CA1066710A - 7-methoxy-6-thiatetracyclines and their preparation - Google Patents
7-methoxy-6-thiatetracyclines and their preparationInfo
- Publication number
- CA1066710A CA1066710A CA232,694A CA232694A CA1066710A CA 1066710 A CA1066710 A CA 1066710A CA 232694 A CA232694 A CA 232694A CA 1066710 A CA1066710 A CA 1066710A
- Authority
- CA
- Canada
- Prior art keywords
- methoxy
- acid
- thiatetracycline
- carbon atoms
- alkyl
- 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.)
- Expired
Links
- 238000002360 preparation method Methods 0.000 title description 5
- 239000002253 acid Substances 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 239000004098 Tetracycline Substances 0.000 claims abstract description 13
- 229940040944 tetracyclines Drugs 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 230000000640 hydroxylating effect Effects 0.000 claims abstract description 5
- -1 phenoxypropyl radical Chemical class 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 13
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 1
- 150000001299 aldehydes Chemical class 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 229910044991 metal oxide Inorganic materials 0.000 claims 1
- 150000004706 metal oxides Chemical class 0.000 claims 1
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims 1
- 239000012022 methylating agents Substances 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000019364 tetracycline Nutrition 0.000 abstract description 12
- 150000003522 tetracyclines Chemical class 0.000 abstract description 10
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 5
- 241000894006 Bacteria Species 0.000 abstract description 2
- 208000035143 Bacterial infection Diseases 0.000 abstract description 2
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 2
- 229940088710 antibiotic agent Drugs 0.000 abstract description 2
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000203 mixture Substances 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000007858 starting material Substances 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 229960002180 tetracycline Drugs 0.000 description 5
- 229930101283 tetracycline Natural products 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 description 4
- 230000033444 hydroxylation Effects 0.000 description 4
- 238000005805 hydroxylation reaction Methods 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000003797 solvolysis reaction Methods 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- SESUUAOAUZDHHP-UHFFFAOYSA-N 2,5-dimethoxybenzenethiol Chemical compound COC1=CC=C(OC)C(S)=C1 SESUUAOAUZDHHP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical group S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 description 3
- SODSCLKYSYCYLH-OZZRDPTJSA-N (5as,6as,7s,10ar)-7-(dimethylamino)-1,10,10a,12-tetrahydroxy-8,11-dioxo-5a,6,6a,7-tetrahydrobenzo[b]thioxanthene-9-carboxamide Chemical compound S1C2=CC=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O SODSCLKYSYCYLH-OZZRDPTJSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- YSFIZZRFIZSROW-UHFFFAOYSA-N 2-phenyl-4h-1,3-thiazol-5-one Chemical compound S1C(=O)CN=C1C1=CC=CC=C1 YSFIZZRFIZSROW-UHFFFAOYSA-N 0.000 description 2
- OXTNCQMOKLOUAM-UHFFFAOYSA-N 3-Oxoglutaric acid Chemical compound OC(=O)CC(=O)CC(O)=O OXTNCQMOKLOUAM-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004280 Sodium formate Substances 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 238000006345 epimerization reaction Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 2
- 235000019254 sodium formate Nutrition 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 125000003441 thioacyl group Chemical class 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 238000006257 total synthesis reaction Methods 0.000 description 2
- XVOUMQNXTGKGMA-OWOJBTEDSA-N (E)-glutaconic acid Chemical compound OC(=O)C\C=C\C(O)=O XVOUMQNXTGKGMA-OWOJBTEDSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GJFNRSDCSTVPCJ-UHFFFAOYSA-N 1,8-bis(dimethylamino)naphthalene Chemical compound C1=CC(N(C)C)=C2C(N(C)C)=CC=CC2=C1 GJFNRSDCSTVPCJ-UHFFFAOYSA-N 0.000 description 1
- FPXSBUFYJKLUNR-UHFFFAOYSA-N 1-n,1-n,2-n,2-n-tetramethylnaphthalene-1,2-diamine Chemical compound C1=CC=CC2=C(N(C)C)C(N(C)C)=CC=C21 FPXSBUFYJKLUNR-UHFFFAOYSA-N 0.000 description 1
- SHELADVIRCCTFN-UHFFFAOYSA-N 2,5-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(OC)C(S(Cl)(=O)=O)=C1 SHELADVIRCCTFN-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940093475 2-ethoxyethanol Drugs 0.000 description 1
- HSHKOBVZFSNIKL-UHFFFAOYSA-N 3-(2,5-dimethoxyphenyl)sulfanylpentanedioic acid Chemical compound COC1=CC=C(OC)C(SC(CC(O)=O)CC(O)=O)=C1 HSHKOBVZFSNIKL-UHFFFAOYSA-N 0.000 description 1
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- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
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- 239000000376 reactant Substances 0.000 description 1
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- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
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- 239000003381 stabilizer Substances 0.000 description 1
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- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- 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
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical group C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- DWCSXQCXXITVKE-UHFFFAOYSA-N triethyloxidanium Chemical compound CC[O+](CC)CC DWCSXQCXXITVKE-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2437487A DE2437487A1 (de) | 1974-08-03 | 1974-08-03 | 7-methoxy-6-thia-tetracycline und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1066710A true CA1066710A (en) | 1979-11-20 |
Family
ID=5922377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA232,694A Expired CA1066710A (en) | 1974-08-03 | 1975-08-01 | 7-methoxy-6-thiatetracyclines and their preparation |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US3988468A (en:Method) |
| JP (1) | JPS5141362A (en:Method) |
| AT (1) | AT344889B (en:Method) |
| BE (1) | BE832015A (en:Method) |
| CA (1) | CA1066710A (en:Method) |
| CS (1) | CS191882B2 (en:Method) |
| DD (1) | DD119426A5 (en:Method) |
| DE (1) | DE2437487A1 (en:Method) |
| DK (1) | DK135842C (en:Method) |
| ES (1) | ES439927A1 (en:Method) |
| FR (1) | FR2280386A1 (en:Method) |
| GB (1) | GB1464678A (en:Method) |
| HU (1) | HU171804B (en:Method) |
| IE (1) | IE41440B1 (en:Method) |
| IL (1) | IL47535A (en:Method) |
| LU (1) | LU73113A1 (en:Method) |
| NL (1) | NL7509205A (en:Method) |
| PL (1) | PL100508B1 (en:Method) |
| SE (1) | SE7508642L (en:Method) |
| ZA (1) | ZA754975B (en:Method) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2442829A1 (de) * | 1974-09-06 | 1976-03-18 | Merck Patent Gmbh | Tetracyclische verbindungen und verfahren zu ihrer herstellung |
| DE2746044C2 (de) * | 1977-10-13 | 1979-09-06 | Merck Patent Gmbh, 6100 Darmstadt | Verfahren zur Herstellung von e-Thiatetracyclinracematen mit natürlicher Konfiguration und ihren optischen Antipoden |
| JPS5845093A (ja) * | 1981-09-11 | 1983-03-16 | Kobe Steel Ltd | 平版用印刷基板 |
| JPS60196396A (ja) * | 1984-03-21 | 1985-10-04 | Ube Ind Ltd | 平版印刷板用基材 |
| KR100997596B1 (ko) * | 2000-07-07 | 2010-11-30 | 파라테크 파마슈티컬스, 인크. | 7-치환 테트라사이클린 화합물 |
| EP2301913A1 (en) * | 2001-03-13 | 2011-03-30 | Paratek Pharmaceuticals, Inc. | 7,9-Substituted tetracycline compounds |
| CN1700922A (zh) * | 2002-07-12 | 2005-11-23 | 帕拉特克药品公司 | 3、10或12a位取代的四环素化合物 |
| AU2005299294B2 (en) * | 2004-10-25 | 2012-06-07 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| CN107021887A (zh) | 2009-05-08 | 2017-08-08 | 四相制药公司 | 四环素类化合物 |
| PL2470500T3 (pl) * | 2009-08-28 | 2018-03-30 | Tetraphase Pharmaceuticals, Inc. | Związki tetracyklinowe |
| EA031523B1 (ru) | 2012-08-31 | 2019-01-31 | Тетрафейз Фармасьютикалс, Инк. | Тетрациклиновые соединения |
| SI3529236T1 (sl) | 2016-10-19 | 2024-08-30 | Tetraphase Pharmaceuticals, Inc. | Kristalinične oblike eravaciklina |
| CN109574868B (zh) * | 2018-12-28 | 2021-11-16 | 天津阿尔塔科技有限公司 | 一种四环素类及其差向异构体氘代内标物的制备方法 |
| CN111518115A (zh) * | 2020-04-15 | 2020-08-11 | 南京欧纳壹有机光电有限公司 | 硫醚取代的2-噻唑啉-4-酮封端的有机半导体化合物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL158172B (nl) * | 1972-09-18 | 1978-10-16 | Farmaceutici Italia | Werkwijze voor het bereiden van tetracyclinederivaten met een substituent op de 7-plaats. |
-
1974
- 1974-08-03 DE DE2437487A patent/DE2437487A1/de not_active Withdrawn
-
1975
- 1975-06-20 IL IL47535A patent/IL47535A/xx unknown
- 1975-07-09 CS CS754878A patent/CS191882B2/cs unknown
- 1975-07-30 US US05/600,377 patent/US3988468A/en not_active Expired - Lifetime
- 1975-07-30 SE SE7508642A patent/SE7508642L/xx unknown
- 1975-07-31 LU LU73113A patent/LU73113A1/xx unknown
- 1975-07-31 BE BE7000685A patent/BE832015A/xx unknown
- 1975-07-31 FR FR7523989A patent/FR2280386A1/fr active Granted
- 1975-08-01 AT AT600375A patent/AT344889B/de not_active IP Right Cessation
- 1975-08-01 CA CA232,694A patent/CA1066710A/en not_active Expired
- 1975-08-01 NL NL7509205A patent/NL7509205A/xx not_active Application Discontinuation
- 1975-08-01 ZA ZA00754975A patent/ZA754975B/xx unknown
- 1975-08-01 DK DK351875A patent/DK135842C/da active
- 1975-08-01 PL PL1975182476A patent/PL100508B1/pl unknown
- 1975-08-01 HU HU75ME00001882A patent/HU171804B/hu unknown
- 1975-08-01 ES ES439927A patent/ES439927A1/es not_active Expired
- 1975-08-01 IE IE1723/75A patent/IE41440B1/en unknown
- 1975-08-01 DD DD187631A patent/DD119426A5/xx unknown
- 1975-08-04 JP JP50095311A patent/JPS5141362A/ja active Pending
- 1975-08-04 GB GB3256475A patent/GB1464678A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US3988468A (en) | 1976-10-26 |
| IL47535A (en) | 1978-04-30 |
| HU171804B (hu) | 1978-03-28 |
| AT344889B (de) | 1978-08-10 |
| DK135842B (da) | 1977-07-04 |
| NL7509205A (nl) | 1976-02-05 |
| DK135842C (da) | 1977-11-28 |
| JPS5141362A (en) | 1976-04-07 |
| GB1464678A (en) | 1977-02-16 |
| DD119426A5 (en:Method) | 1976-04-20 |
| ATA600375A (de) | 1977-12-15 |
| DE2437487A1 (de) | 1976-02-19 |
| CS191882B2 (en) | 1979-07-31 |
| ZA754975B (en) | 1976-07-28 |
| IE41440B1 (en) | 1980-01-02 |
| FR2280386A1 (fr) | 1976-02-27 |
| PL100508B1 (pl) | 1978-10-31 |
| FR2280386B1 (en:Method) | 1979-10-12 |
| IE41440L (en) | 1976-02-03 |
| AU8360175A (en) | 1977-02-03 |
| ES439927A1 (es) | 1977-06-01 |
| IL47535A0 (en) | 1975-08-31 |
| DK351875A (da) | 1976-02-04 |
| BE832015A (nl) | 1976-02-02 |
| SE7508642L (sv) | 1976-02-04 |
| LU73113A1 (en:Method) | 1976-03-02 |
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