IL103319A - 9-Amino-7-(substituted amino)-6-demethyl-6- deoxytetracyclines intermediates thereof their production and pharmaceutical compositions containing them - Google Patents
9-Amino-7-(substituted amino)-6-demethyl-6- deoxytetracyclines intermediates thereof their production and pharmaceutical compositions containing themInfo
- Publication number
- IL103319A IL103319A IL10331992A IL10331992A IL103319A IL 103319 A IL103319 A IL 103319A IL 10331992 A IL10331992 A IL 10331992A IL 10331992 A IL10331992 A IL 10331992A IL 103319 A IL103319 A IL 103319A
- Authority
- IL
- Israel
- Prior art keywords
- methylpropyl
- ethyl
- amino
- alkyl
- propyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 239000000543 intermediate Substances 0.000 title abstract description 7
- 238000004519 manufacturing process Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- 238000000034 method Methods 0.000 claims abstract description 34
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 90
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 75
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 73
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 69
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 64
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 50
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
- -1 3-furan-yl Chemical group 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 33
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 24
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 24
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 23
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 23
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 22
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 21
- 229910052751 metal Chemical class 0.000 claims description 20
- 239000002184 metal Chemical class 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000000039 congener Substances 0.000 claims description 17
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 15
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 229910001960 metal nitrate Inorganic materials 0.000 claims description 2
- 229910052976 metal sulfide Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000002823 nitrates Chemical class 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- DFWBIMRBEDSXHZ-UHFFFAOYSA-N OS(O)(=O)=O.C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O Chemical compound OS(O)(=O)=O.C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O DFWBIMRBEDSXHZ-UHFFFAOYSA-N 0.000 claims 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- RHDSQCIOBQPJGR-UHFFFAOYSA-N n-oxotetracene-2-carboxamide Chemical compound C1=CC=CC2=CC3=CC4=CC(C(=O)N=O)=CC=C4C=C3C=C21 RHDSQCIOBQPJGR-UHFFFAOYSA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000011150 stannous chloride Nutrition 0.000 claims 1
- 239000001119 stannous chloride Substances 0.000 claims 1
- 239000004098 Tetracycline Substances 0.000 abstract description 35
- 235000019364 tetracycline Nutrition 0.000 abstract description 34
- 150000003522 tetracyclines Chemical class 0.000 abstract description 30
- 230000000694 effects Effects 0.000 abstract description 15
- 229940040944 tetracyclines Drugs 0.000 abstract description 10
- 238000001228 spectrum Methods 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 28
- 101150015970 tetM gene Proteins 0.000 description 26
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- 239000007787 solid Substances 0.000 description 20
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 238000001243 protein synthesis Methods 0.000 description 14
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 13
- 125000004344 phenylpropyl group Chemical group 0.000 description 13
- 238000010790 dilution Methods 0.000 description 12
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- 241000588724 Escherichia coli Species 0.000 description 11
- 210000003705 ribosome Anatomy 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000000844 anti-bacterial effect Effects 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
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- 230000005764 inhibitory process Effects 0.000 description 8
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 229960004023 minocycline Drugs 0.000 description 7
- 238000007920 subcutaneous administration Methods 0.000 description 7
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- 230000003115 biocidal effect Effects 0.000 description 6
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Seasonings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
- Quinoline Compounds (AREA)
- Luminescent Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Moulding By Coating Moulds (AREA)
- Tires In General (AREA)
- Spinning Or Twisting Of Yarns (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/771,697 US5281628A (en) | 1991-10-04 | 1991-10-04 | 9-amino-7-(substituted)-6-demethyl-6-deoxytetracyclines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL103319A0 IL103319A0 (en) | 1993-03-15 |
| IL103319A true IL103319A (en) | 1996-07-23 |
Family
ID=25092681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10331992A IL103319A (en) | 1991-10-04 | 1992-10-01 | 9-Amino-7-(substituted amino)-6-demethyl-6- deoxytetracyclines intermediates thereof their production and pharmaceutical compositions containing them |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US5281628A (de) |
| EP (1) | EP0535346B1 (de) |
| JP (1) | JP3183729B2 (de) |
| KR (1) | KR100261528B1 (de) |
| CN (1) | CN1053182C (de) |
| AT (1) | ATE129697T1 (de) |
| AU (1) | AU651734B2 (de) |
| CA (1) | CA2079703C (de) |
| CZ (1) | CZ285015B6 (de) |
| DE (1) | DE69205792T2 (de) |
| DK (1) | DK0535346T3 (de) |
| ES (1) | ES2081005T3 (de) |
| FI (1) | FI111716B (de) |
| GR (1) | GR3017978T3 (de) |
| HK (1) | HK1000319A1 (de) |
| HU (2) | HU211214B (de) |
| IL (1) | IL103319A (de) |
| MX (1) | MX9205573A (de) |
| NO (1) | NO300129B1 (de) |
| NZ (1) | NZ244556A (de) |
| PH (1) | PH30343A (de) |
| PL (2) | PL170933B1 (de) |
| SK (1) | SK281113B6 (de) |
| TW (1) | TW222616B (de) |
| ZA (1) | ZA927608B (de) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5494903A (en) * | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
| USRE40183E1 (en) | 1991-10-04 | 2008-03-25 | Wyeth Holdings Corporation | 7-Substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
| EP0643775B1 (de) * | 1992-05-28 | 2004-07-21 | Centre For Molecular Biology And Medicine, | Quinone-derivate zur verbesserung der zellulare bioenergie |
| US5328902A (en) * | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| US5420272A (en) * | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| US5442059A (en) * | 1992-08-13 | 1995-08-15 | American Cyanamid Company | 9-[(substituted glycyl)amido)]-6-demethyl-6-deoxytetracyclines |
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