SK282058B6 - Deriváty kyseliny octovej, spôsob ich výroby, farmaceutické prostriedky na ich báze a ich použitie na výrobu liečiv - Google Patents
Deriváty kyseliny octovej, spôsob ich výroby, farmaceutické prostriedky na ich báze a ich použitie na výrobu liečiv Download PDFInfo
- Publication number
- SK282058B6 SK282058B6 SK1458-94A SK145894A SK282058B6 SK 282058 B6 SK282058 B6 SK 282058B6 SK 145894 A SK145894 A SK 145894A SK 282058 B6 SK282058 B6 SK 282058B6
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- lower alkyl
- acetic acid
- tert
- acid
- Prior art date
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- 150000001242 acetic acid derivatives Chemical class 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims description 23
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 4
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 4
- 239000000853 adhesive Substances 0.000 claims abstract description 3
- 230000001070 adhesive effect Effects 0.000 claims abstract description 3
- 230000017455 cell-cell adhesion Effects 0.000 claims abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 388
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 220
- -1 hydroxy, carboxy Chemical group 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 36
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims description 32
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000000468 ketone group Chemical group 0.000 claims description 14
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- KSGBFAJYSBCOGG-UHFFFAOYSA-N 2-piperidin-1-ium-4-yloxyacetate Chemical compound OC(=O)COC1CCNCC1 KSGBFAJYSBCOGG-UHFFFAOYSA-N 0.000 claims description 10
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- MGZFVSUXQXCEHM-UHFFFAOYSA-N ethyl 2-phenoxyacetate Chemical compound CCOC(=O)COC1=CC=CC=C1 MGZFVSUXQXCEHM-UHFFFAOYSA-N 0.000 claims description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 8
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 229910052721 tungsten Inorganic materials 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 4
- WHNQTHDJEZTVHS-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(CCC(=O)O)=NC2=C1 WHNQTHDJEZTVHS-UHFFFAOYSA-N 0.000 claims description 3
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- ZPHBHSWREPRVMM-ZDUSSCGKSA-N ethyl 2-[4-[(2S)-2-[[4-(N'-hydroxycarbamimidoyl)benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound NC(C1=CC=C(C(=O)N[C@H](C(=O)C2=CC=C(OCC(=O)OCC)C=C2)C)C=C1)=N/O ZPHBHSWREPRVMM-ZDUSSCGKSA-N 0.000 claims description 3
- KHNNVXSQXFFKRK-SFHVURJKSA-N ethyl 2-[4-[(2s)-2-[[4-(n'-phenoxycarbonylcarbamimidoyl)benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(C(=N)NC(=O)OC=2C=CC=CC=2)C=C1 KHNNVXSQXFFKRK-SFHVURJKSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- CVMPLLOMCQDCHU-SFHVURJKSA-N oxan-4-yl 2-[4-[(2S)-2-[[4-[(ethoxycarbonylhydrazinylidene)methyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound O1CCC(CC1)OC(COC1=CC=C(C=C1)C([C@H](C)NC(C1=CC=C(C=C1)C=NNC(=O)OCC)=O)=O)=O CVMPLLOMCQDCHU-SFHVURJKSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 229930194542 Keto Natural products 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- DSICUYSSROHSRG-UHFFFAOYSA-N 2-[1-[2-methyl-4-[4-[(2-methylpropoxycarbonylhydrazinylidene)methyl]phenyl]-4-oxobutanoyl]piperidin-4-yl]oxyacetic acid Chemical compound C1=CC(C=NNC(=O)OCC(C)C)=CC=C1C(=O)CC(C)C(=O)N1CCC(OCC(O)=O)CC1 DSICUYSSROHSRG-UHFFFAOYSA-N 0.000 claims 1
- BLUGETCPPNDBBJ-UHFFFAOYSA-N 2-[1-[4-[4-[(ethoxycarbonylhydrazinylidene)methyl]phenyl]-4-oxobutanoyl]piperidin-4-yl]oxyacetic acid Chemical compound C1=CC(C=NNC(=O)OCC)=CC=C1C(=O)CCC(=O)N1CCC(OCC(O)=O)CC1 BLUGETCPPNDBBJ-UHFFFAOYSA-N 0.000 claims 1
- XZOZGMBZKNFESF-QNSVNVJESA-N 3-[[2-[1-[(2R)-4-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]-2-methyl-4-oxobutanoyl]piperidin-4-yl]oxyacetyl]oxymethyl]piperidine-1-carboxylic acid Chemical compound C([C@@H](C)C(=O)N1CCC(CC1)OCC(=O)OCC1CN(CCC1)C(O)=O)C(=O)C1=CC=C(C(\N)=N\O)C=C1 XZOZGMBZKNFESF-QNSVNVJESA-N 0.000 claims 1
- JWHXIUOJVLPZMX-INIZCTEOSA-N acetyloxymethyl 4-[2-[[(2S)-1-[4-(2-ethoxy-2-oxoethoxy)phenyl]-1-oxopropan-2-yl]amino]-2-oxoethoxy]piperidine-1-carboxylate Chemical compound C(C)(=O)OCOC(=O)N1CCC(CC1)OCC(N[C@H](C(=O)C1=CC=C(C=C1)OCC(=O)OCC)C)=O JWHXIUOJVLPZMX-INIZCTEOSA-N 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 239000003357 wound healing promoting agent Substances 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 abstract description 9
- 150000002825 nitriles Chemical class 0.000 abstract description 7
- 210000001772 blood platelet Anatomy 0.000 abstract 2
- 230000002776 aggregation Effects 0.000 abstract 1
- 238000004220 aggregation Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 306
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 287
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 249
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 155
- 239000000741 silica gel Substances 0.000 description 155
- 229910002027 silica gel Inorganic materials 0.000 description 155
- 239000000243 solution Substances 0.000 description 147
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 125
- 239000007858 starting material Substances 0.000 description 101
- 239000000047 product Substances 0.000 description 97
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
- 239000000203 mixture Substances 0.000 description 75
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 74
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 239000003480 eluent Substances 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 53
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 49
- 239000012043 crude product Substances 0.000 description 49
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 47
- 238000004587 chromatography analysis Methods 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- 125000004494 ethyl ester group Chemical group 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 30
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 30
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 30
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 30
- 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 30
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 28
- 239000006260 foam Substances 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- 238000002844 melting Methods 0.000 description 27
- 230000008018 melting Effects 0.000 description 27
- 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 26
- 235000019253 formic acid Nutrition 0.000 description 26
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 21
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 20
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 19
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 19
- SBPPZSMHPLLZNQ-UQKRIMTDSA-N OC(=O)C(F)(F)F.CCOC(=O)COc1ccc(cc1)C(=O)[C@H](C)NC(=O)c1ccc(C=NN)cc1 Chemical compound OC(=O)C(F)(F)F.CCOC(=O)COc1ccc(cc1)C(=O)[C@H](C)NC(=O)c1ccc(C=NN)cc1 SBPPZSMHPLLZNQ-UQKRIMTDSA-N 0.000 description 18
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 18
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 17
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- IOFWPTSWSRRIAU-CYBMUJFWSA-N 2-[1-[(2r)-4-(4-cyanophenyl)-2-methyl-4-oxobutanoyl]piperidin-4-yl]oxyacetic acid Chemical compound C([C@@H](C)C(=O)N1CCC(CC1)OCC(O)=O)C(=O)C1=CC=C(C#N)C=C1 IOFWPTSWSRRIAU-CYBMUJFWSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 239000005695 Ammonium acetate Substances 0.000 description 15
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 15
- 235000019257 ammonium acetate Nutrition 0.000 description 15
- 229940043376 ammonium acetate Drugs 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 13
- 239000011347 resin Substances 0.000 description 13
- 229920005989 resin Polymers 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- KFODDTOOBXYLBG-LBPRGKRZSA-N ethyl 2-[4-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(C(=O)[C@H](C)NC(=O)OC(C)(C)C)C=C1 KFODDTOOBXYLBG-LBPRGKRZSA-N 0.000 description 11
- PCOKVBQRZCEGTJ-UHFFFAOYSA-N tert-butyl 2-piperidin-4-yloxyacetate Chemical compound CC(C)(C)OC(=O)COC1CCNCC1 PCOKVBQRZCEGTJ-UHFFFAOYSA-N 0.000 description 11
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
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- 239000000126 substance Substances 0.000 description 2
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- WWVJNQCGTCDNNR-HNNXBMFYSA-N ethyl 2-[1-[(2S)-2-(8-cyano-5-oxo-2,3-dihydro-1,4-benzoxazepin-4-yl)propanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)N1C(=O)C2=CC=C(C#N)C=C2OCC1 WWVJNQCGTCDNNR-HNNXBMFYSA-N 0.000 description 1
- LTHRLMJFRGCGBW-LBPRGKRZSA-N ethyl 2-[1-[(2S)-2-[[5-[(E)-N'-hydroxycarbamimidoyl]pyridine-2-carbonyl]amino]propanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)NC(=O)C1=CC=C(C(\N)=N\O)C=N1 LTHRLMJFRGCGBW-LBPRGKRZSA-N 0.000 description 1
- RCPDQJDRIRNTAJ-GOSISDBHSA-N ethyl 2-[1-[(2r)-2-methyl-4-[4-[n'-(2-methylpropoxycarbonyl)carbamimidoyl]phenyl]-4-oxobutanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)CC(=O)C1=CC=C(C(=N)NC(=O)OCC(C)C)C=C1 RCPDQJDRIRNTAJ-GOSISDBHSA-N 0.000 description 1
- JIYOVRJKERHNOL-OAHLLOKOSA-N ethyl 2-[1-[(2r)-4-(4-cyanophenyl)-2-methyl-4-oxobutanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)CC(=O)C1=CC=C(C#N)C=C1 JIYOVRJKERHNOL-OAHLLOKOSA-N 0.000 description 1
- ANUAMCQBVUVLFY-XMMPIXPASA-N ethyl 2-[1-[(2r)-4-[4-[n,n-bis[(2-methylpropan-2-yl)oxycarbonyl]-n'-(2-methylpropoxycarbonyl)carbamimidoyl]phenyl]-2-methyl-4-oxobutanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)CC(=O)C1=CC=C(C(=NC(=O)OCC(C)C)N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C1 ANUAMCQBVUVLFY-XMMPIXPASA-N 0.000 description 1
- MPRGXDLIAURRGQ-KRWDZBQOSA-N ethyl 2-[1-[(2s)-2-[[4-[(e)-n'-hydroxycarbamimidoyl]benzoyl]amino]butanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](CC)NC(=O)C1=CC=C(C(\N)=N\O)C=C1 MPRGXDLIAURRGQ-KRWDZBQOSA-N 0.000 description 1
- NHJXIGZVZFNDCD-UHFFFAOYSA-N ethyl 2-[1-[3-[4-[(e)-n'-hydroxycarbamimidoyl]anilino]-3-oxopropanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)CC(=O)NC1=CC=C(C(\N)=N\O)C=C1 NHJXIGZVZFNDCD-UHFFFAOYSA-N 0.000 description 1
- AJXZALULDKOXKS-UHFFFAOYSA-N ethyl 2-[1-[4-(4-cyanophenyl)-4-oxobutanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)CCC(=O)C1=CC=C(C#N)C=C1 AJXZALULDKOXKS-UHFFFAOYSA-N 0.000 description 1
- LZCFYQOFMOODBA-UHFFFAOYSA-N ethyl 2-[1-[4-[4-[[(2-methylpropan-2-yl)oxycarbonylhydrazinylidene]methyl]phenyl]-4-oxobutanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)CCC(=O)C1=CC=C(C=NNC(=O)OC(C)(C)C)C=C1 LZCFYQOFMOODBA-UHFFFAOYSA-N 0.000 description 1
- MWVFBPDNGZEBRN-UHFFFAOYSA-N ethyl 2-[4-(4-acetyloxy-2-bromobutanoyl)phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(C(=O)C(Br)CCOC(C)=O)C=C1 MWVFBPDNGZEBRN-UHFFFAOYSA-N 0.000 description 1
- ATMYHNVSKWTBSK-VWLOTQADSA-N ethyl 2-[4-[(2S)-2-[(4-methanehydrazonoylbenzoyl)amino]-3-(4-methoxyphenyl)propanoyl]phenoxy]acetate Chemical compound C(C)OC(COC1=CC=C(C=C1)C([C@H](CC1=CC=C(C=C1)OC)NC(C1=CC=C(C=C1)C=NN)=O)=O)=O ATMYHNVSKWTBSK-VWLOTQADSA-N 0.000 description 1
- ORBKHRLFKHIIRN-UQIIZPHYSA-N ethyl 2-[4-[(2S)-2-[(4-methanehydrazonoylbenzoyl)amino]-3-(4-methoxyphenyl)propanoyl]phenoxy]acetate hydrochloride Chemical compound CCOC(=O)COC1=CC=C(C=C1)C(=O)[C@H](CC2=CC=C(C=C2)OC)NC(=O)C3=CC=C(C=C3)C=NN.Cl ORBKHRLFKHIIRN-UQIIZPHYSA-N 0.000 description 1
- OFPILKNFTZWPJQ-AWEZNQCLSA-N ethyl 2-[4-[(2S)-2-[[4-(aminomethyl)benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(CN)C=C1 OFPILKNFTZWPJQ-AWEZNQCLSA-N 0.000 description 1
- YLNSULROYDCXEF-SFHVURJKSA-N ethyl 2-[4-[(2S)-2-[[4-[[(4-fluorophenoxy)carbonylhydrazinylidene]methyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C(C=C1)=CC=C1C=NNC(=O)OC1=CC=C(F)C=C1 YLNSULROYDCXEF-SFHVURJKSA-N 0.000 description 1
- HBROXBMZNIJXIT-ZDUSSCGKSA-N ethyl 2-[4-[(2S)-2-[[6-(aminomethyl)pyridine-3-carbonyl]amino]propanoyl]phenoxy]acetate Chemical compound NCC1=CC=C(C=N1)C(=O)N[C@H](C(=O)C1=CC=C(OCC(=O)OCC)C=C1)C HBROXBMZNIJXIT-ZDUSSCGKSA-N 0.000 description 1
- BAWFAUYGQJTKGI-QHCPKHFHSA-N ethyl 2-[4-[(2S)-3-[4-(2-methoxyethoxy)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@@H](NC(=O)OC(C)(C)C)CC1=CC=C(OCCOC)C=C1 BAWFAUYGQJTKGI-QHCPKHFHSA-N 0.000 description 1
- PFFSAWYGGBXSNA-FQEVSTJZSA-N ethyl 2-[4-[(2S)-3-acetyloxy-2-[(4-methanehydrazonoylbenzoyl)amino]propanoyl]phenoxy]acetate Chemical compound C(C)OC(COC1=CC=C(C=C1)C([C@H](COC(C)=O)NC(C1=CC=C(C=C1)C=NN)=O)=O)=O PFFSAWYGGBXSNA-FQEVSTJZSA-N 0.000 description 1
- OMOAGNGZRQYBFK-ZDUSSCGKSA-N ethyl 2-[4-[(2s)-2-[(4-carbamothioylbenzoyl)amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(C(N)=S)C=C1 OMOAGNGZRQYBFK-ZDUSSCGKSA-N 0.000 description 1
- RHLXSMYSGMDVAL-ZDUSSCGKSA-N ethyl 2-[4-[(2s)-2-[(4-cyano-2-hydroxybenzoyl)amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(C#N)C=C1O RHLXSMYSGMDVAL-ZDUSSCGKSA-N 0.000 description 1
- FIGATCCAIAEIPM-KRWDZBQOSA-N ethyl 2-[4-[(2s)-2-[[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C=C1 FIGATCCAIAEIPM-KRWDZBQOSA-N 0.000 description 1
- ZBUDTJOFOHJAEX-HNNXBMFYSA-N ethyl 2-[4-[(2s)-2-[[4-[n'-(2-hydroxyethoxycarbonyl)carbamimidoyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(C(N)=NC(=O)OCCO)C=C1 ZBUDTJOFOHJAEX-HNNXBMFYSA-N 0.000 description 1
- MSWSDUNXVHHCRZ-SFHVURJKSA-N ethyl 2-[4-[(2s)-2-[[4-[n'-(4-methoxyphenoxy)carbonylcarbamimidoyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](C)NC(=O)C1=CC=C(C(=N)NC(=O)OC=2C=CC(OC)=CC=2)C=C1 MSWSDUNXVHHCRZ-SFHVURJKSA-N 0.000 description 1
- LLNLNZXCWBVSNF-VIFPVBQESA-N ethyl 2-[4-[(2s)-2-aminopropanoyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(C(=O)[C@H](C)N)C=C1 LLNLNZXCWBVSNF-VIFPVBQESA-N 0.000 description 1
- DSYACSDGDUQYQZ-NDEPHWFRSA-N ethyl 2-[4-[(2s)-3-acetyloxy-2-[[4-[n,n,n'-tris[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](COC(C)=O)NC(=O)C1=CC=C(C(=NC(=O)OC(C)(C)C)N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C1 DSYACSDGDUQYQZ-NDEPHWFRSA-N 0.000 description 1
- ITULPNXLJAPNCC-KRWDZBQOSA-N ethyl 2-[4-[(2s)-3-hydroxy-2-[(2-piperidin-4-yloxyacetyl)amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](CO)NC(=O)COC1CCNCC1 ITULPNXLJAPNCC-KRWDZBQOSA-N 0.000 description 1
- GCZYKLCHYXFUMS-KRWDZBQOSA-N ethyl 2-[4-[(2s)-3-hydroxy-2-[[4-[(e)-n'-hydroxycarbamimidoyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](CO)NC(=O)C1=CC=C(C(\N)=N\O)C=C1 GCZYKLCHYXFUMS-KRWDZBQOSA-N 0.000 description 1
- HANMSYXJEOXNRG-FQEVSTJZSA-N ethyl 2-[4-[(2s)-3-hydroxy-2-[[4-[n'-(2-methoxyethoxycarbonyl)carbamimidoyl]benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)[C@H](CO)NC(=O)C1=CC=C(C(N)=NC(=O)OCCOC)C=C1 HANMSYXJEOXNRG-FQEVSTJZSA-N 0.000 description 1
- HSBFLWXXAUZCIF-HNNXBMFYSA-N ethyl 2-[4-[(2s)-3-methoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(C(=O)[C@H](COC)NC(=O)OC(C)(C)C)C=C1 HSBFLWXXAUZCIF-HNNXBMFYSA-N 0.000 description 1
- RPVOXJZKSVIVBF-BEFAXECRSA-N ethyl 2-[4-[(2s,3r)-3-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(C(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)OC(C)(C)C)C=C1 RPVOXJZKSVIVBF-BEFAXECRSA-N 0.000 description 1
- ZPHBHSWREPRVMM-UHFFFAOYSA-N ethyl 2-[4-[2-[[4-(n'-hydroxycarbamimidoyl)benzoyl]amino]propanoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C(=O)C(C)NC(=O)C1=CC=C(C(\N)=N\O)C=C1 ZPHBHSWREPRVMM-UHFFFAOYSA-N 0.000 description 1
- VBVPKRATPWYWKH-FPCQFERPSA-N ethyl 2-[[(2S)-2-acetyl-1-[2-[(4-cyanobenzoyl)amino]propanoyl]piperidin-4-yl]amino]acetate Chemical compound C(C)OC(CNC1C[C@H](N(CC1)C(C(C)NC(C1=CC=C(C=C1)C#N)=O)=O)C(C)=O)=O VBVPKRATPWYWKH-FPCQFERPSA-N 0.000 description 1
- ILPZTFJWLWKIJV-HNNXBMFYSA-N ethyl 2-[[2-[1-[(2S)-2-[(4-cyanobenzoyl)amino]propanoyl]piperidin-4-yl]oxyacetyl]amino]acetate Chemical compound C1CC(OCC(=O)NCC(=O)OCC)CCN1C(=O)[C@H](C)NC(=O)C1=CC=C(C#N)C=C1 ILPZTFJWLWKIJV-HNNXBMFYSA-N 0.000 description 1
- DCKQRELZKLFNSH-UHFFFAOYSA-N ethyl 2-phenoxyacetate hydrochloride Chemical compound Cl.C(C)OC(COC1=CC=CC=C1)=O DCKQRELZKLFNSH-UHFFFAOYSA-N 0.000 description 1
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- IVHHZZKGSYGTKZ-UHFFFAOYSA-N tert-butyl 6-hydroxy-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound OC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 IVHHZZKGSYGTKZ-UHFFFAOYSA-N 0.000 description 1
- VRSAJWHIFNYJSE-JTQLQIEISA-N tert-butyl N-[(2S)-1-(4-cyanophenyl)-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)C1=CC=C(C#N)C=C1 VRSAJWHIFNYJSE-JTQLQIEISA-N 0.000 description 1
- MPUFHSSFGVOHRK-KRWDZBQOSA-N tert-butyl N-[(2S)-1-(4-hydroxyphenyl)-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)c1ccc(O)cc1 MPUFHSSFGVOHRK-KRWDZBQOSA-N 0.000 description 1
- FIFDUIOLJBHMMD-ZDUSSCGKSA-N tert-butyl N-[(2S)-1-(4-hydroxyphenyl)-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(C)C)C(=O)C1=CC=C(O)C=C1 FIFDUIOLJBHMMD-ZDUSSCGKSA-N 0.000 description 1
- CZDZABWVQDMZBP-QMMMGPOBSA-N tert-butyl N-[(2S)-1-(methoxymethylamino)-1-oxopropan-2-yl]-N-methylcarbamate Chemical compound C(C)(C)(C)OC(N(C)[C@@H](C)C(NCOC)=O)=O CZDZABWVQDMZBP-QMMMGPOBSA-N 0.000 description 1
- NYSHCLRQKMQBPJ-QFIPXVFZSA-N tert-butyl N-[(2S)-1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@H](C(=O)C1=CC=C(C=C1)O[Si](C)(C)C(C)(C)C)CC1=CC=CC=C1)=O NYSHCLRQKMQBPJ-QFIPXVFZSA-N 0.000 description 1
- BFDQQUPFBKCAOW-AWEZNQCLSA-N tert-butyl N-[(2S)-1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 BFDQQUPFBKCAOW-AWEZNQCLSA-N 0.000 description 1
- ZYWDFBVWTTYBQQ-QHCPKHFHSA-N tert-butyl N-[(2S)-1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H](CC1=CC=C(C=C1)OC)C(C1=CC=C(C=C1)O[Si](C)(C)C(C)(C)C)=O)=O ZYWDFBVWTTYBQQ-QHCPKHFHSA-N 0.000 description 1
- QOEKDQWXMQAYHG-SFHVURJKSA-N tert-butyl N-[(2S)-1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)c1ccc(O[Si](C)(C)C(C)(C)C)cc1 QOEKDQWXMQAYHG-SFHVURJKSA-N 0.000 description 1
- LLTDPKFTQBAPMZ-ZDUSSCGKSA-N tert-butyl N-[(2S)-3-(4-hydroxyphenyl)-1-(methoxymethylamino)-1-oxopropan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H](CC1=CC=C(C=C1)O)C(NCOC)=O)=O LLTDPKFTQBAPMZ-ZDUSSCGKSA-N 0.000 description 1
- QIMQIQQSRMQZGF-MNOVXSKESA-N tert-butyl N-[(2S,3R)-1-(methoxymethylamino)-3-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H]([C@@H](C)OC(C)(C)C)C(NCOC)=O)=O QIMQIQQSRMQZGF-MNOVXSKESA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- RDWYGPKWBDBNJZ-SFHVURJKSA-N tert-butyl n-[(2s)-1-(4-hydroxyphenyl)-3-(4-methoxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1C[C@H](NC(=O)OC(C)(C)C)C(=O)C1=CC=C(O)C=C1 RDWYGPKWBDBNJZ-SFHVURJKSA-N 0.000 description 1
- HKARGKNKCBDOLJ-VWLOTQADSA-N tert-butyl n-[(2s)-1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3-[4-(2-methoxyethoxy)phenyl]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OCCOC)=CC=C1C[C@H](NC(=O)OC(C)(C)C)C(=O)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 HKARGKNKCBDOLJ-VWLOTQADSA-N 0.000 description 1
- ZAHRDPIWMGLOQJ-ZDUSSCGKSA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)N(C)OC)CC1=CC=CC=C1 ZAHRDPIWMGLOQJ-ZDUSSCGKSA-N 0.000 description 1
- AAHUYCZMASAMHX-AWEZNQCLSA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)N(C)OC)CC1=CC=C(OC)C=C1 AAHUYCZMASAMHX-AWEZNQCLSA-N 0.000 description 1
- FNPDHWLASAZEEI-JTQLQIEISA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@H](COC(C)(C)C)NC(=O)OC(C)(C)C FNPDHWLASAZEEI-JTQLQIEISA-N 0.000 description 1
- RRBFCGUIFHFYQK-VIFPVBQESA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@H](C(C)C)NC(=O)OC(C)(C)C RRBFCGUIFHFYQK-VIFPVBQESA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
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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
- C07D213/60—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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/10—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C251/16—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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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
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/62—Compounds containing any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylcarbamates
- C07C271/64—Y being a hydrogen or a carbon atom, e.g. benzoylcarbamates
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/40—Y being a hydrogen or a carbon atom
- C07C323/42—Y being a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D207/10—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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- 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
- C07D211/36—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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
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- C—CHEMISTRY; METALLURGY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
- C07F9/2454—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
- C07F9/2479—Compounds containing the structure P(=X)n-N-acyl, P(=X)n-N-heteroatom, P(=X)n-N-CN (X = O, S, Se; n = 0, 1)
- C07F9/2491—Compounds containing the structure P(=X)n-N-acyl, P(=X)n-N-heteroatom, P(=X)n-N-CN (X = O, S, Se; n = 0, 1) containing the structure P(=X)n-N-N (X = O, S, Se; n = 0, 1)
-
- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- General Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Molecular Biology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH360993 | 1993-12-03 | ||
CH319894 | 1994-10-25 |
Publications (2)
Publication Number | Publication Date |
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SK145894A3 SK145894A3 (en) | 1995-09-13 |
SK282058B6 true SK282058B6 (sk) | 2001-10-08 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1458-94A SK282058B6 (sk) | 1993-12-03 | 1994-11-30 | Deriváty kyseliny octovej, spôsob ich výroby, farmaceutické prostriedky na ich báze a ich použitie na výrobu liečiv |
Country Status (29)
Country | Link |
---|---|
US (2) | US5726185A (xx) |
EP (1) | EP0656348B1 (xx) |
JP (1) | JP2901509B2 (xx) |
KR (1) | KR100335541B1 (xx) |
CN (1) | CN1075062C (xx) |
AT (1) | ATE192430T1 (xx) |
AU (1) | AU687905B2 (xx) |
BG (1) | BG62399B1 (xx) |
CA (1) | CA2136903C (xx) |
CZ (1) | CZ290024B6 (xx) |
DE (1) | DE59409322D1 (xx) |
DK (1) | DK0656348T3 (xx) |
ES (1) | ES2147210T3 (xx) |
FI (2) | FI945688A (xx) |
GR (1) | GR3034111T3 (xx) |
HU (1) | HUT71332A (xx) |
IL (1) | IL111784A0 (xx) |
IS (1) | IS4237A (xx) |
LV (1) | LV11318B (xx) |
MY (1) | MY112417A (xx) |
NO (1) | NO302169B1 (xx) |
NZ (1) | NZ270020A (xx) |
PT (1) | PT656348E (xx) |
RO (1) | RO117846B1 (xx) |
RU (1) | RU2151768C1 (xx) |
SI (1) | SI0656348T1 (xx) |
SK (1) | SK282058B6 (xx) |
TW (1) | TW472042B (xx) |
UA (1) | UA35592C2 (xx) |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996011180A1 (fr) * | 1994-10-07 | 1996-04-18 | Meiji Seika Kabushiki Kaisha | COMPOSE η-DICETONE POSSEDANT UN EFFET INHIBITEUR DE L'AGREGATION PLAQUETTAIRE |
JPH08325263A (ja) * | 1995-05-31 | 1996-12-10 | Sumitomo Metal Ind Ltd | 新規2−アミノ−3−フェニルプロピオン酸誘導体 |
US6100423A (en) * | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
US6013651A (en) * | 1995-08-30 | 2000-01-11 | G. D. Searle & Co. | Meta-azacyclic amino benzoic acid compounds and derivatives thereof |
DE69613985T2 (de) * | 1995-08-30 | 2002-06-13 | G.D. Searle & Co., Chicago | Meta-guanidine, harnstoff, thioharnstoff oder azacyklische aminobenzoesäure-derivate als integrin antagonisten |
DE69706407T2 (de) * | 1996-03-29 | 2002-05-29 | G.D. Searle & Co., Chicago | META-SUBSTITUIERTE PHENYLENDERIVATE UND IHRE VERWENDUNG ALS ALPHAvBETA3 INTERGRIN-ANTAGONISTEN ODER INHIBITOREN |
DE19622189A1 (de) * | 1996-06-03 | 1997-12-04 | Bayer Ag | 3-Cyanaryl-pyrazole |
AU747293B2 (en) * | 1997-02-06 | 2002-05-16 | Merck & Co., Inc. | Fibrinogen receptor antagonist prodrugs |
US6025358A (en) * | 1998-06-11 | 2000-02-15 | G. D. Searle & Co. | Double prodrugs of potent GP IIb/IIIa antagonists |
CN1346282A (zh) | 1998-12-23 | 2002-04-24 | G.D.西尔公司 | 在肿瘤的治疗中使用环加氧酶-2-抑制剂与一种或多种抗肿瘤剂作为联合治疗的方法 |
HU226998B1 (en) * | 2000-11-23 | 2010-04-28 | Richter Gedeon Nyrt | Desloratadine hemisulphate, process for the preparation thereof and pharmaceutical compositions containing the same |
US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
US7232924B2 (en) | 2001-06-11 | 2007-06-19 | Xenoport, Inc. | Methods for synthesis of acyloxyalkyl derivatives of GABA analogs |
US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
EP1677783A2 (en) | 2003-10-08 | 2006-07-12 | Nicholas Piramal India Limited | Fibrinogen receptor antagonists and their use |
PL1682537T3 (pl) * | 2003-11-05 | 2012-09-28 | Sarcode Bioscience Inc | Modulatory adhezji komórkowej |
JP5794721B2 (ja) | 2005-05-17 | 2015-10-14 | サーコード バイオサイエンス インコーポレイテッド | 眼障害の治療のための組成物および方法 |
WO2008035359A2 (en) * | 2006-06-12 | 2008-03-27 | Cadila Healthcare Limited | Oximinophenoxyalkanoic acid and phenylalkanoic acid derivatives |
AU2008317473B2 (en) | 2007-10-19 | 2014-07-17 | Bausch + Lomb Ireland Limited | Compositions and methods for treatment of diabetic retinopathy |
WO2009128933A1 (en) * | 2008-04-15 | 2009-10-22 | Sarcode Corporation | Aerosolized lfa-1 antagonists for use in localized treatment of immune related disorders |
EP2276508A4 (en) * | 2008-04-15 | 2011-12-28 | Sarcode Bioscience Inc | RELEASE OF LFA-1 ANTAGONISTS AGAINST THE GAS-DARM SYSTEM |
WO2009139817A2 (en) | 2008-04-15 | 2009-11-19 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
CN102056485A (zh) * | 2008-04-15 | 2011-05-11 | 萨可德公司 | 用于局部治疗免疫相关疾病的局部lfa-1拮抗剂 |
US20110230428A1 (en) * | 2008-07-22 | 2011-09-22 | John Wityak | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
WO2011050175A1 (en) | 2009-10-21 | 2011-04-28 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
BR112014004845A2 (pt) | 2011-08-30 | 2017-04-04 | Chdi Foundation Inc | pelo menos uma entidade química; pelo menos um composto; composição farmacêutica; uso de uma quantidade terapeuticamente eficaz de pelo menos uma entidade química; composição farmacêutica embalada |
PL2750677T3 (pl) | 2011-08-30 | 2017-12-29 | Chdi Foundation, Inc. | Inhibitory 3-monooksygenazy kinureninowej, kompozycje farmaceutyczne i sposoby ich stosowania |
AU2013295706A1 (en) | 2012-07-25 | 2015-02-19 | Sarcode Bioscience Inc. | LFA-1 inhibitor and polymorph thereof |
DE102014108210A1 (de) | 2014-06-11 | 2015-12-17 | Dietrich Gulba | Rodentizid |
BR112017000922A2 (pt) | 2014-07-17 | 2018-01-16 | Chdi Foundation, Inc. | métodos e composições para tratar distúrbios relacionados ao hiv |
US20210371379A1 (en) | 2018-09-20 | 2021-12-02 | Ono Pharmaceutical Co., Ltd. | Novel salt of 4-({(4s)-1-(4-carbamimidoylbenzoyl)-4-[4(methylsulfonyl)piperazin-1-yl]-l-prolyl}amino) benzoic acid and novel crystal form thereof |
CN113075343B (zh) * | 2020-01-04 | 2024-02-23 | 东莞市东阳光仿制药研发有限公司 | 一种羟胺及其盐的检测方法 |
EP4070658A1 (de) | 2021-04-06 | 2022-10-12 | BIORoxx GmbH | Verwendung von blutgerinnungshemmenden verbindungen als rodentizide |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5039805A (en) * | 1988-12-08 | 1991-08-13 | Hoffmann-La Roche Inc. | Novel benzoic and phenylacetic acid derivatives |
US5256812A (en) * | 1989-01-31 | 1993-10-26 | Hoffmann-La Roche Inc. | Carboxamides and sulfonamides |
US5084466A (en) * | 1989-01-31 | 1992-01-28 | Hoffmann-La Roche Inc. | Novel carboxamide pyridine compounds which have useful pharmaceutical utility |
US5273982A (en) * | 1990-03-09 | 1993-12-28 | Hoffmann-La Roche Inc. | Acetic acid derivatives |
RU2097378C1 (ru) * | 1991-03-26 | 1997-11-27 | Ф.Хоффманн-Ля Рош Аг | ПРОИЗВОДНЫЕ N-АЦИЛ- α -АМИНОКИСЛОТЫ ИЛИ ИХ ФИЗИОЛОГИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, ПРОСТЫЕ ИЛИ СЛОЖНЫЕ ЭФИРЫ, АМИДЫ ИЛИ ГИДРАТЫ И КОМПОЗИЦИЯ ИНГИБИРУЮЩАЯ СВЯЗЫВАНИЕ АДГЕЗИВНЫХ ПРОТЕИНОВ С ТРОМБОЦИТАМИ И АГРЕГАЦИЮ ТРОМБОЦИТОВ |
DE4213919A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
JPH08505391A (ja) * | 1992-12-30 | 1996-06-11 | スミスクライン・ビーチャム・コーポレイション | 化合物 |
DE69410193T2 (de) * | 1993-03-17 | 1998-09-03 | Meiji Seika K.K., Tokio/Tokyo | Neue verbindungen mit blutplättchenaggregationshemmender aktivität |
GB9313269D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Allophanic acid derivatives |
EP0706999A1 (en) * | 1993-06-30 | 1996-04-17 | Sumitomo Pharmaceuticals Company, Limited | Novel dipiperidine derivative |
-
1994
- 1994-11-26 EP EP94118645A patent/EP0656348B1/de not_active Expired - Lifetime
- 1994-11-26 PT PT94118645T patent/PT656348E/pt unknown
- 1994-11-26 DE DE59409322T patent/DE59409322D1/de not_active Expired - Lifetime
- 1994-11-26 ES ES94118645T patent/ES2147210T3/es not_active Expired - Lifetime
- 1994-11-26 SI SI9430326T patent/SI0656348T1/xx unknown
- 1994-11-26 DK DK94118645T patent/DK0656348T3/da active
- 1994-11-26 AT AT94118645T patent/ATE192430T1/de not_active IP Right Cessation
- 1994-11-28 IL IL11178494A patent/IL111784A0/xx unknown
- 1994-11-29 CA CA002136903A patent/CA2136903C/en not_active Expired - Fee Related
- 1994-11-29 NZ NZ270020A patent/NZ270020A/en unknown
- 1994-11-29 AU AU79090/94A patent/AU687905B2/en not_active Ceased
- 1994-11-30 HU HU9403441A patent/HUT71332A/hu unknown
- 1994-11-30 SK SK1458-94A patent/SK282058B6/sk unknown
- 1994-12-01 US US08/347,736 patent/US5726185A/en not_active Expired - Lifetime
- 1994-12-01 MY MYPI94003206A patent/MY112417A/en unknown
- 1994-12-02 RO RO94-01923A patent/RO117846B1/ro unknown
- 1994-12-02 NO NO944650A patent/NO302169B1/no unknown
- 1994-12-02 LV LVP-94-234A patent/LV11318B/lv unknown
- 1994-12-02 TW TW083111231A patent/TW472042B/zh not_active IP Right Cessation
- 1994-12-02 CZ CZ19943011A patent/CZ290024B6/cs not_active IP Right Cessation
- 1994-12-02 CN CN94112842A patent/CN1075062C/zh not_active Expired - Fee Related
- 1994-12-02 RU RU94042929/04A patent/RU2151768C1/ru not_active IP Right Cessation
- 1994-12-02 IS IS4237A patent/IS4237A/is unknown
- 1994-12-02 UA UA94129119A patent/UA35592C2/uk unknown
- 1994-12-02 FI FI945688A patent/FI945688A/fi not_active IP Right Cessation
- 1994-12-02 KR KR1019940032546A patent/KR100335541B1/ko not_active IP Right Cessation
- 1994-12-02 BG BG99233A patent/BG62399B1/bg unknown
- 1994-12-05 JP JP6300553A patent/JP2901509B2/ja not_active Expired - Fee Related
-
1997
- 1997-11-03 US US08/963,413 patent/US5973188A/en not_active Expired - Fee Related
-
2000
- 2000-08-02 GR GR20000401808T patent/GR3034111T3/el not_active IP Right Cessation
-
2001
- 2001-10-11 FI FI20011980A patent/FI20011980A/fi not_active IP Right Cessation
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