DE10226921A1 - Antibakterielle Amid-Makrozyklen - Google Patents
Antibakterielle Amid-MakrozyklenInfo
- Publication number
- DE10226921A1 DE10226921A1 DE10226921A DE10226921A DE10226921A1 DE 10226921 A1 DE10226921 A1 DE 10226921A1 DE 10226921 A DE10226921 A DE 10226921A DE 10226921 A DE10226921 A DE 10226921A DE 10226921 A1 DE10226921 A1 DE 10226921A1
- Authority
- DE
- Germany
- Prior art keywords
- substituents
- alkyl
- cycloalkyl
- hydrogen
- amino
- 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- Withdrawn
Links
- -1 amide macrocycles Chemical class 0.000 title claims abstract description 229
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 87
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 110
- 125000001424 substituent group Chemical group 0.000 claims description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 239000001257 hydrogen Substances 0.000 claims description 91
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000000623 heterocyclic group Chemical group 0.000 claims description 80
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 50
- 125000003282 alkyl amino group Chemical group 0.000 claims description 46
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 45
- 150000002367 halogens Chemical class 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 41
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 35
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 34
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 22
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 21
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 21
- 125000000539 amino acid group Chemical group 0.000 claims description 20
- 150000001413 amino acids Chemical class 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 14
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 14
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 6
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 claims description 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 84
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 125000006239 protecting group Chemical group 0.000 description 29
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- 239000003480 eluent Substances 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 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 18
- 229910052796 boron Inorganic materials 0.000 description 18
- 235000019253 formic acid Nutrition 0.000 description 18
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 229960001701 chloroform Drugs 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 13
- 229910052786 argon Inorganic materials 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 239000003960 organic solvent Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 238000013519 translation Methods 0.000 description 11
- 239000007821 HATU Substances 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 229930195733 hydrocarbon Natural products 0.000 description 10
- 150000002430 hydrocarbons Chemical class 0.000 description 10
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 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 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 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 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 9
- 150000008282 halocarbons Chemical class 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 238000001972 liquid chromatography-electrospray ionisation mass spectrometry Methods 0.000 description 9
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000011181 potassium carbonates Nutrition 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 230000014616 translation Effects 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 235000008206 alpha-amino acids Nutrition 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 238000002199 high-resolution Fourier transform ion cyclotron resonance mass spectrometry Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003513 alkali Substances 0.000 description 6
- 150000001371 alpha-amino acids Chemical class 0.000 description 6
- 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 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 244000052769 pathogen Species 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XOSVVZQCJBMLPH-KRWDZBQOSA-N (2s)-3-(5-iodo-2-phenylmethoxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC(I)=CC=C1OCC1=CC=CC=C1 XOSVVZQCJBMLPH-KRWDZBQOSA-N 0.000 description 5
- UDSPRIUGJMVBTJ-MOPGFXCFSA-N (2s,4r)-4-[tert-butyl(dimethyl)silyl]oxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C[C@@H](O[Si](C)(C)C(C)(C)C)CNC(=O)OCC1=CC=CC=C1 UDSPRIUGJMVBTJ-MOPGFXCFSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 108090000331 Firefly luciferases Proteins 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 239000004793 Polystyrene Substances 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 150000001718 carbodiimides Chemical class 0.000 description 5
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 5
- 150000001728 carbonyl compounds Chemical class 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
- 229920002223 polystyrene Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 5
- LHFTUYBCCNRGQH-NRFANRHFSA-N (2s)-3-(5-iodo-2-phenylmethoxyphenyl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC(I)=CC=C1OCC1=CC=CC=C1 LHFTUYBCCNRGQH-NRFANRHFSA-N 0.000 description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 4
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
- C07D245/04—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
-
- 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)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10226921A DE10226921A1 (de) | 2002-06-17 | 2002-06-17 | Antibakterielle Amid-Makrozyklen |
| PT03738012T PT1515983E (pt) | 2002-06-17 | 2003-06-10 | Macrociclos de amida antibacterianos |
| HR20050043A HRP20050043A2 (hr) | 2002-06-17 | 2003-06-10 | Antibakterijski amidni makrocikli |
| DE50306587T DE50306587D1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
| AT03738012T ATE354585T1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
| AU2003245928A AU2003245928B2 (en) | 2002-06-17 | 2003-06-10 | Antibacterial amide macrocycles |
| CNB038192144A CN1326870C (zh) | 2002-06-17 | 2003-06-10 | 抗菌的酰胺大环类物质 |
| EP03738012A EP1515983B1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
| MXPA04012438A MXPA04012438A (es) | 2002-06-17 | 2003-06-10 | Macrociclos de amida antibacterianos. |
| PL03374554A PL374554A1 (en) | 2002-06-17 | 2003-06-10 | Antibacterial amide macrocycles |
| CA002489454A CA2489454A1 (en) | 2002-06-17 | 2003-06-10 | Antibacterial amide macrocycles |
| HK06103632.2A HK1083511B (en) | 2002-06-17 | 2003-06-10 | Antibacterial amide macrocycles |
| US10/518,600 US20070129288A1 (en) | 2002-06-17 | 2003-06-10 | Antibacterial amide macrocycles |
| JP2004513311A JP4437078B2 (ja) | 2002-06-17 | 2003-06-10 | 抗菌性アミドマクロサイクル |
| BR0311948-3A BR0311948A (pt) | 2002-06-17 | 2003-06-10 | Macrociclos de amida antibacterianos |
| ES03738012T ES2282643T3 (es) | 2002-06-17 | 2003-06-10 | Macrociclos de amina antibacterianos. |
| RU2005100954/04A RU2005100954A (ru) | 2002-06-17 | 2003-06-10 | Антибактериальные амидные макроциклы |
| KR10-2004-7020473A KR20050010060A (ko) | 2002-06-17 | 2003-06-10 | 항균성 아미드 마크로사이클 |
| PCT/EP2003/006078 WO2003106480A1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
| ZA200410006A ZA200410006B (en) | 2002-06-17 | 2004-12-10 | Antibacterial amide macrocycles. |
| MA28006A MA28613B1 (fr) | 2002-06-17 | 2004-12-15 | Macrocycles d'amide antibacteriens |
| EC2004005499A ECSP045499A (es) | 2002-06-17 | 2004-12-17 | Macrociclos de amida antibacterianos |
| NO20050210A NO20050210L (no) | 2002-06-17 | 2005-01-13 | Antibakterielle amid-makrocykluser |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10226921A DE10226921A1 (de) | 2002-06-17 | 2002-06-17 | Antibakterielle Amid-Makrozyklen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10226921A1 true DE10226921A1 (de) | 2003-12-24 |
Family
ID=29594575
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10226921A Withdrawn DE10226921A1 (de) | 2002-06-17 | 2002-06-17 | Antibakterielle Amid-Makrozyklen |
| DE50306587T Expired - Lifetime DE50306587D1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50306587T Expired - Lifetime DE50306587D1 (de) | 2002-06-17 | 2003-06-10 | Antibakterielle amid-makrozyklen |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US20070129288A1 (https=) |
| EP (1) | EP1515983B1 (https=) |
| JP (1) | JP4437078B2 (https=) |
| KR (1) | KR20050010060A (https=) |
| CN (1) | CN1326870C (https=) |
| AT (1) | ATE354585T1 (https=) |
| AU (1) | AU2003245928B2 (https=) |
| BR (1) | BR0311948A (https=) |
| CA (1) | CA2489454A1 (https=) |
| DE (2) | DE10226921A1 (https=) |
| EC (1) | ECSP045499A (https=) |
| ES (1) | ES2282643T3 (https=) |
| HR (1) | HRP20050043A2 (https=) |
| MA (1) | MA28613B1 (https=) |
| MX (1) | MXPA04012438A (https=) |
| NO (1) | NO20050210L (https=) |
| PL (1) | PL374554A1 (https=) |
| PT (1) | PT1515983E (https=) |
| RU (1) | RU2005100954A (https=) |
| WO (1) | WO2003106480A1 (https=) |
| ZA (1) | ZA200410006B (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006103009A1 (de) * | 2005-03-30 | 2006-10-05 | Aicuris Gmbh & Co. Kg | Antibakterielle amid-makrozyklen vi |
| US7655643B2 (en) | 2003-12-16 | 2010-02-02 | Aicuris Gmbh & Co. Kg | Antibacterial macrocycles with substituted biphenyl |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7521420B2 (en) | 2003-06-18 | 2009-04-21 | Tranzyme Pharma, Inc. | Macrocyclic antagonists of the motilin receptor |
| CA2540646A1 (en) * | 2003-10-01 | 2005-04-14 | Bayer Healthcare Ag | Antibacterial amide macrocycles |
| DE102004018405A1 (de) * | 2004-04-16 | 2005-11-03 | Bayer Healthcare Ag | Antibakterielle Amid-Makrozyklen II |
| DE102004025731A1 (de) * | 2004-05-26 | 2005-12-15 | Bayer Healthcare Ag | Antibakterielle Amid-Makrozyklen III |
| DE102005014240A1 (de) * | 2004-09-24 | 2006-03-30 | Bayer Healthcare Ag | Antibakterielle Amid-Makrozyklen IV |
| DE102005014245A1 (de) * | 2005-03-30 | 2006-10-05 | Aicuris Gmbh & Co. Kg | Antibakterielle Amid-Makrozyklen V |
| DE102005032781A1 (de) * | 2005-07-14 | 2007-01-18 | Aicuris Gmbh & Co. Kg | Antibakterielle Amid-Markozyklen VII |
| DK1984344T3 (da) | 2005-12-29 | 2013-01-14 | Lexicon Pharmaceuticals Inc | Multicykliske aminosyrederivater og fremgangsmåder til anvendelse heraf |
| KR20110098724A (ko) * | 2008-12-04 | 2011-09-01 | 바이엘 파마 악티엔게젤샤프트 | 방사성동위원소-표지된 리신 및 오르니틴 유도체, 그의 용도 및 그의 제조 방법 |
| US10501493B2 (en) | 2011-05-27 | 2019-12-10 | Rqx Pharmaceuticals, Inc. | Broad spectrum antibiotics |
| EA201590871A1 (ru) * | 2012-11-21 | 2015-11-30 | АрКьюЭкс ФАРМАСЪЮТИКЛС, ИНК. | Макроциклические антибиотики широкого спектра действия |
| JP5437525B1 (ja) * | 2012-12-28 | 2014-03-12 | 株式会社ナード研究所 | チロシン誘導体およびチロシン誘導体の製造方法 |
| BR112016027232A2 (pt) | 2014-05-20 | 2018-06-26 | Genentech Inc | antibióticos macrocíclicos de amplo espectro |
| US10118890B2 (en) | 2014-10-10 | 2018-11-06 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
| UA124303C2 (uk) | 2015-10-27 | 2021-08-25 | Ф. Хоффманн-Ля Рош Аг | Пептидні макроцикли проти acinetobacter baumannii |
| US11072635B2 (en) | 2015-11-20 | 2021-07-27 | Rqx Pharmaceuticals, Inc. | Macrocyclic broad spectrum antibiotics |
| EP3388444A1 (en) | 2017-04-10 | 2018-10-17 | F. Hoffmann-La Roche AG | Anti-bacterial peptide macrocycles and use thereof |
| US11505573B2 (en) | 2018-03-28 | 2022-11-22 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| US11819532B2 (en) | 2018-04-23 | 2023-11-21 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| ES2961566T3 (es) | 2019-05-28 | 2024-03-12 | Hoffmann La Roche | Antibióticos macrocíclicos de amplio espectro |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3452136A (en) * | 1968-04-17 | 1969-06-24 | American Cyanamid Co | Antibiotic af283 and production thereof |
| FR2720066B1 (fr) * | 1994-05-20 | 1996-06-28 | Rhone Poulenc Rorer Sa | Peptides antagonistes de la neurotensine. |
| DE10234422A1 (de) * | 2002-07-29 | 2004-02-12 | Bayer Ag | Antibakterielle Ester-Makrozyklen |
| CA2540646A1 (en) * | 2003-10-01 | 2005-04-14 | Bayer Healthcare Ag | Antibacterial amide macrocycles |
| DE10358824A1 (de) * | 2003-12-16 | 2005-07-21 | Bayer Healthcare Ag | Antibakterielle Makrozyklen mit substituiertem Biphenyl |
| DE102005014240A1 (de) * | 2004-09-24 | 2006-03-30 | Bayer Healthcare Ag | Antibakterielle Amid-Makrozyklen IV |
-
2002
- 2002-06-17 DE DE10226921A patent/DE10226921A1/de not_active Withdrawn
-
2003
- 2003-06-10 RU RU2005100954/04A patent/RU2005100954A/ru not_active Application Discontinuation
- 2003-06-10 AT AT03738012T patent/ATE354585T1/de not_active IP Right Cessation
- 2003-06-10 HR HR20050043A patent/HRP20050043A2/hr not_active Application Discontinuation
- 2003-06-10 PL PL03374554A patent/PL374554A1/xx not_active IP Right Cessation
- 2003-06-10 CA CA002489454A patent/CA2489454A1/en not_active Abandoned
- 2003-06-10 DE DE50306587T patent/DE50306587D1/de not_active Expired - Lifetime
- 2003-06-10 ES ES03738012T patent/ES2282643T3/es not_active Expired - Lifetime
- 2003-06-10 BR BR0311948-3A patent/BR0311948A/pt not_active IP Right Cessation
- 2003-06-10 MX MXPA04012438A patent/MXPA04012438A/es active IP Right Grant
- 2003-06-10 AU AU2003245928A patent/AU2003245928B2/en not_active Ceased
- 2003-06-10 EP EP03738012A patent/EP1515983B1/de not_active Expired - Lifetime
- 2003-06-10 KR KR10-2004-7020473A patent/KR20050010060A/ko not_active Abandoned
- 2003-06-10 WO PCT/EP2003/006078 patent/WO2003106480A1/de not_active Ceased
- 2003-06-10 JP JP2004513311A patent/JP4437078B2/ja not_active Expired - Fee Related
- 2003-06-10 US US10/518,600 patent/US20070129288A1/en not_active Abandoned
- 2003-06-10 PT PT03738012T patent/PT1515983E/pt unknown
- 2003-06-10 CN CNB038192144A patent/CN1326870C/zh not_active Expired - Fee Related
-
2004
- 2004-12-10 ZA ZA200410006A patent/ZA200410006B/xx unknown
- 2004-12-15 MA MA28006A patent/MA28613B1/fr unknown
- 2004-12-17 EC EC2004005499A patent/ECSP045499A/es unknown
-
2005
- 2005-01-13 NO NO20050210A patent/NO20050210L/no not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7655643B2 (en) | 2003-12-16 | 2010-02-02 | Aicuris Gmbh & Co. Kg | Antibacterial macrocycles with substituted biphenyl |
| WO2006103009A1 (de) * | 2005-03-30 | 2006-10-05 | Aicuris Gmbh & Co. Kg | Antibakterielle amid-makrozyklen vi |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003245928B2 (en) | 2009-03-05 |
| JP4437078B2 (ja) | 2010-03-24 |
| US20070129288A1 (en) | 2007-06-07 |
| PT1515983E (pt) | 2007-03-30 |
| WO2003106480A1 (de) | 2003-12-24 |
| NO20050210L (no) | 2005-03-01 |
| ECSP045499A (es) | 2005-03-10 |
| CN1326870C (zh) | 2007-07-18 |
| HK1083511A1 (zh) | 2006-07-07 |
| CA2489454A1 (en) | 2004-12-14 |
| EP1515983A1 (de) | 2005-03-23 |
| MXPA04012438A (es) | 2005-04-19 |
| MA28613B1 (fr) | 2007-06-01 |
| CN1675236A (zh) | 2005-09-28 |
| JP2006511446A (ja) | 2006-04-06 |
| AU2003245928A1 (en) | 2003-12-31 |
| DE50306587D1 (de) | 2007-04-05 |
| ATE354585T1 (de) | 2007-03-15 |
| ZA200410006B (en) | 2006-02-22 |
| HRP20050043A2 (hr) | 2006-04-30 |
| RU2005100954A (ru) | 2005-07-10 |
| EP1515983B1 (de) | 2007-02-21 |
| KR20050010060A (ko) | 2005-01-26 |
| ES2282643T3 (es) | 2007-10-16 |
| PL374554A1 (en) | 2005-10-31 |
| BR0311948A (pt) | 2005-03-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8127 | New person/name/address of the applicant |
Owner name: BAYER HEALTHCARE AG, 51373 LEVERKUSEN, DE |
|
| 8139 | Disposal/non-payment of the annual fee |