EA031589B1 - Трициклические азотсодержащие соединения для лечения инфекции, вызываемой neisseria gonorrhoeae - Google Patents
Трициклические азотсодержащие соединения для лечения инфекции, вызываемой neisseria gonorrhoeae Download PDFInfo
- Publication number
- EA031589B1 EA031589B1 EA201790442A EA201790442A EA031589B1 EA 031589 B1 EA031589 B1 EA 031589B1 EA 201790442 A EA201790442 A EA 201790442A EA 201790442 A EA201790442 A EA 201790442A EA 031589 B1 EA031589 B1 EA 031589B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- dihydro
- methyl
- amino
- piperidinyl
- dione
- Prior art date
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- 208000015181 infectious disease Diseases 0.000 title claims description 27
- 206010018612 Gonorrhoea Diseases 0.000 title abstract description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title abstract description 7
- 241000588653 Neisseria Species 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 61
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- -1 4 - {[(7-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl) methyl] amino} -1-piperidinyl Chemical group 0.000 claims description 460
- 150000001875 compounds Chemical class 0.000 claims description 262
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 170
- 239000012458 free base Substances 0.000 claims description 102
- 238000011282 treatment Methods 0.000 claims description 40
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 27
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims description 24
- MMUYWCUHCPWDAH-UHFFFAOYSA-N 1,4-diazatricyclo[6.3.1.04,12]dodeca-2,6,8(12),9-tetraene-5,11-dione Chemical compound C1=CC(=O)N2C=CN3C(=O)C=CC1=C32 MMUYWCUHCPWDAH-UHFFFAOYSA-N 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- IDEYQVRMVSQTQG-UHFFFAOYSA-N 7-[[[1-[(5,11-dioxo-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-trien-2-yl)methyl]piperidin-4-yl]amino]methyl]-2,3-dihydro-1,4-benzodioxine-5-carbonitrile Chemical compound O1CCOC(C(=C2)C#N)=C1C=C2CNC(CC1)CCN1CC1N2C(=O)C=CC(C=CC3=O)=C2N3C1 IDEYQVRMVSQTQG-UHFFFAOYSA-N 0.000 claims description 2
- DUXFDBOJWHARNV-JOCHJYFZSA-N (2R)-2-[[4-(3,4-dihydro-2H-chromen-6-ylmethylamino)piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound O1CCCC2=CC(CNC3CCN(CC3)C[C@H]3N4C(=O)C=CC=5C=CC(N(C3)C=54)=O)=CC=C21 DUXFDBOJWHARNV-JOCHJYFZSA-N 0.000 claims 4
- IVUXNUDNTONNBG-UHFFFAOYSA-N 1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound C1=CC(=O)N2CCN3C(=O)C=CC1=C32 IVUXNUDNTONNBG-UHFFFAOYSA-N 0.000 claims 2
- CGXOCRHGLTYEET-LJQANCHMSA-N (2R)-2-[[4-(2,3-dihydro-[1,4]oxathiino[2,3-c]pyridin-7-ylmethylamino)-4-methylpiperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound S1CCOC(C=N2)=C1C=C2CNC1(C)CCN(C[C@H]2N3C=4N(C(C=CC=4C=CC3=O)=O)C2)CC1 CGXOCRHGLTYEET-LJQANCHMSA-N 0.000 claims 1
- GXQGKTRBWDNOAV-LJQANCHMSA-N (2R)-2-[[4-(2,3-dihydro-[1,4]oxathiino[2,3-c]pyridin-7-ylmethylamino)piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound S1CCOC(C=N2)=C1C=C2CNC(CC1)CCN1C[C@H]1N2C(=O)C=CC(C=CC3=O)=C2N3C1 GXQGKTRBWDNOAV-LJQANCHMSA-N 0.000 claims 1
- ICEFMYXDABSJEB-OAQYLSRUSA-N (2R)-2-[[4-(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethylamino)piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound C1CCOC(C=N2)=C1C=C2CNC(CC1)CCN1C[C@H]1N2C(=O)C=CC(C=CC3=O)=C2N3C1 ICEFMYXDABSJEB-OAQYLSRUSA-N 0.000 claims 1
- QVFCTNFLPSJPQN-LJQANCHMSA-N (2R)-2-[[4-(3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethylamino)piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound S1CCNC2=NC(CNC3CCN(CC3)C[C@H]3N4C(=O)C=CC=5C=CC(N(C3)C=54)=O)=CC=C21 QVFCTNFLPSJPQN-LJQANCHMSA-N 0.000 claims 1
- MMKKZZRTGQEWMB-GOSISDBHSA-N (2R)-2-[[4-([1,3]oxathiolo[5,4-c]pyridin-6-ylmethylamino)piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound C([C@H]1N2C(=O)C=CC=3C=CC(N(C1)C=32)=O)N(CC1)CCC1NCC(N=C1)=CC2=C1OCS2 MMKKZZRTGQEWMB-GOSISDBHSA-N 0.000 claims 1
- XRKPIHKEOCFNBS-MRXNPFEDSA-N (2R)-2-[[4-[(7-chloro-3-oxo-4H-pyrido[3,2-b][1,4]oxazin-6-yl)methylamino]piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound N12C(=O)C=CC(C=CC3=O)=C1N3C[C@H]2CN(CC1)CCC1NCC1=NC(NC(=O)CO2)=C2C=C1Cl XRKPIHKEOCFNBS-MRXNPFEDSA-N 0.000 claims 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims 1
- HIGACJLWDPTSID-UHFFFAOYSA-N 2-[[4-[(3-oxo-4H-1,4-benzothiazin-6-yl)methylamino]piperidin-1-yl]methyl]-1,4-diazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione Chemical compound N12C(=O)C=CC(C=CC3=O)=C1N3CC2CN(CC1)CCC1NCC1=CC=C2SCC(=O)NC2=C1 HIGACJLWDPTSID-UHFFFAOYSA-N 0.000 claims 1
- 208000001786 gonorrhea Diseases 0.000 abstract description 8
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- 239000000243 solution Substances 0.000 description 195
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- 238000000132 electrospray ionisation Methods 0.000 description 162
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 147
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 144
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 139
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
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- 230000002829 reductive effect Effects 0.000 description 75
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- 238000003756 stirring Methods 0.000 description 24
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- PDBXHPORMXSXKO-UHFFFAOYSA-N 8-benzyl-7-[2-[ethyl(2-hydroxyethyl)amino]ethyl]-1,3-dimethylpurine-2,6-dione;hydron;chloride Chemical class Cl.N=1C=2N(C)C(=O)N(C)C(=O)C=2N(CCN(CCO)CC)C=1CC1=CC=CC=C1 PDBXHPORMXSXKO-UHFFFAOYSA-N 0.000 description 14
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
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- 239000012258 stirred mixture Substances 0.000 description 1
- 239000012607 strong cation exchange resin Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
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- 238000010189 synthetic method Methods 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
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- XZSNVIWYSJXKQK-UHFFFAOYSA-N tert-butyl n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-n-piperidin-4-ylcarbamate Chemical compound C=1C=2OCCOC=2C=NC=1CN(C(=O)OC(C)(C)C)C1CCNCC1 XZSNVIWYSJXKQK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
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Landscapes
- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Reproductive Health (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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| PCT/IB2015/056325 WO2016027249A1 (en) | 2014-08-22 | 2015-08-20 | Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection |
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| WO2016027249A1 (en) * | 2014-08-22 | 2016-02-25 | Glaxosmithkline Intellectual Property Development Limited | Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection |
| AU2017276627A1 (en) * | 2016-06-08 | 2018-12-20 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | New antibacterial compounds |
| WO2018108671A1 (en) | 2016-12-16 | 2018-06-21 | Basf Se | Pesticidal compounds |
| EP3946342A1 (en) * | 2019-04-03 | 2022-02-09 | GlaxoSmithKline Intellectual Property Development Limited | Gepotidacin for use in the treatment of bacterial urinary tract infections |
| US20220184071A1 (en) * | 2019-04-03 | 2022-06-16 | Glaxosmithkline Intellectual Property Development Limited | Gepotidacin for use in the treatment of bacterial urinary tract infections |
| GB201909191D0 (en) * | 2019-06-26 | 2019-08-07 | Ucb Biopharma Sprl | Therapeutic agents |
| US20220257615A1 (en) * | 2019-07-05 | 2022-08-18 | Glaxosmithkline Intellectual Property Development Limied | Combination for the treatment of infections caused by mycoplasma genitalium |
| MX2022006700A (es) | 2019-12-02 | 2022-09-02 | Storm Therapeutics Ltd | Compuestos poliheterociclicos como inhibidores de mettl3. |
| JP2023528560A (ja) * | 2020-04-02 | 2023-07-05 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | ゲポチダシンを用いて淋菌感染症を治療するためのレジメン |
| WO2021219671A1 (en) * | 2020-04-28 | 2021-11-04 | Noorik Biopharmaceuticals Ag | Treatment of pulmonary complications of coronavirus infections |
| WO2021219637A1 (en) | 2020-04-29 | 2021-11-04 | Glaxosmithkline Intellectual Property Development Limited | Crystalline forms of gepotidacin |
| EP4288035A1 (en) * | 2021-02-05 | 2023-12-13 | GlaxoSmithKline Intellectual Property Development Limited | Oral solid dose formulations |
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| WO2009141398A1 (en) * | 2008-05-23 | 2009-11-26 | Glaxo Group Limited | Tricyclic nitrogen containing compounds and their use as antibacterials |
| WO2010043714A1 (en) * | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
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| DE69423383T2 (de) * | 1993-05-13 | 2000-08-24 | American Cyanamid Co., Wayne | Herstellung und Verwendungen von LOS-verminderten Aussenmembran-Proteinen von Gram-negativen Kokken |
| GB0207450D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| FR2798656B1 (fr) | 1999-09-17 | 2004-12-17 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| EP1306038B1 (en) | 2000-07-21 | 2005-12-21 | Ljudmila Petrovna Maljuk | Plate for a stand-up meal |
| DE60125373T2 (de) | 2000-07-26 | 2007-10-18 | Smithkline Beecham P.L.C., Brentford | Aminopiperidin chinoline und ihre azaisosteren analoga mit antibakterieller wirkung |
| IL155092A0 (en) | 2000-09-29 | 2003-10-31 | Glaxo Group Ltd | Compounds useful in the treatment of inflammatory diseases |
| FR2816618B1 (fr) | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
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| EP1345903A1 (en) | 2000-12-21 | 2003-09-24 | Ciba SC Holding AG | Crystalline forms of cerivastatin sodium |
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| AU2002350217A1 (en) | 2001-12-04 | 2003-06-17 | Bristol-Myers Squibb Company | Glycinamides as factor xa inhibitors |
| WO2003064421A1 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine derivatives |
| WO2003064431A2 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| AR040335A1 (es) | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
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| GB0217294D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| FR2844268B1 (fr) | 2002-09-11 | 2004-10-22 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leurs procedes et intermediaires de preparation et les compositions qui les contiennent |
| FR2844270B1 (fr) | 2002-09-11 | 2006-05-19 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur procede et intermediaires de preparation et les compositions qui les contiennent |
| AU2003301414B8 (en) | 2002-10-10 | 2010-06-17 | Morphochem Aktiengesellschaft Fur Kombinatorische Chemie | Novel compounds with antibacterial activity |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| AU2003291227A1 (en) | 2002-11-05 | 2004-06-07 | Smithkline Beecham Corporation | Antibacterial agents |
| TW200427688A (en) | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| TW200507841A (en) | 2003-03-27 | 2005-03-01 | Glaxo Group Ltd | Antibacterial agents |
| FR2852954B1 (fr) | 2003-03-28 | 2006-07-14 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leurs procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| DE10316081A1 (de) | 2003-04-08 | 2004-10-21 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen mit antibakterieller Aktivität |
| WO2004104000A1 (ja) | 2003-05-23 | 2004-12-02 | Japan Tobacco Inc. | トリサイクリック縮合環化合物およびその医薬用途 |
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