NO324003B1 - Etylendiaminderivater og medisin omfattende slike forbindelser - Google Patents
Etylendiaminderivater og medisin omfattende slike forbindelser Download PDFInfo
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- NO324003B1 NO324003B1 NO20024766A NO20024766A NO324003B1 NO 324003 B1 NO324003 B1 NO 324003B1 NO 20024766 A NO20024766 A NO 20024766A NO 20024766 A NO20024766 A NO 20024766A NO 324003 B1 NO324003 B1 NO 324003B1
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- 150000001875 compounds Chemical class 0.000 title claims description 355
- 239000003814 drug Substances 0.000 title claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 title description 7
- -1 tetrahydrothienopyridyl group Chemical group 0.000 claims description 225
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 94
- 150000003839 salts Chemical class 0.000 claims description 29
- 239000012453 solvate Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 150000001204 N-oxides Chemical class 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 17
- 208000007536 Thrombosis Diseases 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000003146 anticoagulant agent Substances 0.000 claims description 7
- 229940127219 anticoagulant drug Drugs 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 208000005189 Embolism Diseases 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- 206010008088 Cerebral artery embolism Diseases 0.000 claims description 3
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 3
- 108010074860 Factor Xa Proteins 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 208000006193 Pulmonary infarction Diseases 0.000 claims description 3
- 206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 201000010849 intracranial embolism Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 230000007575 pulmonary infarction Effects 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 206010038563 Reocclusion Diseases 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 230000009885 systemic effect Effects 0.000 claims description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 561
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 370
- 239000000543 intermediate Substances 0.000 description 363
- 239000000203 mixture Substances 0.000 description 288
- 230000002829 reductive effect Effects 0.000 description 261
- 238000005160 1H NMR spectroscopy Methods 0.000 description 259
- 239000002904 solvent Substances 0.000 description 241
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 216
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 216
- 239000011541 reaction mixture Substances 0.000 description 180
- 239000012044 organic layer Substances 0.000 description 178
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 168
- 239000000243 solution Substances 0.000 description 160
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 141
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 134
- 239000000741 silica gel Substances 0.000 description 134
- 229910002027 silica gel Inorganic materials 0.000 description 134
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 132
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 126
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 121
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 119
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 114
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 114
- 239000007864 aqueous solution Substances 0.000 description 107
- 238000004440 column chromatography Methods 0.000 description 107
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 106
- 239000007787 solid Substances 0.000 description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
- 229920006395 saturated elastomer Polymers 0.000 description 67
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 66
- 235000017557 sodium bicarbonate Nutrition 0.000 description 66
- 238000001914 filtration Methods 0.000 description 65
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 57
- 239000003921 oil Substances 0.000 description 54
- 235000019198 oils Nutrition 0.000 description 54
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 51
- 238000001816 cooling Methods 0.000 description 48
- 238000003756 stirring Methods 0.000 description 39
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 36
- 238000000926 separation method Methods 0.000 description 35
- 239000010410 layer Substances 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000126 substance Substances 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 239000012230 colorless oil Substances 0.000 description 32
- 230000000694 effects Effects 0.000 description 32
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 31
- 239000000706 filtrate Substances 0.000 description 30
- 239000007788 liquid Substances 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 28
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000000843 powder Substances 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 239000002244 precipitate Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 24
- 150000001412 amines Chemical class 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 24
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 22
- 238000004519 manufacturing process Methods 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 22
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 19
- FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000012298 atmosphere Substances 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 16
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000012046 mixed solvent Substances 0.000 description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- DKNUXJJTVOXHBA-UHFFFAOYSA-M lithium;5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C)CCC2=C1SC(C([O-])=O)=N2 DKNUXJJTVOXHBA-UHFFFAOYSA-M 0.000 description 13
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 11
- 150000004985 diamines Chemical class 0.000 description 11
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 239000001569 carbon dioxide Substances 0.000 description 9
- 229910002092 carbon dioxide Inorganic materials 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 150000004682 monohydrates Chemical class 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000012047 saturated solution Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 108090000190 Thrombin Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- YVHPHQBRUPLYOS-UHFFFAOYSA-N dichloromethane;methane Chemical compound C.ClCCl YVHPHQBRUPLYOS-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000002198 insoluble material Substances 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- 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 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- MUOGAJLSOPIRNU-UHFFFAOYSA-N 4,5-bis(bromomethyl)-1,3-thiazole Chemical compound BrCC=1N=CSC=1CBr MUOGAJLSOPIRNU-UHFFFAOYSA-N 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 239000012285 osmium tetroxide Substances 0.000 description 6
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 6
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
- AKVIZYGPJIWKOS-RKDXNWHRSA-N (1R,2R)-trans-N-Boc-1,2-cyclohexanediamine Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1N AKVIZYGPJIWKOS-RKDXNWHRSA-N 0.000 description 5
- RAGCMVFLVAMVGB-UHFFFAOYSA-N 1-(benzenesulfonyl)-5-chloroindole-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC2=CC(Cl)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 RAGCMVFLVAMVGB-UHFFFAOYSA-N 0.000 description 5
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 150000008065 acid anhydrides Chemical class 0.000 description 5
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
- 230000015271 coagulation Effects 0.000 description 5
- 238000005345 coagulation Methods 0.000 description 5
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
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- OWOOGVCCMVDZAA-HBNTYKKESA-N ethyl (1s,3r,4r)-4-azido-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@H]1CC[C@@H](N=[N+]=[N-])[C@H](NC(=O)OC(C)(C)C)C1 OWOOGVCCMVDZAA-HBNTYKKESA-N 0.000 description 2
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
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- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
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- DVVAGRMJGUQHLI-OCAPTIKFSA-N dimethyl (1r,2s)-cyclohex-4-ene-1,2-dicarboxylate Chemical compound COC(=O)[C@H]1CC=CC[C@H]1C(=O)OC DVVAGRMJGUQHLI-OCAPTIKFSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
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- REERHKRKNNLBKG-WOPDTQHZSA-N ethyl (1r,3s,4s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfonyloxycyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@@H]1CC[C@H](OS(C)(=O)=O)[C@@H](NC(=O)OC(C)(C)C)C1 REERHKRKNNLBKG-WOPDTQHZSA-N 0.000 description 1
- CTYSRKTYLJGTDL-MORSLUCNSA-N ethyl (1s,3r,4r)-4-[(5-chloro-1h-indole-2-carbonyl)amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N[C@@H]1C[C@@H](C(=O)OCC)CC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 CTYSRKTYLJGTDL-MORSLUCNSA-N 0.000 description 1
- STWAQGKVYHZJCJ-HBNTYKKESA-N ethyl (1s,3r,4r)-4-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@H]1CC[C@@H](N)[C@H](NC(=O)OC(C)(C)C)C1 STWAQGKVYHZJCJ-HBNTYKKESA-N 0.000 description 1
- YFFMJGAVWORNIZ-HBNTYKKESA-N ethyl (1s,3r,4r)-4-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@H]1CC[C@@H](O)[C@H](NC(=O)OC(C)(C)C)C1 YFFMJGAVWORNIZ-HBNTYKKESA-N 0.000 description 1
- RDLVGFZRIZTRQM-OKZBNKHCSA-N ethyl (1s,3r,4s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(phenylmethoxycarbonylamino)cyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N[C@@H]1C[C@@H](C(=O)OCC)CC[C@@H]1NC(=O)OCC1=CC=CC=C1 RDLVGFZRIZTRQM-OKZBNKHCSA-N 0.000 description 1
- STWAQGKVYHZJCJ-GARJFASQSA-N ethyl (1s,3r,4s)-4-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@H]1CC[C@H](N)[C@H](NC(=O)OC(C)(C)C)C1 STWAQGKVYHZJCJ-GARJFASQSA-N 0.000 description 1
- OWOOGVCCMVDZAA-GARJFASQSA-N ethyl (1s,3r,4s)-4-azido-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@H]1CC[C@H](N=[N+]=[N-])[C@H](NC(=O)OC(C)(C)C)C1 OWOOGVCCMVDZAA-GARJFASQSA-N 0.000 description 1
- ALEAMASTTOYSRW-GJMOJQLCSA-N ethyl (1s,4r,6r)-7-oxabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1[C@H](C(=O)OCC)CC[C@@H]2O[C@@H]21 ALEAMASTTOYSRW-GJMOJQLCSA-N 0.000 description 1
- LUVKHTGJKFFLMR-UHFFFAOYSA-N ethyl 1-propan-2-ylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(C(C)C)CC1 LUVKHTGJKFFLMR-UHFFFAOYSA-N 0.000 description 1
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
- UAZKCHGMWTUOES-UHFFFAOYSA-N ethyl 3-chloro-4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)C(Cl)C1 UAZKCHGMWTUOES-UHFFFAOYSA-N 0.000 description 1
- NWHMYVOPXGENMI-UHFFFAOYSA-N ethyl 4-(1-oxidopyridin-1-ium-2-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=CC=[N+]1[O-] NWHMYVOPXGENMI-UHFFFAOYSA-N 0.000 description 1
- APILFMWCIYSTDV-UHFFFAOYSA-N ethyl 6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OCC)CCC2=C1SC=N2 APILFMWCIYSTDV-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical class OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- QBCFGFMNTRXVHP-UHFFFAOYSA-M lithium;1-propan-2-ylpiperidine-4-carboxylate Chemical compound [Li+].CC(C)N1CCC(C([O-])=O)CC1 QBCFGFMNTRXVHP-UHFFFAOYSA-M 0.000 description 1
- LUCJNYVRPULNIX-UHFFFAOYSA-M lithium;4-(morpholin-4-ylmethyl)-1,3-thiazole-2-carboxylate Chemical compound [Li+].S1C(C(=O)[O-])=NC(CN2CCOCC2)=C1 LUCJNYVRPULNIX-UHFFFAOYSA-M 0.000 description 1
- DZPQUXKGXSJKGZ-UHFFFAOYSA-M lithium;5,6-dimethyl-4,7-dihydro-[1,3]thiazolo[4,5-d]pyridazine-2-carboxylate Chemical compound [Li+].C1N(C)N(C)CC2=C1SC(C([O-])=O)=N2 DZPQUXKGXSJKGZ-UHFFFAOYSA-M 0.000 description 1
- ULLQUTOWSHLEGM-UHFFFAOYSA-M lithium;5-[(2-methylpropan-2-yl)oxycarbonyl]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C(=O)OC(C)(C)C)CCC2=C1SC(C([O-])=O)=N2 ULLQUTOWSHLEGM-UHFFFAOYSA-M 0.000 description 1
- JKQJQLNIJDOKJN-UHFFFAOYSA-M lithium;5-[(dimethylamino)methyl]-1,3-thiazole-2-carboxylate Chemical compound [Li+].CN(C)CC1=CN=C(C([O-])=O)S1 JKQJQLNIJDOKJN-UHFFFAOYSA-M 0.000 description 1
- ZNZANLXXBLATJD-UHFFFAOYSA-M lithium;5-[1-[tert-butyl(diphenyl)silyl]oxy-2-methylpropan-2-yl]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1CC=2N=C(C([O-])=O)SC=2CN1C(C)(C)CO[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 ZNZANLXXBLATJD-UHFFFAOYSA-M 0.000 description 1
- OXZFABXSIQFPET-UHFFFAOYSA-M lithium;5-methyl-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C)CCC2=C1OC(C([O-])=O)=N2 OXZFABXSIQFPET-UHFFFAOYSA-M 0.000 description 1
- YBZCHTKTODOIOB-UHFFFAOYSA-M lithium;5-propan-2-yl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C(C)C)CCC2=C1SC(C([O-])=O)=N2 YBZCHTKTODOIOB-UHFFFAOYSA-M 0.000 description 1
- GNSMVNLOKATLRF-UHFFFAOYSA-M lithium;5-pyridin-4-yl-1,3-thiazole-2-carboxylate Chemical compound [Li+].S1C(C(=O)[O-])=NC=C1C1=CC=NC=C1 GNSMVNLOKATLRF-UHFFFAOYSA-M 0.000 description 1
- WZSZILUPDIJCJS-UHFFFAOYSA-M lithium;5-tert-butyl-4,6-dihydropyrrolo[3,4-d][1,3]thiazole-2-carboxylate Chemical compound [Li+].N1=C(C([O-])=O)SC2=C1CN(C(C)(C)C)C2 WZSZILUPDIJCJS-UHFFFAOYSA-M 0.000 description 1
- LIERAEGMCYGKHX-UHFFFAOYSA-M lithium;5-tert-butyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C(C)(C)C)CCC2=C1SC(C([O-])=O)=N2 LIERAEGMCYGKHX-UHFFFAOYSA-M 0.000 description 1
- ZOKRNTGZVAXUDE-UHFFFAOYSA-M lithium;6,7-dihydro-4h-pyrano[4,3-d][1,3]thiazole-2-carboxylate Chemical compound [Li+].C1COCC2=C1N=C(C(=O)[O-])S2 ZOKRNTGZVAXUDE-UHFFFAOYSA-M 0.000 description 1
- QKNMCTGCCNCGRJ-UHFFFAOYSA-M lithium;6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C)CCC2=C1SC(C([O-])=O)=C2 QKNMCTGCCNCGRJ-UHFFFAOYSA-M 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- VONRZPFIAQZAEQ-KXUCPTDWSA-N methyl (1r,3r,4s)-3-azido-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound COC(=O)[C@@H]1CC[C@H](NC(=O)OC(C)(C)C)[C@H](N=[N+]=[N-])C1 VONRZPFIAQZAEQ-KXUCPTDWSA-N 0.000 description 1
- HGKJLQHBKFKJEE-FJXQXJEOSA-N methyl (2s)-2-(4-chloroanilino)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)NC1=CC=C(Cl)C=C1 HGKJLQHBKFKJEE-FJXQXJEOSA-N 0.000 description 1
- BNSQCCOPPFPWOE-UHFFFAOYSA-N methyl 4-(1-oxidopyridin-1-ium-4-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=[N+]([O-])C=C1 BNSQCCOPPFPWOE-UHFFFAOYSA-N 0.000 description 1
- BSCVUXIUVIUPCJ-UHFFFAOYSA-N methyl 5-chloro-6-fluoro-1h-indole-2-carboxylate Chemical compound ClC1=C(F)C=C2NC(C(=O)OC)=CC2=C1 BSCVUXIUVIUPCJ-UHFFFAOYSA-N 0.000 description 1
- NCHWGVZDMRCMJE-UHFFFAOYSA-N methyl 5-pyridin-4-yl-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OC)=NC=C1C1=CC=NC=C1 NCHWGVZDMRCMJE-UHFFFAOYSA-N 0.000 description 1
- WUHPQWSPWOMPKJ-UHFFFAOYSA-N methyl 6-chloro-4-hydroxynaphthalene-2-carboxylate Chemical compound C1=C(Cl)C=CC2=CC(C(=O)OC)=CC(O)=C21 WUHPQWSPWOMPKJ-UHFFFAOYSA-N 0.000 description 1
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- LOEDCWAILQTWIN-CZUORRHYSA-N n-[(1r,2r)-2-amino-4,4-bis(methoxymethyl)cyclopentyl]-5-chloro-1h-indole-2-carboxamide Chemical compound C1C(COC)(COC)C[C@@H](N)[C@@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 LOEDCWAILQTWIN-CZUORRHYSA-N 0.000 description 1
- WBCLRHUKEKRZIK-TZMCWYRMSA-N n-[(1r,2r)-2-aminocycloheptyl]-5-chloro-1h-indole-2-carboxamide Chemical compound N[C@@H]1CCCCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 WBCLRHUKEKRZIK-TZMCWYRMSA-N 0.000 description 1
- IYZDWWZDSIARIV-MHDYBILJSA-N n-[(1r,2r)-2-aminocyclopentyl]-5-chloro-1h-indole-2-carboxamide;hydrochloride Chemical compound Cl.N[C@@H]1CCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 IYZDWWZDSIARIV-MHDYBILJSA-N 0.000 description 1
- LFWYISVIXRUQIX-VTLYIQCISA-N n-[(1r,2r)-2-aminocyclopentyl]-5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide;hydrochloride Chemical compound Cl.S1C=2CN(C)CCC=2N=C1C(=O)N[C@@H]1CCC[C@H]1N LFWYISVIXRUQIX-VTLYIQCISA-N 0.000 description 1
- GMLJZFBZVPPAEB-GXSJLCMTSA-N n-[(1r,2s)-2-aminocyclobutyl]-5-chloro-1h-indole-2-carboxamide Chemical compound N[C@H]1CC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 GMLJZFBZVPPAEB-GXSJLCMTSA-N 0.000 description 1
- WBCLRHUKEKRZIK-GXTWGEPZSA-N n-[(1r,2s)-2-aminocycloheptyl]-5-chloro-1h-indole-2-carboxamide Chemical compound N[C@H]1CCCCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 WBCLRHUKEKRZIK-GXTWGEPZSA-N 0.000 description 1
- QGNFTAKAIXPYLS-WCQYABFASA-N n-[(1r,2s)-2-aminocyclohexyl]-5-chloro-1h-indole-2-carboxamide Chemical compound N[C@H]1CCCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 QGNFTAKAIXPYLS-WCQYABFASA-N 0.000 description 1
- QXPBJKHOHODSDN-SBKWZQTDSA-N n-[(1r,2s)-2-aminocyclohexyl]-5-chloro-n-methyl-1h-indole-2-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(Cl)=CC=C2NC=1C(=O)N(C)[C@@H]1CCCC[C@@H]1N QXPBJKHOHODSDN-SBKWZQTDSA-N 0.000 description 1
- PSMGFOGNPRGVJV-VHSXEESVSA-N n-[(1r,2s)-2-aminocyclohexyl]-5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide Chemical compound S1C=2CN(C)CCC=2N=C1C(=O)N[C@@H]1CCCC[C@@H]1N PSMGFOGNPRGVJV-VHSXEESVSA-N 0.000 description 1
- CDDIRYOMZASYRO-DZGCQCFKSA-N n-[(1r,2s)-2-aminocyclooctyl]-5-chloro-1h-indole-2-carboxamide Chemical compound N[C@H]1CCCCCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 CDDIRYOMZASYRO-DZGCQCFKSA-N 0.000 description 1
- LQIPCBZSXVZDSZ-DLBZAZTESA-N n-[(1r,2s)-2-aminocyclopentyl]-1-(benzenesulfonyl)-5-chloroindole-2-sulfonamide Chemical compound N[C@H]1CCC[C@H]1NS(=O)(=O)C1=CC2=CC(Cl)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 LQIPCBZSXVZDSZ-DLBZAZTESA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- CPGOEXDHRDANBY-MDZDMXLPSA-N tert-butyl 2-[(e)-2-phenylethenyl]-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine-5-carboxylate Chemical compound O1C=2CN(C(=O)OC(C)(C)C)CCC=2N=C1\C=C\C1=CC=CC=C1 CPGOEXDHRDANBY-MDZDMXLPSA-N 0.000 description 1
- CDSSEIKIKLGYMP-UHFFFAOYSA-N tert-butyl 2-bromo-4,6-dihydropyrrolo[3,4-d][1,3]thiazole-5-carboxylate Chemical compound N1=C(Br)SC2=C1CN(C(=O)OC(C)(C)C)C2 CDSSEIKIKLGYMP-UHFFFAOYSA-N 0.000 description 1
- VSMGCADVQNGHFT-UHFFFAOYSA-N tert-butyl 2-formyl-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1OC(C=O)=N2 VSMGCADVQNGHFT-UHFFFAOYSA-N 0.000 description 1
- MBNHUCDXSFFRLG-UHFFFAOYSA-N tert-butyl 4-(2,2-dibromoethenyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=C(Br)Br)CC1 MBNHUCDXSFFRLG-UHFFFAOYSA-N 0.000 description 1
- KBMHOQKTSBQSCD-UHFFFAOYSA-N tert-butyl 4-(3-methoxy-3-oxoprop-1-ynyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound COC(=O)C#CC1=CCN(C(=O)OC(C)(C)C)CC1 KBMHOQKTSBQSCD-UHFFFAOYSA-N 0.000 description 1
- AVCWKLGFOQHNCY-UHFFFAOYSA-N tert-butyl 4-(3-methoxy-3-oxoprop-1-ynyl)piperidine-1-carboxylate Chemical compound COC(=O)C#CC1CCN(C(=O)OC(C)(C)C)CC1 AVCWKLGFOQHNCY-UHFFFAOYSA-N 0.000 description 1
- HESMDBDUEDHPRG-UHFFFAOYSA-N tert-butyl n-(4-sulfanylidene-1h-pyridin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=CC=C1S HESMDBDUEDHPRG-UHFFFAOYSA-N 0.000 description 1
- XZWFJVPQGUSIJL-HZPDHXFCSA-N tert-butyl n-[(1r,2r)-2-[(5-chloro-1h-indole-2-carbonyl)amino]cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1NC(=O)C1=CC2=CC(Cl)=CC=C2N1 XZWFJVPQGUSIJL-HZPDHXFCSA-N 0.000 description 1
- QMXDBAIQSFJAPO-VHSXEESVSA-N tert-butyl n-[(1r,2s)-2-(methylamino)cyclohexyl]carbamate Chemical compound CN[C@H]1CCCC[C@H]1NC(=O)OC(C)(C)C QMXDBAIQSFJAPO-VHSXEESVSA-N 0.000 description 1
- DMXNKWGMEJMVCQ-HIFRSBDPSA-N tert-butyl n-[(1r,2s)-2-[methyl-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexyl]carbamate Chemical compound N=1C=2CCN(C)CC=2SC=1C(=O)N(C)[C@H]1CCCC[C@H]1NC(=O)OC(C)(C)C DMXNKWGMEJMVCQ-HIFRSBDPSA-N 0.000 description 1
- PAXDIBGWURAVIH-JGVFFNPUSA-N tert-butyl n-[(1r,2s)-2-aminocyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCC[C@@H]1N PAXDIBGWURAVIH-JGVFFNPUSA-N 0.000 description 1
- KLELEYKXKYXLFJ-OLZOCXBDSA-N tert-butyl n-[(1r,2s)-4-methoxyimino-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexyl]carbamate Chemical compound CON=C1CC[C@@H](NC(=O)OC(C)(C)C)[C@@H](NC(=O)OC(C)(C)C)C1 KLELEYKXKYXLFJ-OLZOCXBDSA-N 0.000 description 1
- JDZFUTJGCKYGDP-SDDRHHMPSA-N tert-butyl n-[(1r,2s,5s)-2-azido-5-(tert-butylcarbamoyl)cyclohexyl]carbamate Chemical compound CC(C)(C)NC(=O)[C@H]1CC[C@H](N=[N+]=[N-])[C@H](NC(=O)OC(C)(C)C)C1 JDZFUTJGCKYGDP-SDDRHHMPSA-N 0.000 description 1
- AKVIZYGPJIWKOS-BDAKNGLRSA-N tert-butyl n-[(1s,2r)-2-aminocyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCCC[C@H]1N AKVIZYGPJIWKOS-BDAKNGLRSA-N 0.000 description 1
- CRZBLGVWGNCGHV-UTLUCORTSA-N tert-butyl n-[(1s,2s,4r)-2-azido-4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](CO)C[C@@H]1N=[N+]=[N-] CRZBLGVWGNCGHV-UTLUCORTSA-N 0.000 description 1
- TZNNBYIRSQFXPB-ZODMCCGTSA-N tert-butyl n-[(1s,2s,4r)-2-azido-4-[[tert-butyl(diphenyl)silyl]oxymethyl]cyclohexyl]carbamate Chemical compound C1[C@H](N=[N+]=[N-])[C@@H](NC(=O)OC(C)(C)C)CC[C@H]1CO[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 TZNNBYIRSQFXPB-ZODMCCGTSA-N 0.000 description 1
- IBBVWOZAKKWMOG-TXEJJXNPSA-N tert-butyl n-[(1s,6r)-6-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohex-3-en-1-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CC=CC[C@@H]1NC(=O)OC(C)(C)C IBBVWOZAKKWMOG-TXEJJXNPSA-N 0.000 description 1
- ZFHODXSCHSIOOW-OKILXGFUSA-N tert-butyl n-methyl-n-[(1s,2r)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@H]1CCCC[C@H]1N(C)C(=O)OC(C)(C)C ZFHODXSCHSIOOW-OKILXGFUSA-N 0.000 description 1
- LQTYLRGVMBRKRB-UHFFFAOYSA-N tert-butyl-(cyclohex-3-en-1-ylmethoxy)-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)OCC1CCC=CC1 LQTYLRGVMBRKRB-UHFFFAOYSA-N 0.000 description 1
- KRRBFUJMQBDDPR-UHFFFAOYSA-N tetrabutylazanium;cyanide Chemical compound N#[C-].CCCC[N+](CCCC)(CCCC)CCCC KRRBFUJMQBDDPR-UHFFFAOYSA-N 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 201000005665 thrombophilia Diseases 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
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
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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
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- 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
- C07D495/02—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 two hetero rings
- C07D495/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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Applications Claiming Priority (2)
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JP2000108047 | 2000-04-05 | ||
PCT/JP2001/002945 WO2001074774A1 (fr) | 2000-04-05 | 2001-04-05 | Derives ethylenediamine |
Publications (3)
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NO20024766D0 NO20024766D0 (no) | 2002-10-03 |
NO20024766L NO20024766L (no) | 2002-11-28 |
NO324003B1 true NO324003B1 (no) | 2007-07-30 |
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NO20024766A NO324003B1 (no) | 2000-04-05 | 2002-10-03 | Etylendiaminderivater og medisin omfattende slike forbindelser |
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EP (2) | EP2431370B1 (zh) |
JP (2) | JP4495896B2 (zh) |
KR (1) | KR100769592B1 (zh) |
CN (1) | CN1293057C (zh) |
AR (1) | AR027998A1 (zh) |
AU (2) | AU4683501A (zh) |
BR (1) | BR0110052A (zh) |
CA (1) | CA2405144A1 (zh) |
ES (2) | ES2417860T3 (zh) |
HK (1) | HK1056876A1 (zh) |
IL (1) | IL151710A0 (zh) |
MX (1) | MXPA02009805A (zh) |
NO (1) | NO324003B1 (zh) |
RU (1) | RU2268259C2 (zh) |
TW (2) | TWI288745B (zh) |
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2001
- 2001-04-03 TW TW096119881A patent/TWI288745B/zh not_active IP Right Cessation
- 2001-04-03 TW TW090107988A patent/TWI290136B/zh not_active IP Right Cessation
- 2001-04-04 AR ARP010101613A patent/AR027998A1/es not_active Application Discontinuation
- 2001-04-05 AU AU4683501A patent/AU4683501A/xx active Pending
- 2001-04-05 WO PCT/JP2001/002945 patent/WO2001074774A1/ja active Application Filing
- 2001-04-05 JP JP2001572469A patent/JP4495896B2/ja not_active Expired - Fee Related
- 2001-04-05 MX MXPA02009805A patent/MXPA02009805A/es active IP Right Grant
- 2001-04-05 ES ES11009091T patent/ES2417860T3/es not_active Expired - Lifetime
- 2001-04-05 EP EP11009091.7A patent/EP2431370B1/en not_active Expired - Lifetime
- 2001-04-05 AU AU2001246835A patent/AU2001246835B2/en not_active Ceased
- 2001-04-05 ES ES01919784T patent/ES2389021T3/es not_active Expired - Lifetime
- 2001-04-05 IL IL15171001A patent/IL151710A0/xx unknown
- 2001-04-05 US US10/240,725 patent/US7192968B2/en not_active Expired - Fee Related
- 2001-04-05 BR BR0110052-1A patent/BR0110052A/pt not_active IP Right Cessation
- 2001-04-05 KR KR1020027013005A patent/KR100769592B1/ko not_active IP Right Cessation
- 2001-04-05 EP EP01919784A patent/EP1270557B1/en not_active Expired - Lifetime
- 2001-04-05 RU RU2002129354/04A patent/RU2268259C2/ru not_active IP Right Cessation
- 2001-04-05 CA CA002405144A patent/CA2405144A1/en not_active Abandoned
- 2001-04-05 CN CNB018086187A patent/CN1293057C/zh not_active Expired - Fee Related
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2002
- 2002-09-12 ZA ZA200207331A patent/ZA200207331B/xx unknown
- 2002-10-03 NO NO20024766A patent/NO324003B1/no unknown
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2003
- 2003-12-11 HK HK03109029A patent/HK1056876A1/xx not_active IP Right Cessation
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2005
- 2005-09-02 US US11/217,837 patent/US20060004009A1/en not_active Abandoned
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2009
- 2009-05-13 US US12/465,329 patent/US7935824B2/en not_active Expired - Fee Related
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2010
- 2010-02-04 JP JP2010022631A patent/JP5113200B2/ja not_active Expired - Fee Related
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