NO20001636L - Sufonylderivater - Google Patents
SufonylderivaterInfo
- Publication number
- NO20001636L NO20001636L NO20001636A NO20001636A NO20001636L NO 20001636 L NO20001636 L NO 20001636L NO 20001636 A NO20001636 A NO 20001636A NO 20001636 A NO20001636 A NO 20001636A NO 20001636 L NO20001636 L NO 20001636L
- Authority
- NO
- Norway
- Prior art keywords
- group
- substituent
- substituents
- sulfonyl
- amino
- Prior art date
Links
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 137
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 124
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 81
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 70
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 70
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
- 239000012453 solvate Substances 0.000 claims abstract description 30
- 125000005843 halogen group Chemical group 0.000 claims abstract description 29
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 23
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims description 338
- -1 tetrahydrothienopyridyl group Chemical group 0.000 claims description 263
- 125000003277 amino group Chemical group 0.000 claims description 153
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 125000002947 alkylene group Chemical group 0.000 claims description 69
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 60
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 40
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 33
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 31
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 29
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 22
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 21
- 230000015572 biosynthetic process Effects 0.000 claims description 20
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 17
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 15
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000004967 formylalkyl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 11
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000005182 hydroxyalkylcarbonyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 10
- 238000005345 coagulation Methods 0.000 claims description 10
- 230000015271 coagulation Effects 0.000 claims description 10
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 208000005189 Embolism Diseases 0.000 claims description 7
- 125000004450 alkenylene group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 239000004615 ingredient Substances 0.000 claims description 7
- 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 5
- 108010014173 Factor X Proteins 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000003449 preventive effect Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000006591 (C2-C6) alkynylene 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
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 208000006193 Pulmonary infarction Diseases 0.000 claims description 3
- 206010038563 Reocclusion Diseases 0.000 claims description 3
- 206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 3
- 201000010849 intracranial embolism Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 125000003431 oxalo group Chemical group 0.000 claims description 3
- 230000007575 pulmonary infarction Effects 0.000 claims description 3
- 230000000250 revascularization Effects 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 6
- 102100029117 Coagulation factor X Human genes 0.000 claims 2
- 239000003130 blood coagulation factor inhibitor Substances 0.000 claims 2
- 229940105756 coagulation factor x Drugs 0.000 claims 2
- 125000005725 cyclohexenylene group Chemical group 0.000 claims 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 239000003146 anticoagulant agent Substances 0.000 abstract description 6
- 229940127219 anticoagulant drug Drugs 0.000 abstract description 5
- 230000005923 long-lasting effect Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 255
- 150000001875 compounds Chemical class 0.000 description 203
- 239000000543 intermediate Substances 0.000 description 172
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 145
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 128
- 239000002904 solvent Substances 0.000 description 127
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 120
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- 238000005160 1H NMR spectroscopy Methods 0.000 description 106
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
- 239000000460 chlorine Substances 0.000 description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 71
- 238000006243 chemical reaction Methods 0.000 description 71
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 70
- 239000002585 base Substances 0.000 description 68
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 66
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 61
- 230000002829 reductive effect Effects 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
- 239000000243 solution Substances 0.000 description 55
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 54
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 47
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 46
- 239000012442 inert solvent Substances 0.000 description 46
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 44
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 44
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 43
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 36
- 239000003054 catalyst Substances 0.000 description 36
- 238000004519 manufacturing process Methods 0.000 description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
- 238000004587 chromatography analysis Methods 0.000 description 35
- 238000000921 elemental analysis Methods 0.000 description 34
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- 229960001866 silicon dioxide Drugs 0.000 description 34
- 238000003756 stirring Methods 0.000 description 32
- 125000000623 heterocyclic group Chemical group 0.000 description 31
- 238000001816 cooling Methods 0.000 description 29
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 26
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 26
- 239000007858 starting material Substances 0.000 description 26
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 25
- 125000004122 cyclic group Chemical group 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- 239000002994 raw material Substances 0.000 description 25
- 229910052783 alkali metal Inorganic materials 0.000 description 24
- 150000001340 alkali metals Chemical class 0.000 description 24
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 24
- 125000006239 protecting group Chemical group 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 23
- 150000001342 alkaline earth metals Chemical class 0.000 description 23
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- 150000007530 organic bases Chemical class 0.000 description 22
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 21
- 239000012046 mixed solvent Substances 0.000 description 21
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 21
- 229910000029 sodium carbonate Inorganic materials 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 18
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 18
- 238000005859 coupling reaction Methods 0.000 description 18
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 17
- MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 17
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 17
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 17
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 150000001721 carbon Chemical group 0.000 description 15
- 238000010438 heat treatment Methods 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 15
- 150000003335 secondary amines Chemical class 0.000 description 15
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- 229910052744 lithium Inorganic materials 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 13
- 150000004679 hydroxides Chemical class 0.000 description 13
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 13
- 229910000105 potassium hydride Inorganic materials 0.000 description 13
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 13
- PUWJXVNBKNHYTQ-UHFFFAOYSA-N 1-(6-chloronaphthalen-2-yl)sulfonylpiperazine;hydrochloride Chemical compound Cl.C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N1CCNCC1 PUWJXVNBKNHYTQ-UHFFFAOYSA-N 0.000 description 12
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- 150000001350 alkyl halides Chemical class 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 150000004678 hydrides Chemical class 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 12
- 229910052723 transition metal Inorganic materials 0.000 description 12
- 150000003624 transition metals Chemical class 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 150000004703 alkoxides Chemical class 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 11
- 150000004820 halides Chemical class 0.000 description 11
- 229910052736 halogen Inorganic materials 0.000 description 11
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 11
- 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 11
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 150000002367 halogens Chemical group 0.000 description 10
- 239000012948 isocyanate Substances 0.000 description 10
- 150000002513 isocyanates Chemical class 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 238000007327 hydrogenolysis reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 9
- 125000001544 thienyl group Chemical group 0.000 description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 150000008065 acid anhydrides Chemical class 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 8
- 150000001728 carbonyl compounds Chemical class 0.000 description 8
- 238000010531 catalytic reduction reaction Methods 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 235000008504 concentrate Nutrition 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 8
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
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- 239000003638 chemical reducing agent Substances 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
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- 230000005494 condensation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000001035 drying Methods 0.000 description 2
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
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- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 2
- CGIRTYUXRYHZET-UHFFFAOYSA-N ethyl 4-(6-chloronaphthalen-2-yl)sulfonyl-1-[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]piperazine-2-carboxylate Chemical compound CCOC(=O)C1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(C=C1)=CC=C1C1=CC=[N+]([O-])C=C1 CGIRTYUXRYHZET-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
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- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- VCXZJBRVEJBECK-UHFFFAOYSA-N methyl 2,5-dihydropyrrole-1-carboxylate Chemical compound COC(=O)N1CC=CC1 VCXZJBRVEJBECK-UHFFFAOYSA-N 0.000 description 2
- VLIWPKHBVFHGSO-UHFFFAOYSA-N methyl 3-(4-methoxycarbonylphenyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC)CCC1C1=CC=C(C(=O)OC)C=C1 VLIWPKHBVFHGSO-UHFFFAOYSA-N 0.000 description 2
- 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 2
- HJFLFKCPIXRWCQ-UHFFFAOYSA-N methyl 3h-benzimidazole-5-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C2NC=NC2=C1 HJFLFKCPIXRWCQ-UHFFFAOYSA-N 0.000 description 2
- DQUBUHYEMDZHLH-UHFFFAOYSA-N methyl 4-(1h-imidazol-5-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CNC=N1 DQUBUHYEMDZHLH-UHFFFAOYSA-N 0.000 description 2
- FKEIGGWJRUYGHR-UHFFFAOYSA-N methyl 4-(2-amino-1,3-thiazol-4-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CSC(N)=N1 FKEIGGWJRUYGHR-UHFFFAOYSA-N 0.000 description 2
- PTTPOCCDBYFBGP-UHFFFAOYSA-N methyl 4-(6-aminopyridin-3-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(N)N=C1 PTTPOCCDBYFBGP-UHFFFAOYSA-N 0.000 description 2
- XRZGMNGGCZTNGE-UHFFFAOYSA-N methyl 4-(cyanomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CC#N)C=C1 XRZGMNGGCZTNGE-UHFFFAOYSA-N 0.000 description 2
- SBXYPZOOIIPEJW-UHFFFAOYSA-N methyl 4-(trifluoromethylsulfonyloxy)benzoate Chemical compound COC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 SBXYPZOOIIPEJW-UHFFFAOYSA-N 0.000 description 2
- NRIWUOJTSLHILG-UHFFFAOYSA-N methyl 4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]benzoate Chemical compound COC(=O)C1=CC=C(CCNC(=O)OC(C)(C)C)C=C1 NRIWUOJTSLHILG-UHFFFAOYSA-N 0.000 description 2
- HNVQYNCIKKMFCR-UHFFFAOYSA-N methyl 4-[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(NC(=O)OC(C)(C)C)N=C1 HNVQYNCIKKMFCR-UHFFFAOYSA-N 0.000 description 2
- UDPLKASYJHMKIP-UHFFFAOYSA-N methyl 4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C=C1 UDPLKASYJHMKIP-UHFFFAOYSA-N 0.000 description 2
- XLKDKHRGIJWOSN-UHFFFAOYSA-N methyl 4-bromo-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C(OC)=C1 XLKDKHRGIJWOSN-UHFFFAOYSA-N 0.000 description 2
- SMXKPSLCRALELV-UHFFFAOYSA-N methyl 4-pyridin-3-ylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=CN=C1 SMXKPSLCRALELV-UHFFFAOYSA-N 0.000 description 2
- NNBMIOHXJBOEJZ-UHFFFAOYSA-N methyl 6-[[tert-butyl(dimethyl)silyl]oxymethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate Chemical compound C1C(CO[Si](C)(C)C(C)(C)C)CCC2=CC(C(=O)OC)=CC=C21 NNBMIOHXJBOEJZ-UHFFFAOYSA-N 0.000 description 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
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- 125000005561 phenanthryl group Chemical group 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
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- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
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- SZQHAGCUMNTHMM-CQSZACIVSA-N tert-butyl (3r)-3-(4-methoxycarbonylphenoxy)pyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1O[C@H]1CN(C(=O)OC(C)(C)C)CC1 SZQHAGCUMNTHMM-CQSZACIVSA-N 0.000 description 2
- WOWQZTDPRNUQOH-AWEZNQCLSA-N tert-butyl (3s)-3-(3-methoxycarbonylphenoxy)pyrrolidine-1-carboxylate Chemical compound COC(=O)C1=CC=CC(O[C@@H]2CN(CC2)C(=O)OC(C)(C)C)=C1 WOWQZTDPRNUQOH-AWEZNQCLSA-N 0.000 description 2
- SZQHAGCUMNTHMM-AWEZNQCLSA-N tert-butyl (3s)-3-(4-methoxycarbonylphenoxy)pyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1O[C@@H]1CN(C(=O)OC(C)(C)C)CC1 SZQHAGCUMNTHMM-AWEZNQCLSA-N 0.000 description 2
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- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
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- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
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- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
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- HMVCSEMUDZAOQZ-UHFFFAOYSA-N methyl 1-tritylbenzimidazole-5-carboxylate Chemical compound C1=NC2=CC(C(=O)OC)=CC=C2N1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HMVCSEMUDZAOQZ-UHFFFAOYSA-N 0.000 description 1
- QCGYMYLEOVZEKP-UHFFFAOYSA-N methyl 2-[4-(6-chloronaphthalen-2-yl)sulfonyl-1-(4-pyridin-2-ylbenzoyl)piperazin-2-yl]acetate Chemical compound COC(=O)CC1CN(S(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CCN1C(=O)C(C=C1)=CC=C1C1=CC=CC=N1 QCGYMYLEOVZEKP-UHFFFAOYSA-N 0.000 description 1
- SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 1
- YBEKNOSAAIRRRW-UHFFFAOYSA-N methyl 3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CNC(=O)OC(C)(C)C)=C1 YBEKNOSAAIRRRW-UHFFFAOYSA-N 0.000 description 1
- CPXCDEMFNPKOEF-UHFFFAOYSA-N methyl 3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1 CPXCDEMFNPKOEF-UHFFFAOYSA-N 0.000 description 1
- ZENHKUORQLYZDB-UHFFFAOYSA-N methyl 4-(2-amino-1h-imidazol-5-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CNC(N)=N1 ZENHKUORQLYZDB-UHFFFAOYSA-N 0.000 description 1
- VBWFYEFYHJRJER-UHFFFAOYSA-N methyl 4-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=C(CO)C=C1 VBWFYEFYHJRJER-UHFFFAOYSA-N 0.000 description 1
- URZGKIAIKXPNMU-UHFFFAOYSA-N methyl 4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(NC(=O)OC(C)(C)C)C=C1 URZGKIAIKXPNMU-UHFFFAOYSA-N 0.000 description 1
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- BZOJIISXOHUNRI-UHFFFAOYSA-N methyl 6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate Chemical compound C1C(CO)CCC2=CC(C(=O)OC)=CC=C21 BZOJIISXOHUNRI-UHFFFAOYSA-N 0.000 description 1
- UVYDGGXUZBUYFJ-UHFFFAOYSA-N methyl 6-[(4-methylphenyl)sulfonyloxymethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate Chemical compound C1CC2=CC(C(=O)OC)=CC=C2CC1COS(=O)(=O)C1=CC=C(C)C=C1 UVYDGGXUZBUYFJ-UHFFFAOYSA-N 0.000 description 1
- ZLVLISBXIVELCF-UHFFFAOYSA-N methyl 6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]naphthalene-2-carboxylate Chemical compound C1=C(CNC(=O)OC(C)(C)C)C=CC2=CC(C(=O)OC)=CC=C21 ZLVLISBXIVELCF-UHFFFAOYSA-N 0.000 description 1
- RJPDNALCGZSUGO-UHFFFAOYSA-N methyl 7-(hydroxymethyl)naphthalene-2-carboxylate Chemical compound C1=CC(CO)=CC2=CC(C(=O)OC)=CC=C21 RJPDNALCGZSUGO-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
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- NGGXACLSAZXJGM-UHFFFAOYSA-N n-(diaminomethylidene)acetamide Chemical compound CC(=O)N=C(N)N NGGXACLSAZXJGM-UHFFFAOYSA-N 0.000 description 1
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- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- CKOOABJZYWLHMN-UHFFFAOYSA-N phenyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1=CC=CC=C1.C=1C=CC=CC=1C(=O)OC1=CC=CC=C1 CKOOABJZYWLHMN-UHFFFAOYSA-N 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- HSTPRKSBUJHIIC-UHFFFAOYSA-N piperazin-1-yl-(4-pyridin-4-ylphenyl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C=1C=C(C=2C=CN=CC=2)C=CC=1C(=O)N1CCNCC1 HSTPRKSBUJHIIC-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
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- WVULZDFWPQCPPJ-UHFFFAOYSA-N potassium;hydrochloride Chemical compound Cl.[K] WVULZDFWPQCPPJ-UHFFFAOYSA-N 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- 230000001629 suppression Effects 0.000 description 1
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- MVEOHIGPMSIKIG-VQHVLOKHSA-N tert-butyl 2-[(e)-3-[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-3-oxoprop-1-enyl]-6,7-dihydro-4h-thieno[3,2-c]pyridine-5-carboxylate Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)N3CCN(CC3)C(=O)/C=C/C=3SC=4CCN(CC=4C=3)C(=O)OC(C)(C)C)=CC=C21 MVEOHIGPMSIKIG-VQHVLOKHSA-N 0.000 description 1
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- JZWGNJAIEIWWNL-UHFFFAOYSA-N tert-butyl n-[[6-[[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]methyl]carbamate Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)N3CCN(CC3)CC3CC4=CC=C(C=C4CC3)CNC(=O)OC(C)(C)C)=CC=C21 JZWGNJAIEIWWNL-UHFFFAOYSA-N 0.000 description 1
- KSGGZZRUTBFDTC-UHFFFAOYSA-N tert-butyl n-[[7-[4-(6-chloronaphthalen-2-yl)sulfonylpiperazine-1-carbonyl]naphthalen-2-yl]methyl]carbamate Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)N3CCN(CC3)C(=O)C=3C=CC4=CC=C(C=C4C=3)CNC(=O)OC(C)(C)C)=CC=C21 KSGGZZRUTBFDTC-UHFFFAOYSA-N 0.000 description 1
- AOCGGGJRCUVUQU-UHFFFAOYSA-N tert-butyl n-[[7-[[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]methyl]naphthalen-2-yl]methyl]carbamate Chemical compound C1=C(Cl)C=CC2=CC(S(=O)(=O)N3CCN(CC3)CC=3C=CC4=CC=C(C=C4C=3)CNC(=O)OC(C)(C)C)=CC=C21 AOCGGGJRCUVUQU-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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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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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
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- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Lubricants (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Pyridine Compounds (AREA)
- Dry Shavers And Clippers (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP26711797 | 1997-09-30 | ||
PCT/JP1998/004411 WO1999016747A1 (fr) | 1997-09-30 | 1998-09-30 | Derives sulfonyle |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20001636D0 NO20001636D0 (no) | 2000-03-29 |
NO20001636L true NO20001636L (no) | 2000-03-29 |
Family
ID=17440312
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20001636A NO20001636L (no) | 1997-09-30 | 2000-03-29 | Sufonylderivater |
Country Status (16)
Country | Link |
---|---|
US (2) | US6525042B1 (ja) |
EP (1) | EP1031563B1 (ja) |
JP (1) | JP4256065B2 (ja) |
KR (1) | KR20010015639A (ja) |
CN (1) | CN1278793A (ja) |
AT (1) | ATE314347T1 (ja) |
AU (1) | AU9280698A (ja) |
BR (1) | BR9815377A (ja) |
CA (1) | CA2304285A1 (ja) |
DE (1) | DE69833036T2 (ja) |
DK (1) | DK1031563T3 (ja) |
ES (1) | ES2255733T3 (ja) |
ID (1) | ID23991A (ja) |
IL (1) | IL135180A0 (ja) |
NO (1) | NO20001636L (ja) |
WO (1) | WO1999016747A1 (ja) |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR9815377A (pt) * | 1997-09-30 | 2001-01-16 | Daiichi Pharmaceutical Co Ltda | Derivados de sulfonil |
ATE346050T1 (de) * | 1998-01-27 | 2006-12-15 | Aventis Pharma Inc | Substituierte oxoazaheterocyclyl faktor xa hemmer |
GB9809349D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Heterocyclic derivatives |
GB9809350D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Novel salt |
AU5196399A (en) * | 1998-08-11 | 2000-03-06 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
EP1140839B1 (en) | 1998-12-24 | 2004-03-17 | Eli Lilly And Company | Heterocyclic amides as inhibitors of factor xa |
IL146309A (en) * | 1999-05-21 | 2008-03-20 | Scios Inc | Derivatives of the indole type and pharmaceutical preparations containing them as inhibitors of kinase p38 |
JP2001294572A (ja) * | 2000-02-09 | 2001-10-23 | Dai Ichi Seiyaku Co Ltd | 新規スルホニル誘導体 |
WO2001062763A1 (fr) * | 2000-02-25 | 2001-08-30 | Daiichi Pharmaceutical Co., Ltd. | Procede d'inhibition des proteases serines du type trypsine |
TWI288745B (en) | 2000-04-05 | 2007-10-21 | Daiichi Seiyaku Co | Ethylenediamine derivatives |
ATE374765T1 (de) | 2000-07-27 | 2007-10-15 | Lilly Co Eli | Substituierte heterocyclische amide |
WO2002026720A2 (en) * | 2000-09-29 | 2002-04-04 | Millennium Pharmaceuticals, Inc. | PIPERAZINE BASED INHIBITORS OF FACTOR Xa |
ES2274913T3 (es) * | 2000-10-12 | 2007-06-01 | MERCK & CO., INC. | Aza y poliaza-naftalenil carboxamidas utiles como inhibidores de vih integrada. |
US6919351B2 (en) * | 2000-10-12 | 2005-07-19 | Merck & Co., Inc. | Aza-and polyaza-naphthalenyl-carboxamides useful as HIV integrase inhibitors |
AU1152702A (en) | 2000-10-12 | 2002-04-22 | Merck & Co Inc | Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors |
WO2002076945A1 (en) * | 2001-03-09 | 2002-10-03 | Ortho-Mcneil Pharmaceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
GB0114004D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
GB0114005D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
US7365205B2 (en) | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
EP1405852B9 (en) * | 2001-06-20 | 2013-03-27 | Daiichi Sankyo Company, Limited | Diamine derivatives |
GB0127568D0 (en) | 2001-11-16 | 2002-01-09 | Glaxo Group Ltd | Chemical compounds |
AU2002350172A1 (en) | 2001-12-07 | 2003-06-23 | Eli Lilly And Company | Substituted heterocyclic carboxamides with antithrombotic activity |
US7354932B2 (en) | 2001-12-21 | 2008-04-08 | Anormed, Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
US7323460B2 (en) * | 2002-03-15 | 2008-01-29 | Merck & Co., Inc. | N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as HIV integrase inhibitors |
EP1532115A4 (en) * | 2002-05-22 | 2006-01-11 | Smithkline Beecham Corp | INHIBITORS OF PROTEASE |
PT1569912E (pt) | 2002-12-03 | 2015-09-15 | Pharmacyclics Llc | Derivados 2-(2-hidroxibifenil-3-il)-1h-benzoimidazole-5- carboxamidina como inibidores do fator viia |
RU2333203C2 (ru) * | 2002-12-25 | 2008-09-10 | Дайити Фармасьютикал Ко., Лтд. | Диаминовые производные |
JP4697962B2 (ja) | 2003-02-13 | 2011-06-08 | ウェルスタット セラピューティクス コーポレイション | 代謝性障害の処置のための化合物 |
US20050119266A1 (en) * | 2003-10-01 | 2005-06-02 | Yan Shi | Pyrrolidine and piperidine derivatives as factor Xa inhibitors |
EP1725236A4 (en) * | 2004-03-11 | 2009-05-13 | Glaxo Group Ltd | NEW M3 MUSCARIN ACETYLCHOLINE RECEPTOR ANTAGONISTS |
DE602005018800D1 (de) | 2004-09-09 | 2010-02-25 | Teva Pharma | Verfahren zur herstellung von polypeptidmischungen unter anwendung von aufgereinigter bromwasserstoffsäure |
TW200619206A (en) * | 2004-09-29 | 2006-06-16 | Anormed Inc | Chemokine-binding heterocyclic compound salts, and methods of use thereof |
TW200630337A (en) * | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
WO2007008145A1 (en) * | 2005-07-08 | 2007-01-18 | Astrazeneca Ab | Heterocyclic sulfonamide derivatives as inhibitors of factor xa |
WO2007087505A2 (en) | 2006-01-25 | 2007-08-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
WO2007087504A2 (en) | 2006-01-25 | 2007-08-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
CA2639939A1 (en) | 2006-02-02 | 2007-08-16 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
WO2007110449A1 (en) * | 2006-03-29 | 2007-10-04 | Euro-Celtique S.A. | Benzenesulfonamide compounds and their use |
US8791264B2 (en) * | 2006-04-13 | 2014-07-29 | Purdue Pharma L.P. | Benzenesulfonamide compounds and their use as blockers of calcium channels |
WO2007118854A1 (en) * | 2006-04-13 | 2007-10-25 | Euro-Celtique S.A. | Benzenesulfonamide compounds and the use thereof |
US8017612B2 (en) | 2006-04-18 | 2011-09-13 | Japan Tobacco Inc. | Piperazine compound and use thereof as a HCV polymerase inhibitor |
WO2008124118A1 (en) * | 2007-04-09 | 2008-10-16 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use therof |
US8765736B2 (en) * | 2007-09-28 | 2014-07-01 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
EP2345643A1 (en) * | 2009-12-29 | 2011-07-20 | Polichem S.A. | New tertiary 8-hydroxyquinoline-7-carboxamide derivatives and uses thereof |
ES2907489T3 (es) | 2015-12-14 | 2022-04-25 | X4 Pharmaceuticals Inc | Métodos para el tratamiento del cáncer |
CN109069486A (zh) | 2015-12-14 | 2018-12-21 | X4 制药有限公司 | 治疗癌症的方法 |
DK3393468T3 (da) | 2015-12-22 | 2022-12-19 | X4 Pharmaceuticals Inc | Fremgangsmåder til behandling af en immundefektsygdom |
US11337969B2 (en) | 2016-04-08 | 2022-05-24 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
CN109641838A (zh) | 2016-06-21 | 2019-04-16 | X4 制药有限公司 | Cxcr4抑制剂及其用途 |
CA3027495A1 (en) | 2016-06-21 | 2017-12-28 | X4 Pharmaceuticals, Inc. | Cxcr4 inhibitors and uses thereof |
CN116554168A (zh) | 2016-06-21 | 2023-08-08 | X4 制药有限公司 | Cxcr4抑制剂及其用途 |
US10548889B1 (en) | 2018-08-31 | 2020-02-04 | X4 Pharmaceuticals, Inc. | Compositions of CXCR4 inhibitors and methods of preparation and use |
Family Cites Families (16)
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 |
IL115420A0 (en) * | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
US5731315A (en) | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
US5612353A (en) | 1995-06-07 | 1997-03-18 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
GB9516709D0 (en) | 1995-08-15 | 1995-10-18 | Zeneca Ltd | Medicament |
GB9602294D0 (en) * | 1996-02-05 | 1996-04-03 | Zeneca Ltd | Heterocyclic compounds |
TR199900303T2 (xx) | 1996-08-14 | 1999-06-21 | Zeneca Limited | �kame edilmi� pirimidin t�revleri ve bunlar�n farmas�tik kullan�m�. |
UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
AU726637B2 (en) * | 1996-12-13 | 2000-11-16 | Aventis Pharmaceuticals Inc. | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
CA2287292A1 (en) | 1997-05-30 | 1998-12-03 | Takeda Chemical Industries, Ltd. | Sulfonamide derivatives, their production and use |
BR9815377A (pt) * | 1997-09-30 | 2001-01-16 | Daiichi Pharmaceutical Co Ltda | Derivados de sulfonil |
DE19743435A1 (de) | 1997-10-01 | 1999-04-08 | Merck Patent Gmbh | Benzamidinderivate |
ATE346050T1 (de) | 1998-01-27 | 2006-12-15 | Aventis Pharma Inc | Substituierte oxoazaheterocyclyl faktor xa hemmer |
US6403595B1 (en) | 1998-02-05 | 2002-06-11 | Takeda Chemical Industries, Ltd. | Sulfonamide derivatives, processes for producing the same and utilization thereof |
GB9809349D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Heterocyclic derivatives |
GB9809350D0 (en) | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Novel salt |
-
1998
- 1998-09-30 BR BR9815377-3A patent/BR9815377A/pt not_active Application Discontinuation
- 1998-09-30 JP JP2000513833A patent/JP4256065B2/ja not_active Expired - Fee Related
- 1998-09-30 US US09/508,680 patent/US6525042B1/en not_active Expired - Fee Related
- 1998-09-30 CN CN98810557A patent/CN1278793A/zh active Pending
- 1998-09-30 KR KR1020007003295A patent/KR20010015639A/ko not_active Application Discontinuation
- 1998-09-30 DE DE69833036T patent/DE69833036T2/de not_active Expired - Lifetime
- 1998-09-30 AU AU92806/98A patent/AU9280698A/en not_active Abandoned
- 1998-09-30 CA CA002304285A patent/CA2304285A1/en not_active Abandoned
- 1998-09-30 DK DK98945542T patent/DK1031563T3/da active
- 1998-09-30 WO PCT/JP1998/004411 patent/WO1999016747A1/ja active IP Right Grant
- 1998-09-30 IL IL13518098A patent/IL135180A0/xx unknown
- 1998-09-30 ES ES98945542T patent/ES2255733T3/es not_active Expired - Lifetime
- 1998-09-30 AT AT98945542T patent/ATE314347T1/de not_active IP Right Cessation
- 1998-09-30 EP EP98945542A patent/EP1031563B1/en not_active Expired - Lifetime
- 1998-09-30 ID IDW20000598A patent/ID23991A/id unknown
-
2000
- 2000-03-29 NO NO20001636A patent/NO20001636L/no not_active Application Discontinuation
-
2002
- 2002-12-20 US US10/323,978 patent/US20030232808A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
NO20001636D0 (no) | 2000-03-29 |
ES2255733T3 (es) | 2006-07-01 |
EP1031563A4 (en) | 2000-12-06 |
WO1999016747A1 (fr) | 1999-04-08 |
AU9280698A (en) | 1999-04-23 |
KR20010015639A (ko) | 2001-02-26 |
EP1031563B1 (en) | 2005-12-28 |
ATE314347T1 (de) | 2006-01-15 |
EP1031563A1 (en) | 2000-08-30 |
BR9815377A (pt) | 2001-01-16 |
DK1031563T3 (da) | 2006-05-08 |
CN1278793A (zh) | 2001-01-03 |
DE69833036D1 (de) | 2006-02-02 |
DE69833036T2 (de) | 2006-06-22 |
JP4256065B2 (ja) | 2009-04-22 |
CA2304285A1 (en) | 1999-04-08 |
US6525042B1 (en) | 2003-02-25 |
ID23991A (id) | 2000-06-14 |
IL135180A0 (en) | 2001-05-20 |
US20030232808A1 (en) | 2003-12-18 |
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