EP1996579A2 - Composés antibiotiques - Google Patents

Composés antibiotiques

Info

Publication number
EP1996579A2
EP1996579A2 EP07713226A EP07713226A EP1996579A2 EP 1996579 A2 EP1996579 A2 EP 1996579A2 EP 07713226 A EP07713226 A EP 07713226A EP 07713226 A EP07713226 A EP 07713226A EP 1996579 A2 EP1996579 A2 EP 1996579A2
Authority
EP
European Patent Office
Prior art keywords
pyran
tetrahydro
methoxy
phenyl
ethyl
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.)
Withdrawn
Application number
EP07713226A
Other languages
German (de)
English (en)
Inventor
Jean-Christophe Gauvin
Christian Hubschwerlen
Jean-Philippe Surivet
Cornelia Zumbrunn Acklin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Actelion Pharmaceuticals Ltd
Original Assignee
Actelion Pharmaceuticals Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Actelion Pharmaceuticals Ltd filed Critical Actelion Pharmaceuticals Ltd
Publication of EP1996579A2 publication Critical patent/EP1996579A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention concerns novel antibiotics, pharmaceutical antibacterial compositions containing them and the use thereof in the manufacture of a medicament for the treatment of infections (e.g. bacterial infections).
  • infections e.g. bacterial infections
  • These compounds are useful antimicrobial agents effective against a variety of human and veterinary pathogens including among others Gram positive and Gram negative aerobic and anaerobic bacteria and mycobacteria.
  • - Enteroccocci are quinolone and vancomycin resistant and ⁇ -lactam antibiotics are inefficacious against these strains; - Enterobacteriacea are cephalosporin and quinolone resistant;
  • - P. aeruginosa are ⁇ -lactam and quinolone resistant.
  • microorganisms that are causing persistent infections are increasingly being recognized as causative agents or cofactors of severe chronic diseases like peptic ulcers or heart diseases.
  • a new type of quinoline or naphthyridine derivatives having antibacterial activity and therefore useful for treating infections in mammals, particularly in humans, has been reported in the last few years.
  • WO 99/37635, WO 00/21948, WO 00/21952, WO 00/43383, WO 03/101138, WO 01/025227, WO 02/040474 and WO 2004/011454 disclose quinoline, naphthyridine and quinazoline derivatives containing a 4-methylpiperidinyl spacer.
  • WO 00/78748, WO 02/50040 and WO 02/050061 disclose quinoline and naphthyridine derivatives containing a piperazinyl spacer.
  • WO 01/07432, WO 01/07433, WO 02/08224, WO 02/056882, WO 03/064421, WO 03/064431, WO 2004/02490 and WO 2004/058144 disclose quinoline, quinoxaline and naphthyridine derivatives containing a 4-aminopiperidinyl spacer.
  • WO 04/035569 and WO 2006/014580 disclose quinoline and naphthyridine derivatives containing a 3-aminomethylpiperidinyl spacer.
  • WO 2004/002992, WO 03/087098, WO 2004/014361 and WO 2004/035569 disclose quinoline, quinoxaline and naphthyridine derivatives containing a 4-aminocyclohexyl spacer.
  • R 1 represents alkyl, alkoxy, haloalkoxy, halogen or cyano; one or two of U, V, W and X represent(s) N, the remaining represent CH, or, in the case of U, V and/or W, may also represent CR a and, in the case of X, may also represent CR b ; R a represents halogen; R b represents halogen or alkoxy;
  • D represents alkyl, aryl or heteroaryl
  • M is notably the group M 2 :
  • R 2 represents hydrogen, alkyl, hydroxyalkyl, alkylcarbonyloxyalkyl, carbamoyloxyalkyl, carboxyalkyl or carbamoylalkyl;
  • R 3 and R 4 each independently represent hydrogen, hydroxy or alkylcarbonyloxy; or R 3 and R 4 together represent a bridged dimethylmethylenedioxy chain attached to the carbons bearing R 3 and R 4 ;
  • R 5 represents hydrogen, alkyl or hydroxyalkyl; and the dotted line represents a single bond or, when R 3 and R 4 represent hydrogen, also a double bond.
  • This invention relates to selected compounds of formula (Al) as described above and salts thereof.
  • the invention relates in particular to compounds selected from the following:
  • the compounds of this invention will be selected from the following:
  • the compounds of this invention will in particular be selected from the following:
  • the compounds of this invention can also be selected from the following:
  • the compounds of this invention will be selected from the following:
  • the compounds of this invention will in particular be selected from the following:
  • the compounds of this invention will be selected from the following:
  • the compounds of this invention are suitable for the use as chemotherapeutic active compounds in human and veterinary medicine and as substances for preserving inorganic and organic materials in particular all types of organic materials for example polymers, lubricants, paints, fibres, leather, paper and wood.
  • These compounds according to the invention are particularly active against bacteria and bacteria-like organisms. They are therefore particularly suitable in human and veterinary medicine for the prophylaxis and chemotherapy of local and systemic infections caused by these pathogens as well as disorders related to bacterial infections comprising pneumonia, otitis media, sinusitis, bronchitis, tonsillitis, and mastoiditis related to infection by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Enterococcus faecalis, E. faecium, E. casseliflavus, S. epidermidis, S.
  • haemolyticus or Peptostreptococcus spp.
  • pharyngitis rheumatic fever, and glomerulonephritis related to infection by Streptococcus pyogenes, Groups C and G streptococci, Corynebacterium diphtheriae, or Actinobacillus haemolyticum
  • respiratory tract infections related to infection by Mycoplasma pneumoniae, Legionella pneumophila, Streptococcus pneumoniae, Haemophilus influenzae, or Chlamydia pneumoniae
  • blood and tissue infections including endocarditis and osteomyelitis, caused by S. aureus, S. haemolyticus, E. faecalis, E.
  • faecium E. durans, including strains resistant to known antibacterials such as, but not limited to, beta- lactams, vancomycin, aminoglycosides, quinolones, chloramphenicol, tetracyclines and macrolides; uncomplicated skin and soft tissue infections and abscesses, and puerperal fever related to infection by Staphylococcus aureus, coagulase-negative staphylococci (i.e., S. epidermidis, S.
  • Streptococcus pyogenes Streptococcus agalactiae, Streptococcal groups C-F (minute colony streptococci), viridans streptococci, Corynebacterium minutissimum, Clostridium spp., or Bartonella henselae
  • uncomplicated acute urinary tract infections related to infection by Staphylococcus aureus, coagulase-negative staphylococcal species, or Enterococcus spp.
  • urethritis and cervicitis sexually transmitted diseases related to infection by Chlamydia trachomatis, Haemophilus ducreyi, Treponema pallidum, Ureaplasma urealyticum, or Neiserria gonorrheae
  • aureus food poisoning and toxic shock syndrome
  • Groups A, B, and C streptococci ulcers related to infection by Helicobacter pylori; systemic febrile syndromes related to infection by Borrelia recurrentis; Lyme disease related to infection by Borrelia burgdorferi; conjunctivitis, keratitis, and dacrocystitis related to infection by Chlamydia trachomatis, Neisseria gonorrhoeae, S. aureus, S. pneumoniae, S. pyogenes, H.
  • MAC Mycobacterium avium complex
  • chelonei gastroenteritis related to infection by Campylobacter jejuni; intestinal protozoa related to infection by Cryptosporidium spp.; odontogenic infection related to infection by viridans streptococci; persistent cough related to infection by Bordetella pertussis; gas gangrene related to infection by Clostridium perfringens or Bacteroides spp.; and atherosclerosis or cardiovascular disease related to infection by Helicobacter pylori or Chlamydia pneumoniae.
  • the compounds according to this invention are further useful for the preparation of a medicament for the treatment of infections that are mediated by bacteria such as E. coli, Klebsiella pneumoniae and other Enterobacteriaceae, Acinetobacter spp. , Stenothrophomonas maltophilia, Neisseria meningitidis, Bacillus cereus, Bacillus anthracis, Corynebacterium spp., Propionibacterium acnes and bacteroide spp.
  • bacteria such as E. coli, Klebsiella pneumoniae and other Enterobacteriaceae, Acinetobacter spp. , Stenothrophomonas maltophilia, Neisseria meningitidis, Bacillus cereus, Bacillus anthracis, Corynebacterium spp., Propionibacterium acnes and bacteroide spp.
  • the compounds according to this invention are further useful to treat protozoal infections caused by Plasmodium malaria, Plasmodium falciparum, Toxoplasma gondii, Pneumocystis carinii, Trypanosoma brucei and Leishmania spp.
  • bacterial infections can also be treated in other species like pigs, ruminants, horses, dogs, cats and poultry.
  • the present invention also relates to pharmacologically acceptable salts, or solvates and hydrates, respectively, and to compositions and formulations of the compounds mentioned above.
  • Examples of pharmacologically acceptable salts of sufficiently basic compounds of this invention are selected from the group consisting of salts of physiologically acceptable mineral acids like hydrochloric, hydrobromic, sulfuric and phosphoric acid; or salts of organic acids like methanesulfonic, p-toluenesulfonic, lactic, acetic, trifluoroacetic, citric, succinic, fumaric, maleic and salicylic acid.
  • a sufficiently acidic compound of this invention may form alkali or earth alkaline metal salts, for example sodium, potassium, lithium, calcium or magnesium salts; ammonium salts; or organic base salts, for example methylamine, dimethylamine, trimethylamine, triethylamine, ethylenediamine, ethanolamine, choline hydroxide, meglumin, piperidine, morpholine, tris-(2-hydroxyethyl)amine, lysine or arginine salts.
  • the compounds of this invention may be solvated, especially hydrated. The hydratation can occur during the process of production or as a consequence of the hygroscopic nature of the initially water free compounds of this invention.
  • the pharmaceutical composition according to the present invention contains at least one compound of one of the above compound lists (or a pharmaceutically acceptable salt thereof) as the active agent and optionally carriers and/or diluents and/or adjuvants, and may also contain additional known antibiotics.
  • therapeutically useful agents that contain compounds according to this invention, their solvates, salts or formulations are also comprised in the scope of the present invention.
  • the compounds according to this invention will be administered by using the known and acceptable modes known in the art, either alone or in combination with any other therapeutic agent.
  • Such therapeutically useful agents can be administered by one of the following routes: oral, e.g. as tablets, dragee, coated tablets, pills, semisolids, soft or hard capsules, for example soft and hard gelatine capsules, aqueous or oily solutions, emulsions, suspensions or syrups, parenteral including intravenous, intramuscular and subcutaneous injection, e.g.
  • transdermal delivery system such as a plaster containing the active ingredient, topical or intranasal.
  • TDS transdermal delivery system
  • the substance of the present invention can also be used to impregnate or coated devices that are foreseen for implantation like catheters or artificial joints.
  • the pharmaceutically useful agents may also contain additives for conservation, stabilisation, e.g. UV stabilizers, emulsif ⁇ ers, sweetener, aromatisers, salts to change the osmotic pressure, buffers, coating additives and antioxidants.
  • Another aspect of the invention concerns a method for the treatment of disease comprising the administration to the patient of a pharmaceutically active amount of a compound according to this invention (or a pharmaceutically acceptable salt thereof).
  • the compounds according to this invention may also be used for cleaning purposes, e.g. to remove pathogenic microbes and bacteria from surgical instruments or to make a room or an area aseptic.
  • the compounds according to this invention could be contained in a solution or in a spray formulation.
  • the compounds of this invention can be prepared according to the procedures described in the examples hereafter which illustrate the preparation of the pharmacologically active compounds of the invention but do not limit the scope thereof.
  • the enantiomers can be separated using methods known to one skilled in the art (e.g. by formation and separation of diastereomeric salts or by chromatography on a chiral stationary phase).
  • the invention compounds may be separated by an appropriate combination of silica gel chromatography, high performance liquid chromatography (HPLC) and crystallization techniques.
  • A.iii. 3-methoxy-quinoline-5-carbaldehyde To a solution of intermediate A.ii (10 g) in THF (250 ml) cooled to -78°C, was added n-BuLi (22 ml). After 15 min, a solution of DMF (10 ml) in ether (20 ml) was quickly added. The solution was stirred 15 min and EtOH (5 ml), followed by IM NaHSO 4 (40 ml), was added. After warming to rt, the organic layer was diluted with EA (100 ml). The two layers were separated and the aq. layer was extracted once with EA (100 ml). The combined org.
  • Trifluoromethanesulfonic acid 6-methoxy-[l,5]naphthyridin-4-yl ester (1.5 g, 4.86 mmol), trans -phenylvinyl boronic acid (0.8 g, 5.35 mmol) and K 2 CO 3 (0.9 g, 6.32 mmol) were introduced in a two-neck flask. The atmosphere was flushed with nitrogen. Dioxane (20 ml) and water (5 ml) were added. The mixture was stirred at rt for 5 min and (P(Ph) 3 )4Pd (0.28 g, 0.24 mmol) was added. The mixture was heated at reflux for 5 h.
  • Li. (S)-(l-hydroxymethyl-pent-4-enyl)-carbamic acid tert-butyl ester To a suspension of LiBH 4 (1.15 g, 53 mmol) in THF (300 ml) at rt was added a solution of ( ⁇ -2-tert-butoxycarbonylamino-hex-5-enoic acid methyl ester (12.9 g, 53 mmol, prepared according to J. Org. Chem. (1995), 60, 2210) in THF (100 ml). The mixture was stirred at rt for 4 h, poured into water and extracted with EA. The organic layer was washed with brine, dried over MgSO 4 and concentrated to give the title alcohol (11.4 g, 99% yield) as a colourless oil.
  • the reaction mixture was filtered through a pad of celite and the solvent was removed in vacuo.
  • the residue was extracted twice with EA.
  • the combined org. layers were dried over Na 2 SO 4 , filtered and concentrated in vacuo.
  • the residue was taken up in MeOH (30 ml) and NaBH 4 (0.7 g) was added.
  • the reaction proceeded for 15 min. 10% aq. NaHSO 4 (100 ml) was added.
  • the volatiles were removed in vacuo and the aq. residue was extracted three times with EA (3 x 100 ml).
  • the combined org. layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated to dryness.
  • Example 2 ⁇ (2R,3R,6R)-3- [(£)-3-(2,5-difluoro-phenyl)-acryloylamino] - 6-[2-(3-methoxy-quinolin-5-yl)-ethyl]-tetrahydro-pyran-2-yl ⁇ -acetic acid:
  • Example 3 ⁇ (2R,3R,6R)-6-[2-(3-methoxy-quinolin-5-yl)-ethyl]-3-[(3-oxo-3,4-dihydro- 2H-pyrido [3,2-6] [l,4]thiazine-6-carbonyl)-amino]-tetrahydro-pyran-2-yl ⁇ -acetic acid:
  • step 2.v the title aldehyde (0.372 g, 88% yield) was obtained as a colourless thick oil.
  • the compound was purified by column chromatography over SiO 2 using DCM-MeOH 19-1 as an eluent.
  • Example 6 ⁇ (2R,3R,6R)-3-[(£)-3-(2,5-difluoro-phenyl)-allylamino]-6-[(15)-l-hydroxy- 2-(6-methoxy-[l,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-2-yl ⁇ -acetic acid dihydrochloride:
  • step 2.iii the title amine (0.57 g, 80% yield) was obtained as a brown foam.
  • the compound was obtained as a 2-1 mixture of epimers.
  • Example 8 2- ⁇ (2R,3R,6R)-3- [CEVS- ⁇ S-difluoro-pheny ⁇ -allylamino] -6- [2-(6-methoxy- [l,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-2-yl ⁇ -acetamide dihydrochloride:
  • Example 10 ⁇ (2R,3R,6R)-3- [(£)-3-(2,5-difluoro-phenyl)-allylamino] -6- [2-(6-methoxy- quinolin-4-yl)-ethyl]-tetrahydro-pyran-2-yl ⁇ -acetic acid dihydrochloride:
  • Example 12 2- ⁇ (2R,3R,65)-3-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-6-[(S)-l-hydroxy- 2-(6-methoxy-[l,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-2-yl ⁇ -acetamide:
  • Example 15 3-oxo-3,4-dihydro-2H-pyrido[3,2-6] [l,4]thiazine-6-carboxylic acid ⁇ (2S,3R,65)-6-[(2RS)-2-hydroxy-2-(3-methoxy-quinolin-5-yl)-ethyl]-2-hydroxymethyl- tetr ahydro-pyran-3 -yl ⁇ -amide :
  • Example 17 2- ⁇ (2R,3R,65)-3-[( ⁇ )-3-(2,5-difluoro-phenyl)-allylamino]- 6- [(£)-2-(3-fluoro-6-methoxy- [ 1 ,5] naphthyridin-4-yl)- vinyl] -tetr ahydro-pyran-2-yl ⁇ - acetamide:
  • Example 21 7-fluoro-6-( ⁇ (3R,6S)-6-[(lS)-l-hydroxy-2-(6-methoxy-quinolin-4-yl)- ethyl] -tetrahydr o-pyran-3-ylamino ⁇ -methyl)-4H-benzo [ 1 ,4] thiazin-3-one:
  • Example 22 3-(2-fluoro-phenyl)-7V- ⁇ (3R,65)-6-[(lS)-l-hydroxy-2-(6-methoxy-quinolin- 4-yl)-ethyl] -tetrahydro-pyran-3-yl ⁇ -(£)-acrylamide:
  • Example 24 8-((lR,2R)-2- ⁇ (2S,5R)-5-[( ⁇ )-3-(2,5-difluoro-phenyl)-allylamino]- tetrahydro-pyr an-2-yl ⁇ - 1 ,2-dihydroxy-ethyl)-quinoline-2-carbonitrile :
  • Example 25 [( ⁇ -S-Cl ⁇ -difluoro-pheny ⁇ -allyll-ISR ⁇ -o-I ⁇ -l-CS-fluoro-o-methoxy- quinolin-5-yl)-vinyl]-tetrahydro-pyran-3-yl ⁇ -amine:
  • Example 27 6-( ⁇ (3R,6S)-6-[2-(6-fluoro-3-methoxy-quinolin-4-yl)-ethyl]-tetrahydro- pyran-3-ylamino ⁇ -methyl)-4H-pyrido[3,2-6][l,4]thiazin-3-one:
  • Example 29 [( ⁇ -S-Cl ⁇ -difluoro-pheny ⁇ -allyll-iCSS ⁇ RJ- ⁇ -o-Il-Co-fluoro-quinolin- 4-yl)-vinyl] -tetrahydro-pyr an-3-yl ⁇ -amine :
  • Example 30 [( ⁇ -S-Cl ⁇ -difluoro-pheny ⁇ -allyll-KS ⁇ O ⁇ -o-Il-CO-fluoro-quinolin ⁇ -yl)- ethyl] -tetrahydro-pyr an-3-yl ⁇ -amine :
  • the compound was purified by chromatography using Hept-EA 1-2 as an eluent. The compound was obtained as a 2-1 mixture of epimers and a 3-1 E-Z mixture. MS (ESI, m/z): 517.1 [M+H + ].
  • step 1.x (reductive amination, 91% yield).
  • the crude reaction mixture was purified by chromatography over SiO 2 using respectively DCM-MeOH 6-1 containing 1% aq. NH 4 OH and DCM-MeOH 9-1 containing 1% aq.
  • Example 35 ⁇ (2R,3R,65)-3-[( ⁇ )-3-(2,5-difluoro-phenyl)-allylamino]- 6- [(£)-2-(6-methoxy- [ 1 ,5] naphthyridin-4-yl)-vinyl] -tetrahydro-pyr an-2-yl ⁇ -acetic acid:
  • Example 36 [(2R,3R,65)-3-[(£)-3-(2,5-difluoro-phenyl)-allylamino]-6-(6-methoxy- [l,5]naphthyridin-4-ylcarbamoyl)-tetrahydro-pyran-2-yl]-acetic acid:
  • the reaction mixture was diluted with EA (150 ml) and the solids were removed by filtration. MeOH (30 ml) was added and the resulting suspension was filtered. The filtrate was treated with aq. 10% NaHSO 3 (60 ml). The phases were separated and the aq. layer was extracted three times with EA. The combined org. layers were washed with brine, dried over Na 2 SO 4 , filtered and evaporated under reduced pressure to give a brown foam (quant.). The compound was obtained as a 2-1 mixture of epimers. MS (ESI, m/z): 360.1 [M+H + ].
  • the compound was obtained as a 2-1 mixture of epimers.

Abstract

La présente invention concerne des antibiotiques sélectionnés de formule (A1) où R1 représente un groupement alkyle, alcoxy, halogénoalcoxy, halogéno ou cyano ; un ou deux des groupements U, V, W et X représentent N, le reste représentant CH ou, dans le cas de U, V et/ou W, pouvant également représenter CRa et, dans le cas de X, pouvant également représenter CRb, Ra représentant un atome d'halogène et Rb représentant un atome d'halogène ou un groupement alcoxy ; A3 représente NHCO, CH2CH2, CH=CH, COCH2, CH(OH)CH2, CH2CH(OH), CH(OH)CH(OH) ou OCH2 ; A4 représente CH2, CO, CH2CH=CH, COCH=CH ou CH2CONH ; R2 représente un atome d'hydrogène ou un groupement alkyle, hydroxyalkyle, alkylcarbonyloxyalkyle, carbamoyloxyalkyle, carboxyalkyle ou carbamoylalkyle ; R3 et R4 représentent chacun de façon indépendante un atome d'hydrogène ou un groupement hydroxy ou alkylcarbonyloxy ; ou R3 et R4 représentent ensemble une chaîne diméthylméthylènedioxy pontée attachée aux carbones portant R3 et R4 ; R5 représente un atome d'hydrogène ou un groupement alkyle ou hydroxyalkyle ; et la ligne pointillée représente une liaison simple ou, lorsque R3 et R4 représentent des atomes d'hydrogène, une double liaison ; et D représente un groupement alkyle, aryle ou hétéroaryle. L'un des exemples d'un tel antibiotique est le (E)-2-{(2R,3R,6R)-3-[3-(2,5-difluoro-phényl)- allylamino]-6-[2-(6-méthoxy-[1,5]naphtyridin-4-yl)-éthyl]-tétrahydro-pyrann-2-yl}-éthanol.
EP07713226A 2006-03-10 2007-03-09 Composés antibiotiques Withdrawn EP1996579A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IB2006050762 2006-03-10
PCT/IB2007/050784 WO2007105154A2 (fr) 2006-03-10 2007-03-09 Composés antibiotiques

Publications (1)

Publication Number Publication Date
EP1996579A2 true EP1996579A2 (fr) 2008-12-03

Family

ID=38267680

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07713226A Withdrawn EP1996579A2 (fr) 2006-03-10 2007-03-09 Composés antibiotiques

Country Status (5)

Country Link
EP (1) EP1996579A2 (fr)
JP (1) JP2009529525A (fr)
CN (1) CN101400674A (fr)
CA (1) CA2643962A1 (fr)
WO (1) WO2007105154A2 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE520687T1 (de) * 2007-06-15 2011-09-15 Actelion Pharmaceuticals Ltd 3-amino-6-(1-amino-ethyl)-tetrahydropyranderiva e
EP2245028B1 (fr) 2007-12-18 2012-02-22 Actelion Pharmaceuticals Ltd. Dérivés 5-aminocyclylméthyloxazolidin-2-one
ES2435596T3 (es) 2008-12-12 2013-12-20 Actelion Pharmaceuticals Ltd. Derivados de 5-amino-2-(1-hidroxi-etil)-tetrahidropirano
KR20210066857A (ko) * 2018-09-27 2021-06-07 쉔젠 칩스크린 바이오사이언스 씨오., 엘티디. 인돌아민-2,3-디옥시게나아제 억제 활성을 갖는 퀴놀린 유도체
CN115677708A (zh) * 2022-10-19 2023-02-03 五邑大学 一种吡咯并喹喔啉的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2500320A1 (fr) * 2002-10-10 2004-04-29 Morphochem Aktiengesellschaft Fuer Kombinatorische Chemie Nouveaux composes antibacteriens
DE10316081A1 (de) * 2003-04-08 2004-10-21 Morphochem AG Aktiengesellschaft für kombinatorische Chemie Neue Verbindungen mit antibakterieller Aktivität
JP4887297B2 (ja) * 2004-09-24 2012-02-29 アクテリオン ファーマシューティカルズ リミテッド 新規二環式抗生物質
WO2006125974A1 (fr) * 2005-05-24 2006-11-30 Astrazeneca Ab Quinoleines d’aminopiperidine et leurs analogues azaisosteriques presentant une activite antibacterienne
CA2635126A1 (fr) * 2006-01-26 2007-08-02 Actelion Pharmaceuticals Ltd Antibiotiques de type tetrahydropyranne

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007105154A2 *

Also Published As

Publication number Publication date
CA2643962A1 (fr) 2007-09-20
WO2007105154A3 (fr) 2007-12-13
WO2007105154A2 (fr) 2007-09-20
JP2009529525A (ja) 2009-08-20
CN101400674A (zh) 2009-04-01

Similar Documents

Publication Publication Date Title
EP2144910B1 (fr) Antibiotiques à base d'oxazolidinone
CA2580621A1 (fr) Nouveaux antibiotiques bicycliques
KR101294962B1 (ko) 트리사이클 옥사졸리디논 항생제 화합물
CA2689102C (fr) Derives de 3-amino-6-(1-amino-ethyl)-tetrahydropyrane
EP2066678B1 (fr) Dérivés spiraniques antibiotiques
US20070173532A1 (en) New Piperidine Antibiotics
TWI426076B (zh) ５－胺基－２－（１－羥基－乙基）－四氫哌喃衍生物
NZ577538A (en) 5-hydroxymethyl-2-oxo-oxazolidine-quinoline and 5-hydroxymethyl-2-oxo-oxazolidine-naphthyridine derivatives
WO2010041219A1 (fr) 2-benzothiophényl- et 2-naphtyl-oxazolidinones et leurs analogues isostères aza utilisés comme agents antibactériens
WO2007105154A2 (fr) Composés antibiotiques
EP1981881B1 (fr) Antibiotiques de type tétrahydropyranne
WO2009034546A2 (fr) Dérivés de trans-décahydroisoquinoline
EP1799676A2 (fr) Nouveaux antibiotiques bicycliques
EP1799674A1 (fr) Nouveaux antibiotiques de piperidine

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20081010

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR

RIN1 Information on inventor provided before grant (corrected)

Inventor name: ZUMBRUNN ACKLIN, CORNELIA

Inventor name: SURIVET, JEAN-PHILIPPE

Inventor name: GAUVIN, JEAN-CHRISTOPHE

Inventor name: HUBSCHWERLEN, CHRISTIAN

17Q First examination report despatched

Effective date: 20100203

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20120425