CA2507607C - Composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases - Google Patents
Composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases Download PDFInfo
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- CA2507607C CA2507607C CA2507607A CA2507607A CA2507607C CA 2507607 C CA2507607 C CA 2507607C CA 2507607 A CA2507607 A CA 2507607A CA 2507607 A CA2507607 A CA 2507607A CA 2507607 C CA2507607 C CA 2507607C
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- Prior art keywords
- oxo
- tetrahydro
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- trans
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- 239000003814 drug Substances 0.000 title claims description 12
- 239000003112 inhibitor Substances 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title abstract description 15
- 102000006635 beta-lactamase Human genes 0.000 title description 12
- 108020004256 Beta-lactamase Proteins 0.000 title description 9
- 230000000844 anti-bacterial effect Effects 0.000 title description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 229940088710 antibiotic agent Drugs 0.000 title 1
- -1 CONHOH Chemical group 0.000 claims abstract description 362
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 239000002253 acid Substances 0.000 claims abstract description 74
- 125000003118 aryl group Chemical group 0.000 claims abstract description 70
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 16
- 229910006069 SO3H Inorganic materials 0.000 claims abstract description 15
- 150000007513 acids Chemical class 0.000 claims abstract description 14
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 9
- PWEBUXCTKOWPCW-UHFFFAOYSA-L squarate Chemical compound [O-]C1=C([O-])C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-L 0.000 claims abstract description 7
- 229910004727 OSO3H Inorganic materials 0.000 claims abstract description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 180
- 238000000034 method Methods 0.000 claims description 175
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 124
- 239000000203 mixture Substances 0.000 claims description 121
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 118
- 125000004432 carbon atom Chemical group C* 0.000 claims description 111
- 159000000000 sodium salts Chemical class 0.000 claims description 94
- 150000003254 radicals Chemical class 0.000 claims description 85
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 67
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
- 229910052757 nitrogen Inorganic materials 0.000 claims description 43
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 239000002585 base Substances 0.000 claims description 25
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000001301 oxygen Chemical group 0.000 claims description 15
- 239000011593 sulfur Chemical group 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 150000003536 tetrazoles Chemical group 0.000 claims description 12
- 238000010511 deprotection reaction Methods 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000004224 protection Effects 0.000 claims description 8
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 7
- 238000005810 carbonylation reaction Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- KBCJUXYWXREELB-FRJORHAFSA-N OC(COC=1C=CC2=C([C@H]3N(C(N([C@H]2C(=O)N)C3)=O)OS(=O)(=O)O)C1)CO Chemical compound OC(COC=1C=CC2=C([C@H]3N(C(N([C@H]2C(=O)N)C3)=O)OS(=O)(=O)O)C1)CO KBCJUXYWXREELB-FRJORHAFSA-N 0.000 claims description 6
- 150000005840 aryl radicals Chemical class 0.000 claims description 6
- 230000006315 carbonylation Effects 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- JXMAIZVIPNCKBN-OCCSQVGLSA-N C(C)C1=C(C=CC=C1)C1=CC2=C([C@H](N3C(N([C@@H]2C3)OS(=O)(=O)O)=O)C(=O)N)S1 Chemical compound C(C)C1=C(C=CC=C1)C1=CC2=C([C@H](N3C(N([C@@H]2C3)OS(=O)(=O)O)=O)C(=O)N)S1 JXMAIZVIPNCKBN-OCCSQVGLSA-N 0.000 claims description 5
- VEKFEUOQPWMIJD-UHFFFAOYSA-N C=12N=C(NC(=C3C1C=CC=C3)C(=O)OCC)C2 Chemical compound C=12N=C(NC(=C3C1C=CC=C3)C(=O)OCC)C2 VEKFEUOQPWMIJD-UHFFFAOYSA-N 0.000 claims description 5
- INAMPWIZNOOJJJ-WDEREUQCSA-N O=C1N2[C@H](C3=C([C@@H](N1OS(=O)(=O)O)C2)C=C(C=C3)OCCOS(=O)(=O)O)C(=O)N Chemical compound O=C1N2[C@H](C3=C([C@@H](N1OS(=O)(=O)O)C2)C=C(C=C3)OCCOS(=O)(=O)O)C(=O)N INAMPWIZNOOJJJ-WDEREUQCSA-N 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- LAQGFTYHWCONOH-UHFFFAOYSA-N O=C1N(OS(O)(=O)=O)C2CN1CC1=C2C=NN1C(=O)N Chemical compound O=C1N(OS(O)(=O)=O)C2CN1CC1=C2C=NN1C(=O)N LAQGFTYHWCONOH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 230000026030 halogenation Effects 0.000 claims description 4
- 238000005658 halogenation reaction Methods 0.000 claims description 4
- 150000004678 hydrides Chemical class 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 238000007127 saponification reaction Methods 0.000 claims description 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 4
- JRTQUTGTRIIJSJ-YPMHNXCESA-N CC1=C(C=CC=C1)C1=CC2=C([C@H](N3C(N([C@@H]2C3)OS(=O)(=O)O)=O)C(=O)N)S1 Chemical compound CC1=C(C=CC=C1)C1=CC2=C([C@H](N3C(N([C@@H]2C3)OS(=O)(=O)O)=O)C(=O)N)S1 JRTQUTGTRIIJSJ-YPMHNXCESA-N 0.000 claims description 3
- WHZYJUULDFYKFE-UHFFFAOYSA-N S1CC=C2C1=C(N=CN=C2)C(=O)OC Chemical compound S1CC=C2C1=C(N=CN=C2)C(=O)OC WHZYJUULDFYKFE-UHFFFAOYSA-N 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 230000021235 carbamoylation Effects 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
- 238000006473 carboxylation reaction Methods 0.000 claims description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims description 3
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical class ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 3
- 238000005695 dehalogenation reaction Methods 0.000 claims description 3
- 238000005906 dihydroxylation reaction Methods 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000005670 sulfation reaction Methods 0.000 claims description 3
- 238000005694 sulfonylation reaction Methods 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 claims description 3
- YTAXUUFAWLVCIP-UHFFFAOYSA-N C1=CC(OC)=CC=C1CN1C(CN2CC3N(C2=O)OS(O)(=O)=O)=C3C=N1 Chemical compound C1=CC(OC)=CC=C1CN1C(CN2CC3N(C2=O)OS(O)(=O)=O)=C3C=N1 YTAXUUFAWLVCIP-UHFFFAOYSA-N 0.000 claims description 2
- YGATWVBXKHEMDB-UONOGXRCSA-N CONC(=O)[C@@H]1N2C(N([C@H](C3=C1C=CC(=C3)OCOCCOC)C2)OS(=O)(=O)O)=O Chemical compound CONC(=O)[C@@H]1N2C(N([C@H](C3=C1C=CC(=C3)OCOCCOC)C2)OS(=O)(=O)O)=O YGATWVBXKHEMDB-UONOGXRCSA-N 0.000 claims description 2
- 101100134929 Gallus gallus COR9 gene Proteins 0.000 claims description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- HFETUMKPIBKEEE-UHFFFAOYSA-N S1CC=C2C1=CN=CN=C2C(=O)OCC Chemical compound S1CC=C2C1=CN=CN=C2C(=O)OCC HFETUMKPIBKEEE-UHFFFAOYSA-N 0.000 claims description 2
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- 230000029936 alkylation Effects 0.000 claims description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 2
- 230000021523 carboxylation Effects 0.000 claims description 2
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- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
- 230000019635 sulfation Effects 0.000 claims description 2
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- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 2
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- 230000001012 protector Effects 0.000 claims 5
- 229940124350 antibacterial drug Drugs 0.000 claims 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- PUHBFGZZWLUWQD-INPHSSGZSA-N CC1(OCC(O1)COC=1C=CC2=C([C@H]3N(C(N([C@H]2C(=O)N)C3)=O)OS(=O)(=O)O)C1)C Chemical compound CC1(OCC(O1)COC=1C=CC2=C([C@H]3N(C(N([C@H]2C(=O)N)C3)=O)OS(=O)(=O)O)C1)C PUHBFGZZWLUWQD-INPHSSGZSA-N 0.000 claims 1
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- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims 1
- MAYKNZIDKSZHQI-UHFFFAOYSA-N [7-carbamoyl-9-oxo-4-(phenylcarbamoyl)-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2,5-dien-10-yl] hydrogen sulfate Chemical compound N1=C2C(C(=O)N)N(C(N3OS(O)(=O)=O)=O)CC3C2=CN1C(=O)NC1=CC=CC=C1 MAYKNZIDKSZHQI-UHFFFAOYSA-N 0.000 claims 1
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- 238000004587 chromatography analysis Methods 0.000 description 42
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- 230000000144 pharmacologic effect Effects 0.000 description 1
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- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
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- ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 description 1
- 229960003342 pivampicillin Drugs 0.000 description 1
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- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- BESQLCCRQYTQQI-UHFFFAOYSA-N propan-2-yl 2-cyanoacetate Chemical compound CC(C)OC(=O)CC#N BESQLCCRQYTQQI-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229960004932 sulbenicillin Drugs 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- SOROUYSPFADXSN-SUWVAFIASA-N talampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OC2C3=CC=CC=C3C(=O)O2)(C)C)=CC=CC=C1 SOROUYSPFADXSN-SUWVAFIASA-N 0.000 description 1
- 229960002780 talampicillin Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- AQYOGXPFIQCXKH-UHFFFAOYSA-N thieno[3,2-c]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=NC=CC2=C1C=CS2 AQYOGXPFIQCXKH-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle 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
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/18—Bridged systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR02/15428 | 2002-12-06 | ||
| FR0215428A FR2848210B1 (fr) | 2002-12-06 | 2002-12-06 | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases |
| PCT/FR2003/003523 WO2004052891A1 (fr) | 2002-12-06 | 2003-11-28 | Composes heterocyclique, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2507607A1 CA2507607A1 (fr) | 2004-06-24 |
| CA2507607C true CA2507607C (fr) | 2014-06-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2507607A Expired - Fee Related CA2507607C (fr) | 2002-12-06 | 2003-11-28 | Composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1569935B1 (https=) |
| JP (1) | JP4954477B2 (https=) |
| KR (1) | KR101146802B1 (https=) |
| AT (1) | ATE405567T1 (https=) |
| AU (1) | AU2003294104A1 (https=) |
| CA (1) | CA2507607C (https=) |
| DE (1) | DE60323135D1 (https=) |
| FR (1) | FR2848210B1 (https=) |
| WO (1) | WO2004052891A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2844273B1 (fr) | 2002-09-05 | 2008-04-04 | Aventis Pharma Sa | Nouveaux composes heterocycliques, procede et intermediaires de preparation et utilisation comme medicament, notamment comme inhibiteurs de beta-lactamases et anti-bacteriens. |
| KR101594898B1 (ko) | 2005-07-15 | 2016-02-18 | 알바니 몰레큘라 리써치, 인크. | 아릴- 및 헤테로아릴-치환된 테트라히드로벤자제핀, 및 노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기 위한 용도 |
| CA2783572C (en) | 2005-12-07 | 2016-08-09 | Basilea Pharmaceutica Ag | Useful combinations of monobactam antibiotics with beta-lactamase inhibitors |
| FR2914923B1 (fr) * | 2007-04-12 | 2013-06-14 | Novexel | Nouveaux composes heterocycliques azotes,leur preparation et leur utilisation comme medicaments antibacteriens. |
| FR2921060B1 (fr) * | 2007-09-14 | 2012-06-15 | Novexel | Nouveau procede de preparation d'une piperidine disubsituee et nouveaux intermediaires |
| FR2936798B1 (fr) * | 2008-10-03 | 2012-09-28 | Novexel | Nouveaux composes heterocycliques azotes, leur preparation et leur utilisation comme medicaments antibacteriens. |
| FR2937034B1 (fr) | 2008-10-10 | 2012-11-23 | Novexel | Nouveaux composes heterocycliques azotes, leur preparation et leur utilisation comme medicaments antibacteriens |
| FR2936951B1 (fr) * | 2008-10-10 | 2010-12-03 | Novexel | Nouvelles combinaisons de composes heterocycliques azotes antibacteriens avec d'autres composes antibacteriens et leur utilisation comme medicaments |
| US8796257B2 (en) | 2011-12-02 | 2014-08-05 | Naeja Pharmaceutical Inc. | Bicyclic compounds and their use as antibacterial agents and β-lactamase inhibitors |
| US9505761B2 (en) | 2011-12-02 | 2016-11-29 | Fedora Pharmaceuticals Inc. | Bicyclic compounds and their use as antibacterial agents and beta-lactamase inhibitors |
| BR112015003592B1 (pt) * | 2012-08-25 | 2020-04-14 | Wockhardt Ltd | derivados de 1,6-diazabiciclo[3,2,1]octan-7-ona e seu uso no tratamento de infecções bacterianas |
| UA111925C2 (uk) | 2012-12-11 | 2016-06-24 | Федора Фармасьютікалз Інк. | БІЦИКЛІЧНІ СПОЛУКИ ТА ЇХ ВИКОРИСТАННЯ ЯК АНТИБАКТЕРІАЛЬНИХ АГЕНТІВ ТА ІНГІБІТОРІВ β-ЛАКТАМАЗИ |
| WO2014141132A1 (en) * | 2013-03-14 | 2014-09-18 | Naeja Pharmaceutical Inc. | NEW HETEROCYCLIC COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS AND β-LACTAMASE INHIBITORS |
| KR102542392B1 (ko) * | 2014-11-17 | 2023-06-09 | 엔타시스 테라퓨틱스 리미티드 | 내성 박테리아 감염의 치료를 위한 배합물 치료제 |
| CN114591223B (zh) | 2016-09-16 | 2025-01-24 | 恩塔西斯治疗有限公司 | β-内酰胺酶抑制剂化合物 |
| JOP20190061A1 (ar) | 2016-09-28 | 2019-03-26 | Novartis Ag | مثبطات بيتا-لاكتاماز |
| NZ758200A (en) | 2017-05-08 | 2025-12-19 | Entasis Therapeutics Inc | Compounds and methods for treating bacterial infections |
| EP3604309A1 (en) | 2018-07-30 | 2020-02-05 | Mutabilis | Heterocyclic compounds and their use in preventing or treating bacterial infections |
| EP3604315A1 (en) * | 2018-07-30 | 2020-02-05 | Mutabilis | Heterocyclic compounds and their use in preventing or treating bacterial infections |
| EP4146650B1 (en) | 2020-09-01 | 2026-01-21 | Ningxia Academy of Agriculture and Forestry Sciences | Beta-lactamase inhibitors and their preparation |
| US12410166B2 (en) | 2021-05-07 | 2025-09-09 | Ningxia Academy Of Agriculture And Forestry Sciences | Sulfonylamidine substituted compounds and their use as beta-lactamase inhibitors |
| WO2024227071A1 (en) * | 2023-04-26 | 2024-10-31 | Entasis Therapeutics Limited | Synthesis of durlobactam |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2676230B1 (fr) * | 1991-05-07 | 1993-08-27 | Centre Nat Rech Scient | Nouveaux derives de pyrrolo [1,4]-benzodiazepines, leur procede de preparation et medicaments les contenant. |
| HUT74682A (en) * | 1993-12-29 | 1997-01-28 | Pfizer | Diazabicyclic neurokinin antagonists and pharmaceutical compositions containing them |
| DE19627431A1 (de) * | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| AU4698399A (en) * | 1998-06-30 | 2000-01-17 | Du Pont Pharmaceuticals Company | 1,3-benzodiazepin-2-ones and 1,3-benzoxazepin-2-ones useful as hiv reverse transcriptase inhibitors |
| CO5180550A1 (es) * | 1999-04-19 | 2002-07-30 | Smithkline Beecham Corp | Inhibidores de fab i |
| FR2812635B1 (fr) * | 2000-08-01 | 2002-10-11 | Aventis Pharma Sa | Nouveaux composes heterocycliques, preparation et utilisation comme medicaments notamment comme anti- bacteriens |
| FR2825705B1 (fr) * | 2001-06-08 | 2005-05-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens |
| FR2835186B1 (fr) * | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
-
2002
- 2002-12-06 FR FR0215428A patent/FR2848210B1/fr not_active Expired - Fee Related
-
2003
- 2003-11-28 EP EP03789523A patent/EP1569935B1/fr not_active Expired - Lifetime
- 2003-11-28 AU AU2003294104A patent/AU2003294104A1/en not_active Abandoned
- 2003-11-28 WO PCT/FR2003/003523 patent/WO2004052891A1/fr not_active Ceased
- 2003-11-28 CA CA2507607A patent/CA2507607C/fr not_active Expired - Fee Related
- 2003-11-28 DE DE60323135T patent/DE60323135D1/de not_active Expired - Lifetime
- 2003-11-28 AT AT03789523T patent/ATE405567T1/de not_active IP Right Cessation
- 2003-11-28 KR KR1020057010234A patent/KR101146802B1/ko not_active Expired - Fee Related
- 2003-11-28 JP JP2004558137A patent/JP4954477B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60323135D1 (de) | 2008-10-02 |
| AU2003294104A1 (en) | 2004-06-30 |
| EP1569935A1 (fr) | 2005-09-07 |
| JP4954477B2 (ja) | 2012-06-13 |
| ATE405567T1 (de) | 2008-09-15 |
| FR2848210A1 (fr) | 2004-06-11 |
| KR101146802B1 (ko) | 2012-05-21 |
| FR2848210B1 (fr) | 2007-10-19 |
| WO2004052891A8 (fr) | 2005-07-28 |
| KR20050088302A (ko) | 2005-09-05 |
| JP2006512335A (ja) | 2006-04-13 |
| EP1569935B1 (fr) | 2008-08-20 |
| WO2004052891A1 (fr) | 2004-06-24 |
| CA2507607A1 (fr) | 2004-06-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20181128 |