式(1)の化合物は、それ
自体公知の方法により、例えば、塩酸、リン酸、硫酸、
コハク酸、プロピオン酸、クエン酸等と共に処理するこ
とにより、酸付加塩に変えることができる。The compound of formula (1) produced as described above can be produced by a method known per se, such as hydrochloric acid, phosphoric acid, sulfuric acid,
It can be converted into an acid addition salt by treatment with succinic acid, propionic acid, citric acid, etc.
なお、式(n)の化合物は公知の化合物であって、公知
の化合物(n)生産菌を培養し、分離・精製することに
よって得られる。生産菌の一例を挙げれば、次の通りで
ある。これらはいずれも当業者の容易に入手しうる微生
物である。The compound of formula (n) is a known compound, and can be obtained by culturing a known compound (n)-producing bacterium, followed by isolation and purification. An example of producing bacteria is as follows. All of these microorganisms are easily available to those skilled in the art.
化合物の有用性
本発明により提供される前記式(1)の化合物およびそ
の塩は、各種のグラム陽性細菌やマイコプラズマ等の病
原微生物に対して強い抗菌力と優れた生体利用効率を示
す物質である。その高い活性は以下の試験により立証さ
れる。Usefulness of the Compound The compound of formula (1) and its salt provided by the present invention are substances that exhibit strong antibacterial activity and excellent bioavailability against pathogenic microorganisms such as various Gram-positive bacteria and mycoplasma. . Its high activity is evidenced by the following tests.
試験管内抗菌活性
本発明による前記式(1)の化合物は種々の微生物に対
して抗菌活性を示す物質であり、最小増殖阻11−濃度
(MIC1μg / ml )を寒天平板希釈法により
求めた結果は第1表の通りである。なお、対照として、
ジョサマイシンおよびタイロシンのMICを併記しであ
る。また、化合物の名称および構造は、前記具体例の通
りである。In vitro antibacterial activity The compound of the formula (1) according to the present invention is a substance that exhibits antibacterial activity against various microorganisms, and the minimum growth inhibitory concentration (MIC 1 μg/ml) was determined by the agar plate dilution method. It is as shown in Table 1. In addition, as a control,
The MICs of josamycin and tylosin are also shown. Further, the names and structures of the compounds are as in the above specific examples.
MICは、106個/mlに検定間の菌体懸濁液を調製
し、ミクロブランターで接種して、培養後の生育の有無
で判定した。ミューター・ヒントン寒天培地/pH7,
3/37℃/20時間。The MIC was determined by preparing a cell suspension between assays at 10 6 cells/ml, inoculating it with a microblunter, and determining the presence or absence of growth after culturing. Muter-Hinton agar/pH 7,
3/37℃/20 hours.
in vIvo抗菌活性
化合物〔l〕のマウス実験感染症に対する治療効果につ
いての実験例を示す。An example of an experiment on the therapeutic effect of an in vIvo antibacterial active compound [l] on experimental infections in mice is shown.
動 物nICR系雄性系中性マウス±Ig。 Animals: ICR male-neutral mice ± Ig.
1群6匹
試験ra:ミニスタフィロコッカスウレウス・スミス
接種菌量:1〜3X105CFU
/マウス
前培養した試験菌を5%胃粘膜ムチン
(gastric wucln )に懸濁させ、i、I
)、で所定量接種した。Test RA: 6 animals per group: Ministaphylococcus ureus Smith inoculation amount: 1 to 3 x 105 CFU/mouse The pre-cultured test bacteria were suspended in 5% gastric mucin, and
), the prescribed amount was inoculated.
薬剤投与:各薬剤を196 Tveen 80に懸濁さ
せ、菌接種1時間後、経口投与した。Drug administration: Each drug was suspended in 196 Tveen 80 and orally administered 1 hour after inoculation.
E D 5o値の算出方法:マウスは感染後7日間観察
し5Bchrons−Kacrbcr法によりEDso
値(1g/マウス)を算出した。Calculation method of ED5o value: Mice were observed for 7 days after infection, and EDso was determined by the 5Bchrons-Kacrbcr method.
The value (1 g/mouse) was calculated.
第2表の通りである。なお対照としてジョサマイシンと
タイロシンのEDso値を併記した。また、化合物の名
称および構造は前記具体例の通りである。It is as shown in Table 2. As a control, the EDso values of josamycin and tylosin are also shown. Further, the names and structures of the compounds are as in the above specific examples.
化合物III (JM−2MP) 4.6ジ
ヨサマイシン 4.4化合物IV
(TL −2MP) 1. 6タイロシン
5.2毒性
本発明の化合物(JM−2MPあるいはTL−2MP)
の400mg/kgマウスの徽をマウスに経口投与した
場合、70間の観察でマウスは金側生存していた。Compound III (JM-2MP) 4.6 Diyosamycin 4.4 Compound IV
(TL-2MP) 1. 6 Tylosin
5.2 Toxicity Compound of the present invention (JM-2MP or TL-2MP)
When a dose of 400 mg/kg of the drug was orally administered to mice, the mice survived on the gold side for 70 days.
化合物の用途
本発明により提供される新規化合物(I)は優れた抗菌
作用を有するものであって、各種細菌による感染症の予
防および治療のための抗菌剤の活性成分として使用する
ことができる。Uses of the Compound The novel compound (I) provided by the present invention has excellent antibacterial activity and can be used as an active ingredient of antibacterial agents for the prevention and treatment of infectious diseases caused by various bacteria.
感染症の予防および治療のための薬剤としての使用に際
して、化合物(1)およびその塩は、製剤として通常使
用されている種々の媒体、例えば水、塩溶液、アルコー
ル、植物油、ポリエチレングリコール、ゼラチン、ラク
トース、アミロース、ステアリン酸マグネシウム、タル
ク、シリル酸、パラフィン、芳谷油、脂肪酸モノグリセ
リド、ジグリセリド、ヒドロキシメチルセルロース等を
用い、カプセル剤、錠剤、散剤、シロップ剤、軟膏剤、
串刺、注射剤などの製剤型態にして投与することができ
る。投与量は、公知の親化合物について知られている値
より一般に少ないということができる。When used as a drug for the prevention and treatment of infectious diseases, compound (1) and its salts can be used in various media commonly used as formulations, such as water, salt solutions, alcohol, vegetable oils, polyethylene glycols, gelatin, Using lactose, amylose, magnesium stearate, talc, silylic acid, paraffin, Yoshitani oil, fatty acid monoglyceride, diglyceride, hydroxymethylcellulose, etc., capsules, tablets, powders, syrups, ointments,
It can be administered in the form of a skewer or injection. Dosages can generally be lower than those known for the known parent compounds.
化合物(I)は、また、新規な医薬品の合成中間体とし
ても角用な物質である。Compound (I) is also a useful substance as a synthetic intermediate for new pharmaceuticals.
実験例 下記の実施例は、本発明を説明するためのものである。Experimental example The following examples are intended to illustrate the invention.
実施例1(化合物m (JM−2MP)の合成)ジョサ
マイシン1.00gをジクロロメタン10m1に溶解し
、氷冷した。別に、DCC623agをジクロロメタン
10m1に溶解し、水冷下に2−メルカプトプロピオン
酸536μlを滴下して0℃で30分間撹拌した後、ジ
メチルアミノピリジンを100mg添加してさらに撹拌
した。この溶液を水冷下に先のジョサマイシン溶液に徐
々に加え、室温にして3日間撹拌した。反応混合物をク
ロロホルムで希釈し、飽和重曹水と共に振とうして、ク
ロロホルム層を分取した。水層をさらにクロロホルムで
2回抽出し、クロロホルム層を合せて無水硫酸ナトリウ
ムで乾燥した後、減圧下に溶媒を留去した。得られた残
渣を、クロロホルム−メタノール■100:1を溶出溶
媒系とするシリカゲルカラムクロマトグラフィーにて精
製後、ヘキサン沈殿により、無色粉末状の目的化合物(
0,34g)を得た。得られた化合物の分析値は、次の
通りである6
(イ)FD−MS (m/z):
917 ([M+1]” )。Example 1 (Synthesis of compound m (JM-2MP)) 1.00 g of josamycin was dissolved in 10 ml of dichloromethane and cooled on ice. Separately, DCC623ag was dissolved in 10 ml of dichloromethane, 536 μl of 2-mercaptopropionic acid was added dropwise under water cooling, and the mixture was stirred at 0° C. for 30 minutes, and then 100 mg of dimethylaminopyridine was added and further stirred. This solution was gradually added to the previous josamycin solution under water cooling, and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with chloroform, shaken with saturated aqueous sodium bicarbonate solution, and the chloroform layer was separated. The aqueous layer was further extracted twice with chloroform, the chloroform layers were combined and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography using chloroform-methanol (100:1) as the eluent system, and then precipitated with hexane to obtain the target compound as a colorless powder (
0.34 g) was obtained. The analytical values of the obtained compound are as follows: 6 (a) FD-MS (m/z): 917 ([M+1]'').
(ロ) ’H−NMR(500MHz、CDC13ゝ
内部標準TMS)δppm :
0、98.1.01、1.13.1、14.1、27.
1.29.1. 57.2. 13.2、31.2.5
2.2.73.3.30.3、 55.3. 89.4
. 19.4.45.4、 63.5. 08.5.4
9.5.64.6、06.6.58゜
実施例2(化合物IV (TL −2MP)の合成)タ
イロシン1.oo、、をジクロロメタン10m1に溶解
し、氷冷した。別に、DCC675a+gをジクロロメ
タン10m1に溶解し、水冷下に2:メルカプトプロピ
オン酸484μlを滴下して0℃で30分間撹拌した後
、ジメチルアミノピリジンを100mg添加して、さら
に撹拌した。この溶液を水冷下に先のタイロシン溶液に
徐々に加え、室温にして3日間撹拌した。反応混合物を
クロロホルムで希釈し、飽和重曹水と共に振とうして、
クロロホルム層を分取した。水層をさらにクロロホルム
で2回抽出し、クロロホルム層を合せて無水硫酸ナトリ
ウムで乾燥した後、減圧下に溶媒を留去した。得られた
残渣を、クロロホルム−メタノール−80:1〜50:
1を溶出溶媒系とするシリカゲルカラムクロマトグラフ
ィーにて精製後、ヘキサン沈殿により、無色粉末状の目
的化合物(0,48g)を得た。得られた化合物の分析
値は、次の通りである。(b) 'H-NMR (500 MHz, CDC13ゝ internal standard TMS) δppm: 0, 98.1.01, 1.13.1, 14.1, 27.
1.29.1. 57.2. 13.2, 31.2.5
2.2.73.3.30.3, 55.3. 89.4
.. 19.4.45.4, 63.5. 08.5.4
9.5.64.6, 06.6.58° Example 2 (Synthesis of Compound IV (TL-2MP)) Tylosin 1. oo was dissolved in 10 ml of dichloromethane and cooled on ice. Separately, DCC675a+g was dissolved in 10 ml of dichloromethane, 484 μl of 2:mercaptopropionic acid was added dropwise under water cooling, and the mixture was stirred at 0° C. for 30 minutes, followed by adding 100 mg of dimethylaminopyridine and further stirring. This solution was gradually added to the above tylosin solution while cooling with water, and the mixture was stirred for 3 days at room temperature. The reaction mixture was diluted with chloroform, shaken with saturated aqueous sodium bicarbonate,
The chloroform layer was separated. The aqueous layer was further extracted twice with chloroform, the chloroform layers were combined and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was mixed with chloroform-methanol-80:1-50:
After purification by silica gel column chromatography using 1 as the elution solvent, the desired compound (0.48 g) was obtained as a colorless powder by hexane precipitation. The analytical values of the obtained compound are as follows.
(イ)FD−MS (m/z): 1004 ((M+1) )。(a) FD-MS (m/z): 1004 ((M+1)).
(0) ’H−NMR(500MHz、CDC13ゝ
内部標準TMS)δppIl:
0.94.1.01.1.20.1.22.1.24.
1.26.1.29.1,58.1.79.2,49.
3.48.3.49.3.62.4,30.4.56.
4.98.5.08.5.55.5.92.6.25.
7.33゜
出願人代理人 佐 藤 −雄(0) 'H-NMR (500 MHz, CDC13ゝ internal standard TMS) δppIl: 0.94.1.01.1.20.1.22.1.24.
1.26.1.29.1, 58.1.79.2, 49.
3.48.3.49.3.62.4, 30.4.56.
4.98.5.08.5.55.5.92.6.25.
7.33゜Applicant's agent Mr. Sato
Claims (1)
合物又はその酸付加塩。 ▲数式、化学式、表等があります▼ 〔 I 〕 (式中、nは0又は1であり、R_0はH又は直鎖もし
くは分枝アルキル基を表わし、AはHO−、O=あるい
は▲数式、化学式、表等があります▼を表わし、 R_1はOCH_3又はCH_3を表わし、R_2はH
又はCH_3を表わし、R_3はH、CH_3CH_2
OH 又は▲数式、化学式、表等があります▼を表わし、 R_4はCH_3又はC_2H_5を表わし、R_5は
H、COCH_3又はCOC_2H_5を表わし、R_
6はH又はCOC_2H_5を表わし、R_7はH、C
OCH_3、COC_2H_5、COC_3H_7又は
COCH_2CH(CH_3)_2を表わす)[Scope of Claims] A 16-membered ring macrolade compound represented by the following formula [I] or an acid addition salt thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] (In the formula, n is 0 or 1, R_0 represents H or a straight chain or branched alkyl group, A is HO-, O= or ▲Mathical formula, There are chemical formulas, tables, etc. Represents ▼, R_1 represents OCH_3 or CH_3, R_2 represents H
or represents CH_3, R_3 is H, CH_3CH_2
OH or ▲There are mathematical formulas, chemical formulas, tables, etc.▼, R_4 represents CH_3 or C_2H_5, R_5 represents H, COCH_3 or COC_2H_5, R_
6 represents H or COC_2H_5, R_7 represents H, C
OCH_3, COC_2H_5, COC_3H_7 or COCH_2CH(CH_3)_2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15482687A JPS6497A (en) | 1987-06-22 | 1987-06-22 | 16-membered ring macrolide compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15482687A JPS6497A (en) | 1987-06-22 | 1987-06-22 | 16-membered ring macrolide compound |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH0197A true JPH0197A (en) | 1989-01-05 |
JPS6497A JPS6497A (en) | 1989-01-05 |
Family
ID=15592725
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP15482687A Pending JPS6497A (en) | 1987-06-22 | 1987-06-22 | 16-membered ring macrolide compound |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6497A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9567725B2 (en) | 2011-04-14 | 2017-02-14 | Harnischfeger Technologies, Inc. | Swing automation for rope shovel |
-
1987
- 1987-06-22 JP JP15482687A patent/JPS6497A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9567725B2 (en) | 2011-04-14 | 2017-02-14 | Harnischfeger Technologies, Inc. | Swing automation for rope shovel |
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