EA016099B1 - Замещенный аналог тетрациклина (варианты) и способ получения замещенного аналога тетрациклина - Google Patents
Замещенный аналог тетрациклина (варианты) и способ получения замещенного аналога тетрациклина Download PDFInfo
- Publication number
- EA016099B1 EA016099B1 EA200900632A EA200900632A EA016099B1 EA 016099 B1 EA016099 B1 EA 016099B1 EA 200900632 A EA200900632 A EA 200900632A EA 200900632 A EA200900632 A EA 200900632A EA 016099 B1 EA016099 B1 EA 016099B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- tetracycline
- substituted
- compounds
- reactive
- dimethylamino
- Prior art date
Links
- 239000004098 Tetracycline Substances 0.000 title claims abstract description 119
- 235000019364 tetracycline Nutrition 0.000 title claims abstract description 117
- 229960002180 tetracycline Drugs 0.000 title claims abstract description 102
- 229930101283 tetracycline Natural products 0.000 title claims abstract description 100
- 238000000034 method Methods 0.000 title abstract description 38
- -1 tetracycline compound Chemical class 0.000 title abstract description 32
- 150000003522 tetracyclines Chemical class 0.000 claims abstract description 107
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 58
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 46
- 125000000391 vinyl group Chemical class [H]C([*])=C([H])[H] 0.000 claims abstract description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- RRSINVIGTLUHIA-UHFFFAOYSA-N O=C1C2=C(O)C=CC=C2C(C)=C2C1=C(O)C1(O)C(=O)C(C(N)=O)C(O)=CC1=C2O Chemical compound O=C1C2=C(O)C=CC=C2C(C)=C2C1=C(O)C1(O)C(=O)C(C(N)=O)C(O)=CC1=C2O RRSINVIGTLUHIA-UHFFFAOYSA-N 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 37
- 239000003054 catalyst Substances 0.000 abstract description 35
- 239000002243 precursor Substances 0.000 abstract description 33
- 229910052723 transition metal Inorganic materials 0.000 abstract description 28
- 150000003624 transition metals Chemical class 0.000 abstract description 28
- 150000001336 alkenes Chemical class 0.000 abstract description 13
- 239000012954 diazonium Substances 0.000 abstract description 12
- 239000000543 intermediate Substances 0.000 abstract description 11
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 abstract description 7
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 22
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- 239000000203 mixture Substances 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 18
- 229940040944 tetracyclines Drugs 0.000 description 17
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- 125000000217 alkyl group Chemical group 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- MTCQOMXDZUULRV-ADOAZJKMSA-N (4s,4as,5ar,12ar)-4-(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=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 MTCQOMXDZUULRV-ADOAZJKMSA-N 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 11
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- 229950000614 sancycline Drugs 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 9
- 239000012713 reactive precursor Substances 0.000 description 9
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- 150000002431 hydrogen Chemical class 0.000 description 7
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 150000001733 carboxylic acid esters Chemical class 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 6
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- 238000003756 stirring Methods 0.000 description 6
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- 125000004448 alkyl carbonyl group Chemical group 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
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- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000004099 Chlortetracycline Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- 150000000475 acetylene derivatives Chemical class 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
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- 125000000304 alkynyl group Chemical group 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 4
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- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=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 CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 4
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- 150000001989 diazonium salts Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 229940042016 methacycline Drugs 0.000 description 4
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- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[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 IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 4
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- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical class COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 3
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Classifications
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- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- 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
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- 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
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
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- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15470199P | 1999-09-14 | 1999-09-14 | |
| US23209100P | 2000-09-12 | 2000-09-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200900632A1 EA200900632A1 (ru) | 2009-10-30 |
| EA016099B1 true EA016099B1 (ru) | 2012-02-28 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
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| EA200900632A EA016099B1 (ru) | 1999-09-14 | 2000-09-13 | Замещенный аналог тетрациклина (варианты) и способ получения замещенного аналога тетрациклина |
| EA200200366A EA005118B1 (ru) | 1999-09-14 | 2000-09-13 | Замещенный аналог тетрациклина (варианты) и способ его получения (варианты) |
| EA200400944A EA012203B1 (ru) | 1999-09-14 | 2000-09-13 | Замещенные производные тетрациклина, фармацевтическая композиция и способ лечения субъекта с их использованием |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200200366A EA005118B1 (ru) | 1999-09-14 | 2000-09-13 | Замещенный аналог тетрациклина (варианты) и способ его получения (варианты) |
| EA200400944A EA012203B1 (ru) | 1999-09-14 | 2000-09-13 | Замещенные производные тетрациклина, фармацевтическая композиция и способ лечения субъекта с их использованием |
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| EP (5) | EP2327687A3 (https=) |
| JP (2) | JP5093953B2 (https=) |
| KR (1) | KR100764992B1 (https=) |
| CN (2) | CN102336680A (https=) |
| AT (2) | ATE323671T1 (https=) |
| AU (3) | AU781439C (https=) |
| BR (1) | BR0013993A (https=) |
| CA (2) | CA2672722C (https=) |
| CY (1) | CY1105094T1 (https=) |
| CZ (1) | CZ301835B6 (https=) |
| DE (1) | DE60027465T2 (https=) |
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| HR (1) | HRP20020322B1 (https=) |
| HU (1) | HUP0202798A3 (https=) |
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| MX (1) | MXPA02002595A (https=) |
| PT (1) | PT1240133E (https=) |
| WO (1) | WO2001019784A1 (https=) |
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