IL228220A - Tricyclic inhibitors of the gyrase enzyme - Google Patents
Tricyclic inhibitors of the gyrase enzymeInfo
- Publication number
- IL228220A IL228220A IL228220A IL22822013A IL228220A IL 228220 A IL228220 A IL 228220A IL 228220 A IL228220 A IL 228220A IL 22822013 A IL22822013 A IL 22822013A IL 228220 A IL228220 A IL 228220A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- optionally substituted
- mixture
- solution
- stirred
- Prior art date
Links
- 239000002271 gyrase inhibitor Substances 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 375
- 238000000034 method Methods 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims description 99
- 150000003335 secondary amines Chemical class 0.000 claims description 38
- 150000003512 tertiary amines Chemical class 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 150000001412 amines Chemical class 0.000 claims description 24
- 125000004122 cyclic group Chemical group 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 19
- 239000000651 prodrug Substances 0.000 abstract description 10
- 229940002612 prodrug Drugs 0.000 abstract description 10
- 150000002148 esters Chemical class 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 description 180
- 239000000243 solution Substances 0.000 description 149
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 140
- 238000002360 preparation method Methods 0.000 description 67
- 238000006243 chemical reaction Methods 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 229910001868 water Inorganic materials 0.000 description 55
- 239000011541 reaction mixture Substances 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- 239000007787 solid Substances 0.000 description 47
- 239000012044 organic layer Substances 0.000 description 46
- 229940093499 ethyl acetate Drugs 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 229910000027 potassium carbonate Inorganic materials 0.000 description 35
- 125000004429 atom Chemical group 0.000 description 34
- 239000000725 suspension Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- 229910052799 carbon Inorganic materials 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 23
- -1 hexafluorophosphate Chemical compound 0.000 description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 22
- 239000000543 intermediate Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000013058 crude material Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 14
- 239000005457 ice water Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 11
- 108010054814 DNA Gyrase Proteins 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 150000003141 primary amines Chemical class 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 150000004985 diamines Chemical class 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000008241 heterogeneous mixture Substances 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 108010041052 DNA Topoisomerase IV Proteins 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 208000035143 Bacterial infection Diseases 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- 229940126062 Compound A Drugs 0.000 description 6
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 108091006112 ATPases Proteins 0.000 description 5
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 229910019213 POCl3 Inorganic materials 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
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- 238000000338 in vitro Methods 0.000 description 5
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
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- 239000000872 buffer Substances 0.000 description 2
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- 239000011575 calcium Substances 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
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- 235000011009 potassium phosphates Nutrition 0.000 description 1
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- 238000011321 prophylaxis Methods 0.000 description 1
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- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
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- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161453011P | 2011-03-15 | 2011-03-15 | |
| PCT/US2012/029104 WO2012125746A1 (en) | 2011-03-15 | 2012-03-14 | Tricyclic gyrase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL228220A0 IL228220A0 (en) | 2013-11-25 |
| IL228220A true IL228220A (en) | 2017-04-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL228220A IL228220A (en) | 2011-03-15 | 2013-09-01 | Tricyclic inhibitors of the gyrase enzyme |
Country Status (16)
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|---|---|
| US (2) | US9732083B2 (https=) |
| EP (1) | EP2686320B1 (https=) |
| JP (1) | JP6140083B2 (https=) |
| KR (2) | KR20140059164A (https=) |
| CN (1) | CN103562208B (https=) |
| AR (1) | AR085806A1 (https=) |
| AU (1) | AU2012229997B2 (https=) |
| BR (1) | BR112013023266B8 (https=) |
| CA (1) | CA2829939C (https=) |
| IL (1) | IL228220A (https=) |
| MX (1) | MX345780B (https=) |
| PH (1) | PH12013501800A1 (https=) |
| RU (1) | RU2626979C2 (https=) |
| TW (1) | TWI527818B (https=) |
| WO (1) | WO2012125746A1 (https=) |
| ZA (1) | ZA201307583B (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2686320B1 (en) * | 2011-03-15 | 2016-05-18 | Merck Sharp & Dohme Corp. | Tricyclic gyrase inhibitors |
| EP2807165B1 (en) * | 2012-01-27 | 2019-05-15 | Université de Montréal | Pyrimido[4,5-b]indole derivatives and use thereof in the expansion of hematopoietic stem cells |
| CN105189505B (zh) * | 2012-09-12 | 2019-03-22 | 默克夏普&多梅有限公司 | 用作抗菌剂的三环促旋酶抑制剂 |
| CN103304488B (zh) * | 2013-06-13 | 2015-12-09 | 暨明医药科技（苏州）有限公司 | 光学纯2-（1-羟基乙基）-5-羟基嘧啶的制备方法 |
| CN105899511B (zh) * | 2013-09-11 | 2019-06-07 | 默沙东公司 | 三环促旋酶抑制剂 |
| US20170007615A1 (en) | 2014-02-03 | 2017-01-12 | Biota Europe Ltd | Antibacterial Compounds |
| WO2015150337A1 (en) * | 2014-04-01 | 2015-10-08 | Amakem Nv | Lim kinase inhibitors |
| CA3057431A1 (en) | 2017-03-24 | 2018-09-27 | Taisho Pharmaceutical Co., Ltd. | 2(1h)-quinolinone derivative |
| CN110475777B (zh) * | 2017-03-30 | 2022-04-15 | 豪夫迈·罗氏有限公司 | 用于治疗和预防细菌感染的新吡啶并[2,3-b]吲哚化合物 |
| CN108504647B (zh) * | 2018-03-09 | 2021-11-05 | 中山大学 | 一种dna促旋酶的药物结合口袋及其应用 |
| JP7296992B2 (ja) * | 2018-05-28 | 2023-06-23 | エフ． ホフマン－ラ ロシュ アーゲー | 細菌感染症の処置および予防のための新規オキソキノリジン化合物 |
| WO2020064661A1 (en) * | 2018-09-26 | 2020-04-02 | F. Hoffmann-La Roche Ag | Substituted pyridoindoles for the treatment and prophylaxis of bacterial infection |
| EP3887370B1 (en) * | 2018-11-27 | 2023-01-18 | F. Hoffmann-La Roche AG | Tricyclic compounds for the treatment and prophylaxis of bacterial infection |
| WO2020109191A1 (en) | 2018-11-27 | 2020-06-04 | F. Hoffmann-La Roche Ag | Aryl compounds for the treatment and prophylaxis of bacterial infection |
| WO2020127624A1 (en) | 2018-12-20 | 2020-06-25 | F. Hoffmann-La Roche Ag | Oxopyrido[1,2-a]pyrimidine compounds for the treatment and prophylaxis of bacterial infection |
| CN114763357B (zh) * | 2021-01-15 | 2024-06-18 | 中国科学院上海药物研究所 | 吲哚并嘧啶三环类化合物及其制备方法和用途 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN157280B (https=) | 1983-07-15 | 1986-02-22 | Hoechst India | |
| CA1336090C (en) | 1988-08-31 | 1995-06-27 | Isao Hayakawa | Spiro-substituted cyclic amines of quinolone derivatives |
| DE4030059A1 (de) | 1990-09-22 | 1992-03-26 | Bayer Ag | Verfahren zur herstellung von 5-hydroxy-3,4,5,6-tetrahydro-pyrimidin-derivaten |
| DE4032560A1 (de) | 1990-10-13 | 1992-04-16 | Bayer Ag | 7-(2,7-diazabicyclo(3.3.0)octyl)-3-chinolon- und -naphtyridoncarbonsaeure-derivate |
| ES2150941T3 (es) | 1992-04-03 | 2000-12-16 | Upjohn Co | Aminas biciclicas-heterociclicas eficaces farmaceuticamente. |
| US5279359A (en) | 1992-06-26 | 1994-01-18 | Erickson Donald C | Rotary trisorption heat pump |
| US5350791A (en) | 1992-07-02 | 1994-09-27 | Henkel Corporation | Hydrophilicizing treatment for metal objects |
| US5527910A (en) | 1992-12-30 | 1996-06-18 | Cheil Foods & Chemicals, Inc. | Pyridone carboxylic acid compounds and their uses for treating infectious diseases caused by bacteria |
| RU2158127C2 (ru) * | 1994-12-23 | 2000-10-27 | Варнер-Ламберт Компани | Способы ингибирования тирозинкиназы рецептора эпидермального фактора роста, азотсодержащие трициклические соединения, фармацевтическая композиция, предназначенная для введения ингибитора тирозинкиназы рецептора эпидермального фактора роста, например, erb-b2, erb-b3 или erb-b4, и противозачаточная композиция |
| NZ304519A (en) | 1995-03-02 | 2000-01-28 | Upjohn Co | Pydrimido[4,5-b]indoles |
| SI9620103A (sl) * | 1995-07-06 | 1998-10-31 | Novartis Ag | Pirolopirimidini in postopki za njihovo pripravo |
| WO1998029397A1 (en) | 1996-12-27 | 1998-07-09 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused pyrimidine compounds and medicinal use thereof |
| SI0964865T1 (en) | 1997-01-08 | 2003-08-31 | Pharmacia & Upjohn Company | Pharmaceutically active tricyclic amines |
| ATE265847T1 (de) | 1997-07-29 | 2004-05-15 | Upjohn Co | Selbstemulgierbare formulierung enthaltend lipophile verbindungen |
| US6147085A (en) | 1999-04-01 | 2000-11-14 | Neurogen Corporation | Aminoalkyl substituted 9H-pyridino[2,3-b] indole and 9H-pyrimidino[4,5-b] indole derivatives |
| EP1068207A1 (en) | 1998-04-02 | 2001-01-17 | Neurogen Corporation | AMINOALKYL SUBSTITUTED 9H-PYRIDINO 2,3-b]INDOLE AND 9H-PYRIMIDINO 4,5-b]INDOLE DERIVATIVES |
| US6221875B1 (en) | 1998-04-02 | 2001-04-24 | Neurogen Corporation | Substituted 9H-pyridino [2,3-B]indole and 9H-pyrimidino [4,5-B]indole derivatives: selective neuropeptide Y receptor ligands |
| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| WO2000066585A1 (en) | 1999-04-30 | 2000-11-09 | Neurogen Corporation | 9H-PYRIMIDO[4,5-b]INDOLE DERIVATIVES: CRF1 SPECIFIC LIGANDS |
| SK10572002A3 (sk) | 2000-01-24 | 2003-10-07 | Warner-Lambert Company | 3-Aminochinazolín-2,4-diónové antibakteriálne činidlá |
| FR2816509B1 (fr) | 2000-11-15 | 2004-02-06 | Sod Conseils Rech Applic | Association d'inhibiteurs de calpaine et de piegeurs des formes reactives de l'oxygene |
| JP2005515173A (ja) | 2001-10-31 | 2005-05-26 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | ピリミド［４，５−ｂ］インドール誘導体 |
| CA2466266A1 (en) * | 2001-11-08 | 2003-07-31 | Antex Pharma, Inc. | Novel substituted alkane compounds and uses thereof |
| WO2003057149A2 (en) | 2001-12-28 | 2003-07-17 | Bayer Corporation | 4-substituted fused heteropyrimidines and fused hetero-4-pyrimidones |
| TWI270549B (en) | 2002-12-26 | 2007-01-11 | Taisho Pharmaceutical Co Ltd | Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group |
| WO2004058764A1 (en) * | 2002-12-27 | 2004-07-15 | Bayer Healthcare Ag | 4-phenyl-pyrimido [4,5-b] indole derivatives |
| JP4845736B2 (ja) | 2003-10-14 | 2011-12-28 | アリゾナ ボード オブ リージェンツ オン ビハーフ ザ ユニバーシティー オブ アリゾナ | プロテインキナーゼ阻害剤 |
| US20090143399A1 (en) | 2003-10-14 | 2009-06-04 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Protein Kinase Inhibitors |
| US20080051414A1 (en) | 2003-10-14 | 2008-02-28 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Protein Kinase Inhibitors |
| US20090099165A1 (en) | 2003-10-14 | 2009-04-16 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Protein Kinase Inhibitors |
| JP2006036762A (ja) | 2004-06-25 | 2006-02-09 | Taisho Pharmaceut Co Ltd | 環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体 |
| JP2007161585A (ja) | 2004-06-25 | 2007-06-28 | Taisho Pharmaceut Co Ltd | 環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体 |
| WO2008007113A2 (en) | 2006-07-14 | 2008-01-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| CA2604284A1 (en) | 2005-04-28 | 2006-11-02 | Supergen, Inc. | Protein kinase inhibitors |
| EP1749822B1 (en) * | 2005-08-05 | 2008-10-15 | Hybrigenics S.A. | Novel cysteine protease inhibitors and their therapeutic applications |
| US20070049591A1 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Inhibitors of MAPK/Erk Kinase |
| JP2007169216A (ja) | 2005-12-22 | 2007-07-05 | Taisho Pharmaceut Co Ltd | 環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体 |
| US20080207632A1 (en) | 2006-10-31 | 2008-08-28 | Supergen, Inc. | Protein kinase inhibitors |
| US8618121B2 (en) | 2007-07-02 | 2013-12-31 | Cancer Research Technology Limited | 9H-pyrimido[4,5-B]indoles, 9H-pyrido[4',3':4,5]pyrrolo[2,3-D]pyridines, and 9H 1,3,6,9 tetraaza-fluorenes as CHK1 kinase function inhibitors |
| US7982035B2 (en) | 2007-08-27 | 2011-07-19 | Duquesne University Of The Holy Spirit | Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof |
| US7960400B2 (en) * | 2007-08-27 | 2011-06-14 | Duquesne University Of The Holy Ghost | Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof |
| WO2009091476A1 (en) | 2008-01-14 | 2009-07-23 | Irm Llc | Compositions and methods for treating cancers |
| ATE546448T1 (de) * | 2008-08-02 | 2012-03-15 | Janssen Pharmaceutica Nv | Urotensin-ii-rezeptorantagonisten |
| WO2011056739A1 (en) | 2009-11-03 | 2011-05-12 | Glaxosmithkline Llc | Compounds and methods |
| EP2686320B1 (en) * | 2011-03-15 | 2016-05-18 | Merck Sharp & Dohme Corp. | Tricyclic gyrase inhibitors |
| CN105189505B (zh) * | 2012-09-12 | 2019-03-22 | 默克夏普&多梅有限公司 | 用作抗菌剂的三环促旋酶抑制剂 |
| CN105899511B (zh) * | 2013-09-11 | 2019-06-07 | 默沙东公司 | 三环促旋酶抑制剂 |
| WO2016067009A1 (en) * | 2014-10-28 | 2016-05-06 | Redx Pharma Plc | Compounds with activity against bacteria and mycobacteria |
-
2012
- 2012-03-14 EP EP12710633.4A patent/EP2686320B1/en active Active
- 2012-03-14 RU RU2013140798A patent/RU2626979C2/ru active
- 2012-03-14 CN CN201280020849.4A patent/CN103562208B/zh active Active
- 2012-03-14 AR ARP120100830A patent/AR085806A1/es active IP Right Grant
- 2012-03-14 US US13/496,188 patent/US9732083B2/en active Active
- 2012-03-14 JP JP2013558143A patent/JP6140083B2/ja active Active
- 2012-03-14 KR KR1020137026970A patent/KR20140059164A/ko not_active Ceased
- 2012-03-14 KR KR1020197025342A patent/KR102132574B1/ko active Active
- 2012-03-14 WO PCT/US2012/029104 patent/WO2012125746A1/en not_active Ceased
- 2012-03-14 BR BR112013023266A patent/BR112013023266B8/pt active IP Right Grant
- 2012-03-14 PH PH1/2013/501800A patent/PH12013501800A1/en unknown
- 2012-03-14 CA CA2829939A patent/CA2829939C/en active Active
- 2012-03-14 MX MX2013010511A patent/MX345780B/es active IP Right Grant
- 2012-03-14 TW TW101108646A patent/TWI527818B/zh active
- 2012-03-14 AU AU2012229997A patent/AU2012229997B2/en active Active
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- 2013-09-01 IL IL228220A patent/IL228220A/en active IP Right Grant
- 2013-10-11 ZA ZA2013/07583A patent/ZA201307583B/en unknown
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- 2017-07-07 US US15/643,760 patent/US10858360B2/en active Active
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