CA2160459A1 - Serine derivative - Google Patents
Serine derivativeInfo
- Publication number
- CA2160459A1 CA2160459A1 CA002160459A CA2160459A CA2160459A1 CA 2160459 A1 CA2160459 A1 CA 2160459A1 CA 002160459 A CA002160459 A CA 002160459A CA 2160459 A CA2160459 A CA 2160459A CA 2160459 A1 CA2160459 A1 CA 2160459A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- thienyl
- lower alkyl
- hydrogen atom
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000003354 serine derivatives Chemical class 0.000 title claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 25
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
- 125000006239 protecting group Chemical group 0.000 claims abstract description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 238000009833 condensation Methods 0.000 claims abstract description 7
- 230000005494 condensation Effects 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
- 229940001470 psychoactive drug Drugs 0.000 claims abstract description 4
- 239000004089 psychotropic agent Substances 0.000 claims abstract description 4
- 229940079593 drug Drugs 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 23
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 7
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 3
- LZMUCXPFAYDNAP-UHFFFAOYSA-N 2-amino-3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-3-hydroxypropanoic acid Chemical compound S1C(C(O)C(N)C(O)=O)=CC=C1CN1CCCCCC1 LZMUCXPFAYDNAP-UHFFFAOYSA-N 0.000 claims description 2
- 206010003805 Autism Diseases 0.000 claims description 2
- 208000020706 Autistic disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000036626 Mental retardation Diseases 0.000 claims description 2
- 230000002205 anti-dementic effect Effects 0.000 claims description 2
- 230000002932 anti-schizophrenic effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- MRNMDQLQWDFOHM-UHFFFAOYSA-N ethyl 3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=C(CN2CCCCCC2)SC=1C(O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 MRNMDQLQWDFOHM-UHFFFAOYSA-N 0.000 claims description 2
- YUNOJFKSJMWANV-UHFFFAOYSA-N ethyl 3-[5-[3-(azepan-1-yl)propyl]thiophen-2-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=C(CCCN2CCCCCC2)SC=1C(O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 YUNOJFKSJMWANV-UHFFFAOYSA-N 0.000 claims description 2
- 230000000366 juvenile effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 abstract description 9
- 229950010883 phencyclidine Drugs 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- -1 thiazolyl serine derivative Chemical class 0.000 description 115
- 150000001875 compounds Chemical class 0.000 description 84
- 238000005481 NMR spectroscopy Methods 0.000 description 75
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 58
- 239000007858 starting material Substances 0.000 description 47
- 239000002585 base Substances 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 101150041968 CDC13 gene Proteins 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 238000004519 manufacturing process Methods 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- DCERDOKWNNXNOV-UHFFFAOYSA-N ethyl 3-[5-(azepan-2-ylmethyl)thiophen-2-yl]-2-piperidin-1-ylpropanoate Chemical compound C1CCCCN1C(C(=O)OCC)CC(S1)=CC=C1CC1CCCCCN1 DCERDOKWNNXNOV-UHFFFAOYSA-N 0.000 description 16
- 239000011259 mixed solution Substances 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000010828 elution Methods 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- GIVLTHTZQWITLV-UHFFFAOYSA-N tert-butyl 3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=C(CN2CCCCCC2)SC=1C(O)C(C(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 GIVLTHTZQWITLV-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 238000007598 dipping method Methods 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- SLLZQDLIAPDHFC-UHFFFAOYSA-N 1-(thiophen-2-ylmethyl)azepane Chemical compound C=1C=CSC=1CN1CCCCCC1 SLLZQDLIAPDHFC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WTYCQNUNUTYUOQ-UHFFFAOYSA-N C=1C=C(CN2CCCC2)SC=1C(O)C(NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 Chemical compound C=1C=C(CN2CCCC2)SC=1C(O)C(NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WTYCQNUNUTYUOQ-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- NCKDZTAODISTPK-UHFFFAOYSA-N trimethylsilyl cyanate Chemical compound C[Si](C)(C)OC#N NCKDZTAODISTPK-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VUUSTLFFRIFAIC-YFKPBYRVSA-N (2s)-3-hydroxy-2-(thiophen-2-ylamino)propanoic acid Chemical class OC[C@@H](C(O)=O)NC1=CC=CS1 VUUSTLFFRIFAIC-YFKPBYRVSA-N 0.000 description 2
- YROBBMZHLTZBGZ-UHFFFAOYSA-N 1-[[5-(2-nitroprop-1-enyl)thiophen-2-yl]methyl]pyrrolidine Chemical compound S1C(C=C(C)[N+]([O-])=O)=CC=C1CN1CCCC1 YROBBMZHLTZBGZ-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KSEIVDDEKPZVAR-UHFFFAOYSA-N 2-amino-1-[5-(azepan-2-ylmethyl)thiophen-2-yl]butan-1-ol Chemical compound S1C(C(O)C(N)CC)=CC=C1CC1NCCCCC1 KSEIVDDEKPZVAR-UHFFFAOYSA-N 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- WOLYHJPQTHFZEP-UHFFFAOYSA-N C=1C=C(CC2NCCCCC2)SC=1C(O)C(C(O)=O)N1CCCCC1 Chemical compound C=1C=C(CC2NCCCCC2)SC=1C(O)C(C(O)=O)N1CCCCC1 WOLYHJPQTHFZEP-UHFFFAOYSA-N 0.000 description 2
- XWCAZNAXHCNYNN-UHFFFAOYSA-N C=1C=C(CN2CCCC2)SC=1C(O)C(C)NC(=O)OCC1=CC=CC=C1 Chemical compound C=1C=C(CN2CCCC2)SC=1C(O)C(C)NC(=O)OCC1=CC=CC=C1 XWCAZNAXHCNYNN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- MPPHIXMLBUROHJ-UHFFFAOYSA-N S1C(C(O)C(NC(=O)OC(C)(C)C)C(O)=O)=CC=C1CC1NCCCCC1 Chemical compound S1C(C(O)C(NC(=O)OC(C)(C)C)C(O)=O)=CC=C1CC1NCCCCC1 MPPHIXMLBUROHJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- KVVAHTZOTLRBII-UHFFFAOYSA-N benzyl n-[1-[5-(azepan-2-ylmethyl)thiophen-2-yl]-1-hydroxybutan-2-yl]carbamate Chemical compound C=1C=C(CC2NCCCCC2)SC=1C(O)C(CC)NC(=O)OCC1=CC=CC=C1 KVVAHTZOTLRBII-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical group OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- YCQDBJLOBIFQGK-UHFFFAOYSA-N benzyl n-(1-oxobut-3-yn-2-yl)carbamate Chemical compound O=CC(C#C)NC(=O)OCC1=CC=CC=C1 YCQDBJLOBIFQGK-UHFFFAOYSA-N 0.000 description 1
- RBUMMIPBGUTLAB-UHFFFAOYSA-N benzyl n-[1-[5-(azepan-1-ylmethyl)thiophen-2-yl]-1-hydroxypropan-2-yl]carbamate Chemical compound C=1C=C(CN2CCCCCC2)SC=1C(O)C(C)NC(=O)OCC1=CC=CC=C1 RBUMMIPBGUTLAB-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229910021419 crystalline silicon Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- FZQGLIFOFGFRCX-UHFFFAOYSA-N ethyl 2-(3-phenylpropylamino)acetate Chemical compound CCOC(=O)CNCCCC1=CC=CC=C1 FZQGLIFOFGFRCX-UHFFFAOYSA-N 0.000 description 1
- HAIHOTOFCDNWDA-UHFFFAOYSA-N ethyl 2-(phenylmethoxycarbonylamino)acetate Chemical compound CCOC(=O)CNC(=O)OCC1=CC=CC=C1 HAIHOTOFCDNWDA-UHFFFAOYSA-N 0.000 description 1
- CNIBHMMDDXGDNR-UHFFFAOYSA-N ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound CCOC(=O)CNC(=O)OC(C)(C)C CNIBHMMDDXGDNR-UHFFFAOYSA-N 0.000 description 1
- MHEYZMSFNOJFGL-UHFFFAOYSA-N ethyl 2-acetamido-3-hydroxy-3-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propanoate Chemical compound S1C(C(O)C(NC(C)=O)C(=O)OCC)=CC=C1CN1CCCC1 MHEYZMSFNOJFGL-UHFFFAOYSA-N 0.000 description 1
- AMBDTBHJFINMSE-UHFFFAOYSA-N ethyl 2-acetamidoacetate Chemical compound CCOC(=O)CNC(C)=O AMBDTBHJFINMSE-UHFFFAOYSA-N 0.000 description 1
- FXTODILPGYUYDD-UHFFFAOYSA-N ethyl 2-amino-3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-3-hydroxypropanoate Chemical compound S1C(C(O)C(N)C(=O)OCC)=CC=C1CN1CCCCCC1 FXTODILPGYUYDD-UHFFFAOYSA-N 0.000 description 1
- KOIPSAUAINEMMO-UHFFFAOYSA-N ethyl 3-[2-(azepan-1-ylmethyl)-1,3-thiazol-5-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1N=C(CN2CCCCCC2)SC=1C(O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 KOIPSAUAINEMMO-UHFFFAOYSA-N 0.000 description 1
- HADBXYRKDNOBBO-UHFFFAOYSA-N ethyl 3-[5-(3,4-dihydro-1h-isoquinolin-2-ylmethyl)thiophen-2-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=C(CN2CC3=CC=CC=C3CC2)SC=1C(O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 HADBXYRKDNOBBO-UHFFFAOYSA-N 0.000 description 1
- LOUGZHHFOLEUIK-UHFFFAOYSA-N ethyl 3-[5-(3,6-dihydro-2h-pyridin-1-ylmethyl)thiophen-2-yl]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=C(CN2CC=CCC2)SC=1C(O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 LOUGZHHFOLEUIK-UHFFFAOYSA-N 0.000 description 1
- DIXATKAPYAMEPH-UHFFFAOYSA-N ethyl 3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-2-(benzylcarbamoylamino)-3-hydroxypropanoate Chemical compound C=1C=C(CN2CCCCCC2)SC=1C(O)C(C(=O)OCC)NC(=O)NCC1=CC=CC=C1 DIXATKAPYAMEPH-UHFFFAOYSA-N 0.000 description 1
- JBKHUTCRFWODIE-UHFFFAOYSA-N ethyl 3-[5-(azepan-2-ylmethyl)thiophen-2-yl]-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound S1C(C(O)C(NC(=O)OC(C)(C)C)C(=O)OCC)=CC=C1CC1NCCCCC1 JBKHUTCRFWODIE-UHFFFAOYSA-N 0.000 description 1
- ISDOKOWRJLJQAQ-UHFFFAOYSA-N ethyl 3-[5-(azepan-2-ylmethyl)thiophen-2-yl]-3-hydroxy-2-piperidin-1-ylpropanoate Chemical compound C1CCCCN1C(C(=O)OCC)C(O)C(S1)=CC=C1CC1CCCCCN1 ISDOKOWRJLJQAQ-UHFFFAOYSA-N 0.000 description 1
- ZMKFTRAPVZXFJY-UHFFFAOYSA-N ethyl 3-[5-(azepan-2-ylmethyl)thiophen-2-yl]-3-hydroxypropanoate Chemical compound S1C(C(O)CC(=O)OCC)=CC=C1CC1NCCCCC1 ZMKFTRAPVZXFJY-UHFFFAOYSA-N 0.000 description 1
- OEOHKSHAIRMSOO-UHFFFAOYSA-N ethyl 3-hydroxy-2-piperidin-1-yl-3-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propanoate Chemical compound C1CCCCN1C(C(=O)OCC)C(O)C(S1)=CC=C1CN1CCCC1 OEOHKSHAIRMSOO-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical class 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
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- XCOSEWGIPBFSOS-UHFFFAOYSA-N methyl 3-[5-(azepan-2-ylmethyl)thiophen-2-yl]-2-(phenylmethoxycarbonylamino)prop-2-enoate Chemical compound C=1C=C(CC2NCCCCC2)SC=1C=C(C(=O)OC)NC(=O)OCC1=CC=CC=C1 XCOSEWGIPBFSOS-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- LNEVAODRSKJUCH-UHFFFAOYSA-N n,n-dimethyl-1-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propan-2-amine Chemical compound S1C(CC(C)N(C)C)=CC=C1CN1CCCC1 LNEVAODRSKJUCH-UHFFFAOYSA-N 0.000 description 1
- SJNSAPDNKFMHCT-UHFFFAOYSA-N n-[1-[5-(2,3-dihydroindol-1-ylmethyl)thiophen-2-yl]propan-2-yl]acetamide Chemical compound S1C(CC(C)NC(C)=O)=CC=C1CN1C2=CC=CC=C2CC1 SJNSAPDNKFMHCT-UHFFFAOYSA-N 0.000 description 1
- NPFJHTMAEQYUQV-UHFFFAOYSA-N n-[1-[5-(3,6-dihydro-2h-pyridin-1-ylmethyl)thiophen-2-yl]propan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)CC(S1)=CC=C1CN1CCC=CC1 NPFJHTMAEQYUQV-UHFFFAOYSA-N 0.000 description 1
- MXGCOOYMYJUEGC-UHFFFAOYSA-N n-[1-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)CC(S1)=CC=C1CN1CCCC1 MXGCOOYMYJUEGC-UHFFFAOYSA-N 0.000 description 1
- HPOBJYUBYRRELF-UHFFFAOYSA-N n-[1-[5-[(4-benzylpiperidin-1-yl)methyl]thiophen-2-yl]propan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)CC(S1)=CC=C1CN(CC1)CCC1CC1=CC=CC=C1 HPOBJYUBYRRELF-UHFFFAOYSA-N 0.000 description 1
- ZMGKCLUOSSFVGG-UHFFFAOYSA-N n-[1-[5-[[4-(3-phenylpropyl)piperidin-1-yl]methyl]thiophen-2-yl]propan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)CC(S1)=CC=C1CN(CC1)CCC1CCCC1=CC=CC=C1 ZMGKCLUOSSFVGG-UHFFFAOYSA-N 0.000 description 1
- GBZUBOPDSUSVGL-UHFFFAOYSA-N n-[1-hydroxy-1-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propan-2-yl]acetamide Chemical compound S1C(C(O)C(NC(C)=O)C)=CC=C1CN1CCCC1 GBZUBOPDSUSVGL-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229940083045 riax Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KMDZNXNSKRENFT-UHFFFAOYSA-N tert-butyl 2-amino-3-hydroxy-3-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]propanoate Chemical compound S1C(C(O)C(N)C(=O)OC(C)(C)C)=CC=C1CN1CCCC1 KMDZNXNSKRENFT-UHFFFAOYSA-N 0.000 description 1
- SYCFTTNWNMNUSV-UHFFFAOYSA-N tert-butyl 3-[5-(azepan-1-ylmethyl)thiophen-2-yl]-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)OC(C)(C)C)CC(S1)=CC=C1CN1CCCCCC1 SYCFTTNWNMNUSV-UHFFFAOYSA-N 0.000 description 1
- DEWDOZOOIRGMFQ-UHFFFAOYSA-N tert-butyl 3-hydroxy-3-[3-methyl-5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]-2-(phenylmethoxycarbonylamino)propanoate Chemical compound S1C(C(O)C(NC(=O)OCC=2C=CC=CC=2)C(=O)OC(C)(C)C)=C(C)C=C1CN1CCCC1 DEWDOZOOIRGMFQ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001544 thienyl group Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
- MCULRUJILOGHCJ-UHFFFAOYSA-N triisobutylaluminium Chemical compound CC(C)C[Al](CC(C)C)CC(C)C MCULRUJILOGHCJ-UHFFFAOYSA-N 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
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JPHEI-5-123454 | 1993-04-27 | ||
| JP12345493 | 1993-04-27 | ||
| JP23642893 | 1993-09-22 | ||
| JPHEI-5-236428 | 1993-09-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2160459A1 true CA2160459A1 (en) | 1994-11-10 |
Family
ID=26460383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002160459A Abandoned CA2160459A1 (en) | 1993-04-27 | 1994-04-26 | Serine derivative |
Country Status (7)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW414795B (en) * | 1996-07-01 | 2000-12-11 | Yamanouchi Pharma Co Ltd | A thiophene derivative and the pharmaceutical composition |
| DK1073432T3 (da) * | 1998-04-14 | 2007-12-17 | Gen Hospital Corp | Anvendelse af D serin eller D alanin til behandling af skizofreni |
| DE60045821D1 (de) * | 1999-09-02 | 2011-05-19 | Shionogi & Co | Derivate von aromatische heterocyclen enthaltende integraseinhibitoren |
| EP1957476A1 (en) * | 2005-11-23 | 2008-08-20 | AstraZeneca AB | L-alanine derivatives |
| EP2049490A1 (en) * | 2006-06-09 | 2009-04-22 | Astra Zeneca AB | N-(benzoyl)-o- [2- (pyridin- 2 -ylamino) ethyl]-l-tyrosine derivatives and related compounds as a5b1 antagonists for the treatment of solid tumors |
| US20090062267A1 (en) * | 2007-01-29 | 2009-03-05 | Astrazeneca Ab | L-ALANINE DERIVATIVES AS a5beta1 ANTAGONISTS |
| WO2008125811A1 (en) * | 2007-04-11 | 2008-10-23 | Astrazeneca Ab | N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4382929A (en) * | 1979-10-23 | 1983-05-10 | Glaxo Group Limited | Thiophene derivatives and their pharmaceutical compositions and method of use |
| US4598153A (en) * | 1984-12-19 | 1986-07-01 | The United States Of America As Represented By The Department Of Health And Human Services | Metaphit, a specific acylating agent for the [3 H] phencyclidine |
| ATE114305T1 (de) * | 1990-03-13 | 1994-12-15 | Hoechst Roussel Pharma | 1-alkyl-, 1-alkenyl- und 1-alkynylaryl-2-amino- 1,3-propandiole und verwandte verbindungen, verfahren und zwischenverbindungen zu ihrer herstellung und ihre verwendung als medikamente. |
| JP3176063B2 (ja) * | 1991-04-17 | 2001-06-11 | ファルマシア・アンド・アップジョン・カンパニー | 新規中枢神経作用性置換フェニルアザシクロアルカン類 |
| EP0596120A4 (en) * | 1991-08-09 | 1994-07-06 | Yoshitomi Pharmaceutical | Thiophene compound. |
| JPH05262759A (ja) * | 1992-01-23 | 1993-10-12 | Yoshitomi Pharmaceut Ind Ltd | チオフェン化合物 |
-
1994
- 1994-04-26 EP EP94913822A patent/EP0696586A1/en not_active Withdrawn
- 1994-04-26 HU HU9503072A patent/HUT75032A/hu unknown
- 1994-04-26 US US08/535,047 patent/US5834460A/en not_active Expired - Fee Related
- 1994-04-26 WO PCT/JP1994/000697 patent/WO1994025450A1/ja not_active Application Discontinuation
- 1994-04-26 CA CA002160459A patent/CA2160459A1/en not_active Abandoned
- 1994-04-26 CN CN94191891A patent/CN1121713A/zh active Pending
- 1994-04-27 TW TW083103787A patent/TW290548B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| HU9503072D0 (en) | 1995-12-28 |
| EP0696586A1 (en) | 1996-02-14 |
| TW290548B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1996-11-11 |
| HUT75032A (en) | 1997-03-28 |
| EP0696586A4 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1996-03-27 |
| CN1121713A (zh) | 1996-05-01 |
| US5834460A (en) | 1998-11-10 |
| WO1994025450A1 (en) | 1994-11-10 |
| AU681655B2 (en) | 1997-09-04 |
| AU6582494A (en) | 1994-11-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |