CA2460646A1 - Antibacterial macrocycles - Google Patents
Antibacterial macrocycles Download PDFInfo
- Publication number
- CA2460646A1 CA2460646A1 CA002460646A CA2460646A CA2460646A1 CA 2460646 A1 CA2460646 A1 CA 2460646A1 CA 002460646 A CA002460646 A CA 002460646A CA 2460646 A CA2460646 A CA 2460646A CA 2460646 A1 CA2460646 A1 CA 2460646A1
- Authority
- CA
- Canada
- Prior art keywords
- denotes
- alkyl
- hydrogen
- general formula
- halogen
- 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.)
- Abandoned
Links
- 230000000844 anti-bacterial effect Effects 0.000 title description 5
- 150000002678 macrocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- -1 trifluoromethoxy, nitro, amino Chemical group 0.000 claims description 172
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims description 99
- 239000001257 hydrogen Substances 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 82
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 52
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical group 0.000 claims description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 239000011737 fluorine Chemical group 0.000 claims description 25
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 22
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 5
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 13
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 145
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 75
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 68
- 239000000243 solution Substances 0.000 description 65
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- 238000004128 high performance liquid chromatography Methods 0.000 description 44
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
- 239000000203 mixture Substances 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- 239000000047 product Substances 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
- 239000002904 solvent Substances 0.000 description 37
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 32
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
- 235000017557 sodium bicarbonate Nutrition 0.000 description 22
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 21
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 21
- 239000007821 HATU Substances 0.000 description 21
- 239000002585 base Substances 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 230000014759 maintenance of location Effects 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- 239000011734 sodium Substances 0.000 description 20
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 19
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- 229910052786 argon Inorganic materials 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 238000010792 warming Methods 0.000 description 17
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
- 101150041968 CDC13 gene Proteins 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- 238000000746 purification Methods 0.000 description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- 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 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 239000004215 Carbon black (E152) Substances 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 229930195733 hydrocarbon Natural products 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 9
- 150000008041 alkali metal carbonates Chemical class 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 150000002430 hydrocarbons Chemical class 0.000 description 9
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 9
- 150000007530 organic bases Chemical class 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000011736 potassium bicarbonate Substances 0.000 description 9
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 9
- 235000015497 potassium bicarbonate Nutrition 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 229940093956 potassium carbonate Drugs 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 9
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 9
- 229940083542 sodium Drugs 0.000 description 9
- 235000015424 sodium Nutrition 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 125000005270 trialkylamine group Chemical group 0.000 description 9
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 8
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 8
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- 239000004793 Polystyrene Substances 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 150000001718 carbodiimides Chemical class 0.000 description 8
- 150000001728 carbonyl compounds Chemical class 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- 229960001701 chloroform Drugs 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 238000009833 condensation Methods 0.000 description 8
- 230000005494 condensation Effects 0.000 description 8
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 8
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 8
- 229920002223 polystyrene Polymers 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- JCJODSMQBXMELN-UHFFFAOYSA-N 2-ethyl-5-phenyl-1,2-oxazol-2-ium Chemical compound O1[N+](CC)=CC=C1C1=CC=CC=C1 JCJODSMQBXMELN-UHFFFAOYSA-N 0.000 description 7
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 7
- 235000015165 citric acid Nutrition 0.000 description 7
- 244000005700 microbiome Species 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- YURNCBVQZBJDAJ-AATRIKPKSA-N (E)-hept-2-enoic acid Chemical compound CCCC\C=C\C(O)=O YURNCBVQZBJDAJ-AATRIKPKSA-N 0.000 description 6
- MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
- GYEYFOYXHNRMGO-UHFFFAOYSA-N 3-cyclohexylprop-2-enoic acid Chemical compound OC(=O)C=CC1CCCCC1 GYEYFOYXHNRMGO-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- ORPJQSFBLBHKPN-UHFFFAOYSA-N dichloromethane;methylsulfinylmethane Chemical compound ClCCl.CS(C)=O ORPJQSFBLBHKPN-UHFFFAOYSA-N 0.000 description 1
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- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
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- 229910052749 magnesium Inorganic materials 0.000 description 1
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- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
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- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
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- OHYNJBJSASQULK-INIZCTEOSA-N phenacyl (2s)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound N([C@@H](CO)C(=O)OCC(=O)C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 OHYNJBJSASQULK-INIZCTEOSA-N 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
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- 125000003386 piperidinyl group Chemical group 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
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- 125000006239 protecting group Chemical group 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YOQXMBIKAFGORT-RDJZCZTQSA-N tert-butyl (2s)-2-[[(2s)-1-oxo-1-phenylmethoxypropan-2-yl]carbamoyl]piperidine-1-carboxylate Chemical compound N([C@@H](C)C(=O)OCC=1C=CC=CC=1)C(=O)[C@@H]1CCCCN1C(=O)OC(C)(C)C YOQXMBIKAFGORT-RDJZCZTQSA-N 0.000 description 1
- SONXDRNJXIDYGX-LNLFQRSKSA-N tert-butyl (2s)-2-[methyl-[(2s)-1-oxo-1-[[(2s)-1-oxo-1-phenylmethoxypropan-2-yl]amino]propan-2-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound CN([C@@H](C)C(=O)N[C@@H](C)C(=O)OCC=1C=CC=CC=1)C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C SONXDRNJXIDYGX-LNLFQRSKSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 238000002560 therapeutic procedure Methods 0.000 description 1
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- 125000005500 uronium group Chemical group 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10146104.6 | 2001-09-19 | ||
| DE10146104A DE10146104A1 (de) | 2001-09-19 | 2001-09-19 | Antibakterielle Markrozyklen |
| PCT/EP2002/009968 WO2003024996A2 (de) | 2001-09-19 | 2002-09-06 | Antibakterielle makrozyklen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2460646A1 true CA2460646A1 (en) | 2003-03-27 |
Family
ID=7699507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002460646A Abandoned CA2460646A1 (en) | 2001-09-19 | 2002-09-06 | Antibacterial macrocycles |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7405201B2 (enExample) |
| EP (1) | EP1430075B1 (enExample) |
| JP (1) | JP4427326B2 (enExample) |
| AU (1) | AU2002329267A1 (enExample) |
| CA (1) | CA2460646A1 (enExample) |
| DE (2) | DE10146104A1 (enExample) |
| ES (1) | ES2280566T3 (enExample) |
| WO (1) | WO2003024996A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2528375C (en) | 2003-06-18 | 2013-11-19 | Tranzyme Pharma, Inc. | Macrocyclic antagonists of the motilin receptor |
| US9428845B1 (en) | 2010-12-28 | 2016-08-30 | Warp Drive Bio, Inc. | Identifying new therapeutic agents |
| US9193767B2 (en) | 2011-03-30 | 2015-11-24 | Brown University | Enopeptins, uses thereof, and methods of synthesis thereto |
| EP3038640B1 (en) | 2013-08-30 | 2019-01-02 | St. Jude Children's Research Hospital | Substituted urea depsipeptide analogs as activators of the clpp endopeptidase |
| WO2016112295A1 (en) | 2015-01-09 | 2016-07-14 | Warp Drive Bio, Inc. | Compounds that participate in cooperative binding and uses thereof |
| WO2016141351A1 (en) * | 2015-03-04 | 2016-09-09 | St. Jude Children's Research Hospital | Substituted urea depsipeptide analogs as activators of the clpp endopeptidase |
| WO2018045313A1 (en) * | 2016-09-02 | 2018-03-08 | St. Jude Children's Research Hospital | Substituted urea depsipeptide analogs as activators of the clpp endopeptidase |
| KR20240033100A (ko) * | 2017-04-05 | 2024-03-12 | 레볼루션 메디슨즈, 인크. | 협동 결합에 참여하는 화합물 및 그의 용도 |
| WO2024242056A1 (ja) * | 2023-05-22 | 2024-11-28 | 学校法人近畿大学 | 環状ペプチド化合物とそれを含む抗菌剤 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4492650A (en) * | 1982-09-27 | 1985-01-08 | Eli Lilly And Company | A54556 Antibiotics and process for production thereof |
| JPH0565297A (ja) | 1991-01-17 | 1993-03-19 | Rikagaku Kenkyusho | エノペプチンａ、その製造方法、並びに抗ウイルス剤 |
| JP3036923B2 (ja) | 1991-10-28 | 2000-04-24 | 理化学研究所 | デプシペプチドａ、ｂその製造方法、並びに抗ウイルス剤及び抗菌剤 |
| US5858971A (en) * | 1994-10-25 | 1999-01-12 | Sekisui Chemical Co., Ltd. | Cyclic peptide and method of making same by culturing a strain of actinomyces S. nobilis |
| ES2204681T3 (es) * | 1999-07-27 | 2004-05-01 | Aventis Pharma S.A. | Derivados de estreptograminas, su preparacion y composiciones que los contienen. |
-
2001
- 2001-09-19 DE DE10146104A patent/DE10146104A1/de not_active Withdrawn
-
2002
- 2002-09-06 DE DE50209187T patent/DE50209187D1/de not_active Expired - Lifetime
- 2002-09-06 WO PCT/EP2002/009968 patent/WO2003024996A2/de not_active Ceased
- 2002-09-06 US US10/490,192 patent/US7405201B2/en not_active Expired - Fee Related
- 2002-09-06 CA CA002460646A patent/CA2460646A1/en not_active Abandoned
- 2002-09-06 AU AU2002329267A patent/AU2002329267A1/en not_active Abandoned
- 2002-09-06 JP JP2003528842A patent/JP4427326B2/ja not_active Expired - Fee Related
- 2002-09-06 EP EP02764872A patent/EP1430075B1/de not_active Expired - Lifetime
- 2002-09-06 ES ES02764872T patent/ES2280566T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US7405201B2 (en) | 2008-07-29 |
| JP2005510468A (ja) | 2005-04-21 |
| DE50209187D1 (de) | 2007-02-15 |
| EP1430075B1 (de) | 2007-01-03 |
| AU2002329267A1 (en) | 2003-04-01 |
| JP4427326B2 (ja) | 2010-03-03 |
| DE10146104A1 (de) | 2003-04-03 |
| ES2280566T3 (es) | 2007-09-16 |
| US20050107288A1 (en) | 2005-05-19 |
| WO2003024996A2 (de) | 2003-03-27 |
| EP1430075A2 (de) | 2004-06-23 |
| WO2003024996A3 (de) | 2004-01-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |