CN110403939A - 用于治疗淋病奈瑟球菌感染的三环含氮化合物 - Google Patents
用于治疗淋病奈瑟球菌感染的三环含氮化合物 Download PDFInfo
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- CN110403939A CN110403939A CN201910738641.XA CN201910738641A CN110403939A CN 110403939 A CN110403939 A CN 110403939A CN 201910738641 A CN201910738641 A CN 201910738641A CN 110403939 A CN110403939 A CN 110403939A
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- Prior art keywords
- dihydro
- methyl
- amino
- base
- diketone
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- -1 nitrogenous compound Chemical class 0.000 title claims abstract description 298
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- 241000588652 Neisseria gonorrhoeae Species 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 58
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 297
- 150000001875 compounds Chemical class 0.000 claims description 195
- 239000000243 solution Substances 0.000 claims description 184
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 171
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 97
- 229910052760 oxygen Inorganic materials 0.000 claims description 80
- 239000001301 oxygen Substances 0.000 claims description 74
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 73
- 241000534944 Thia Species 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 49
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 125000004429 atom Chemical group 0.000 claims description 38
- HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 claims description 36
- YBKGERLDRMINOV-UHFFFAOYSA-N oxathiine Chemical compound O1SC=CC=C1 YBKGERLDRMINOV-UHFFFAOYSA-N 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 33
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
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- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 21
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- IVAATAQAFOAALG-UHFFFAOYSA-N 2h-cyclopenta[c]pyridine Chemical compound C1=CNC=C2C=CC=C21 IVAATAQAFOAALG-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- GVUSWMIMPJDWNW-UHFFFAOYSA-N 4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound C1=CN=C2NC(=O)CSC2=C1 GVUSWMIMPJDWNW-UHFFFAOYSA-N 0.000 claims description 8
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- 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 description 6
- GTFMIJNXNMDHAB-UHFFFAOYSA-N 4h-1,4-benzothiazin-3-one Chemical compound C1=CC=C2NC(=O)CSC2=C1 GTFMIJNXNMDHAB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 125000005647 linker group Chemical group 0.000 claims description 6
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- UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical class C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 claims description 5
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- TUBKTGGJHLCCDG-UHFFFAOYSA-N 2-chloro-4H-pyrido[3,2-b][1,4]oxazin-3-one Chemical class ClC1Oc2cccnc2NC1=O TUBKTGGJHLCCDG-UHFFFAOYSA-N 0.000 claims description 5
- ANHQLUBMNSSPBV-UHFFFAOYSA-N 4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical class C1=CN=C2NC(=O)COC2=C1 ANHQLUBMNSSPBV-UHFFFAOYSA-N 0.000 claims description 5
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 5
- 238000010790 dilution Methods 0.000 claims description 5
- 239000012895 dilution Substances 0.000 claims description 5
- WNNQCWLSQDNACP-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carbonitrile Chemical compound O1CCOC2=C1C=CC=C2C#N WNNQCWLSQDNACP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
- WZJQUSOPMHPFOX-UHFFFAOYSA-N 8h-pyrimido[5,4-b][1,4]thiazin-7-one Chemical compound N1=CN=C2NC(=O)CSC2=C1 WZJQUSOPMHPFOX-UHFFFAOYSA-N 0.000 claims description 3
- 238000004458 analytical method Methods 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 3
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 3
- 229910052721 tungsten Inorganic materials 0.000 claims description 3
- LLVAAXYHCINONR-XMMPIXPASA-N C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC=C(CCCO2)C2=C1 Chemical compound C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC=C(CCCO2)C2=C1 LLVAAXYHCINONR-XMMPIXPASA-N 0.000 claims description 2
- GEIPNIWJRQAXOV-XMMPIXPASA-N C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC=C2OCCCC2=C1 Chemical compound C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC=C2OCCCC2=C1 GEIPNIWJRQAXOV-XMMPIXPASA-N 0.000 claims description 2
- QSGXWZBLRRJPTI-UHFFFAOYSA-N C1C(OC2=C(N1)N=CC=C2)Cl Chemical class C1C(OC2=C(N1)N=CC=C2)Cl QSGXWZBLRRJPTI-UHFFFAOYSA-N 0.000 claims description 2
- NCUQBRIZXJFYIN-UHFFFAOYSA-N C1C(SC2=C(N1)N=CC=C2)Cl Chemical compound C1C(SC2=C(N1)N=CC=C2)Cl NCUQBRIZXJFYIN-UHFFFAOYSA-N 0.000 claims description 2
- FDKRRQLAGUENCK-UHFFFAOYSA-N ClN1C=NC=C2OCC(N=C21)=O Chemical class ClN1C=NC=C2OCC(N=C21)=O FDKRRQLAGUENCK-UHFFFAOYSA-N 0.000 claims description 2
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- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 claims 3
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- JLTONFFKKMXNOG-XMMPIXPASA-N C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC(CCC2)=C2C=N1 Chemical compound C([C@H](CN1CC=C2)N3C1=C2C=CC3)N(CC1)CCC1NCC1=CC(CCC2)=C2C=N1 JLTONFFKKMXNOG-XMMPIXPASA-N 0.000 claims 1
- 241001646725 Mycobacterium tuberculosis H37Rv Species 0.000 claims 1
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- 230000001580 bacterial effect Effects 0.000 claims 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/4353—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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- A61K31/435—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
- A61K31/44—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- 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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- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| ES2981617T3 (es) * | 2019-07-05 | 2024-10-09 | Glaxosmithkline Intellectual Property Dev | Combinación para el tratamiento de infecciones provocadas por Mycoplasma genitalium |
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| 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 |
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| WO2010043714A1 (en) * | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
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2017
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2019
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2020
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| CN101687887A (zh) * | 2007-04-20 | 2010-03-31 | 葛兰素集团有限公司 | 用作抗菌剂的含氮三环化合物 |
| WO2010043714A1 (en) * | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
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