TWI568727B - 磺醯基胺基吡咯啶酮衍生物，彼等之製造及治療應用 - Google Patents
磺醯基胺基吡咯啶酮衍生物，彼等之製造及治療應用 Download PDFInfo
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- TWI568727B TWI568727B TW101148829A TW101148829A TWI568727B TW I568727 B TWI568727 B TW I568727B TW 101148829 A TW101148829 A TW 101148829A TW 101148829 A TW101148829 A TW 101148829A TW I568727 B TWI568727 B TW I568727B
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- TW
- Taiwan
- Prior art keywords
- pyrrolidin
- amino
- isoquinolin
- sulfonylamino
- propionic acid
- Prior art date
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- 230000001225 therapeutic effect Effects 0.000 title claims description 3
- MAMRCGKAOGCJAM-UHFFFAOYSA-N 1-(sulfonylamino)pyrrolidin-2-one Chemical class O=C1CCCN1N=S(=O)=O MAMRCGKAOGCJAM-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 119
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 61
- -1 -OH Chemical group 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 38
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 208000007536 Thrombosis Diseases 0.000 claims description 16
- 230000015271 coagulation Effects 0.000 claims description 16
- 238000005345 coagulation Methods 0.000 claims description 16
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
- 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 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000006242 amine protecting group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 230000009424 thromboembolic effect Effects 0.000 claims description 5
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- ONHZVHMZTKZTFT-DLBZAZTESA-N (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C=C2C=CN=C(C2=CC=1OC(F)(F)F)N)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CCCC1 ONHZVHMZTKZTFT-DLBZAZTESA-N 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000004703 alkoxides Chemical class 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 238000003780 insertion Methods 0.000 claims description 3
- 230000037431 insertion Effects 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 2
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000005189 Embolism Diseases 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 238000002399 angioplasty Methods 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 238000013171 endarterectomy Methods 0.000 claims description 2
- 238000001631 haemodialysis Methods 0.000 claims description 2
- 230000000322 hemodialysis Effects 0.000 claims description 2
- 230000007574 infarction Effects 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 230000000302 ischemic effect Effects 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 230000002537 thrombolytic effect Effects 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 230000003902 lesion Effects 0.000 claims 3
- 229940017219 methyl propionate Drugs 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- JCWXCNZCCMAWTL-IDDVYCCLSA-N (2R)-3-[3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3S)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]cyclohexyl]oxycarbonyloxy-2-methylpropanoic acid Chemical compound C[C@H](COC(=O)OC1CCCC(C1N2CC[C@@H](C2=O)NS(=O)(=O)C3=CN=C(S3)N4CCCC4)C5=C(C=C6C(=C5)C=CN=C6N)OC(F)(F)F)C(=O)O JCWXCNZCCMAWTL-IDDVYCCLSA-N 0.000 claims 1
- SYIZRHNKMPFMEA-ZWKOTPCHSA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C=C2C=CN=C(C2=CC=1Cl)N)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CCCC1 SYIZRHNKMPFMEA-ZWKOTPCHSA-N 0.000 claims 1
- CQOCPYQVKHQTQU-DLBZAZTESA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[2-(azetidin-1-yl)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C=C2C=CN=C(C2=CC=1Cl)N)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CCC1 CQOCPYQVKHQTQU-DLBZAZTESA-N 0.000 claims 1
- DYRGULRRGUHACC-JKSUJKDBSA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound S1C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)Cl)C(O)=O)CC1 DYRGULRRGUHACC-JKSUJKDBSA-N 0.000 claims 1
- JBMASIMCPHNGJF-RBUKOAKNSA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[2-[cyclobutyl(methyl)amino]-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N=1C=C(S(=O)(=O)N[C@@H]2C(N([C@H](CC=3C(=CC4=C(N)N=CC=C4C=3)Cl)C(O)=O)CC2)=O)SC=1N(C)C1CCC1 JBMASIMCPHNGJF-RBUKOAKNSA-N 0.000 claims 1
- KLFSLDKLJLSVFR-RBUKOAKNSA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=C(Cl)C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)Cl)C(O)=O)CC1 KLFSLDKLJLSVFR-RBUKOAKNSA-N 0.000 claims 1
- QHLZKZFIYMQOKP-VQTJNVASSA-N (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)-5-methylpyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=C(C)C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)Cl)C(O)=O)CC1 QHLZKZFIYMQOKP-VQTJNVASSA-N 0.000 claims 1
- WDERBQGYQKUKDB-ZWKOTPCHSA-N (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1CC)C(O)=O)S(=O)(=O)C1=CN=C(N(C)C)S1 WDERBQGYQKUKDB-ZWKOTPCHSA-N 0.000 claims 1
- NKIIFGVYSMCJAQ-LEWJYISDSA-N (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1CC)C(O)=O)S(=O)(=O)C1=CN=C(N(C)C)C(Cl)=C1 NKIIFGVYSMCJAQ-LEWJYISDSA-N 0.000 claims 1
- DAVMEQIDLFGLFH-LEWJYISDSA-N (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1CC)C(O)=O)S(=O)(=O)C1=CC=C(N(C)C)N=C1 DAVMEQIDLFGLFH-LEWJYISDSA-N 0.000 claims 1
- MMKNYJALKTVJIC-RBUKOAKNSA-N (2r)-3-(1-amino-7-fluoroisoquinolin-6-yl)-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=C(Cl)C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)F)C(O)=O)CC1 MMKNYJALKTVJIC-RBUKOAKNSA-N 0.000 claims 1
- XAFKLXZJDNZCCE-VQTJNVASSA-N (2r)-3-(1-amino-7-fluoroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)-5-methylpyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=C(C)C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)F)C(O)=O)CC1 XAFKLXZJDNZCCE-VQTJNVASSA-N 0.000 claims 1
- SZUJJQUYAIDMRR-RBUKOAKNSA-N (2r)-3-(1-amino-7-fluoroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=NC(N(C)C)=CC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)F)C(O)=O)CC1 SZUJJQUYAIDMRR-RBUKOAKNSA-N 0.000 claims 1
- MASLUDJVSFZZCR-DLBZAZTESA-N (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[2-(3,3-difluoropyrrolidin-1-yl)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OC)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CCC(F)(F)C1 MASLUDJVSFZZCR-DLBZAZTESA-N 0.000 claims 1
- UBSFFMVIWJYHAX-BPQIPLTHSA-N (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[2-[(3r)-3-fluoropyrrolidin-1-yl]-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OC)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CC[C@@H](F)C1 UBSFFMVIWJYHAX-BPQIPLTHSA-N 0.000 claims 1
- FINXSQWTTVFKNX-RBUKOAKNSA-N (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OC)C(O)=O)S(=O)(=O)C1=CN=C(N(C)C)C(Cl)=C1 FINXSQWTTVFKNX-RBUKOAKNSA-N 0.000 claims 1
- RQLRLQMOCZXBHM-DLBZAZTESA-N (2r)-3-(1-amino-7-methylisoquinolin-6-yl)-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound S1C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)C)C(O)=O)CC1 RQLRLQMOCZXBHM-DLBZAZTESA-N 0.000 claims 1
- KEHAQUINLNOUGX-ZWKOTPCHSA-N (2r)-3-[1-amino-7-(2-methoxyethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OCCOC)C(O)=O)S(=O)(=O)C1=CN=C(N(C)C)S1 KEHAQUINLNOUGX-ZWKOTPCHSA-N 0.000 claims 1
- BQQOIJPWHPKKRX-LSDHHAIUSA-N (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound S1C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)OC(F)(F)F)C(O)=O)CC1 BQQOIJPWHPKKRX-LSDHHAIUSA-N 0.000 claims 1
- LERNDWIYHSCVBK-ZWKOTPCHSA-N (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=C(Cl)C(N(C)C)=NC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)OC(F)(F)F)C(O)=O)CC1 LERNDWIYHSCVBK-ZWKOTPCHSA-N 0.000 claims 1
- WCNFGOBCQACIGW-DLBZAZTESA-N (2r)-3-[1-amino-7-(trifluoromethyl)isoquinolin-6-yl]-2-[(3s)-3-[[2-(azetidin-1-yl)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C=C2C=CN=C(C2=CC=1C(F)(F)F)N)C(O)=O)S(=O)(=O)C(S1)=CN=C1N1CCC1 WCNFGOBCQACIGW-DLBZAZTESA-N 0.000 claims 1
- SNMOFBUTBIIIQV-RBUKOAKNSA-N (2r)-3-[1-amino-7-(trifluoromethyl)isoquinolin-6-yl]-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound C1=NC(N(C)C)=CC=C1S(=O)(=O)N[C@@H]1C(=O)N([C@H](CC=2C(=CC3=C(N)N=CC=C3C=2)C(F)(F)F)C(O)=O)CC1 SNMOFBUTBIIIQV-RBUKOAKNSA-N 0.000 claims 1
- YQTHNJPAIOCZDD-RBUKOAKNSA-N C(C)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)NC(C)(C)C)=O)=O Chemical compound C(C)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)NC(C)(C)C)=O)=O YQTHNJPAIOCZDD-RBUKOAKNSA-N 0.000 claims 1
- RMJZCCBTSNPIAC-NZAZLUKGSA-N C(C)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1[C@H](C(CC1)NS(=O)(=O)C1=CN=C(S1)N1CCCC1)OC1=CC=CC=C1)=O Chemical compound C(C)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1[C@H](C(CC1)NS(=O)(=O)C1=CN=C(S1)N1CCCC1)OC1=CC=CC=C1)=O RMJZCCBTSNPIAC-NZAZLUKGSA-N 0.000 claims 1
- QFQJKOAXVCAMES-RBUKOAKNSA-N C(CC)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)N(C)C)=O)=O Chemical compound C(CC)OC([C@@H](CC=1C=C2C=CN=C(C2=CC1OC)N)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)N(C)C)=O)=O QFQJKOAXVCAMES-RBUKOAKNSA-N 0.000 claims 1
- MERYYXZEZYIKRX-DYVFJYSZSA-N N-[(3S)-1-[(2R)-1-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]propan-2-yl]-2-oxopyrrolidin-3-yl]-2-(3,3-difluoropyrrolidin-1-yl)-1,3-thiazole-5-sulfonamide Chemical compound NC1=NC=CC2=CC(=C(C=C12)OC(F)(F)F)C[C@@H](C)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)N1CC(CC1)(F)F)=O MERYYXZEZYIKRX-DYVFJYSZSA-N 0.000 claims 1
- 208000001435 Thromboembolism Diseases 0.000 claims 1
- MMIVREPFWLEGKF-ZMAUEPLISA-N [(2R)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3S)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]butyl] propanoate Chemical compound C(CC)(=O)OC[C@@H](C(C)C=1C=C2C=CN=C(C2=CC1OC(F)(F)F)N)N1C([C@H](CC1)NS(=O)(=O)C1=CN=C(S1)N1CCCC1)=O MMIVREPFWLEGKF-ZMAUEPLISA-N 0.000 claims 1
- 210000004351 coronary vessel Anatomy 0.000 claims 1
- MEJMIZVFTUQQKE-LEWJYISDSA-N cyclopropylmethyl (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[2-(3,3-difluoropyrrolidin-1-yl)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OC)C(=O)OCC1CC1)S(=O)(=O)C(S1)=CN=C1N1CCC(F)(F)C1 MEJMIZVFTUQQKE-LEWJYISDSA-N 0.000 claims 1
- YHTYOGLMOBEAHD-VQTJNVASSA-N cyclopropylmethyl (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC1=CC2=CC=NC(N)=C2C=C1OC)C(=O)OCC1CC1)S(=O)(=O)C1=CN=C(N(C)C)S1 YHTYOGLMOBEAHD-VQTJNVASSA-N 0.000 claims 1
- GRJHEMMZIHJVAN-LEWJYISDSA-N cyclopropylmethyl (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C=C2C=CN=C(C2=CC=1OC(F)(F)F)N)C(=O)OCC1CC1)S(=O)(=O)C(S1)=CN=C1N1CCCC1 GRJHEMMZIHJVAN-LEWJYISDSA-N 0.000 claims 1
- 230000010102 embolization Effects 0.000 claims 1
- ODSCZIBKMJGDDR-FCHUYYIVSA-N ethyl (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-2-oxo-3-[(2-pyrrolidin-1-yl-1,3-thiazol-5-yl)sulfonylamino]pyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)CC)C(=O)OCC)S(=O)(=O)C(S1)=CN=C1N1CCCC1 ODSCZIBKMJGDDR-FCHUYYIVSA-N 0.000 claims 1
- ITRJDLYCFJNYLW-LOSJGSFVSA-N ethyl (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-2-oxo-3-[(6-pyrrolidin-1-ylpyridin-3-yl)sulfonylamino]pyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)CC)C(=O)OCC)S(=O)(=O)C(C=N1)=CC=C1N1CCCC1 ITRJDLYCFJNYLW-LOSJGSFVSA-N 0.000 claims 1
- CIXVLMHLWCZZNJ-VQTJNVASSA-N ethyl (2r)-3-(1-amino-7-ethylisoquinolin-6-yl)-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)CC)C(=O)OCC)S(=O)(=O)C1=CN=C(N(C)C)S1 CIXVLMHLWCZZNJ-VQTJNVASSA-N 0.000 claims 1
- XZTFENHOUYDXRR-LEWJYISDSA-N ethyl (2r)-3-(1-amino-7-methoxyisoquinolin-6-yl)-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)OC)C(=O)OCC)S(=O)(=O)C1=CN=C(N(C)C)C(Cl)=C1 XZTFENHOUYDXRR-LEWJYISDSA-N 0.000 claims 1
- UIIJMUGOGFMNFD-VQTJNVASSA-N ethyl (2r)-3-[1-amino-7-(2-methoxyethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)OCCOC)C(=O)OCC)S(=O)(=O)C1=CN=C(N(C)C)S1 UIIJMUGOGFMNFD-VQTJNVASSA-N 0.000 claims 1
- JEFCXHOSQJYWCU-RBUKOAKNSA-N methyl (2r)-3-(1-amino-5-fluoroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=C2C=CN=C(N)C2=CC=1)F)C(=O)OC)S(=O)(=O)C1=CC=C(N(C)C)N=C1 JEFCXHOSQJYWCU-RBUKOAKNSA-N 0.000 claims 1
- JUNXSIBFIARCRB-ZWKOTPCHSA-N methyl (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[2-(3,3-difluoropyrrolidin-1-yl)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)Cl)C(=O)OC)S(=O)(=O)C(S1)=CN=C1N1CCC(F)(F)C1 JUNXSIBFIARCRB-ZWKOTPCHSA-N 0.000 claims 1
- WWGCBICRHPVMBA-LEWJYISDSA-N methyl (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)-5-methylpyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)Cl)C(=O)OC)S(=O)(=O)C1=CN=C(N(C)C)C(C)=C1 WWGCBICRHPVMBA-LEWJYISDSA-N 0.000 claims 1
- XIKIVOVOHHNTKK-VQTJNVASSA-N methyl (2r)-3-(1-amino-7-chloroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)Cl)C(=O)OC)S(=O)(=O)C1=CC=C(N(C)C)N=C1 XIKIVOVOHHNTKK-VQTJNVASSA-N 0.000 claims 1
- ZSOJZMMMEDURSU-LEWJYISDSA-N methyl (2r)-3-(1-amino-7-fluoroisoquinolin-6-yl)-2-[(3s)-3-[[6-(dimethylamino)-5-methylpyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)F)C(=O)OC)S(=O)(=O)C1=CN=C(N(C)C)C(C)=C1 ZSOJZMMMEDURSU-LEWJYISDSA-N 0.000 claims 1
- SZFZHTXOJIXHBU-JKSUJKDBSA-N methyl (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[2-(dimethylamino)-1,3-thiazol-5-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)OC(F)(F)F)C(=O)OC)S(=O)(=O)C1=CN=C(N(C)C)S1 SZFZHTXOJIXHBU-JKSUJKDBSA-N 0.000 claims 1
- KSZGZPHHCGNFER-RBUKOAKNSA-N methyl (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[5-chloro-6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)OC(F)(F)F)C(=O)OC)S(=O)(=O)C1=CN=C(N(C)C)C(Cl)=C1 KSZGZPHHCGNFER-RBUKOAKNSA-N 0.000 claims 1
- WUUVDHVYCJVNHJ-RBUKOAKNSA-N methyl (2r)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3s)-3-[[6-(dimethylamino)pyridin-3-yl]sulfonylamino]-2-oxopyrrolidin-1-yl]propanoate Chemical compound N([C@H]1CCN(C1=O)[C@H](CC=1C(=CC2=C(N)N=CC=C2C=1)OC(F)(F)F)C(=O)OC)S(=O)(=O)C1=CC=C(N(C)C)N=C1 WUUVDHVYCJVNHJ-RBUKOAKNSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11306733.4A EP2606893A1 (en) | 2011-12-21 | 2011-12-21 | Sulphonylaminopyrrolidinone derivatives, their preparation and their therapeutic application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201331195A TW201331195A (zh) | 2013-08-01 |
| TWI568727B true TWI568727B (zh) | 2017-02-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101148829A TWI568727B (zh) | 2011-12-21 | 2012-12-20 | 磺醯基胺基吡咯啶酮衍生物，彼等之製造及治療應用 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US9150544B2 (https=) |
| EP (2) | EP2606893A1 (https=) |
| JP (1) | JP6104936B2 (https=) |
| KR (1) | KR20140106703A (https=) |
| CN (1) | CN104136030B (https=) |
| AR (1) | AR089397A1 (https=) |
| AU (1) | AU2012357123B2 (https=) |
| BR (1) | BR112014014869A2 (https=) |
| CA (1) | CA2859575A1 (https=) |
| ES (1) | ES2559854T3 (https=) |
| IL (1) | IL233238A (https=) |
| IN (1) | IN2014CN04861A (https=) |
| MX (1) | MX347620B (https=) |
| RU (1) | RU2014129787A (https=) |
| SG (1) | SG11201403336QA (https=) |
| TW (1) | TWI568727B (https=) |
| UY (1) | UY34543A (https=) |
| WO (1) | WO2013092756A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1307759B1 (it) | 1998-03-31 | 2001-11-19 | Schurr Stahlecker & Grill | Dispositivo per condensare un composito di fibre stirato. |
| DE19838762B4 (de) | 1998-08-26 | 2009-04-16 | Maschinenfabrik Rieter Ag | Spinnmaschine mit einer Vielzahl von Spinnstellen |
| DE102014108210A1 (de) | 2014-06-11 | 2015-12-17 | Dietrich Gulba | Rodentizid |
| CN104557928B (zh) * | 2015-02-14 | 2016-08-24 | 佛山市赛维斯医药科技有限公司 | 一种含二环酰胺结构凝血因子Xa抑制剂、其制备方法及其用途 |
| CN112969698A (zh) * | 2018-11-08 | 2021-06-15 | 葛兰素史密斯克莱知识产权发展有限公司 | 化学化合物 |
| EP4070658A1 (de) | 2021-04-06 | 2022-10-12 | BIORoxx GmbH | Verwendung von blutgerinnungshemmenden verbindungen als rodentizide |
| CN113264819B (zh) * | 2021-05-25 | 2024-11-05 | 都创(上海)医药开发有限公司 | 一种基于连续流反应技术快速合成3-溴-2-氟苯甲醛的方法 |
| TW202404583A (zh) | 2022-06-08 | 2024-02-01 | 加拿大商再諾製藥公司 | 吡啶胺衍生物及其作為鉀通道調節劑之用途 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001039759A2 (en) * | 1999-12-02 | 2001-06-07 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
| US6602864B1 (en) | 1996-12-13 | 2003-08-05 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
| IL130152A0 (en) * | 1996-12-13 | 2000-06-01 | Rhone Poulenc Rorer Pharma | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclyamide compounds |
| IL123986A (en) * | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
-
2011
- 2011-12-21 EP EP11306733.4A patent/EP2606893A1/en not_active Withdrawn
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2012
- 2012-12-19 KR KR1020147019821A patent/KR20140106703A/ko not_active Ceased
- 2012-12-19 IN IN4861CHN2014 patent/IN2014CN04861A/en unknown
- 2012-12-19 WO PCT/EP2012/076224 patent/WO2013092756A1/en not_active Ceased
- 2012-12-19 JP JP2014547988A patent/JP6104936B2/ja not_active Expired - Fee Related
- 2012-12-19 MX MX2014007671A patent/MX347620B/es active IP Right Grant
- 2012-12-19 AU AU2012357123A patent/AU2012357123B2/en not_active Ceased
- 2012-12-19 BR BR112014014869A patent/BR112014014869A2/pt not_active Application Discontinuation
- 2012-12-19 US US14/366,402 patent/US9150544B2/en not_active Expired - Fee Related
- 2012-12-19 CN CN201280070270.9A patent/CN104136030B/zh not_active Expired - Fee Related
- 2012-12-19 EP EP12805694.2A patent/EP2793887B1/en not_active Not-in-force
- 2012-12-19 SG SG11201403336QA patent/SG11201403336QA/en unknown
- 2012-12-19 CA CA2859575A patent/CA2859575A1/en not_active Abandoned
- 2012-12-19 RU RU2014129787A patent/RU2014129787A/ru not_active Application Discontinuation
- 2012-12-19 ES ES12805694.2T patent/ES2559854T3/es active Active
- 2012-12-20 TW TW101148829A patent/TWI568727B/zh not_active IP Right Cessation
- 2012-12-21 AR ARP120104901A patent/AR089397A1/es unknown
- 2012-12-21 UY UY0001034543A patent/UY34543A/es not_active Application Discontinuation
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2014
- 2014-06-18 IL IL233238A patent/IL233238A/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001039759A2 (en) * | 1999-12-02 | 2001-06-07 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| AR089397A1 (es) | 2014-08-20 |
| TW201331195A (zh) | 2013-08-01 |
| CN104136030B (zh) | 2017-03-01 |
| EP2793887A1 (en) | 2014-10-29 |
| MX2014007671A (es) | 2014-11-25 |
| AU2012357123B2 (en) | 2016-12-15 |
| JP2015502382A (ja) | 2015-01-22 |
| MX347620B (es) | 2017-05-04 |
| WO2013092756A1 (en) | 2013-06-27 |
| KR20140106703A (ko) | 2014-09-03 |
| AU2012357123A1 (en) | 2014-07-10 |
| IL233238A0 (en) | 2014-08-31 |
| IN2014CN04861A (https=) | 2015-09-18 |
| US9150544B2 (en) | 2015-10-06 |
| EP2606893A1 (en) | 2013-06-26 |
| JP6104936B2 (ja) | 2017-03-29 |
| IL233238A (en) | 2016-10-31 |
| EP2793887B1 (en) | 2015-10-21 |
| SG11201403336QA (en) | 2014-07-30 |
| BR112014014869A2 (pt) | 2017-06-13 |
| RU2014129787A (ru) | 2016-02-10 |
| UY34543A (es) | 2013-06-28 |
| ES2559854T3 (es) | 2016-02-16 |
| CA2859575A1 (en) | 2013-06-27 |
| CN104136030A (zh) | 2014-11-05 |
| US20140329801A1 (en) | 2014-11-06 |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |