IL104049A - Antibiotic Derivatives of 7 (Dimotoxy) 7 Amino Forformicin Preparation and Pharmaceutical Preparations Containing Them - Google Patents
Antibiotic Derivatives of 7 (Dimotoxy) 7 Amino Forformicin Preparation and Pharmaceutical Preparations Containing ThemInfo
- Publication number
- IL104049A IL104049A IL10404992A IL10404992A IL104049A IL 104049 A IL104049 A IL 104049A IL 10404992 A IL10404992 A IL 10404992A IL 10404992 A IL10404992 A IL 10404992A IL 104049 A IL104049 A IL 104049A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- hydroxy
- group
- halogen
- ether
- Prior art date
Links
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- RQNVIKXOOKXAJQ-UHFFFAOYSA-N naphthazarin Chemical compound O=C1C=CC(=O)C2=C1C(O)=CC=C2O RQNVIKXOOKXAJQ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims description 100
- -1 cinnamyloxycarbonyl Chemical group 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 79
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 229910052736 halogen Chemical group 0.000 claims description 28
- 150000002367 halogens Chemical group 0.000 claims description 27
- 239000003054 catalyst Substances 0.000 claims description 24
- 238000005984 hydrogenation reaction Methods 0.000 claims description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 239000000376 reactant Substances 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 206010046914 Vaginal infection Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 8
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 150000007860 aryl ester derivatives Chemical class 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical group CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 239000003495 polar organic solvent Substances 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 239000000908 ammonium hydroxide Substances 0.000 claims description 3
- 150000007514 bases Chemical class 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 238000007336 electrophilic substitution reaction Methods 0.000 claims description 3
- 150000002334 glycols Chemical class 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 claims description 3
- YFEXZJKJPFNYKB-UHFFFAOYSA-N 2-(oxolan-2-yloxy)oxolane Chemical compound C1CCOC1OC1OCCC1 YFEXZJKJPFNYKB-UHFFFAOYSA-N 0.000 claims description 2
- NIRCAUPPZAUKDX-UHFFFAOYSA-N 5-benzyl-2-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-6-methylpyridazin-3-one Chemical compound O=C1C=C(CC=2C=CC=CC=2)C(C)=NN1CN(CC1)CCN1C1=CC=CC(Cl)=C1 NIRCAUPPZAUKDX-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 229910017009 AsCl3 Inorganic materials 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229910010220 LiAl4 Inorganic materials 0.000 claims description 2
- 229910020667 PBr3 Inorganic materials 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- OEYOHULQRFXULB-UHFFFAOYSA-N arsenic trichloride Chemical compound Cl[As](Cl)Cl OEYOHULQRFXULB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 2
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 2
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims 1
- DNKORVAXOJKDEO-UHFFFAOYSA-N 1,1,1-trichloro-2-(2,2,2-trichloroethoxymethoxymethoxy)ethane Chemical compound ClC(Cl)(Cl)COCOCOCC(Cl)(Cl)Cl DNKORVAXOJKDEO-UHFFFAOYSA-N 0.000 claims 1
- GAHRWPUTGHCERR-UHFFFAOYSA-N 1-[bis(2-chloroethoxy)methoxy-(2-chloroethoxy)methoxy]-2-chloroethane Chemical compound ClCCOC(OCCCl)OC(OCCCl)OCCCl GAHRWPUTGHCERR-UHFFFAOYSA-N 0.000 claims 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 claims 1
- GPAAEZIXSQCCES-UHFFFAOYSA-N 1-methoxy-2-(2-methoxyethoxymethoxymethoxy)ethane Chemical compound COCCOCOCOCCOC GPAAEZIXSQCCES-UHFFFAOYSA-N 0.000 claims 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims 1
- GBWMWHHLQDBPFP-UHFFFAOYSA-N 2-(thian-2-yloxy)thiane Chemical compound S1CCCCC1OC1SCCCC1 GBWMWHHLQDBPFP-UHFFFAOYSA-N 0.000 claims 1
- JMTBNBFBHBCERV-UHFFFAOYSA-N 2-(thiolan-2-yloxy)thiolane Chemical compound C1CCSC1OC1SCCC1 JMTBNBFBHBCERV-UHFFFAOYSA-N 0.000 claims 1
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 claims 1
- DPYDQXCMDBCRRK-UHFFFAOYSA-N 3-bromo-2-(3-bromooxan-2-yl)oxyoxane Chemical compound BrC1CCCOC1OC1C(Br)CCCO1 DPYDQXCMDBCRRK-UHFFFAOYSA-N 0.000 claims 1
- ZQVMXWDQXLWKLE-UHFFFAOYSA-N 4-methoxy-2-(4-methoxyoxan-2-yl)oxyoxane Chemical compound C1C(OC)CCOC1OC1OCCC(OC)C1 ZQVMXWDQXLWKLE-UHFFFAOYSA-N 0.000 claims 1
- ZXTCTDQZUWWAEY-UHFFFAOYSA-N 4-methoxy-2-(4-methoxythian-2-yl)oxythiane Chemical compound C1C(OC)CCSC1OC1SCCC(OC)C1 ZXTCTDQZUWWAEY-UHFFFAOYSA-N 0.000 claims 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 1
- 239000007868 Raney catalyst Substances 0.000 claims 1
- 229910000564 Raney nickel Inorganic materials 0.000 claims 1
- 229910006124 SOCl2 Inorganic materials 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 claims 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims 1
- 239000012320 chlorinating reagent Substances 0.000 claims 1
- 229930016911 cinnamic acid Natural products 0.000 claims 1
- 235000013985 cinnamic acid Nutrition 0.000 claims 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 claims 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims 1
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 claims 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 claims 1
- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 claims 1
- OZUGVJIHUINCMG-UHFFFAOYSA-N Purpuromycin Natural products COC(=O)C1=Cc2cc3C(O)CC4(Cc5c(O)c6C(=O)C=CC(=O)c6c(O)c5O4)Oc3c(O)c2C(=O)O1 OZUGVJIHUINCMG-UHFFFAOYSA-N 0.000 description 71
- 239000000243 solution Substances 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 39
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
- VGXVKHPGBHVPMW-UHFFFAOYSA-N methyl 4,4',9',10-tetrahydroxy-7'-methoxy-5',8',9-trioxospiro[3,4-dihydropyrano[4,3-g]chromene-2,2'-3h-benzo[f][1]benzofuran]-7-carboxylate Chemical class OC1=C2C(=O)C(OC)=CC(=O)C2=C(O)C(C2)=C1OC12CC(O)C(C=C2C=C(OC(=O)C2=C2O)C(=O)OC)=C2O1 VGXVKHPGBHVPMW-UHFFFAOYSA-N 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 229940035423 ethyl ether Drugs 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 229960001866 silicon dioxide Drugs 0.000 description 13
- CKLKRRFSZZUFKT-UHFFFAOYSA-N gammarRubromycin Natural products OC1=C2C(=O)C(OC)=CC(=O)C2=C(O)C(C2)=C1OC12CCC(C=C2C=C(OC(=O)C2=C2O)C(=O)OC)=C2O1 CKLKRRFSZZUFKT-UHFFFAOYSA-N 0.000 description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000002245 particle Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 7
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- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical group C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 229940037649 staphylococcus haemolyticus Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 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 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP91121674 | 1991-12-18 | ||
| EP92118035 | 1992-10-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL104049A0 IL104049A0 (en) | 1993-05-13 |
| IL104049A true IL104049A (en) | 1998-07-15 |
Family
ID=26129132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10404992A IL104049A (en) | 1991-12-18 | 1992-12-10 | Antibiotic Derivatives of 7 (Dimotoxy) 7 Amino Forformicin Preparation and Pharmaceutical Preparations Containing Them |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US5475010A (de) |
| EP (1) | EP0641346B1 (de) |
| JP (1) | JPH07502030A (de) |
| AT (1) | ATE138662T1 (de) |
| AU (1) | AU662943B2 (de) |
| CA (1) | CA2126216A1 (de) |
| DE (1) | DE69211161T2 (de) |
| DK (1) | DK0641346T3 (de) |
| ES (1) | ES2087567T3 (de) |
| IL (1) | IL104049A (de) |
| WO (1) | WO1993012115A1 (de) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5475010A (en) * | 1991-12-18 | 1995-12-12 | Gruppo Lepetit S.P.A. | 7'-amino-naphthazarin antibiotic derivatives |
| JP3490154B2 (ja) | 1994-09-30 | 2004-01-26 | 財団法人微生物化学研究会 | 新規抗生物質ルビマイシン、その製造法及びその用途 |
| US5530133A (en) * | 1995-05-25 | 1996-06-25 | Gruppo Lepetit Spa | 7'-amino-naphthazarin antibiotic derivatives |
| RU2135494C1 (ru) | 1995-12-01 | 1999-08-27 | Санкио Компани Лимитед | Гетероциклические соединения и композиция на их основе, проявляющая антагонистическое действие в отношении рецепторов тахикинина |
| US20100125146A1 (en) * | 2008-11-19 | 2010-05-20 | Johnson Matthey Public Limited Company | Method for making pharmaceutical compounds |
| US11589579B2 (en) * | 2017-09-22 | 2023-02-28 | Biotenzz Gesellschaft Für Biotechnologie Mbh | Polymeric particles containing microorganisms |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1455128A (en) * | 1973-03-19 | 1976-11-10 | Lepetit Spa | Purpuromycin and its derivatives |
| EP0447813A1 (de) * | 1990-02-28 | 1991-09-25 | GRUPPO LEPETIT S.p.A. | Wasserlösliche Salze von Purpuromycin und dieses enthaltende pharmazeutische Zusammensetzungen |
| US5475010A (en) * | 1991-12-18 | 1995-12-12 | Gruppo Lepetit S.P.A. | 7'-amino-naphthazarin antibiotic derivatives |
-
1992
- 1992-11-30 US US08/244,353 patent/US5475010A/en not_active Expired - Fee Related
- 1992-11-30 WO PCT/EP1992/002764 patent/WO1993012115A1/en not_active Ceased
- 1992-11-30 EP EP92924626A patent/EP0641346B1/de not_active Expired - Lifetime
- 1992-11-30 ES ES92924626T patent/ES2087567T3/es not_active Expired - Lifetime
- 1992-11-30 DE DE69211161T patent/DE69211161T2/de not_active Expired - Fee Related
- 1992-11-30 JP JP5510556A patent/JPH07502030A/ja active Pending
- 1992-11-30 DK DK92924626.2T patent/DK0641346T3/da active
- 1992-11-30 CA CA002126216A patent/CA2126216A1/en not_active Abandoned
- 1992-11-30 AU AU30833/92A patent/AU662943B2/en not_active Ceased
- 1992-11-30 AT AT92924626T patent/ATE138662T1/de not_active IP Right Cessation
- 1992-12-10 IL IL10404992A patent/IL104049A/en not_active IP Right Cessation
-
1995
- 1995-05-25 US US08/450,194 patent/US5559249A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2087567T3 (es) | 1996-07-16 |
| DE69211161T2 (de) | 1996-10-02 |
| AU3083392A (en) | 1993-07-19 |
| IL104049A0 (en) | 1993-05-13 |
| WO1993012115A1 (en) | 1993-06-24 |
| US5475010A (en) | 1995-12-12 |
| ATE138662T1 (de) | 1996-06-15 |
| EP0641346B1 (de) | 1996-05-29 |
| DK0641346T3 (da) | 1996-07-29 |
| JPH07502030A (ja) | 1995-03-02 |
| DE69211161D1 (de) | 1996-07-04 |
| US5559249A (en) | 1996-09-24 |
| EP0641346A1 (de) | 1995-03-08 |
| AU662943B2 (en) | 1995-09-21 |
| CA2126216A1 (en) | 1993-06-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| HP | Change in proprietorship | ||
| RH1 | Patent not in force |