AU2016313794B2 - Substituted 1,2-dihydro-3H-pyrrolo[1,2-c]imidazol-3-one antibacterial compounds - Google Patents
Substituted 1,2-dihydro-3H-pyrrolo[1,2-c]imidazol-3-one antibacterial compounds Download PDFInfo
- Publication number
- AU2016313794B2 AU2016313794B2 AU2016313794A AU2016313794A AU2016313794B2 AU 2016313794 B2 AU2016313794 B2 AU 2016313794B2 AU 2016313794 A AU2016313794 A AU 2016313794A AU 2016313794 A AU2016313794 A AU 2016313794A AU 2016313794 B2 AU2016313794 B2 AU 2016313794B2
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- Australia
- Prior art keywords
- methyl
- hydroxy
- imidazol
- pyrrolo
- oxo
- 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.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 644
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 17
- XTYMYZJHPHOJAW-UHFFFAOYSA-N 1,2-dihydropyrrolo[1,2-c]imidazol-3-one Chemical class C1=CN2C(=O)NCC2=C1 XTYMYZJHPHOJAW-UHFFFAOYSA-N 0.000 title 1
- -1 3-fluoroazetidin-3-yl Chemical group 0.000 claims description 465
- 238000000034 method Methods 0.000 claims description 324
- 125000000217 alkyl group Chemical group 0.000 claims description 155
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 100
- 150000003839 salts Chemical class 0.000 claims description 70
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
- DRSDBVZXZAWGDF-UHFFFAOYSA-N 2-methylsulfonylbutanamide Chemical compound CCC(C(N)=O)S(C)(=O)=O DRSDBVZXZAWGDF-UHFFFAOYSA-N 0.000 claims description 53
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 44
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 37
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 35
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 34
- 229910052731 fluorine Chemical group 0.000 claims description 30
- 239000011737 fluorine Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 29
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 27
- 230000002265 prevention Effects 0.000 claims description 27
- 208000035143 Bacterial infection Diseases 0.000 claims description 26
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 25
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 229910052796 boron Inorganic materials 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 4
- OHZUEFKOZYWUFF-UHFFFAOYSA-N 4-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CCN(C(O)=O)CC1 OHZUEFKOZYWUFF-UHFFFAOYSA-N 0.000 claims description 4
- 229910018828 PO3H2 Inorganic materials 0.000 claims description 4
- 125000006300 thietan-3-yl group Chemical group [H]C1([H])SC([H])([H])C1([H])* 0.000 claims description 4
- KNWWGBNAUNTSRV-UHFFFAOYSA-N 4-methylpiperazine-1-carboxylic acid Chemical compound CN1CCN(C(O)=O)CC1 KNWWGBNAUNTSRV-UHFFFAOYSA-N 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 3
- 208000027096 gram-negative bacterial infections Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
- SNBYDHCSBZIOQL-UHFFFAOYSA-N 3-hydroxyazetidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)C1 SNBYDHCSBZIOQL-UHFFFAOYSA-N 0.000 claims description 2
- GMIQMQBHYROSKY-UHFFFAOYSA-N benzyl n-(2-hydroxyethyl)-n-methylcarbamate Chemical compound OCCN(C)C(=O)OCC1=CC=CC=C1 GMIQMQBHYROSKY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 10
- QFNHKTSOHATKEL-QHCPKHFHSA-N (3r)-8-cyclopropyl-6-(morpholin-4-ylmethyl)-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid Chemical compound C([C@H](N1C(=O)C(CN2CCOCC2)=C2CC=3C4=CC=CC=C4C=CC=3)C(=O)O)SC1=C2C1CC1 QFNHKTSOHATKEL-QHCPKHFHSA-N 0.000 claims 1
- XJWSNDGCJMGHSR-UHFFFAOYSA-N benzyl 3-hydroxyazetidine-1-carboxylate Chemical compound C1C(O)CN1C(=O)OCC1=CC=CC=C1 XJWSNDGCJMGHSR-UHFFFAOYSA-N 0.000 claims 1
- LWZKZYOPPZAUQW-UHFFFAOYSA-N benzyl 4-methylpiperazine-1-carboxylate Chemical compound C1CN(C)CCN1C(=O)OCC1=CC=CC=C1 LWZKZYOPPZAUQW-UHFFFAOYSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- PDCPSVRSNHMDJH-UHFFFAOYSA-N methyl 3-hydroxyazetidine-1-carboxylate Chemical compound COC(=O)N1CC(O)C1 PDCPSVRSNHMDJH-UHFFFAOYSA-N 0.000 claims 1
- PWPJWHXPIKDVAY-UHFFFAOYSA-N methyl 4-methylpiperazine-1-carboxylate Chemical compound COC(=O)N1CCN(C)CC1 PWPJWHXPIKDVAY-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 description 314
- 238000005481 NMR spectroscopy Methods 0.000 description 214
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 202
- 239000007787 solid Substances 0.000 description 191
- 238000000746 purification Methods 0.000 description 148
- 239000000543 intermediate Substances 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 136
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 124
- 239000000243 solution Substances 0.000 description 99
- 238000006243 chemical reaction Methods 0.000 description 98
- 238000002953 preparative HPLC Methods 0.000 description 92
- 239000000203 mixture Substances 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- 239000011541 reaction mixture Substances 0.000 description 77
- 239000003921 oil Substances 0.000 description 70
- 235000019198 oils Nutrition 0.000 description 70
- 238000001704 evaporation Methods 0.000 description 61
- 230000008020 evaporation Effects 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- HJZVHUQSQGITAM-UHFFFAOYSA-N butanamide Chemical compound CC[CH]C(N)=O HJZVHUQSQGITAM-UHFFFAOYSA-N 0.000 description 47
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- 239000002904 solvent Substances 0.000 description 33
- 238000004296 chiral HPLC Methods 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 208000015181 infectious disease Diseases 0.000 description 26
- 241000894006 Bacteria Species 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 125000004432 carbon atom Chemical group C* 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 239000003480 eluent Substances 0.000 description 19
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 125000003545 alkoxy group Chemical group 0.000 description 18
- 239000011630 iodine Substances 0.000 description 18
- 229910052740 iodine Inorganic materials 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- 239000002585 base Substances 0.000 description 14
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 241000588747 Klebsiella pneumoniae Species 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- 235000015320 potassium carbonate Nutrition 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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- 230000003115 biocidal effect Effects 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 9
- BQTRMYJYYNQQGK-UHFFFAOYSA-N 1-(bromomethyl)-4-iodobenzene Chemical compound BrCC1=CC=C(I)C=C1 BQTRMYJYYNQQGK-UHFFFAOYSA-N 0.000 description 8
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 8
- YWRPAKATXRUAAF-UHFFFAOYSA-N 2-methyl-2-methylsulfonylbutanamide Chemical compound CCC(C)(C(N)=O)S(C)(=O)=O YWRPAKATXRUAAF-UHFFFAOYSA-N 0.000 description 8
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- 239000003242 anti bacterial agent Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
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- 238000001514 detection method Methods 0.000 description 8
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 8
- 238000010561 standard procedure Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
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- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 description 7
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- 230000002401 inhibitory effect Effects 0.000 description 7
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- 238000003756 stirring Methods 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 6
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 6
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- 150000001412 amines Chemical class 0.000 description 6
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 6
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
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- 239000000463 material Substances 0.000 description 5
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- 238000004809 thin layer chromatography Methods 0.000 description 5
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- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 1
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2015/070144 | 2015-09-03 | ||
| EP2015070144 | 2015-09-03 | ||
| PCT/EP2016/070695 WO2017037221A1 (en) | 2015-09-03 | 2016-09-02 | Substituted 1,2-dihydro-3h-pyrrolo[1,2-c]imidazol-3-one antibacterial compounds |
Publications (2)
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| AU2016313794A1 AU2016313794A1 (en) | 2018-04-19 |
| AU2016313794B2 true AU2016313794B2 (en) | 2020-06-04 |
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| AU2016313794A Expired - Fee Related AU2016313794B2 (en) | 2015-09-03 | 2016-09-02 | Substituted 1,2-dihydro-3H-pyrrolo[1,2-c]imidazol-3-one antibacterial compounds |
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| EP (1) | EP3344630B1 (enExample) |
| JP (1) | JP2018526391A (enExample) |
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| MX (1) | MX2018002644A (enExample) |
| PH (1) | PH12018500323A1 (enExample) |
| TW (1) | TW201714885A (enExample) |
| WO (1) | WO2017037221A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AR099612A1 (es) | 2014-03-04 | 2016-08-03 | Actelion Pharmaceuticals Ltd | Derivados antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona |
| AR105646A1 (es) | 2015-08-11 | 2017-10-25 | Actelion Pharmaceuticals Ltd | Agentes antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituida |
| TW201840569A (zh) * | 2017-03-01 | 2018-11-16 | 瑞士商愛杜西亞製藥有限公司 | (2r)-n-羥基-4-(6-((1-(2-羥基乙基)氮雜環丁烷-3-基)丁-1,3-二炔-1-基)-3-氧基-1h-吡咯并[1,2-c]咪唑-2(3h)-基)-2-甲基-2-(甲磺醯基)丁醯胺之結晶形式 |
| WO2018224455A1 (en) | 2017-06-07 | 2018-12-13 | Basf Se | Substituted cyclopropyl derivatives |
| WO2019038362A1 (en) | 2017-08-24 | 2019-02-28 | Idorsia Pharmaceuticals Ltd | ANTIBACTERIAL PYRROLOIMIDAZOLONES |
| WO2019086452A1 (en) | 2017-10-31 | 2019-05-09 | Idorsia Pharmaceuticals Ltd | Antibacterial heteroaromatic compounds |
| WO2019121143A1 (en) | 2017-12-20 | 2019-06-27 | Basf Se | Substituted cyclopropyl derivatives |
| JP7156199B2 (ja) * | 2018-08-09 | 2022-10-19 | 信越化学工業株式会社 | レジスト材料及びパターン形成方法 |
| KR20220034739A (ko) | 2019-05-31 | 2022-03-18 | 이케나 온콜로지, 인코포레이티드 | Tead 억제제 및 이의 용도 |
| KR20220030222A (ko) | 2019-05-31 | 2022-03-10 | 이케나 온콜로지, 인코포레이티드 | Tead 억제제 및 이의 용도 |
| CA3157279A1 (en) * | 2019-11-21 | 2021-05-27 | Paul Richard Sebahar | Trpv4 receptor ligands |
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| WO2011073845A1 (en) * | 2009-12-16 | 2011-06-23 | Pfizer Inc. | N-linked hydroxamic acid derivatives useful as antibacterial agents |
| WO2015036964A1 (en) * | 2013-09-13 | 2015-03-19 | Actelion Pharmaceuticals Ltd | Antibacterial 2h-indazole derivatives |
| WO2015132228A1 (en) * | 2014-03-04 | 2015-09-11 | Actelion Pharmaceuticals Ltd | 1,2-dihydro-3h-pyrrolo[1,2-c]imidazol-3-one derivatives and their use as antibacterial agents |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2478374C (en) | 2002-03-13 | 2009-01-06 | Eli M. Wallace | N3 alkylated benzimidazole derivatives as mek inhibitors |
| UA80500C2 (en) | 2003-10-17 | 2007-09-25 | Basf Ag | Fungicidal mixture and agent for controlling rice pathogens, containing triazolopyrimidine derivative and metalaxyl-m, method for controlling rice pathogens and sowing material |
| DE102008044132A1 (de) | 2008-11-27 | 2010-06-02 | BSH Bosch und Siemens Hausgeräte GmbH | Kältegerät mit zweiseitig anschlagbarer Tür |
| CA2774250C (en) | 2009-10-13 | 2013-12-17 | Pfizer Inc. | C-linked hydroxamic acid derivatives useful as antibacterial agents |
| JP2014501274A (ja) | 2011-01-03 | 2014-01-20 | ハンミ ファーム． シーオー．， エルティーディー． | Ｇタンパク質共役受容体調節のための新規な二環式化合物 |
| AP3336A (en) | 2011-03-07 | 2015-07-31 | Pfizer | Fluoro-pyridinone derivatives useful as antibacterial agents |
| SG193458A1 (en) | 2011-04-08 | 2013-10-30 | Pfizer | Imidazole, pyrazole, and triazole derivatives useful as antibacterial agents |
| CN103717582B (zh) | 2011-04-08 | 2015-09-30 | 辉瑞大药厂 | 用作抗菌剂的异*唑衍生物 |
| WO2013170165A1 (en) | 2012-05-10 | 2013-11-14 | Achaogen, Inc. | Antibacterial agents |
| CA2891569A1 (en) | 2012-11-16 | 2014-05-22 | Bristol-Myers Squibb Company | Pyrrolidine gpr40 modulators |
| WO2014165075A1 (en) | 2013-03-12 | 2014-10-09 | Achaogen, Inc. | Antibacterial agents |
| WO2015066413A1 (en) | 2013-11-01 | 2015-05-07 | Novartis Ag | Oxazolidinone hydroxamic acid compounds for the treatment of bacterial infections |
| TR201807881T4 (tr) | 2013-12-19 | 2018-06-21 | Idorsia Pharmaceuticals Ltd | Antibakteriyel 1h-ındazol ve 1h-ındol türevleri. |
| JP2017515906A (ja) | 2014-05-16 | 2017-06-15 | アクテリオン ファーマシューティカルズ リミテッドＡｃｔｅｌｉｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ | 抗菌性キナゾロン−４（３ｈ）−オン誘導体 |
| KR20170086079A (ko) | 2014-11-19 | 2017-07-25 | 액테리온 파마슈티칼 리미티드 | 항균성 벤조티아졸 유도체 |
| AR105646A1 (es) * | 2015-08-11 | 2017-10-25 | Actelion Pharmaceuticals Ltd | Agentes antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituida |
| US20190031676A1 (en) | 2015-08-28 | 2019-01-31 | Idorsia Pharmaceuticals Ltd | Antibacterial annulated pyrrolidin-2-one derivatives |
| AR105848A1 (es) | 2015-08-31 | 2017-11-15 | Actelion Pharmaceuticals Ltd | Derivados heterocíclicos antibacterianos |
| RU2018124788A (ru) | 2015-12-08 | 2020-01-15 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Замещенные бензазиноны в качестве антибактериальных соединений |
| AR108488A1 (es) | 2016-05-17 | 2018-08-22 | Idorsia Pharmaceuticals Ltd | Derivados 6-(buta-1,3-diin-1-il)benzo[d]tiazol |
-
2016
- 2016-09-01 AR ARP160102671A patent/AR105889A1/es unknown
- 2016-09-02 WO PCT/EP2016/070695 patent/WO2017037221A1/en not_active Ceased
- 2016-09-02 US US15/756,366 patent/US10314823B2/en not_active Expired - Fee Related
- 2016-09-02 CA CA2994996A patent/CA2994996A1/en not_active Abandoned
- 2016-09-02 JP JP2018511713A patent/JP2018526391A/ja not_active Ceased
- 2016-09-02 AU AU2016313794A patent/AU2016313794B2/en not_active Expired - Fee Related
- 2016-09-02 BR BR112018004343-5A patent/BR112018004343A2/pt not_active Application Discontinuation
- 2016-09-02 HK HK18115746.5A patent/HK1256614A1/zh unknown
- 2016-09-02 KR KR1020187009472A patent/KR20180049017A/ko not_active Withdrawn
- 2016-09-02 TW TW105128540A patent/TW201714885A/zh unknown
- 2016-09-02 EA EA201890626A patent/EA201890626A1/ru unknown
- 2016-09-02 CN CN201680049395.1A patent/CN108137596A/zh active Pending
- 2016-09-02 MX MX2018002644A patent/MX2018002644A/es unknown
- 2016-09-02 EP EP16759792.1A patent/EP3344630B1/en active Active
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2018
- 2018-02-13 PH PH12018500323A patent/PH12018500323A1/en unknown
- 2018-02-27 IL IL257757A patent/IL257757A/en unknown
- 2018-02-28 CL CL2018000533A patent/CL2018000533A1/es unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011073845A1 (en) * | 2009-12-16 | 2011-06-23 | Pfizer Inc. | N-linked hydroxamic acid derivatives useful as antibacterial agents |
| WO2015036964A1 (en) * | 2013-09-13 | 2015-03-19 | Actelion Pharmaceuticals Ltd | Antibacterial 2h-indazole derivatives |
| WO2015132228A1 (en) * | 2014-03-04 | 2015-09-11 | Actelion Pharmaceuticals Ltd | 1,2-dihydro-3h-pyrrolo[1,2-c]imidazol-3-one derivatives and their use as antibacterial agents |
Also Published As
| Publication number | Publication date |
|---|---|
| US10314823B2 (en) | 2019-06-11 |
| CA2994996A1 (en) | 2017-03-09 |
| CL2018000533A1 (es) | 2018-06-29 |
| WO2017037221A1 (en) | 2017-03-09 |
| MX2018002644A (es) | 2018-06-20 |
| TW201714885A (zh) | 2017-05-01 |
| PH12018500323A1 (en) | 2018-08-13 |
| BR112018004343A2 (pt) | 2018-09-25 |
| KR20180049017A (ko) | 2018-05-10 |
| IL257757A (en) | 2018-04-30 |
| EP3344630B1 (en) | 2020-12-09 |
| AU2016313794A1 (en) | 2018-04-19 |
| US20180250273A1 (en) | 2018-09-06 |
| EA201890626A1 (ru) | 2018-09-28 |
| EP3344630A1 (en) | 2018-07-11 |
| CN108137596A (zh) | 2018-06-08 |
| JP2018526391A (ja) | 2018-09-13 |
| AR105889A1 (es) | 2017-11-22 |
| HK1256614A1 (zh) | 2019-09-27 |
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| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |