ES2526687T3 - Derivados de isoxazol útiles como agentes antibacterianos - Google Patents
Derivados de isoxazol útiles como agentes antibacterianos Download PDFInfo
- Publication number
- ES2526687T3 ES2526687T3 ES12716624.7T ES12716624T ES2526687T3 ES 2526687 T3 ES2526687 T3 ES 2526687T3 ES 12716624 T ES12716624 T ES 12716624T ES 2526687 T3 ES2526687 T3 ES 2526687T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- methylsulfonyl
- hydroxy
- isoxazol
- butanamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003242 anti bacterial agent Substances 0.000 title description 5
- 150000002545 isoxazoles Chemical class 0.000 title description 2
- -1 (C3-C13) -NR4- Chemical group 0.000 claims abstract description 143
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 239000001257 hydrogen Substances 0.000 claims abstract description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 36
- 125000003118 aryl group Chemical group 0.000 claims abstract description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 21
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 20
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 17
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 16
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 9
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 5
- 125000005368 heteroarylthio group Chemical group 0.000 claims abstract description 5
- 125000005366 cycloalkylthio group Chemical group 0.000 claims abstract description 4
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 27
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 19
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 8
- 208000035143 Bacterial infection Diseases 0.000 claims description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- NXOTUZBMBWOEIM-MRXNPFEDSA-N (2r)-4-[3-(2-fluoro-3-methoxyphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC(C2=NOC(CC[C@](C)(C(=O)NO)S(C)(=O)=O)=C2)=C1F NXOTUZBMBWOEIM-MRXNPFEDSA-N 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- RBBXLEHJWRFFEE-UHFFFAOYSA-N n-[[3-[4-(hydroxyamino)-3-methyl-3-methylsulfonyl-4-oxobutyl]-1,2-oxazol-5-yl]methyl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NCC1=CC(CCC(C)(C(=O)NO)S(C)(=O)=O)=NO1 RBBXLEHJWRFFEE-UHFFFAOYSA-N 0.000 claims 1
- HXIRTSKHPFRRKO-UHFFFAOYSA-N o-methyl carbamothioate Chemical compound COC(N)=S HXIRTSKHPFRRKO-UHFFFAOYSA-N 0.000 claims 1
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- 229940079593 drug Drugs 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
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Classifications
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
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| ES (1) | ES2526687T3 (enExample) |
| IL (2) | IL228799A (enExample) |
| MX (1) | MX2013011526A (enExample) |
| SG (1) | SG193367A1 (enExample) |
| WO (1) | WO2012137094A1 (enExample) |
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| EP2334636A2 (en) | 2008-09-19 | 2011-06-22 | Pfizer Inc. | Hydroxamic acid derivatives useful as antibacterial agents |
| JP5793766B2 (ja) | 2009-12-16 | 2015-10-14 | ファイザー・インク | 抗菌剤として有用なｎ−結合型ヒドロキサム酸誘導体 |
| AP3336A (en) | 2011-03-07 | 2015-07-31 | Pfizer | Fluoro-pyridinone derivatives useful as antibacterial agents |
| WO2012137099A1 (en) | 2011-04-08 | 2012-10-11 | Pfizer Inc. | Imidazole, pyrazole, and triazole derivatives useful as antibacterial agents |
| CN103717582B (zh) | 2011-04-08 | 2015-09-30 | 辉瑞大药厂 | 用作抗菌剂的异*唑衍生物 |
| AR097617A1 (es) | 2013-09-13 | 2016-04-06 | Actelion Pharmaceuticals Ltd | Derivados antibacterianos del 2h-indazol |
| US9937156B2 (en) * | 2013-10-16 | 2018-04-10 | The Board Of Regents Of The University Of Texas System | Modulation of MRTF-A activity in pathologic fibrosis and wound healing |
| PL3083567T3 (pl) | 2013-12-19 | 2018-08-31 | Idorsia Pharmaceuticals Ltd | Przeciwbakteryjne pochodne 1h-indazolu i 1h-indolu |
| AR099612A1 (es) * | 2014-03-04 | 2016-08-03 | Actelion Pharmaceuticals Ltd | Derivados antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona |
| EP3134401B1 (en) * | 2014-04-22 | 2018-06-13 | Novartis AG | Isoxazoline hydroxamic acid derivatives as lpxc inhibitors |
| SG11201609286VA (en) | 2014-05-16 | 2016-12-29 | Actelion Pharmaceuticals Ltd | Antibacterial quinazoline-4(3h)-one derivatives |
| CA2963875A1 (en) | 2014-11-19 | 2016-05-26 | Actelion Pharmaceuticals Ltd | Antibacterial benzothiazole derivatives |
| CR20170260A (es) | 2014-12-16 | 2017-08-21 | Novartis Ag | COMPUESTOS DE ISOXAZOL DE ÁCIDO HIDROXÁMICO COMO INHIBIDORES DE LpxC |
| AR105646A1 (es) | 2015-08-11 | 2017-10-25 | Actelion Pharmaceuticals Ltd | Agentes antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituida |
| AR105848A1 (es) * | 2015-08-31 | 2017-11-15 | Actelion Pharmaceuticals Ltd | Derivados heterocíclicos antibacterianos |
| AR105889A1 (es) | 2015-09-03 | 2017-11-22 | Actelion Pharmaceuticals Ltd | Compuestos antibacterianos 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituidos |
| US10590498B2 (en) * | 2016-05-17 | 2020-03-17 | Lawrence Livermore National Security, Llc | Compounds for reactivation of acetylcholinesterase and related compositions methods and systems |
| ES2820502T3 (es) * | 2016-06-14 | 2021-04-21 | Novartis Ag | Forma cristalina de (R)-4-(5-(ciclopropiletilinil)isoxazol-3-il)-N-hidroxi-2-metil-2-(metilsulfonil)butanamida como agente antibacteriano |
| DE102016113269A1 (de) | 2016-07-19 | 2018-01-25 | Osram Opto Semiconductors Gmbh | Leuchtvorrichtung für ein mobiles endgerät |
| TWI604678B (zh) * | 2016-09-07 | 2017-11-01 | 國立暨南國際大學 | Radio transmission system |
| US10160724B2 (en) * | 2016-09-28 | 2018-12-25 | Dong-A St Co., Ltd. | Tetrahydropyridine derivatives and their use as antibacterial agents |
| US11186548B2 (en) | 2017-11-23 | 2021-11-30 | Lawrence Livermore National Security, Llc | Compounds for central reactivation of organophosphorus-based compound-inhibited acetylcholinesterase and/or inactivation of organophosphorus-based acetylcholinesterase inhibitors and related compositions methods and systems for making and using them |
| AU2019383674A1 (en) * | 2018-11-21 | 2021-06-10 | Taisho Pharmaceutical Co., Ltd. | Novel imidazole derivative |
| CN111944719B (zh) * | 2020-08-14 | 2022-04-29 | 暨南大学 | 一株二恶烷降解菌is20及其制备方法和应用 |
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| US4769461A (en) | 1986-09-16 | 1988-09-06 | American Home Products Corporation | Quinolinyl benzene hydroxamic acids as anti-inflammatory/antiallergic agents |
| US5110831A (en) | 1990-11-30 | 1992-05-05 | Du Pont Merck Pharmaceutical Company | Vinylogous hydroxamic acids and derivatives thereof as 5-lipoxygenase inhibitors |
| AU749699B2 (en) | 1998-02-07 | 2002-07-04 | British Biotech Pharmaceuticals Limited | Antibacterial agents |
| GB9925470D0 (en) | 1999-10-27 | 1999-12-29 | Smithkline Beecham Plc | Novel compounds |
| WO2002074298A1 (en) | 2001-03-21 | 2002-09-26 | Ono Pharmaceutical Co., Ltd. | Il-6 production inhibitors |
| ES2180456B1 (es) * | 2001-07-20 | 2004-05-01 | Laboratorios S.A.L.V.A.T., S.A. | Isoxazoles sustituidos y su utilizacion como antibioticos. |
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-
2012
- 2012-03-23 CN CN201280016114.4A patent/CN103717582B/zh not_active Expired - Fee Related
- 2012-03-23 MX MX2013011526A patent/MX2013011526A/es not_active Application Discontinuation
- 2012-03-23 JP JP2014503238A patent/JP2014510132A/ja active Pending
- 2012-03-23 CA CA2830920A patent/CA2830920C/en not_active Expired - Fee Related
- 2012-03-23 AU AU2012238374A patent/AU2012238374B2/en not_active Ceased
- 2012-03-23 US US14/110,157 patent/US8748466B2/en not_active Expired - Fee Related
- 2012-03-23 SG SG2013067616A patent/SG193367A1/en unknown
- 2012-03-23 ES ES12716624.7T patent/ES2526687T3/es active Active
- 2012-03-23 EP EP12716624.7A patent/EP2694488B1/en not_active Not-in-force
- 2012-03-23 KR KR1020137029552A patent/KR20130140868A/ko not_active Abandoned
- 2012-03-23 WO PCT/IB2012/051406 patent/WO2012137094A1/en not_active Ceased
- 2012-03-23 DK DK12716624.7T patent/DK2694488T3/en active
-
2013
- 2013-09-09 ZA ZA2013/06736A patent/ZA201306736B/en unknown
- 2013-10-08 IL IL228799A patent/IL228799A/en not_active IP Right Cessation
-
2015
- 2015-07-21 IL IL240078A patent/IL240078A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2012238374A1 (en) | 2013-09-26 |
| AU2012238374B2 (en) | 2015-04-02 |
| US8748466B2 (en) | 2014-06-10 |
| DK2694488T3 (en) | 2014-12-15 |
| JP2014510132A (ja) | 2014-04-24 |
| CN103717582B (zh) | 2015-09-30 |
| SG193367A1 (en) | 2013-10-30 |
| EP2694488A1 (en) | 2014-02-12 |
| IL240078A0 (en) | 2015-08-31 |
| CA2830920A1 (en) | 2012-10-11 |
| CN103717582A (zh) | 2014-04-09 |
| KR20130140868A (ko) | 2013-12-24 |
| CA2830920C (en) | 2015-07-14 |
| IL228799A (en) | 2015-08-31 |
| IL228799A0 (en) | 2013-12-31 |
| WO2012137094A1 (en) | 2012-10-11 |
| MX2013011526A (es) | 2013-12-06 |
| EP2694488B1 (en) | 2014-11-12 |
| ZA201306736B (en) | 2014-11-26 |
| US20140024690A1 (en) | 2014-01-23 |
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