JPH055828B2 - - Google Patents
Info
- Publication number
- JPH055828B2 JPH055828B2 JP61199202A JP19920286A JPH055828B2 JP H055828 B2 JPH055828 B2 JP H055828B2 JP 61199202 A JP61199202 A JP 61199202A JP 19920286 A JP19920286 A JP 19920286A JP H055828 B2 JPH055828 B2 JP H055828B2
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- methyl
- hydroxy
- ethyl ester
- acid ethyl
- 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.)
- Expired - Lifetime
Links
- -1 pyridoyloxy Chemical group 0.000 claims description 230
- 239000000203 mixture Substances 0.000 claims description 143
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 130
- 150000001875 compounds Chemical class 0.000 claims description 122
- 150000003839 salts Chemical class 0.000 claims description 122
- 239000002253 acid Substances 0.000 claims description 74
- 238000000034 method Methods 0.000 claims description 74
- 125000003545 alkoxy group Chemical group 0.000 claims description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical group 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000004423 acyloxy group Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 23
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 18
- 125000001118 alkylidene group Chemical group 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 13
- 230000001777 nootropic effect Effects 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 10
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 claims description 9
- 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 239000002664 nootropic agent Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 239000005973 Carvone Substances 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 238000003797 solvolysis reaction Methods 0.000 claims description 5
- UMIVXZPTRXBADB-UHFFFAOYSA-N benzocyclobutene Chemical compound C1=CC=C2CCC2=C1 UMIVXZPTRXBADB-UHFFFAOYSA-N 0.000 claims description 4
- PZGOWXPGHVSKNO-UHFFFAOYSA-N 4-methoxybicyclo[4.2.0]octa-1(6),2,4-triene Chemical compound COC1=CC=C2CCC2=C1 PZGOWXPGHVSKNO-UHFFFAOYSA-N 0.000 claims description 3
- ZBYKDEIZQLFOCC-UHFFFAOYSA-N ethyl 1-(6-methoxy-2,3-dihydro-1h-inden-1-yl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1C1C2=CC(OC)=CC=C2CC1 ZBYKDEIZQLFOCC-UHFFFAOYSA-N 0.000 claims description 3
- YVFZJEZNDYOHAO-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1CC1=CC2=CC=C(OC)C=C12 YVFZJEZNDYOHAO-UHFFFAOYSA-N 0.000 claims description 3
- LFDJBPPJFWTQOS-UHFFFAOYSA-N ethyl 1-[(5-methoxy-2,3-dihydro-1h-inden-2-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1CC2=CC(OC)=CC=C2C1 LFDJBPPJFWTQOS-UHFFFAOYSA-N 0.000 claims description 3
- VRXDWIHGAORJGV-UHFFFAOYSA-N ethyl 4-amino-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(N)CCN1CC1=CC2=CC=C(OC)C=C12 VRXDWIHGAORJGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 12
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims 5
- AWXYKOIYQGUKOH-UHFFFAOYSA-N 4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]piperidine-3-carboxamide Chemical compound C=12C=C(OC)C=CC2=CC=1CN1CCC(O)C(C(N)=O)C1 AWXYKOIYQGUKOH-UHFFFAOYSA-N 0.000 claims 2
- OVJUZXSMKYBBCD-IAGOWNOFSA-N ethyl (3r,4r)-1-(7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenylmethyl)-4-methylsulfonyloxypiperidine-3-carboxylate Chemical compound C1C[C@@H](OS(C)(=O)=O)[C@H](C(=O)OCC)CN1CC1=C(C=CC=C2)C2=C1 OVJUZXSMKYBBCD-IAGOWNOFSA-N 0.000 claims 2
- HTCQTXXDDFUSPS-DNQXCXABSA-N ethyl (3r,4r)-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-phenylmethoxypiperidine-3-carboxylate Chemical compound O([C@@H]1CCN(CC=2C3=CC(OC)=CC=C3C=2)C[C@H]1C(=O)OCC)CC1=CC=CC=C1 HTCQTXXDDFUSPS-DNQXCXABSA-N 0.000 claims 2
- KZMAPSUZQICBIM-RTBURBONSA-N ethyl (3r,4r)-4-acetyloxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](OC(C)=O)[C@H](C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 KZMAPSUZQICBIM-RTBURBONSA-N 0.000 claims 2
- QCEJPTXCLKCXIW-IAGOWNOFSA-N ethyl (3r,4r)-4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](O)[C@H](C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 QCEJPTXCLKCXIW-IAGOWNOFSA-N 0.000 claims 2
- CRPLVAZTGBGPKN-QZTJIDSGSA-N ethyl (3r,4r)-4-hydroxy-1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](O)[C@H](C(=O)OCC)CN1CCC1=CC2=CC=C(OC)C=C12 CRPLVAZTGBGPKN-QZTJIDSGSA-N 0.000 claims 2
- VEKLYJBJGWOCKQ-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)-4-hydroxy-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1C1=C(C=CC=C2)C2=C1 VEKLYJBJGWOCKQ-UHFFFAOYSA-N 0.000 claims 2
- JFBZZYORKLGCOK-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenyl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1C1=CC2=CC=CC=C12 JFBZZYORKLGCOK-UHFFFAOYSA-N 0.000 claims 2
- MDCMFWDHSQCGGZ-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenylmethyl)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=CCCN1CC1=CC2=CC=CC=C12 MDCMFWDHSQCGGZ-UHFFFAOYSA-N 0.000 claims 2
- GYNOOWYMUBHFHF-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenylmethyl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=CC=C12 GYNOOWYMUBHFHF-UHFFFAOYSA-N 0.000 claims 2
- FKIJREGCUZPRLB-UHFFFAOYSA-N ethyl 1-[(3-methoxy-5-methyl-8-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=C1C=C(OC)C=C2C FKIJREGCUZPRLB-UHFFFAOYSA-N 0.000 claims 2
- FXBUXUOZKHERJT-UHFFFAOYSA-N ethyl 1-[(4-chloro-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=C(Cl)C=C12 FXBUXUOZKHERJT-UHFFFAOYSA-N 0.000 claims 2
- WLCPBCHFDPDGDI-UHFFFAOYSA-N ethyl 1-[(4-chloro-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-4-hydroxy-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(Cl)C=C2)C2=C1 WLCPBCHFDPDGDI-UHFFFAOYSA-N 0.000 claims 2
- XEPPCWBHENIJRW-UHFFFAOYSA-N ethyl 1-[(4-methoxy-8-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC(OC)=CC=C12 XEPPCWBHENIJRW-UHFFFAOYSA-N 0.000 claims 2
- QAOYFXZQEHSYTI-UHFFFAOYSA-N ethyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1C2=CC(OC)=CC=C2CC1 QAOYFXZQEHSYTI-UHFFFAOYSA-N 0.000 claims 2
- MWOJEEMOXIJYKO-UHFFFAOYSA-N ethyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=CCCN1CC1C2=CC(OC)=CC=C2CCC1 MWOJEEMOXIJYKO-UHFFFAOYSA-N 0.000 claims 2
- BMHQHXGIIIROGI-UHFFFAOYSA-N ethyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1C2=CC(OC)=CC=C2CCC1 BMHQHXGIIIROGI-UHFFFAOYSA-N 0.000 claims 2
- JNCKCUQZAHDEMO-UHFFFAOYSA-N ethyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=CCCN1CCC1=CC2=CC=C(OC)C=C12 JNCKCUQZAHDEMO-UHFFFAOYSA-N 0.000 claims 2
- NHMNSYNQCSJACM-UHFFFAOYSA-N ethyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CCC1=CC2=CC=C(OC)C=C12 NHMNSYNQCSJACM-UHFFFAOYSA-N 0.000 claims 2
- HPFSJRSDRANYQS-UHFFFAOYSA-N ethyl 1-[2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CCC1C2=CC(OC)=CC=C2CC1 HPFSJRSDRANYQS-UHFFFAOYSA-N 0.000 claims 2
- JULBLEVTDJCOGP-UHFFFAOYSA-N ethyl 4-hydroxy-1-(6-methoxy-2,3-dihydro-1h-inden-1-yl)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1C1C2=CC(OC)=CC=C2CC1 JULBLEVTDJCOGP-UHFFFAOYSA-N 0.000 claims 2
- CPNJBZSRVHFBSX-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-hydroxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(O)C=C2)C2=C1 CPNJBZSRVHFBSX-UHFFFAOYSA-N 0.000 claims 2
- XFOSFGLRDKGMEG-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-2-methyl-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(OC)C=C2C)C2=C1 XFOSFGLRDKGMEG-UHFFFAOYSA-N 0.000 claims 2
- MIRANYBANLDUOZ-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(OC)C=C2)C2=C1 MIRANYBANLDUOZ-UHFFFAOYSA-N 0.000 claims 2
- XFKGDMODQINPDC-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-7-methyl-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1(C)C2=CC(OC)=CC=C2C1 XFKGDMODQINPDC-UHFFFAOYSA-N 0.000 claims 2
- FVIDBUBWKWQWFC-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-8-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=CC(OC)=C2)C2=C1 FVIDBUBWKWQWFC-UHFFFAOYSA-N 0.000 claims 2
- LIRIVFMHBLEIGF-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(5-methoxy-2,3-dihydro-1H-inden-2-yl)methyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound C(C)OC(=O)C=1CN(CCC1O)CC1CC2=CC(=CC=C2C1)OC LIRIVFMHBLEIGF-UHFFFAOYSA-N 0.000 claims 2
- HZABDQRYRHROBD-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1C2=CC(OC)=CC=C2CC1 HZABDQRYRHROBD-UHFFFAOYSA-N 0.000 claims 2
- KSCSVTXFNVHEPS-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1C2=CC(OC)=CC=C2CCC1 KSCSVTXFNVHEPS-UHFFFAOYSA-N 0.000 claims 2
- GPKMTQAGCOVWSO-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound C(C)OC(=O)C=1CN(CCC1O)CC1CC2=CC(=CC=C2CC1)OC GPKMTQAGCOVWSO-UHFFFAOYSA-N 0.000 claims 2
- YLZCHDCWYIEPJG-UHFFFAOYSA-N ethyl 4-hydroxy-1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CCC1=CC2=CC=C(OC)C=C12 YLZCHDCWYIEPJG-UHFFFAOYSA-N 0.000 claims 2
- UIVWVTQOGSSCLH-UHFFFAOYSA-N ethyl 4-hydroxy-1-[2-(6-methoxy-2,3-dihydro-1H-inden-1-yl)ethyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound C(C)OC(=O)C=1CN(CCC1O)CCC1CCC2=CC=C(C=C12)OC UIVWVTQOGSSCLH-UHFFFAOYSA-N 0.000 claims 2
- UUZUBCCNOUACBN-UHFFFAOYSA-N ethyl 4-imino-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1CC(=N)C(C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 UUZUBCCNOUACBN-UHFFFAOYSA-N 0.000 claims 2
- GVAVPPMSQKUHIR-UHFFFAOYSA-N methyl 1-(5-methoxy-2,3-dihydro-1h-inden-2-yl)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1C1CC2=CC(OC)=CC=C2C1 GVAVPPMSQKUHIR-UHFFFAOYSA-N 0.000 claims 2
- UNLLAMJDGOZEEH-UHFFFAOYSA-N methyl 1-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1C1CC2=CC(OC)=CC=C2CC1 UNLLAMJDGOZEEH-UHFFFAOYSA-N 0.000 claims 2
- LDTDZOMQBSFRAP-UHFFFAOYSA-N methyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1=CC2=CC=C(OC)C=C12 LDTDZOMQBSFRAP-UHFFFAOYSA-N 0.000 claims 2
- FWXQRMJNMBKTJI-UHFFFAOYSA-N methyl 1-[(5-methoxy-2,3-dihydro-1h-inden-2-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1CC2=CC(OC)=CC=C2C1 FWXQRMJNMBKTJI-UHFFFAOYSA-N 0.000 claims 2
- ZOHQIWWFJAUEMC-UHFFFAOYSA-N methyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1C2=CC(OC)=CC=C2CC1 ZOHQIWWFJAUEMC-UHFFFAOYSA-N 0.000 claims 2
- JTOFVGPEDUADTD-UHFFFAOYSA-N methyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1C2=CC(OC)=CC=C2CC1 JTOFVGPEDUADTD-UHFFFAOYSA-N 0.000 claims 2
- DIAVOXYNTHHDFL-UHFFFAOYSA-N methyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1CC2=CC(OC)=CC=C2CC1 DIAVOXYNTHHDFL-UHFFFAOYSA-N 0.000 claims 2
- DQCMEJMRRQLZEU-UHFFFAOYSA-N methyl 1-[2-(2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CCC1C2=CC=CC=C2CC1 DQCMEJMRRQLZEU-UHFFFAOYSA-N 0.000 claims 2
- BFQJBEYGXCVWOG-UHFFFAOYSA-N methyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CCC1=CC2=CC=C(OC)C=C12 BFQJBEYGXCVWOG-UHFFFAOYSA-N 0.000 claims 2
- SDYHCWDOLLRGHT-UHFFFAOYSA-N methyl 1-[2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CCC1C2=CC(OC)=CC=C2CC1 SDYHCWDOLLRGHT-UHFFFAOYSA-N 0.000 claims 2
- DCFGTZIAKOCQEP-UHFFFAOYSA-N methyl 4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=C(O)CCN1CC1=C(C=C(OC)C=C2)C2=C1 DCFGTZIAKOCQEP-UHFFFAOYSA-N 0.000 claims 2
- VVEIESYVPHIUHK-UHFFFAOYSA-N methyl 4-hydroxy-1-[(6-methoxy-2,3-dihydro-1H-inden-1-yl)methyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound COC(=O)C=1CN(CCC1O)CC1CCC2=CC=C(C=C12)OC VVEIESYVPHIUHK-UHFFFAOYSA-N 0.000 claims 2
- BNKXWOULDSELIW-UHFFFAOYSA-N methyl 4-hydroxy-1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=C(O)CCN1CCC1=C(C=C(OC)C=C2)C2=C1 BNKXWOULDSELIW-UHFFFAOYSA-N 0.000 claims 2
- BCDBHIAXYFPJCT-UHFFFAOYSA-N methyl piperidine-3-carboxylate Chemical compound COC(=O)C1CCCNC1 BCDBHIAXYFPJCT-UHFFFAOYSA-N 0.000 claims 2
- YBVLHYSOWMKSBK-UHFFFAOYSA-N 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]piperidin-4-one Chemical compound C12=CC(OC)=CC=C2C=C1CN1CCC(=O)CC1 YBVLHYSOWMKSBK-UHFFFAOYSA-N 0.000 claims 1
- RMZQUHGQYLQKIC-UHFFFAOYSA-N 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]piperidine-3-carboxylic acid Chemical compound C12=CC(OC)=CC=C2C=C1CN1CCCC(C(O)=O)C1 RMZQUHGQYLQKIC-UHFFFAOYSA-N 0.000 claims 1
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims 1
- 125000004849 alkoxymethyl group Chemical group 0.000 claims 1
- 150000001555 benzenes Chemical group 0.000 claims 1
- JCEMYMBOEZPQCM-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-methyl-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1(C)C2=CC(OC)=CC=C2C1 JCEMYMBOEZPQCM-UHFFFAOYSA-N 0.000 claims 1
- PJXPLQDWGMEUTM-UHFFFAOYSA-N methyl 1-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1C1CC2=CC(OC)=CC=C2CC1 PJXPLQDWGMEUTM-UHFFFAOYSA-N 0.000 claims 1
- KXGSKLBVPJMYNX-UHFFFAOYSA-N methyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1CC2=CC(OC)=CC=C2CC1 KXGSKLBVPJMYNX-UHFFFAOYSA-N 0.000 claims 1
- 125000005554 pyridyloxy group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 224
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 196
- 239000000243 solution Substances 0.000 description 177
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 171
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 130
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- 235000002639 sodium chloride Nutrition 0.000 description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 61
- 238000002844 melting Methods 0.000 description 54
- 230000008018 melting Effects 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 45
- 239000007858 starting material Substances 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 41
- 239000012074 organic phase Substances 0.000 description 38
- 239000002585 base Substances 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 238000004821 distillation Methods 0.000 description 36
- 238000003756 stirring Methods 0.000 description 34
- 125000004494 ethyl ester group Chemical group 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 150000002148 esters Chemical class 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
- 229940095574 propionic acid Drugs 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 23
- 239000000284 extract Substances 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 239000012312 sodium hydride Substances 0.000 description 20
- 229910000104 sodium hydride Inorganic materials 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 238000001816 cooling Methods 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000007788 liquid Substances 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 150000007513 acids Chemical class 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 239000006185 dispersion Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 239000002480 mineral oil Substances 0.000 description 11
- 235000010446 mineral oil Nutrition 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 230000002378 acidificating effect Effects 0.000 description 10
- 150000003973 alkyl amines Chemical class 0.000 description 10
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 9
- 239000000454 talc Substances 0.000 description 9
- 229910052623 talc Inorganic materials 0.000 description 9
- 235000012222 talc Nutrition 0.000 description 9
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 8
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 8
- 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 8
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 235000010755 mineral Nutrition 0.000 description 8
- 239000011707 mineral Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 239000003513 alkali Substances 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 description 6
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000004144 cyclobuten-1-yl group Chemical group [H]C1=C(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000032050 esterification Effects 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 229910052776 Thorium Inorganic materials 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 229910052737 gold Inorganic materials 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- VMXMDKOMXHVKRH-UHFFFAOYSA-N (4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl methanesulfonate Chemical compound COC1=CC=C2C=C(COS(C)(=O)=O)C2=C1 VMXMDKOMXHVKRH-UHFFFAOYSA-N 0.000 description 3
- YHEXOAUOAPCUFJ-UHFFFAOYSA-N (6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl methanesulfonate Chemical compound COC1=CC=C2CCC(COS(C)(=O)=O)C2=C1 YHEXOAUOAPCUFJ-UHFFFAOYSA-N 0.000 description 3
- KXEAZJHCOWBLLF-UHFFFAOYSA-N 3-methyl-3-(3-methylpentan-3-yloxy)pentane Chemical compound CCC(C)(CC)OC(C)(CC)CC KXEAZJHCOWBLLF-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003638 chemical reducing agent 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
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 3
- DOXOETUWVNVADB-UHFFFAOYSA-N methyl 1,2,3,6-tetrahydropyridine-5-carboxylate;hydrobromide Chemical compound Br.COC(=O)C1=CCCNC1 DOXOETUWVNVADB-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000003419 tautomerization reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- SJTLKMRJESNHKN-UHFFFAOYSA-N (6-methoxy-2,3-dihydro-1h-inden-1-yl)methanamine Chemical compound COC1=CC=C2CCC(CN)C2=C1 SJTLKMRJESNHKN-UHFFFAOYSA-N 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
- PFKXQLPGRNYCCJ-UHFFFAOYSA-N 1-(azidomethyl)-6-methoxy-2,3-dihydro-1h-indene Chemical compound COC1=CC=C2CCC(CN=[N+]=[N-])C2=C1 PFKXQLPGRNYCCJ-UHFFFAOYSA-N 0.000 description 2
- NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical group COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 2
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 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
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical compound O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- NTVVLLJSRCBEFL-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 NTVVLLJSRCBEFL-UHFFFAOYSA-N 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- DYPLDWLIOGXSSE-UHFFFAOYSA-N guvacoline Chemical compound COC(=O)C1=CCCNC1 DYPLDWLIOGXSSE-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 150000003053 piperidines Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- OGNVQLDIPUXYDH-ZPKKHLQPSA-N (2R,3R,4S)-3-(2-methylpropanoylamino)-4-(4-phenyltriazol-1-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Chemical compound CC(C)C(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(O)=O)=C[C@@H]1N1N=NC(C=2C=CC=CC=2)=C1 OGNVQLDIPUXYDH-ZPKKHLQPSA-N 0.000 description 1
- SFQXDDWQGPHOKL-UHFFFAOYSA-N (3-methoxy-5-methyl-8-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methanamine Chemical compound CC1=CC(OC)=CC2=C1C=C2CN SFQXDDWQGPHOKL-UHFFFAOYSA-N 0.000 description 1
- KOHJDWDEOLDZEG-UHFFFAOYSA-N (4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl 4-methylbenzenesulfonate Chemical compound C12=CC(OC)=CC=C2C=C1COS(=O)(=O)C1=CC=C(C)C=C1 KOHJDWDEOLDZEG-UHFFFAOYSA-N 0.000 description 1
- XDSRGROSZZUGOM-UHFFFAOYSA-N (7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methanol Chemical compound C1CC(CO)CC2=CC(OC)=CC=C21 XDSRGROSZZUGOM-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- QMDFHZOGAYONLN-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine-3-carboxylic acid Chemical compound OC(=O)C1CNC=CC1 QMDFHZOGAYONLN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RQNOFUZGXHSHOT-UHFFFAOYSA-N 1-(diethylamino)ethanol Chemical compound CCN(CC)C(C)O RQNOFUZGXHSHOT-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- GGZQLTVZPOGLCC-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-dioxolane Chemical compound BrCCC1OCCO1 GGZQLTVZPOGLCC-UHFFFAOYSA-N 0.000 description 1
- ALAUISTUIQUUFF-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)acetic acid Chemical compound COC1=CC=C2CCC(CC(O)=O)C2=C1 ALAUISTUIQUUFF-UHFFFAOYSA-N 0.000 description 1
- LCBMTXZTEDATHA-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)acetonitrile Chemical compound COC1=CC=C2CCC(CC#N)C2=C1 LCBMTXZTEDATHA-UHFFFAOYSA-N 0.000 description 1
- MKFQCOXFGMBPAP-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethanamine Chemical compound COC1=CC=C2CCC(CCN)C2=C1 MKFQCOXFGMBPAP-UHFFFAOYSA-N 0.000 description 1
- HUOPTHNRTPLXRB-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl methanesulfonate Chemical compound COC1=CC=C2CCC(CCOS(C)(=O)=O)C2=C1 HUOPTHNRTPLXRB-UHFFFAOYSA-N 0.000 description 1
- BGTJPQBSNPHFLF-UHFFFAOYSA-N 2-(azidomethyl)-7-methoxy-1,2,3,4-tetrahydronaphthalene Chemical compound C1CC(CN=[N+]=[N-])CC2=CC(OC)=CC=C21 BGTJPQBSNPHFLF-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- FVTWJXMFYOXOKK-UHFFFAOYSA-N 2-fluoroacetamide Chemical compound NC(=O)CF FVTWJXMFYOXOKK-UHFFFAOYSA-N 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- WPPWEFVZGFJESZ-UHFFFAOYSA-N 5-methoxy-2,3-dihydro-1h-indene Chemical compound COC1=CC=C2CCCC2=C1 WPPWEFVZGFJESZ-UHFFFAOYSA-N 0.000 description 1
- NYAXSJZIUOHLMW-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1h-indene-1-carboxylic acid Chemical compound COC1=CC=C2CCC(C(O)=O)C2=C1 NYAXSJZIUOHLMW-UHFFFAOYSA-N 0.000 description 1
- DAXIBFTVCDGGMC-UHFFFAOYSA-N 7-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=C(OC)C=C2CC(NC)CCC2=C1 DAXIBFTVCDGGMC-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000206761 Bacillariophyta Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- GXGJIOMUZAGVEH-UHFFFAOYSA-N Chamazulene Chemical group CCC1=CC=C(C)C2=CC=C(C)C2=C1 GXGJIOMUZAGVEH-UHFFFAOYSA-N 0.000 description 1
- 240000004270 Colocasia esculenta var. antiquorum Species 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 235000002723 Dioscorea alata Nutrition 0.000 description 1
- 235000007056 Dioscorea composita Nutrition 0.000 description 1
- 235000009723 Dioscorea convolvulacea Nutrition 0.000 description 1
- 235000005362 Dioscorea floribunda Nutrition 0.000 description 1
- 235000004868 Dioscorea macrostachya Nutrition 0.000 description 1
- 235000005361 Dioscorea nummularia Nutrition 0.000 description 1
- 235000005360 Dioscorea spiculiflora Nutrition 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- 241000257465 Echinoidea Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- QTDZOWFRBNTPQR-UHFFFAOYSA-N Guvacine Natural products OC(=O)C1=CCCNC1 QTDZOWFRBNTPQR-UHFFFAOYSA-N 0.000 description 1
- 241001487835 Hesperocyparis goveniana Species 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
- 235000006350 Ipomoea batatas var. batatas Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002807 Thiomer Polymers 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- ZHGYVIRAWURONG-UHFFFAOYSA-N [1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridin-4-yl]oxy-trimethylsilane Chemical compound C=12C=C(OC)C=CC2=CC=1CN1CCC(O[Si](C)(C)C)=CC1 ZHGYVIRAWURONG-UHFFFAOYSA-N 0.000 description 1
- NJVHJTQSGGRHGP-UHFFFAOYSA-K [Li].[Al+3].[Cl-].[Cl-].[Cl-] Chemical compound [Li].[Al+3].[Cl-].[Cl-].[Cl-] NJVHJTQSGGRHGP-UHFFFAOYSA-K 0.000 description 1
- AVAYCNNAMOJZHO-UHFFFAOYSA-N [Na+].[Na+].[O-]B[O-] Chemical compound [Na+].[Na+].[O-]B[O-] AVAYCNNAMOJZHO-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000010953 base metal Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- RNKJKBFDTANUPF-UHFFFAOYSA-N bicyclo[4.2.0]octa-1,3,5,7-tetraen-7-amine Chemical compound C1=CC=C2C(N)=CC2=C1 RNKJKBFDTANUPF-UHFFFAOYSA-N 0.000 description 1
- 229910010277 boron hydride Inorganic materials 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229910001576 calcium mineral Chemical class 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- BAQSIYCDSSZDHG-UHFFFAOYSA-K calcium;sodium;carbonate;hydroxide Chemical class [OH-].[Na+].[Ca+2].[O-]C([O-])=O BAQSIYCDSSZDHG-UHFFFAOYSA-K 0.000 description 1
- 150000004653 carbonic acids Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001753 carvones Chemical class 0.000 description 1
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KDYCEANSZSUKAO-UHFFFAOYSA-N cyclobuten-1-ylmethanamine Chemical compound NCC1=CCC1 KDYCEANSZSUKAO-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 235000004879 dioscorea Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- ALWVNDLNOZDPDB-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenylmethyl)-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=CC=C12 ALWVNDLNOZDPDB-UHFFFAOYSA-N 0.000 description 1
- YUTJOUFGLJSDCN-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical class C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 YUTJOUFGLJSDCN-UHFFFAOYSA-N 0.000 description 1
- RPCVDZPTRCPHIP-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1C(C(=O)OCC)CCCN1CC1=CC2=CC=C(OC)C=C12 RPCVDZPTRCPHIP-UHFFFAOYSA-N 0.000 description 1
- SAMRHDQHKLXAFP-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=CCCN1CC1=C(C=C(OC)C=C2)C2=C1 SAMRHDQHKLXAFP-UHFFFAOYSA-N 0.000 description 1
- WJIBAKMAWMCQDU-UHFFFAOYSA-N ethyl 2-ethoxypyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1OCC WJIBAKMAWMCQDU-UHFFFAOYSA-N 0.000 description 1
- URRCBLGXCFTNSR-UHFFFAOYSA-N ethyl 7-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C1=C(OC)C=C2CC(C(=O)OCC)CCC2=C1 URRCBLGXCFTNSR-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011133 lead Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 159000000003 magnesium salts Chemical class 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- FGSCTRBUBMUFDX-UHFFFAOYSA-N methyl 1-(5-methoxy-2,3-dihydro-1H-inden-2-yl)-4-oxopiperidine-3-carboxylate Chemical compound COC(=O)C1CN(CCC1=O)C1CC2=CC=C(C=C2C1)OC FGSCTRBUBMUFDX-UHFFFAOYSA-N 0.000 description 1
- RMOPJLIMRSAIMD-UHFFFAOYSA-N methyl 2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=CC=C2CC(C(=O)OC)CC2=C1 RMOPJLIMRSAIMD-UHFFFAOYSA-N 0.000 description 1
- JXRBXNDFMVNTGU-UHFFFAOYSA-N methyl 6-methoxy-2,3-dihydro-1h-indene-1-carboxylate Chemical compound C1=C(OC)C=C2C(C(=O)OC)CCC2=C1 JXRBXNDFMVNTGU-UHFFFAOYSA-N 0.000 description 1
- PBTHJVDBCFJQGG-UHFFFAOYSA-N methyl azide Chemical compound CN=[N+]=[N-] PBTHJVDBCFJQGG-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- FWRYEKOMXUTCMO-UHFFFAOYSA-N methyl pyridine-3-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CN=C1 FWRYEKOMXUTCMO-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical group CCCCNCC QHCCDDQKNUYGNC-UHFFFAOYSA-N 0.000 description 1
- NVSYANRBXPURRQ-UHFFFAOYSA-N naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CN)=CC=CC2=C1 NVSYANRBXPURRQ-UHFFFAOYSA-N 0.000 description 1
- RMHJJUOPOWPRBP-UHFFFAOYSA-N naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=CC2=C1 RMHJJUOPOWPRBP-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- AHKZTVQIVOEVFO-UHFFFAOYSA-N oxide(2-) Chemical class [O-2] AHKZTVQIVOEVFO-UHFFFAOYSA-N 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 238000011302 passive avoidance test Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- XIMLAVRHZBUYBE-UHFFFAOYSA-N piperidin-2-one;hydrate;hydrochloride Chemical compound O.Cl.O=C1CCCCN1 XIMLAVRHZBUYBE-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium 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
- 239000012429 reaction media Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 235000001508 sulfur Nutrition 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH3669/85-5 | 1985-08-27 | ||
CH366985 | 1985-08-27 | ||
CH2586/86-3 | 1986-06-26 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6251650A JPS6251650A (ja) | 1987-03-06 |
JPH055828B2 true JPH055828B2 (no) | 1993-01-25 |
Family
ID=4260962
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP19920286A Granted JPS6251650A (ja) | 1985-08-27 | 1986-08-27 | ヒドロピリジン誘導体、その製造法及び向知性薬 |
Country Status (3)
Country | Link |
---|---|
JP (1) | JPS6251650A (no) |
DD (1) | DD259189A5 (no) |
ZA (1) | ZA866442B (no) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07159A (ja) * | 1991-08-30 | 1995-01-06 | Noritake Co Ltd | 篩い作動式焙煎機における炒成機構 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57179141A (en) * | 1981-04-28 | 1982-11-04 | Takeda Chem Ind Ltd | Bicyclic compound and its preparation |
-
1986
- 1986-08-25 DD DD86293839A patent/DD259189A5/de not_active IP Right Cessation
- 1986-08-26 ZA ZA866442A patent/ZA866442B/xx unknown
- 1986-08-27 JP JP19920286A patent/JPS6251650A/ja active Granted
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57179141A (en) * | 1981-04-28 | 1982-11-04 | Takeda Chem Ind Ltd | Bicyclic compound and its preparation |
Also Published As
Publication number | Publication date |
---|---|
DD259189A5 (de) | 1988-08-17 |
JPS6251650A (ja) | 1987-03-06 |
ZA866442B (en) | 1987-04-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2756742B2 (ja) | N−アシル−2,3−ベンゾジアゼピン誘導体、その製造法、それを含有する医薬組成物、およびその製造法 | |
ZIERING et al. | PIPERIDINE DERIVATIVES. PART III. 4-ARYLPIPERIDINES1 | |
CH648553A5 (de) | Neue 3,4-dihydro-5h-2,3-benzodiazepin-derivate und verfahren zur herstellung derselben. | |
JPS6289679A (ja) | ピペリジン誘導体 | |
AU646686B2 (en) | Excitatory amino acid antagonistic indole derivatives | |
EP0330469A2 (en) | Tetrahydroisoquinoline derivatives | |
JP2001505198A (ja) | Pde阻害剤としての置換ジヒドロベンゾフラン | |
US3271416A (en) | Indolyl aliphatic acids | |
US3957850A (en) | Phenylacetic acid derivatives | |
AU608692B2 (en) | Tetrazole excitatory amino acid receptor antagonists | |
JPH01265100A (ja) | 2―置換アデノシン誘導体 | |
BG60472B2 (bg) | Производни на 1-(циклохексил или циклохексенил)-4-арил-4- пиперидинкарбоксилова киселина | |
DE3543982A1 (de) | Indolderivate, verfahren zu ihrer herstellung und sie enthaltende, pharmazeutische zubereitungen | |
DD279674A5 (de) | Verfahren zur herstellung von hydrierten 1-benzooxacycloalkyl-pyridincarbonsaeureverbindungen | |
US3531487A (en) | 4-(n,n-disubstituted-amino)-piperidines | |
EP0501997B1 (en) | N-acyl-substituted azacyclic compounds, processes for their preparation, and their use as pharmaceuticals | |
JPH055828B2 (no) | ||
US2956058A (en) | Novel substituted piperidines and pyrrolidines | |
AU610492B2 (en) | 5-substituted octahydroindolizine analgesics compounds and 7-keto intermediates | |
KR910000034B1 (ko) | 하이드로피리딘 유도체의 제조방법 | |
US4923863A (en) | Morpholine derivatives, pharmaceutical compositions and use | |
JPH037280A (ja) | 新規ベンゾチオピラニルアミン | |
JPH01203379A (ja) | さらに水素化された1―ベンゾオキサシクロアルキルピリジンカルボン酸類 | |
JP3160041B2 (ja) | アミン誘導体の製造方法 | |
JPS6039069B2 (ja) | アミン誘導体 |