WO2018216823A1 - Dérivés d'alpha-amino-amide - Google Patents
Dérivés d'alpha-amino-amide Download PDFInfo
- Publication number
- WO2018216823A1 WO2018216823A1 PCT/JP2018/021101 JP2018021101W WO2018216823A1 WO 2018216823 A1 WO2018216823 A1 WO 2018216823A1 JP 2018021101 W JP2018021101 W JP 2018021101W WO 2018216823 A1 WO2018216823 A1 WO 2018216823A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- amino
- phenyl
- hydrochloride
- hydroxy
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000004599 antimicrobial Substances 0.000 claims description 7
- 125000004419 alkynylene group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229940123346 LpxC inhibitor Drugs 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
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- 229940079593 drug Drugs 0.000 abstract description 22
- 239000003814 drug Substances 0.000 abstract description 19
- 241000894006 Bacteria Species 0.000 abstract description 15
- 241000589517 Pseudomonas aeruginosa Species 0.000 abstract description 10
- 230000000845 anti-microbial effect Effects 0.000 abstract description 5
- 208000035143 Bacterial infection Diseases 0.000 abstract description 4
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 4
- -1 2-hydroxypropyl group Chemical group 0.000 description 71
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 68
- 239000000203 mixture Substances 0.000 description 55
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 46
- 238000001819 mass spectrum Methods 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
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- 239000000243 solution Substances 0.000 description 32
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- 230000015572 biosynthetic process Effects 0.000 description 27
- 238000010898 silica gel chromatography Methods 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
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- 239000012044 organic layer Substances 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
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- 239000004305 biphenyl Substances 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
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- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 9
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 9
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- 230000002401 inhibitory effect Effects 0.000 description 8
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- 239000012043 crude product Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 7
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- 239000002904 solvent Substances 0.000 description 7
- 125000003396 thiol group Chemical group [H]S* 0.000 description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ISMDILRWKSYCOD-GNKBHMEESA-N C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O Chemical compound C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O ISMDILRWKSYCOD-GNKBHMEESA-N 0.000 description 6
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- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Definitions
- This invention relates to novel alpha-amino amide derivatives or salts thereof, which exhibit an activity for inhibiting uridyldiphospho(UDP)-3-0-acyl-N-acetylglucosamine deacetylase (LpxC) and antimicrobial pharmaceuticals comprising the same.
- Gram-negative bacteria have an outer membrane composed of a lipid bilayer inexistent in gram-positive bacteria, and thus are more resistant to drugs, as compared with gram-positive bacteria, due to the problem of drug permeability. Gram-negative bacteria are also known to have a plurality of drug efflux proteins, which are known to be involved in drug resistance (Non-Patent Document 1). Furthermore, lipopolysaccharide (LPS), one of the main constituents of the outer membrane, is involved in toxicity as an endotoxin.
- LPS lipopolysaccharide
- Pseudomonas aeruginosa Among gram-negative bacteria, Pseudomonas aeruginosa, in particular, has a strong tendency to show natural resistance to various antimicrobial agents. In recent years,
- Non-Patent Document 2 Pseudomonas aeruginosa strains, which has gained resistance to carbapenem drugs, quinolone drugs or aminoglycoside drugs, has been clinically isolated in medical settings. Moreover, multi-drug resistant Pseudomonas aeruginosa which has obtained resistance to all of these three types of drugs has been isolated (Non-Patent Document 3). Emergence of multi-drug resistant Pseudomonas aeruginosa has become a major healthcare problem worldwide, because there have been few useful therapeutic drugs. Hence, there is a keen demand for the development of a drug having a novel mechanism of action.
- UDP-3-O-acyl-N-acetylglucosamine deacetylase is an enzyme in charge of the synthesis of lipid A (hydrophobic anchor of LPS which is the constituent of the outer membrane).
- Lipid A biosynthesis consists of reactions in ten stages, and LpxC catalyzes the second stage of the biosynthesis reactions to remove the acetyl group of UDP-3-O-acyl-N- acetylglucosamine (Non-Patent Document 4).
- Lipid A is a component essential for the formation of the outer membrane, and is consequently indispensable for the survival of gram- negative bacteria (Non-Patent Document 5).
- LpxC is a rate-determining enzyme in the process of lipid A biosynthesis, and is an indispensable enzyme for lipid A biosynthesis.
- a drug inhibiting the activity of LpxC is highly expected to be an antimicrobial agent effective against gram-negative bacteria including Pseudomonas aeruginosa, particularly against drug resistant Pseudomonas aeruginosa and other gram-negative bacteria, because such a drug has a mechanism of action different from those of conventional drugs.
- LpxC has been the focus of several pharmaceutical drug development programs over the last decade. LpxC has the catalytic zinc ion in its active site and many of the potent LpxC inhibitors identified so far contain a zinc-binding hydroxamic acid group.
- Patent Document 1 International Publication 15/085238 pamphlet.
- Non-Patent Document 1 Antimicrobial Resistance (2002) Mar 1, 34, pp. 634-640.
- Non-Patent Document 2 J. Antimicrob. Chemother. (2003) Jan 14, 51, pp. 347-352.
- Non-Patent Document 3 J Hosp Med. (2013) Sep 10, 8, pp. 559-563.
- Non-Patent Document 4 J. Biol. Chem. (1995) Dec 22, 270, pp. 30384-30391.
- Non-Patent Document 5 J. Bacteriol. (1987), 169, pp. 5408-5415.
- Non-Patent Document 6 Cold Spring Harb Perspect Med. (2016), July 1 ; 6(7), a025304.
- Non-Patent Document 7 Curr Top Med Chem. (2016) 16(21), pp. 2379-2430.
- An object of the present invention is to find novel compounds that do not contain a hydroxamic acid group and inhibit LpxC or pharmaceutically acceptable salts thereof, and provide new pharmaceutical drugs that exhibit antimicrobial activity against gram-negative bacteria including Pseudomonas aeruginosa and their drug resistant strains and that are useful in treating bacterial infections.
- the present inventors have conducted in-depth studies in an attempt to find out a compound having LpxC-inhibiting activity. As a result, they have found that a non-hydroxamic acid compound represented by the following general formula [1] or a pharmaceutically acceptable salt thereof attains the above object. Based on this finding, they have accomplished the present invention.
- the present invention will be described below.
- the present invention provides (1) A compound represented by the following general formula [1] or a pharmaceutically acceptable salt thereof:
- Y represents a group selected from the following formula [3]:
- R 1 represents a group selected from the following formula [4]:
- L represents a bond or a C alkylene group
- R 2 represents a phenyl group or a halogen atom
- R 3 represents a group selected from the following formula [5] :
- L 3 represents a C alkylene group, a C alkynylene group, -0-, -OCH2-, -CH2O-, a bond,
- R 4 represents a group selected from the following formula [6] :
- L 4 represents -C ⁇ C-, a CM alkylene group or a bond
- R 5 represents a group selected from the following formula [7]
- L 5 represents -C ⁇ C ⁇ , a CM alkylene group or a bond
- R 6 represents a group selected from the following formula [8]:
- L 6 represents ⁇ C ⁇ C-, a C 1-4 alkylene group or a bond
- W represents a hydrogen atom, a halogen atom, a phenyl group, a CM hydroxyalkyl group, HOCH 2 CH 2 0- HOOC-CH2CH2- or N-morpholinomethyl group, n represents 1 or 2, and * indicates the site of the attachment of a moiety;
- R 1 , R 3 , R 4 and R 5 are as defined in item (1).
- R 6 is as defined in item (1)
- a pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items (1) to (6);
- An LpxC inhibitor comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items (1) to (6).
- An antimicrobial agent comprising the compound or the pharmaceutically
- the compound or the pharmaceutically acceptable salt thereof according to the present invention has a strong LpxC-inhibiting action.
- the compound or its pharmaceutically acceptable salt is useful as a pharmaceutical composition and as an antimicrobial agent against gram-negative bacteria.
- n- means normal, "i-" iso, "sec-” secondary, “tert-” tertiary, “c-” cyclo, "o-" ortho, "m-” meta, and "p-" para.
- halogen atom means a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
- C M alkyl group refers to a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms. Its examples are a methyl group, an ethyl group, a n-propyl group, a n-butyl group, an isopropyl group, an isobutyl group, a tert-butyl group and a sec-butyl group.
- C 2-4 alkynyl group refers to a straight-chain or branched-chain alkynyl group with 2 to 4 carbon atoms which has one or more triple bonds at any position(s) of the above-mentioned "d- 8 alkyl group”. Its examples are an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group and a 3-butynyl group.
- C M hydroxyalkyl group refers to an alkyl group in which one or more of the hydrogen atoms of the above-mentioned "CM alkyl group” has been or have been substituted with a hydroxyl group or hydroxyl groups. Its examples are a hydroxymethyl group, a 1 - hydroxyethyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, a 3-hydroxypropyl group, a 1-hydroxybutyl group, a 2-hydroxybutyl group, a 3-hydroxybutyl group and a 4- hydroxybutyl group.
- C M alkylene group refers to a straight-chain or branched-chain alkylene group having 1 to 4 carbon atoms. Its examples are -CH 2 -, -(CH 2 ) 2 -, -(CH 2 ) 3 -, -CH 2 -CH(CH 3 , -C(CH 3 ) 2 -, -(CH 2 ) 4 -, -(CH 2 ) 2 -CH(CH 3 )-, -CH 2 -CH(CH 3 )-CH 2 - and -CH(CH 3 )-(CH 2 ) 2 -.
- C 2- 4 alkynylene group refers to a straight-chain or branched-chain alkynylene group having 2 to 4 carbon atoms which has one or more triple bonds in the chain.
- protecting group for an amino group include all groups usable usually as protecting groups for an amino group, and includes, for example, the groups described in P.G.M. Wuts et al., Protective Groups in Organic Synthesis, 5th Ed., 2014, John Wiley Sons, Inc.
- the "leaving group” includes, for example, a halogen atom, a methnesulfonyloxy group, a ethanesulfonyloxy group, a isopropanesulfonyloxy group, a trifluoromethanesulfonyloxy group, benzensulfonyloxy group and a p-toluenesulfonyloxy group.
- the "antimicrobial agent” refers to a substance which has the ability to act on bacteria, such as gram-positive bacteria or gram-negative bacteria, thereby suppressing their growth or destroying them.
- the antimicrobial agent may be one which keeps down propagation of bacteria, or kills some of bacteria to decrease their count.
- Examples of gram-positive bacteria are the genus Staphylococcus (Staphylococcus aureus, Staphylococcus epidermidis, etc.), the genus Streptococcus (Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, etc.), and the genus Enterococcus (Enterococcus faecalis, Enterococcus faecium, etc.).
- Staphylococcus Staphylococcus aureus, Staphylococcus epidermidis, etc.
- the genus Streptococcus Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, etc.
- Enterococcus Enterococcus faecalis, Enterococcus faecium, etc.
- Examples of gram-negative bacteria are the genus Pseudomonas (Pseudomonas aeruginosa, etc.), the genus Escherichia (Escherichia coli, etc.), the genus Klebsiella
- Acinetobacter calcoaceticus, etc. the genus Legionella (Legionella pneumophila, etc.), the genus Bacteroides (Bacteroides fragilis, etc.), the genus Neisseria (Neisseria gonorrhoeae, Neisseria meningitides, etc.), the genus Moraxella (Moraxella catarrhalis, etc.), the genus Chlamydia (Chlamydia trachomatis, Chlamydia psittaci, etc.), and the genus Helicobacter (Helicobacter pylori, etc.).
- Preferred X is a rou represented by the followin formula 2a] :
- R 1 , R 3 , R 4 and R 5 are defined above,
- Preferred Y is a group represented b the following formula 3a]
- X is a group represented by the following formula [3b]:
- Preferred R is a group represented by the following formula [4]:
- W is a hydrogen atom, a C 1-4 hydroxyalkyl group, HOCH 2 CH 2 0- or N-morpholinomethyl group.
- a preferred sent invention is as follows
- the compounds represented by the formula [1] of the present invention have asymmetric carbon at alpha-carbon atom.
- the compounds of the present invention may be used in racemic form or as a specific enantiomer.
- the compounds represented by the following formula [10] are preferred:
- the compounds of the present invention can exist as tautomers, stereoisomers such as geometrical isomers, and optical isomers, and the present invention includes them.
- the present invention also includes various hydrates, solvates and polymorphic substances of the compounds of the invention and their salts.
- the pharmaceutically acceptable salts refer to salts which are used in chemotherapy and prevention of bacterial infections.
- Their examples are salts with acids such as formic acid, acetic acid, propionic acid, butyric acid, trifluoroacetic acid, maleic acid, tartaric acid, citric acid, stearic acid, succinic acid, ethylsuccinic acid, malonic acid, lactobionic acid, gluconic acid, glucoheptonic acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid (tosic acid), laurylsulfuric acid, malic acid, aspartic acid, glutamic acid, adipic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, hydriodic acid, nicotinic acid, oxalic
- the compound of the present invention can be made into a medicinal preparation upon combination with one or more pharmaceutically acceptable carriers, excipients or diluents.
- carriers, excipients and diluents include water, lactose, dextrose, fructose, sucrose, sorbitol, mannitol, polyethylene glycol, propylene glycol, starch, gum, gelatin, alginate, calcium silicate, calcium phosphate, cellulose, aqueous syrup, methyl cellulose, polyvinyl pyrrolidone, alkylparahydroxybenzosorbate, talc, magnesium stearate, stearic acid, glycerin, sesame oil, olive oil, soy oil, and various other seed oils.
- the above carriers, excipients or diluents can be mixed, as needed, with commonly used additives such as thickeners, binders, disintegrants, pH regulators, and solvents, and can be prepared as an oral or parenteral drug, such as tablets, pills, capsules, granules, powders, liquids, emulsions, suspensions, ointments, injections, or skin patches, by a customary pharmaceutical technology.
- the compound of the present invention can be administered intravenously, orally or parenterally to an adult patient in a dose of 10 to 5,000 mg as a single daily dose or as divided portions per day. This dose can be increased or decreased, as appropriate, according to the type of the disease to be treated, or the age, body weight, symptoms, etc. of the patient.
- the compound of the present invention can also be used in combination with other drugs.
- the compound of the present invention can be synthesized, for example, by methods to be shown below, but the present invention is in no way limited to these methods of
- a compound represented by the general formula (I-A) (where R Ia -NH-R Ib is a compound represented in formula [2] defined above) is reacted with a compound represented by the general formula (I-B) (where R Ic is a hydroxyl group or a halogen atom, PG is a protecting group for an amino group, and Y is as defined above) in the presence of a condensing agent (in case R Ic is a hydroxyl group) and in the presence or absence of a base, whereby a compound represented by the general formula (I-C) can be obtained. Then, the compound represented by the general formula (I-C) is reacted under appropriate conditions in
- a compound having a benzylpiperidine group represented in formula [2] can be synthesized in the following scheme II.
- a compound represented by the general formula (II-A) (where W is as defined above) is reacted with a compound represented by the general formula (II-B) (where R IIa is a leaving group, PG is a protecting group for an amino group, and the other symbol is as defined above) in the presence of catalysts, such as bis(triphenylphosphine)dichloropalladium and cupper iodide, in the presence or absence of a base, and in the presence or absence of a ligand, whereby a compound represented by the general formula (II-C) (where the symbols are as defined above) can be obtained.
- catalysts such as bis(triphenylphosphine)dichloropalladium and cupper iodide
- a compound having the other group represented in formula [2] (a benzylidenepiperidine group substituted by R 2 , an indoline group substituted by R 3 , a 1,2,3,4-tetrahydroisoquinoline group substituted by R 4 , a lH-indol-3 -amine group substituted by R 5 or an aniline group substituted by R 6 ) can be synthesized in the same manner as scheme II by replacing the compound of the general formula (II-B) with the corresponding compound.
- the sequence of the reaction steps can be changed as needed. If an amino group, a hydroxyl group, a formyl group, and a carboxy group are present in the compounds obtained in the respective reaction steps and their intermediates, the reactions can be performed, with the protective groups for them being removed for deprotection or being used in appropriately changed combinations.
- examples of the base used in any of the above reactions are sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acetate, potassium acetate, potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium methoxide, potassium tert-butoxide, sodium hydride, lithium hydride, triethylamine, diisopropylethylamine, dimethylaniline, diethylaniline, pyridine, pyrrolidine, and N-methylmorpholine.
- Examples of the catalyst are palladium acetate, palladium chloride,
- Examples of the ligand are tri-tert-butylphosphine, tricyclohexylphosphine,
- triphenylphosphine tritolylphosphine, tributyl phosphite, tricyclohexyl phosphite, triphenyl phosphite, 1 , 1 '-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)- 1 , ⁇ - binaphthyl, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino- 2',4',6'-triisopropylbiphenyl, 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl, and 2- (di-tert-butylphosphino)biphenyl.
- the solvent is not limited, if it is stable under the reaction conditions concerned, is inert, and does not impede the reaction.
- the solvent are polar solvents (e.g., water and alcoholic solvents such as methanol, ethanol and isopropanol), inert solvents (e.g., halogenated hydrocarbon-based solvents such as chloroform, methylene chloride, dichloroethane and carbon tetrachloride, ether-based solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1 ,4-dioxane and dimethoxyethane, aprotic solvents such as dimethylformamide, dimethyl sulfoxide, ethyl acetate, tert-butyl acetate, acetonitrile and propionitrile, aromatics such as benzene, toluene and anisole, or hydrocarbons such as cyclohexane),
- the reaction can be performed at an appropriate temperature selected from a range of from -78°C to the boiling point of the solvent used in the reaction, at ordinary pressure or under pressurized conditions, and under microwave irradiation or the like.
- a microwave synthesizer Initiator "1" (Biotage) was used for a microwave reaction condition.
- OH-type silica gel column chromatography was performed using SNAP Ultra (Biotage) or using REVELERIS 40 ⁇ (Grace), and amino-type type silica gel chromatography was performed using SNAPCartridge ISOLUTE Flash-NH 2 (Biotage) or Grace REVELERIS Amino 40 ⁇ (Grace).
- Preparative chromatography was performed using PLC Silica gel 60F254 (Merck), and amino-type preparative chromatography was performed using NH 2 Silica Gel 60 F 254 Plate- Wako (Wako).
- the prep-HPLC purifications were performed using Agilent 1260 Infinity or Agilent 6130 (ionization method: Electron Spray Ionization (ESI)), and Agilent 385-ELSD were used when the ELSD detector was attached.
- Agilent 1260 Infinity or Agilent 6130 ionization method: Electron Spray Ionization (ESI)
- ESI Electron Spray Ionization
- a Agilent 1290 Infinity for LC system Agilent 6130 or 6150 for Quadrupole LC/MS system, and Agilent 385-ELSD when a ELSD detector is attached.
- Ionization method ESI APCI (atmospheric pressure chemical ionization) dual source.
- Ionization method ESI/APCI (electrospray ionization / atmospheric pressure c hemical ionization) dual source.
- (+)-CSA (+)-10-camphorsulfonic acid
- HATU 0-(7-azabenzotriazol- 1 -yl)-N,N,N ⁇ N'-tetramethyluronium hexafluorophosphate HC1: Hydrochloride
- HMDS Hexamethyldisilazane
- PEPPSI (l,3-bis(2,6-diisopropylphenyl)imidazolidene)(3-chloropyridyl)palladium(II) dichloride
- PdCb(dppf) CH2C12 1 , 1 -bi s(diphenylphosphino)ferrocenepalladium(II) chloride dichloromethane complex
- PdCl 2 (PPh 3 ) 2 Bis(triphenylphosphine)palladium(II) dichloride
- Pd(PPh 3 ) 4 Tetrakis(triphenylphosphine)palladium(0)
- T3P Propylphosphonic anhydride
- TBDPS Tert-butyldiphenylsilyl
- TBS Tert-butyldimethylsilyl
- TrCl Triphenylmethyl chloride
- TsCl 4-Methylbenzenesulfonyl chloride
- WSC HCl l-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride
- Table 1 Reference Compound List. Reference Compound ID, chemical structures, MS data,
- Reference Compound R-184 3 ⁇ 4 NMR (400 MHz, CHLOROFORM-d) ⁇ ppm 3.43 (s, 3 H), 3.69 - 3.82 (m, 2 H), 3.91 - 3.96 (m, 1 H), 4.11 - 4.19 (m, 1 H), 4.21 - 4.31 (m, 1 H), 6.80 - 6.85 (m, 2 H), 6.94 - 6.97 (m, 1 H), 7.05 (s, 1 H), 7.19 - 7.31 (m, 2 H), 7.50 (s, 1 H).
- Chemical names of the Reference Compounds in Table- 1 are follows:
- R-2 N-[l,r-biphenyl]-3-ylglycinamide ⁇ hydrochloride
- R-3 N-methyl-N-[3-(trifluoromethoxy)phenyl]glycinamide— hydrochloride
- R-4 N 2 ,N 2 -dimethyl-N- [3 -(trifluoromethoxy)phenyl] glycinamide— hydrochloride
- R-5 2-(4-ethylpiperazin-l-yl)-N-[3-(trifluoromethoxy)phenyl]acetamide ⁇ hydrochloride
- R-6 2-(morpholin-4-yl)-N-[3-(trifluoromethoxy)phenyl]acetamide
- R-7 N- ⁇ 4'- [3 -(morpholin-4-yl)propoxy] [1,1 -biphenyl] -3 -yl ⁇ glycinamide— hydrochloride
- R-8 3 ,3 ,3-trifluoro-N- [3 -(trifluoromethoxy)phenyl] alaninamide
- R- 10 N- [3 -(trifluoromethoxy)phenyl] -D-alpha-glutamine— hydrochloride
- R- 1 1 N- [3 -(trifluoromethoxy)phenyl]-D-histidinamide
- R-12 3-pyridin-4-yl-N-[3-(trifluoromethoxy)phenyl]-D-alaninamide ⁇ 2 hydrochloride
- R-13 3-pyridin-3-yl-N-[3-(trifluoromethoxy)phenyl]-D-alaninamide ⁇ 2 hydrochloride
- R-l 4 N-(4-hydroxypyridin-3-yl)glycinamide— 2 hydrochloride
- R-l 5 N-(5-bromo-4-hydroxypyridin-3-yl)glycinamide— 2 hydrochloride
- R-l 7 N-[3-(trifluoromethoxy)phenyl]-D-homoserinamide
- R-18 2-amino-N 1 -methyl-N 3 -[3-(trifluoromethoxy)phenyl]propanediamide ⁇ hydrochloride
- R- 19 2-amino-N 1 - [3 -(trifluoromethoxy)phenyl]propanediamide— hydrochloride
- R-21 (2R)-2-amino-4-[(methanesulfonyl)amino]-N-[3-(trifluoromethoxy)phenyl]butanarnide
- R-22 3-pyridin-2-yl-N-[3-(trifluoromethoxy)phenyl]-L-alaninamide— 2 hydrochloride
- R-23 (2R)-2,4-diamino-N-[3-(trifluoromethoxy)phenyl]butanamide
- R-24 1 - [(O-methyl-3 -oxoseryl)amino] -3 -(trifluoromethoxy)benzene-- hydrochloride
- R-25 N-(3-bromo-2-propylphenyl)-N-methylglycinamide ⁇ hydrochloride
- R-28 N 5 -acetyl-N-[3-(trifluoromethoxy)phenyl]-D-ornithinamide
- R-29 N-(4-hydroxy-5-methoxypyridin-3-yl)glycinamide ⁇ 2 hydrochloride
- R-32 N-(6-chloro-4-hydroxypyridin-3-yl)glycinamide— 2 hydrochloride
- R-33 3-acetamido-N-[3-(trifluoromethoxy)phenyl]-D-alaninamide
- R-34 3 - [(methanesulfonyl)amino] -N- [3 -(trifluoromethoxy)phenyl] -D-alaninamide
- R-35 N-phenyl-D-serinamide— hydrochloride
- R-36 N-[3-(trifluoromethoxy)phenyl]-D-lysinamide
- R-40 l-[(3-oxidanylideneseryl)amino]-3-(trifluoromethoxy)benzene— hydrochloride
- R-41 N-(5-nitropyridin-2-yl)glycinamide ⁇ 2 hydrochloride
- R-42 2-amino-2-(pyridin-3-yl)-N-[3-(trifluoromethoxy)phenyl]acetamide ⁇ 2 hydrochloride
- R-43 N-[3-(propan-2-yl)phenyl]-D-serinamide—trifluoroacetate
- R-44 3-(l ,3-thiazol-2-yl)-N-[3-(trifluoromethoxy)phenyl]alaninamide ⁇ hydrochloride
- R-45 N-[4-(trifluoromethoxy)phenyl]-D-serinamide—trifluoroacetate
- R-48 N-(3-ethoxyphenyl)-D-serinamide—trifluoroacetate
- R-52 N-[3-(2-phenylethoxy)phenyl]-D-serinamide—trifluoroacetate
- R-53 N-[3-(hexyloxy)phenyl]-D-serinamide— trifluoroacetate
- R-54 3-(2-oxo- 1 ,2-dihydroquinolin-4-yl)-N-[3-(trifluoromethoxy)phenyl]alaninamide ⁇ hydrochloride
- R-56 N-[3-(phenylethynyl)phenyl]-D-serinamide— hydrochloride
- R-58 N- ⁇ [3-(aminomethyl)phenyl]methyl ⁇ -D-serinamide— 2 hydrochloride .
- R-62 (2R)-2-amino-3 -hydroxy- 1 - [4-(2-phenylethyl)piperidin- 1 -yljpropan- 1 -one— hydrochloride
- R-66 N-(5-phenyl-lH-pyrazol-3-yl)-D-serinamide ⁇ hydrochloride
- R-74 N- [(3 -sulfamoylphenyl)methyl] -D-serinamide— hydrochloride
- R-75 N-[(4-sulfamoylphenyl)methyl] -D-serinamide— hydrochloride
- R-76 N-[(4'-amino[l,r-biphenyl]-4-yl)methyl]-D-serinamide— 2 hydrochloride
- R-77 N- ⁇ [6-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl ⁇ -D-serinamide— 2 hydrochloride
- R-78 N-[2-(benzylamino)ethyl]-D-serinamide— 2 hydrochloride
- R-79 N- ⁇ [2-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl ⁇ -D-serinamide— 2 hydrochloride
- R-80 N-[2-hydroxy-2-(3-phenoxyphenyl)ethyl]-D-serinamide— hydrochloride
- R-82 N-(5-bromopyridin-3-yl)-D-serinamide
- R-84 3 - [(2,2-difluoroethyl)amino] -N- [3 -(trifluoromethoxy)phenyl] -D-alaninamide
- R-85 (2R)-2-amino-l -[4-(4-fluorobenzoyl)piperazin-l-yl]-3-hydroxypropan-l-one— hydrochloride
- R-88 1 -[(4-tert-butylphenyl)methyl]-4-D-serylpiperazin-2-one ⁇ hydrochloride
- R-93 (2R)-2-amino-3 -hydroxy- 1 -(4-phenoxypiperidin- 1 -yl)propan- 1 -one— hydrochloride
- R-94 (2R)-2-amino-3 -hydroxy- 1 -(1 'H,2H,4H-spiro[ 1 -benzopyran-3,4'-piperidin]- 1 '- yl)propan-l -one— hydrochloride
- R-96 (2R)-2-amino-3 -hydroxy- 1 -(3 -phenoxyazetidin- 1 -yl)propan- 1 -one— hydrochloride
- R-97 N-(2-phenyl-lH-imidazol-4-yl)-D-serinamide
- R-99 3- ⁇ [2-(methanesulfonyl)ethyl]amino ⁇ -N-[3-(trifluoromethoxy)phenyl]-D-alaninamide
- R- 100 3 -amino- 1 , 1 -dioxo-N- [3 -(trifluoromethoxy)phenyl] - 1 lambda 6 -thiolane-3 - carboxamide— hydrochloride
- R-101 S-methyl-N-[3-(trifluoromethoxy)phenyl]-D-cysteinamide
- R- 102 3 -(methanesulfony 1)-N- [3 -(trifluoromethoxy)phenyl] -D-alaninamide
- R- 103 N- ⁇ 1 -[(4-chlorophenyl)methyl] - 1 H-pyrazol-3 -yl ⁇ -D-serinamide
- R-l 04 3-hydroxy-N-[3-(trifluoromethoxy)phenyl]-alpha-asparagine
- R-105 (2R)-2-amino-3 -hydroxy- l-(4-phenylpiperazin-l-yl)propan-l -one— 2 hydrochloride
- R- 106 (2R)-2-amino-3 -hydroxy- 1 -(4-phenyl-3,6-dihydropyridin- 1 (2H)-yl)propan- 1 -one— hydrochloride
- R- 107 (2R)-2-amino- 1 -( 1 ,3 -dihydro-2H-isoindol-2-yl)-3 -hydroxypropan- 1 -one—
- R- 108 (2R)-2-amino-3 -hydroxy- 1 -(4-phenylpiperidin- 1 -yl)propan- 1 -one— hydrochloride
- R- 109 (2R)-2-amino-3 -hydroxy- 1 - [(3 S)-3 -phenylpyrrolidin- 1 -yljpropan- 1 -one—
- R-l 10 (2R)-2-amino-3-hydroxy-l -[(3R)-3-phenylpyrrolidin-l -yljpropan- 1 -one— hydrochloride
- R-111 (2R)-2-amino-3-hydroxy-l-(l ,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)propan-l-one— hydrochloride
- R-112 (2R)-2-amino-3 -hydroxy- 1 -(3 -phenylazetidin-l-yl)propan-l -one— hydrochloride
- R- 1 13 (2R)-2-amino-3 -hydroxy- 1 - [4-(4-methylbenzene- 1 -sulfonyl)piperidin- 1 -yljpropan- 1 - one— hydrochloride
- R- 1 14 N- 1 H-pyrrolo [3 ,2-b]pyridin-3 -yl-D-serinamide
- R-116 (2R)-2-amino-l-(4-benzylpiperidin-l-yl)-3 -hydroxypropan- 1 -one— hydrochloride
- R-117 N- ⁇ 3 - [(naphthalen-2-yl)methoxy]phenyl ⁇ -D-serinamide
- R-118 N-(2-hydroxyethyl)-N-[3-(propan-2-yl)phenyl]glycinamide
- R-119 (2R)-2-amino-3-hydroxy-l-[(3S)-3-phenylpiperidin-l-yl]propan-l-one formate
- R- 120 formic acid— (2R)-2-amino-3 -hydroxy- 1 - [(3R)-3 -phenylpiperidin- 1 -yl]propan- 1 -one formate
- R-121 N- ⁇ 3-[([l,l'-biphenyl]-4-yl)methoxy]phenyl ⁇ -D-serinamide
- R-122 glycyl-N-[3-(propan-2-yl)phenyl]glycine ⁇ hydrochloride
- R-123 N-( 1 -benzyl- 1 H-pyrazol-3-yl)-D-serinamide
- R- 124 ethyl 3 -hydroxy-N- [3 -(trifluoromethoxy)phenyl] -alpha-asparaginate
- R-125 N-methyl-N-(3-phenoxypropyl)-D-serinamide— hydrochloride
- R- 126 N-methyl-N-(4-phenylbutyl)-D-serinamide ⁇ hydrochloride
- R- 127 2-amino- 1 - ⁇ 4- [(4-methylphenyl)methyl]piperidin- 1 -yl ⁇ ethan- 1 -one
- R-128 (2R)-2-amino- 1 -(4-benzyl-3,6-dihydropyridin- 1 (2H)-yl)-3 -hydroxypropan- 1 -one
- R-129 (2R)-2-amino-3-(4-benzylpiperidin-l-yl)-3-oxopropyl
- R-130 (2R)-2-amino-2-(l,l-dioxo-llambda 6 -thietan-3-yl)-N-[3- (trifluoromethoxy)phenyl]acetamide ⁇ hydrochloride
- R- 132 (3R)-3-amino- 1 -([ 1 , 1 '-biphenyl]-4-yl)piperidin-2-one ⁇ hydrochloride
- R- 133 (2R)-2-amino-3 -hydroxy- 1 -(4- ⁇ [3-(phenylethynyl)phenyl]methyl ⁇ piperidin- 1 - yl)propan-l-one— hydrochloride
- R- 134 (2R)-2-amino- 1 - ⁇ 4- [([ 1 , 1 -biphenyl] -3 -yl)methyl]piperidin- 1 -yl ⁇ -3 -hydroxypropan- 1 - one— hydrochloride
- R- 135 (2R)-2-amino- 1 -(4-benzyl-4-hydroxypiperidin- 1 -yl)-3-hydroxypropan- 1 -one
- R- 136 (2R)-2-amino-3 -hydroxy- 1 - ⁇ 4- [hydroxy(phenyl)methyl]piperidin- 1 -yl ⁇ propan- 1 -one
- R- 137 (2R)-2-amino- 1 -( 1 ,3-dihydro- 1 ⁇ -spiro [indene-2,4'-piperidin]- 1 '-yl)-3- hydroxypropan- 1 -one
- R- 138 (2R)-2-amino-3 -hydroxy- 1 - [4-(4-methylbenzoyl)piperidin- 1 -yljpropan- 1 -one
- R-140 N-tl '-biphenylJ-S-yl-D-serinamide
- R- 141 (2R)-2-amino-3-hydroxy- 1 - ⁇ 4-[(4-methylphenyl)methyl]-3 ,6-dihydropyridin- 1 (2H)- yl ⁇ propan-l-one
- R- 142 (2R)-2-amino- 1 -(7-bromo-3 ,4-dihydroisoquinolin-2( 1 H)-yl)-3 -hydroxypropan- 1 -one- - hydrochloride
- R- 143 2-amino-6- [(naphthalen-2-yl)methoxy] -3 ,4-dihydronaphthalen- 1 (2H)-one— hydrochloride
- R-144 (3S)-3-amino-l-[3-(trifluoromethoxy)phenyl]pyrrolidin-2-one ⁇ hydrochloride
- R- 145 (3R)-3-amino- 1 -[3-(trifluoromethoxy)phenyl]pyrrolidin-2-one— hydrochloride
- R-146 (2R)-2-amino-N-(lH-indol-3-yl)-4-(methanesulfonyl)butanamide ⁇ hydrochloride
- R-147 (3R)-3-amino-l -[3-(benzyloxy)phenyl]pyrrolidin-2-one ⁇ hydrochloride
- R-148 (3R)-3-amino-l- ⁇ 3-[(4-methylphenoxy)methyl]phenyl ⁇ pyrrolidin-2-one—
- R-l 49 (2R)-2-amino- 1 -(5-bromo-2,3 -dihydro- 1 H-indol- 1 -yl)-3-hydroxypropan- 1 -one
- R-l 50 N-[(4-bromophenyl)methyl]-N-methyl-D-serinamide ⁇ hydrochloride
- R-l 52 3-amino-l-(6-bromopyridin-2-yl)pyrrolidin-2-one ⁇ hydrochloride
- R-154 formic acid ⁇ (2R)-2-amino-3-hydroxy-l-(4-phenoxy-2,3-dihydro-lH-indol-l- yl)propan-l-one (1/1)
- R- 155 3-amino- 1 -([ 1 , 1 '-biphenyl]-3-yl)pyrrolidin-2-one
- R- 156 3-amino-l -[3-(phenylethynyl)phenyl]pyrrolidin-2-one— hydrochloride
- R- 157 (2R)-2-amino-l -(2,3-dihydro-l H-pyrrolo[2,3-b]pyridin- 1 -yl)-3 -hydroxypropan- 1 -one
- R- 158 (2R)-2-amino- 1 -(2,3-dihydro- 1 H-pyrrolo [3 ,2-c]pyridin- 1 -yl)-3 -hydroxypropan- 1 -one
- R- 159 (2R)-2-amino- 1 -(2,3-dihydro- 1 H-pyrrolo[3 ,2-b]pyridin- 1 -yl)-3 -hydroxypropan- 1 -one
- R- 160 (2R)-2-amino-3 -hydroxy- 1 -(2-phenyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin- 5-yl)propan-l-one ⁇ hydrochloride
- R-l 61 N-l H-pyrrolo [2,3 -b]pyridin-3-yl-D-serinamide
- R-162 (2R)-2-amino-3-hydroxy-l-(l-phenyl-l ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin- 5 -yl)propan- 1 -one
- R-163 (2R)-2-amino-3-hydroxy-l-(6-hydroxy-2,3-dihydro-lH-indol-l-yl)propan-l-one
- R- 164 (2R)-2-amino-3 -hydroxy-2-methyl- 1 - ⁇ 4- [(4-methylphenyl)methyl]piperidin- 1 - yl ⁇ propan-l-one
- R-l 65 2-methyl-N-[3-(propan-2-yl)phenyl]-D-serinamide
- R- 166 3 -amino-2-hydroxy- 1 - ⁇ 4- [(4-methylpheny l)methyl]piperidin- 1 -yl ⁇ propan- 1 -one
- R-l 67 (2 R)-2-amino-3 -hydroxy- 1 -(2 -methyl -2, 3 -dihydro- 1 H-indol- 1 -yl)propan-l -one
- R- 168 (2R)-2-amino-3-hydroxy- 1 -(spiro [cyclobutane- 1 ,3 -indol]- 1 '(2'H)-yl)propan- 1 -one
- R- 169 (2R)-2-amino- 1 -[3-(2-aminoethyl)-2,3-dihydro- 1 H-indol-1 -yl]-3 -hydroxypropan- 1 - one
- R-170 N-lH-pyrrolo[3,2-c]pyridin-3-yl-D-serinamide
- R-171 3-amino-l-[([l,r-biphenyl]-4-yl)methyl]pyrrolidin-2-one
- R- 172 (2R)-2-amino-3-hydroxy- 1 -( 1 ⁇ -spiro [cyclopropane- 1 ,4'-isoquinolin]-2'(3 ⁇ )- yl)propan-l -one— hydrochloride
- R-173 N-lH-pyrrolo[2,3-b]pyridin-5-yl-D-alpha-asparagine
- R- 174 (2R)-2-amino- 1 -(5-bromo- 1 ,3-dihydro-2H-isoindol-2-yl)-3-hydroxypropan- 1 -one
- R- 175 (2R)-2-amino- 1 -(4-bromo- 1 ,3 -dihydro-2H-isoindol-2-yl)-3 -hydroxypropan- 1 -one
- R- 176 5 - ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ - 1 H-imidazole
- R-178 N-( ⁇ 4-[(2-phenylethyl)sulfanyl]pyridin-2-yl ⁇ methyl)methanesulfonamide
- R-l 79 methyl 4- ⁇ [2-([l , 1 '-biphenyl]-4-yl)ethyl]sulfanyl ⁇ pyridine-2-carboxylate
- R-180 4- ⁇ [2-([l,l'-biphenyl]-4-yl)ethyl]sulfanyl ⁇ pyridine-2-carboxylic acid
- R-181 l-(lH-imidazol-l-yl)-3-phenoxypropan-2-one
- R- 182 N-(4-chlorophenyl)-3 -( 1 H-imidazol- 1 -yl)propanamide
- R- 184 1 -[3-(4-chlorophenoxy)-2-methoxypropyl]- 1 H-imidazole
- R-l 85 l-(4-chlorophenoxy)-3-(l H-imidazol- l-yl)propan-2-amine
- R- 186 1 -[2-(4-chlorophenoxy)ethyl]-4-nitro- 1 H-imidazole
- R-l 87 l-[4-(4-chlorophenyl)butyl]-l H-imidazole
- R- 192 1 - [3 -(4-chlorophenyl)propyl] - 1 H-imidazol-2 -amine
- R- 193 1 - [3 -(4-chlorophenyl)propyl] - 1 H-imidazole-2-carboxylic acid
- R-l 94 ethyl l-[3-(4-chlorophenyl)propyl]-lH-imidazole-2-carboxylate
- R- 196 1 - [4-(4-chlorophenyl)butyl] - 1 H-imidazole-2-carboxylic acid
- R- 197 1 -[3-(4-chlorophenyl)propyl]- 1 H-imidazole-2-carboxamide
- R-l 98 l-[3-(4-chlorophenyl)propyl]-N-methyl-lH-imidazole-2-carboxamide
- R- 199 4-bromo- 1 - [3 -(4-chlorophenyl)propyl] - 1 H-imidazole
- R-200 5-bromo- l-[3-(4-chlorophenyl)propyl]-l H-imidazole
- R-201 1 - [3 -(4-chlorophenyl)propyl] -4-methyl- 1 H-imidazole
- R-202 methyl 1 - [3 -(4-chlorophenyl)propyl] - 1 H-imidazole-5 -carboxylate
- R-203 methyl l-[3-(4-chlorophenyl)propyl]-lH-imidazole-4-carboxylate
- R-204 1 - [3 -(4-chlorophenyl)propyl] - 1 H-imidazole-4-carboxylic acid
- R-205 1 -[3-(4-chlorophenyl)propyl]- 1 H-imidazole-5-carboxylic acid
- R-206 3- ⁇ [3-(4-chlorophenyl)propyl]sulfanyl ⁇ -4H-l ,2,4-triazole
- R-207 l-[3-(4-chlorophenyl)propyl]-lH-imidazol-4-amine ⁇ hydrochloride
- R-208 l-[3-(4-chlorophenyl)propyl]-5-methyl-lH-imidazole
- R-209 2-[3-(4-chlorophenyl)propyl]-4-methyl-2,4-dihydro-3H-l,2,4-triazole-3-thione
- R-210 l-[3-(4-chlorophenyl)propyl]-lH-imidazol-5-amine ⁇ hydrochloride
- R-21 1 N-( ⁇ l-[3-(4-chlorophenyl)propyl]-lH-imidazol-2-yl ⁇ methyl)-2- (methanesulfonyl)ethan-l -amine
- R-212 4- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ pyridine-2-carboxylic acid
- R-213 4- ⁇ [2-(4-chlorophenyl)ethyl]sulfanyl ⁇ pyridine
- R-214 N- ⁇ 1 -[2-(4-chlorophenoxy)ethyl]- 1 H-imidazol-2-yl ⁇ acetamide
- R-215 l-[3-(4-chlorophenyl)propyl]-4-fluoro-lH-imidazole
- R-216 3-hydroxy-5-[(E)-2-phenylethenyl]pyridin-2(lH)-one
- R-217 3-hydroxy-5-[(2-phenylethyl)sulfanyl]pyridin-2(lH)-one
- R-218 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -3 -hydro xypyridin-2( 1 H)-one
- R-219 3-hydroxy-5-[(2-phenoxyethyl)sulfanyl]pyridin-2( 1 H)-one
- R-220 5-[(2-phenylethyl)sulfanyl]pyridin-2(l H)-one
- R-221 5- ⁇ [2-([l,l'-biphenyl]-4-yl)ethyl]sulfanyl ⁇ -3-methoxypyridin-2(lH)-one
- R-222 5- ⁇ [2-([ 1 , 1 '-biphenyl] -4-yl)ethyl] sulfanyl ⁇ -3 -hydroxypyridin-2( 1 H)-one
- R-224 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -2-ethoxy-3 -methoxypyridine
- R-225 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -3 -methoxypyridin-2( 1 H)-one
- R-226 5- ⁇ [2-(4-chlorophenyl)ethyl]sulfanyl ⁇ pyridin-2(lH)-one
- R-227 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -3 -methoxypyrazin-2( 1 H)-one
- R-228 5-[(3-fluorophenyl)sulfanyl]-3-hydroxypyridin-2(lH)-one
- R-229 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ - 1 ,4-dihydropyrazine-2,3 -dione
- R-230 5 - [(3-chloro-5 -fluorophenyl)sulfanyl]-3 -hydroxypyridin-2( 1 H)-one
- R-231 4- ⁇ [2-(4-chlorophenyl)ethyl]sulfanyl ⁇ thieno[2,3-c]pyridin-7(6H)-one
- R-233 4- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -7-methoxy- 1 H-pyrrolo [2,3 -c]pyridine
- R-234 3-chloro-5- ⁇ [2-(4-chlorophenyl)ethyl]sulfanyl ⁇ pyridin-2(lH)-one
- R-235 4- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ - 1 ,6-dihydro-7H-pyrrolo [2,3 -c]pyridin-7-one
- R-236 5 - [(3 -fluoro-5-propoxyphenyl)sulfanyl] -3 -hydroxypyridin-2( 1 H)-one
- R-237 5- ⁇ [2-(3 -chloropheny l)ethyl] sulfanyl ⁇ -3 -hydroxypyridin-2( 1 H)-one
- R-238 5-[(4-chlorophenyl)sulfanyl]-3-hydroxypyridin-2( 1 H)-one
- R-239 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -2-oxo- 1 ,2-dihydropyridine-3 -carboxylic acid
- R-240 5- ⁇ [2-(4-chlorophenyl)ethyl] sulfanyl ⁇ -3 -(hydroxymethyl)pyridin-2( 1 H)-one
- R-243 5-( ⁇ 2-[4-(benzyloxy)phenyl]ethyl ⁇ sulfanyl)-3-hydroxypyridin-2(lH)-one
- R-244 5-[2-(4-chlorophenyl)ethanesulfonyl]-3-hydroxypyridin-2(l H)-one
- R-245 3-hydroxy-5- ⁇ [2-(4-hydroxyphenyl)ethyl]sulfanyl ⁇ pyridin-2(lH)-one
- R-246 3-hydroxy-5-( ⁇ 3 - [4-(phenylethynyl)phenyl]propyl ⁇ sulfanyl)pyridin-2( 1 H)-one
- R-247 5 - ⁇ [3 - ( [ 1 , l'-biphenyl] -4-yl)propyl] sulfanyl ⁇ -3 -hydroxypyridin-2( 1 H)-one
- R-248 3-hydroxy-5-( ⁇ 2-[4-(phenylethynyl)phenyl]ethyl ⁇ sulfanyl)pyridin-2(lH)-one
- R-249 3-hydroxy-5-( ⁇ 3-[4-(2-phenylethyl)phenyl]propyl ⁇ sulfanyl)pyridin-2(l H)-one
- R-250 3-hydroxy-5- ⁇ [5-(pyridin-4-yl)-4H-l ,2,4-triazol-3-yl]sulfanyl ⁇ pyridin-2(lH)-one
- R-251 3-hydroxy-5-[(4- ⁇ [4-(3-hydroxypropyl)phenyl]ethynyl ⁇ phenyl)sulfanyl]pyridin- 2(lH)-one
- R-252 5- ⁇ [2-(4-chlorophenyl)ethyl]sulfanyl ⁇ -4-fluoro-3-hydroxypyridin-2(lH)-one
- R-256 5- ⁇ [3 -(4-chlorophenyl)- 1 H-1 ,2,4-triazol- 1 -yljmethyl ⁇ -3 -hydroxypyridin-2( 1 H)-one
- R-257 [4-(4-chlorophenyl)butyl]propanedioic acid
- R-258 2-(4-chlorophenyl)-5 - ⁇ [(4H- 1 ,2,4-triazol-3 -yl)sulfanyl]methyl ⁇ - 1 ,3 ,4-oxadiazole
- R-259 2-(lH-pyrrol-l-yl)benzoic acid
- R-260 (3-ethyl-l,2,4-oxadiazol-5-yl)methyl carbamimidothioate— hydrochloride
- R-261 5- ⁇ [4-(4-chlorophenyl)-l,2,3-triazol-l-yl]methyl ⁇ -3-hydroxy-lH-pyridin-2-one
- R-262 (E)-5-(3 -(4-chlorophenyl)prop- 1 -en- 1 -yl)-3 -hydroxypyridin-2( 1 H)-one
- R-263 (E)-5-(2-(4-chlorophenyl)prop- 1 -en- 1 -yl)-3-hydroxypyridin-2(l H)-one
- reaction mixture was allowed to warm to room temperature, stirred further 3 hours, quenched with a saturated aqueous sodium bicarbonate and extracted with CHC1 3 three times.
- the organic layer was passed through a phase separator and concentrated in vacuo onto ISOLUTE® HM-N.
- the residue was purified with OH-type silica gel column chromatography (8-31 % EtOAc in n-hexane) to give the title compound (1.2 g, 15 % yield) as a yellow oil.
- triphenylphosphine (0.18 g), hexamethyldisilazane (0.52 mL) and triethylamine (1.7 g) in DMF (8.4 mL) was evacuated and backfilled with nitrogen three times. The mixture was stirred for 10 minutes at 1 10 °C. 2-[2-(4-Ethynylphenoxy)ethoxy]tetrahydropyran (0.83 g). was added into the mixture. The reaction mixture was stirred for 5 hours at 110 °C and overnight at room temperature, quenched with water and extracted with EtOAc. The organic layer was washed with water twice, dried over MgS0 4 , filtered and concentrated in vacuo.
- tert-butyl 3-oxopyrrolidine-l- carboxylate (0.15 g) in THF was added into the mixture.
- the reaction mixture was allowed to warm to room temperature and stirred further 2 hours.
- the mixture was quenched with a saturated aqueous sodium bicarbonate and extracted three times with CHCI3.
- the organic layer was passed through a phase separator and concentrated in vacuo onto ISOLUTE® HM- N.
- Example Compounds in Table 2 and Table 3 were obtained in a manner as with above experimental procedures or general procedures using the corresponding materials.
- Example Compounds (Compound- 1 to Compound-33). Compound ID, chemical structures, 'H-NMR data, MS data and LCMS retention time (minutes) data are shown.
- Test 1 Evaluation of the inhibitory activities on Pseudomonas aeruginosa LpxC enzyme Inhibitory activities on P. aeruginosa LpxC enzyme of compounds were evaluated using the following LCMS method.
- LpxC was reacted with its substrate UDP-3-0-(R-3-hydroxydecanoyl)-N-acetylglucosamine.
- the amounts of substrate and reacted product were determined with a liquid chromatography-tandem mass spectrometry (LC/MS/MS).
- LC/MS/MS liquid chromatography-tandem mass spectrometry
- aeruginosa LpxC genes incorporating the genes into a vector, and expressing in Escherichia coli
- UDP-3-0-(R-3 -hydroxy decanoyl)-N-acetylglucosamine Alberta Research Council
- the reaction was performed in 40 mmol/L of Hepes buffer solution (pH 8.0) supplemented with 0.02% (v/v) Brij 35 and 25 nmol/L of ZnCl 2 .
- acetonitrile containing 25 ⁇ /L of UDP-GlcNAc as internal standard was added.
- the mixture was centrifuged and supernatant was injected into LC/MS/MS.
- the samples were separated with Inertsil Amide (3.0 ⁇ , 50 mm x 2.1 mm I.D., GLScience, Japan).
- the mobile phase was 8 mmol/L ammonium acetate containing 72% acetonitrile and flow rate was 0.2mL/min.
- MS/MS detection of each component was performed using a TSQ Quantum system with electrospray interface (ThermoFisher Scientific, USA) in negative ion detection mode.
- An inhibition curve was constructed for each test compound by performing the aforementioned reaction at varying concentrations of the test compound. From this inhibition curve, the concentration of the test compound at which the formation of the reaction product was suppressed by 50% was determined as the IC 50 of the test compound, which was an index for the inhibitory activity on P. aeruginosa LpxC enzyme.
- the present invention enables providing novel compounds that inhibit LpxC or
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Abstract
L'invention concerne de nouveaux composés représentés par la formule générale suivante [1] ou des sels pharmaceutiquement acceptables de ceux-ci, qui inhibent la LpxC, ainsi que des médicaments pharmaceutiques comprenant ces composés ou des sels pharmaceutiquement acceptables de ceux-ci, qui présentent une activité antimicrobienne contre des bactéries à Gram-négatif comprenant Pseudomonas aeruginosa et leurs souches résistantes aux médicaments et sont utiles dans le traitement d'infections bactériennes, dans la formule, X est choisi parmi la formule suivante [2] : Y est choisi parmi la formule suivante [3].
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GB1708390.8 | 2017-05-25 |
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CN111187218A (zh) * | 2020-02-26 | 2020-05-22 | 四川大学 | 1-取代-1H-咪唑-2-羧酸类化合物在制备金属β-内酰胺酶抑制剂中的用途 |
CN111253317A (zh) * | 2020-02-26 | 2020-06-09 | 四川大学 | 一种1-取代-1h-咪唑-2-羧酸类化合物 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008027466A1 (fr) * | 2006-08-31 | 2008-03-06 | Schering Corporation | Derives d'hydantoine utiles en tant qu'agents antibacteriens |
WO2015024016A2 (fr) * | 2013-08-16 | 2015-02-19 | Duke University | N,3-dihydroxybutanamides substitués par 2-pipéridinyle |
WO2015085238A1 (fr) * | 2013-12-05 | 2015-06-11 | The Regents Of The University Of California, A California Corporation | Inhibiteurs de lpxc |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2307365B1 (fr) * | 2008-06-25 | 2013-03-27 | Merck Sharp & Dohme Corp. | Synthèse et utilisation d agents antibactériens hétérocycliques |
WO2010100475A1 (fr) * | 2009-03-02 | 2010-09-10 | Astrazeneca Ab | Dérivés de l'acide hydroxamique en tant qu'agents contre des bactéries à gram négatif |
WO2013170165A1 (fr) * | 2012-05-10 | 2013-11-14 | Achaogen, Inc. | Agents antibactériens |
-
2017
- 2017-05-25 GB GB1708390.8A patent/GB2562777A/en not_active Withdrawn
-
2018
- 2018-05-25 WO PCT/JP2018/021101 patent/WO2018216823A1/fr active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008027466A1 (fr) * | 2006-08-31 | 2008-03-06 | Schering Corporation | Derives d'hydantoine utiles en tant qu'agents antibacteriens |
WO2015024016A2 (fr) * | 2013-08-16 | 2015-02-19 | Duke University | N,3-dihydroxybutanamides substitués par 2-pipéridinyle |
WO2015085238A1 (fr) * | 2013-12-05 | 2015-06-11 | The Regents Of The University Of California, A California Corporation | Inhibiteurs de lpxc |
Non-Patent Citations (19)
Title |
---|
DATABASE PubChem Compound [online] NCBI; 10 December 2015 (2015-12-10), XP002783890, Database accession no. CID 93255515 * |
DATABASE PubChem Compound [online] NCBI; 10 December 2015 (2015-12-10), XP002783891, Database accession no. CID 93255514 * |
DATABASE PubChem Compound [online] NCBI; 13 January 2016 (2016-01-13), XP002783889, Database accession no. CID 103793796 * |
DATABASE PubChem Compound [online] NCBI; 15 January 2016 (2016-01-15), XP002783888, Database accession no. CID 107569415 * |
DATABASE PubChem Compound [online] NCBI; 15 June 2016 (2016-06-15), XP002783887, Database accession no. CID 119278459 * |
DATABASE PubChem Compound [online] NCBI; 19 October 2012 (2012-10-19), XP002783893, Database accession no. CID 61369680 * |
DATABASE PubChem Compound [online] NCBI; 21 July 2009 (2009-07-21), XP002783894, Database accession no. CID 43650160 * |
DATABASE PubChem Compound [online] NCBI; 23 October 2012 (2012-10-23), XP002783892, Database accession no. CID 64894681 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 11 April 2010 (2010-04-11), XP002783905, Database accession no. 1218176-49-8 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 13 April 2014 (2014-04-13), XP002783902, Database accession no. 1583749-66-9 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 13 June 2011 (2011-06-13), XP002783903, Database accession no. 1309019-85-9 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 19 May 2014 (2014-05-19), XP002783900, Database accession no. 1606869-65-1 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 21 April 2014 (2014-04-21), XP002783901, Database accession no. 1587535-60-1 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 27 December 2015 (2015-12-27), XP002783896, Database accession no. 1837399-88-8 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 27 December 2015 (2015-12-27), XP002783897, Database accession no. 1837399-87-7 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 27 December 2015 (2015-12-27), XP002783898, Database accession no. 1837365-39-5 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 27 December 2015 (2015-12-27), XP002783899, Database accession no. 1837365-38-4 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 31 May 2016 (2016-05-31), XP002783895, Database accession no. 1921463-32-2 * |
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 6 May 2011 (2011-05-06), XP002783904, Database accession no. 1290756-76-1 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111187218A (zh) * | 2020-02-26 | 2020-05-22 | 四川大学 | 1-取代-1H-咪唑-2-羧酸类化合物在制备金属β-内酰胺酶抑制剂中的用途 |
CN111253317A (zh) * | 2020-02-26 | 2020-06-09 | 四川大学 | 一种1-取代-1h-咪唑-2-羧酸类化合物 |
CN111253317B (zh) * | 2020-02-26 | 2023-08-04 | 四川大学 | 一种1-取代-1h-咪唑-2-羧酸类化合物 |
CN111187218B (zh) * | 2020-02-26 | 2023-08-04 | 四川大学 | 1-取代-1H-咪唑-2-羧酸类化合物在制备金属β-内酰胺酶抑制剂中的用途 |
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