DD215539A5 - Verfahren zur herstellung neuer substituierter pyrrolidinderivate - Google Patents

Verfahren zur herstellung neuer substituierter pyrrolidinderivate Download PDF

Info

Publication number: DD215539A5
Authority: DD; German Democratic Republic
Prior art keywords: hydrogen; formula; compound; radical; substituted
Prior art date: 1983-01-27

Application number

DD84259604A

Other languages

German (de)

English (en)

Inventor

William Bencze

Bruno Kamber

Angelo Storni

Original Assignee

Ciba Geigy Ag

Priority date (The priority date 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 date listed.)

1983-01-27

Filing date

1984-01-25

Publication date

1984-11-14

1984-01-25 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1984-11-14 Publication of DD215539A5 publication Critical patent/DD215539A5/de

Links

238000004519 manufacturing process Methods 0.000 title description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 164
239000001257 hydrogen Substances 0.000 claims abstract description 142
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 142
125000000217 alkyl group Chemical group 0.000 claims abstract description 98
238000000034 method Methods 0.000 claims abstract description 81
150000003839 salts Chemical class 0.000 claims abstract description 66
125000003118 aryl group Chemical group 0.000 claims abstract description 42
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 41
230000008569 process Effects 0.000 claims abstract description 24
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims abstract description 20
238000002360 preparation method Methods 0.000 claims abstract description 17
150000001408 amides Chemical class 0.000 claims abstract description 14
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
239000001301 oxygen Substances 0.000 claims abstract description 11
229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
150000002431 hydrogen Chemical class 0.000 claims abstract 26
-1 arainocarbonyl Chemical group 0.000 claims description 253
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 74
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 66
238000006243 chemical reaction Methods 0.000 claims description 49
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 43
239000007858 starting material Substances 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 37
125000006239 protecting group Chemical group 0.000 claims description 32
125000001424 substituent group Chemical group 0.000 claims description 28
125000000524 functional group Chemical group 0.000 claims description 26
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
125000004423 acyloxy group Chemical group 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 21
150000002367 halogens Chemical group 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 19
125000003277 amino group Chemical group 0.000 claims description 16
239000000460 chlorine Substances 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
125000003368 amide group Chemical group 0.000 claims description 14
229910052801 chlorine Inorganic materials 0.000 claims description 14
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 11
229910052721 tungsten Inorganic materials 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 9
125000004429 atom Chemical group 0.000 claims description 9
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 9
125000005236 alkanoylamino group Chemical group 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
239000011737 fluorine Substances 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
230000000269 nucleophilic effect Effects 0.000 claims description 7
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 6
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 5
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 5
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
238000006237 Beckmann rearrangement reaction Methods 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
239000003638 chemical reducing agent Substances 0.000 claims description 4
125000000468 ketone group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 3
125000003544 oxime group Chemical group 0.000 claims description 2
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 14
230000006872 improvement Effects 0.000 abstract description 5
108090000765 processed proteins & peptides Proteins 0.000 abstract description 5
150000004040 pyrrolidinones Chemical class 0.000 abstract description 5
230000007334 memory performance Effects 0.000 abstract description 4
150000001413 amino acids Chemical class 0.000 abstract description 3
239000003814 drug Substances 0.000 abstract description 3
150000003951 lactams Chemical class 0.000 abstract description 3
238000001228 spectrum Methods 0.000 abstract description 2
108010016626 Dipeptides Proteins 0.000 abstract 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 92
239000002253 acid Substances 0.000 description 80
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
235000002639 sodium chloride Nutrition 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 54
150000003254 radicals Chemical class 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
150000008064 anhydrides Chemical class 0.000 description 29
239000002585 base Substances 0.000 description 29
150000002148 esters Chemical class 0.000 description 29
239000003795 chemical substances by application Substances 0.000 description 24
238000002844 melting Methods 0.000 description 24
230000008018 melting Effects 0.000 description 24
150000007513 acids Chemical class 0.000 description 23
239000002904 solvent Substances 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
239000000706 filtrate Substances 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 19
238000003756 stirring Methods 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
239000007787 solid Substances 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
238000001816 cooling Methods 0.000 description 15
239000000725 suspension Substances 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
241001465754 Metazoa Species 0.000 description 13
150000004820 halides Chemical class 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
229910052783 alkali metal Inorganic materials 0.000 description 12
238000010438 heat treatment Methods 0.000 description 12
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
239000012299 nitrogen atmosphere Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
JZYOALCNQWIADB-UHFFFAOYSA-N 2-amino-n-(2-amino-2-oxoethyl)acetamide;hydrochloride Chemical compound Cl.NCC(=O)NCC(N)=O JZYOALCNQWIADB-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 10
125000001931 aliphatic group Chemical group 0.000 description 10
150000001340 alkali metals Chemical class 0.000 description 10
206010028980 Neoplasm Diseases 0.000 description 9
150000001718 carbodiimides Chemical class 0.000 description 9
239000011261 inert gas Substances 0.000 description 9
238000007363 ring formation reaction Methods 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 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
238000009835 boiling Methods 0.000 description 8
150000001735 carboxylic acids Chemical class 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 7
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 7
150000007522 mineralic acids Chemical class 0.000 description 7
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 7
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 7
239000011877 solvent mixture Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 6
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
230000004913 activation Effects 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
150000003863 ammonium salts Chemical class 0.000 description 6
150000004945 aromatic hydrocarbons Chemical group 0.000 description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
125000000753 cycloalkyl group Chemical group 0.000 description 6
238000005886 esterification reaction Methods 0.000 description 6
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
238000011065 in-situ storage Methods 0.000 description 6
150000002825 nitriles Chemical class 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
241000699800 Cricetinae Species 0.000 description 5
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000037396 body weight Effects 0.000 description 5
239000013078 crystal Substances 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
238000001035 drying Methods 0.000 description 5
230000032050 esterification Effects 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
239000000155 melt Substances 0.000 description 5
238000006263 metalation reaction Methods 0.000 description 5
239000002480 mineral oil Substances 0.000 description 5
235000010446 mineral oil Nutrition 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
239000000047 product Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
229960002317 succinimide Drugs 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000004215 Carbon black (E152) Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
206010014357 Electric shock Diseases 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
150000008044 alkali metal hydroxides Chemical class 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
150000003973 alkyl amines Chemical class 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
150000001768 cations Chemical class 0.000 description 4
150000001805 chlorine compounds Chemical class 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
239000012043 crude product Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000008298 dragée Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
239000010410 layer Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
150000002923 oximes Chemical class 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000000902 placebo Substances 0.000 description 4
229940068196 placebo Drugs 0.000 description 4
229920003023 plastic Polymers 0.000 description 4
239000004033 plastic Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
229920001592 potato starch Polymers 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
230000035939 shock Effects 0.000 description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
239000000454 talc Substances 0.000 description 4
235000012222 talc Nutrition 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 4
PWBAMNPGOQBZCZ-ZETCQYMHSA-N (2s)-2-[[2-[[2-(2-oxopyrrolidin-1-yl)acetyl]amino]acetyl]amino]propanamide Chemical compound NC(=O)[C@H](C)NC(=O)CNC(=O)CN1CCCC1=O PWBAMNPGOQBZCZ-ZETCQYMHSA-N 0.000 description 3
QNFWNBZLOVVBRO-UHFFFAOYSA-N 2-(2,2-dimethyl-5-oxopyrrolidin-1-yl)acetic acid Chemical compound CC1(C)CCC(=O)N1CC(O)=O QNFWNBZLOVVBRO-UHFFFAOYSA-N 0.000 description 3
JGPIWNNFLKDTSR-UHFFFAOYSA-N 2-(2-oxopyrrolidin-1-yl)acetic acid Chemical compound OC(=O)CN1CCCC1=O JGPIWNNFLKDTSR-UHFFFAOYSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-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
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
230000010933 acylation Effects 0.000 description 3
150000001335 aliphatic alkanes Chemical class 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
150000007860 aryl ester derivatives Chemical class 0.000 description 3
150000005840 aryl radicals Chemical class 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
150000004649 carbonic acid derivatives Chemical class 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000002490 cerebral effect Effects 0.000 description 3
229920001429 chelating resin Polymers 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
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
238000006266 etherification reaction Methods 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
239000007789 gas Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000005457 ice water Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
229920000137 polyphosphoric acid Polymers 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
QAZCPUUJMFBNJO-UHFFFAOYSA-N pyrrolidin-2-one;sodium Chemical compound [Na].O=C1CCCN1 QAZCPUUJMFBNJO-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
150000003460 sulfonic acids Chemical class 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000012549 training Methods 0.000 description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
LNQSVSRPXBTZLL-UHFFFAOYSA-N (2,3,4,5,6-pentachlorophenyl) 2-(2-oxopyrrolidin-1-yl)acetate Chemical compound ClC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1OC(=O)CN1C(=O)CCC1 LNQSVSRPXBTZLL-UHFFFAOYSA-N 0.000 description 2
WKMHRZQCACUPFQ-DFWYDOINSA-N (2s)-2-[(2-aminoacetyl)amino]propanamide;hydrochloride Chemical compound Cl.NC(=O)[C@H](C)NC(=O)CN WKMHRZQCACUPFQ-DFWYDOINSA-N 0.000 description 2
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
WKFYEWXSRFQOKX-UHFFFAOYSA-N 1,4-dioxane;toluene Chemical compound C1COCCO1.CC1=CC=CC=C1 WKFYEWXSRFQOKX-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
FFRLQQDGACOVRC-UHFFFAOYSA-N 2-(4-naphthalen-1-yl-2-oxopyrrolidin-1-yl)acetic acid Chemical compound C1C(=O)N(CC(=O)O)CC1C1=CC=CC2=CC=CC=C12 FFRLQQDGACOVRC-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
HWBAHOVOSOAFLE-UHFFFAOYSA-N 2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(=O)NCC(O)=O HWBAHOVOSOAFLE-UHFFFAOYSA-N 0.000 description 2
NGMLDNHYPRTIBB-UHFFFAOYSA-N 2-[[2-[[2-[[2-(2-oxopyrrolidin-1-yl)acetyl]amino]acetyl]amino]acetyl]amino]acetamide Chemical compound NC(=O)CNC(=O)CNC(=O)CNC(=O)CN1CCCC1=O NGMLDNHYPRTIBB-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
IOGISYQVOGVIEU-UHFFFAOYSA-N 4-hydroxypyrrolidin-2-one Chemical compound OC1CNC(=O)C1 IOGISYQVOGVIEU-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
206010008190 Cerebrovascular accident Diseases 0.000 description 2
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 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
241000282414 Homo sapiens Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
238000007126 N-alkylation reaction Methods 0.000 description 2
AQDJWXUZFUBNEG-UHFFFAOYSA-N O=C1CC(O)CN1CC(=O)OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl Chemical compound O=C1CC(O)CN1CC(=O)OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl AQDJWXUZFUBNEG-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
238000006434 Ritter amidation reaction Methods 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
208000030886 Traumatic Brain injury Diseases 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
125000004442 acylamino group Chemical group 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
239000003513 alkali Substances 0.000 description 2
229910000272 alkali metal oxide Inorganic materials 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
125000003435 aroyl group Chemical group 0.000 description 2
125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
235000013877 carbamide Nutrition 0.000 description 2
150000001728 carbonyl compounds Chemical class 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
238000000576 coating method Methods 0.000 description 2
150000003950 cyclic amides Chemical class 0.000 description 2
239000000824 cytostatic agent Substances 0.000 description 2
230000001085 cytostatic effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000000539 dimer Substances 0.000 description 2
229960001760 dimethyl sulfoxide Drugs 0.000 description 2
ORMNPSYMZOGSSV-UHFFFAOYSA-N dinitrooxymercury Chemical compound [Hg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ORMNPSYMZOGSSV-UHFFFAOYSA-N 0.000 description 2
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000002635 electroconvulsive therapy Methods 0.000 description 2
239000002702 enteric coating Substances 0.000 description 2
238000009505 enteric coating Methods 0.000 description 2
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
FCVRPAJFGUTGBM-UHFFFAOYSA-N ethyl 2-(4-naphthalen-1-yl-2-oxopyrrolidin-1-yl)acetate Chemical compound C1C(=O)N(CC(=O)OCC)CC1C1=CC=CC2=CC=CC=C12 FCVRPAJFGUTGBM-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 2
YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
125000001183 hydrocarbyl group Chemical group 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
238000002955 isolation Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
150000002736 metal compounds Chemical class 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
238000002156 mixing Methods 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
235000015497 potassium bicarbonate Nutrition 0.000 description 2
230000008707 rearrangement Effects 0.000 description 2
210000002345 respiratory system Anatomy 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000007017 scission Effects 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
150000007970 thio esters Chemical class 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
229920001567 vinyl ester resin Polymers 0.000 description 2
239000008096 xylene Substances 0.000 description 2
PFJVIOBMBDFBCJ-UHFFFAOYSA-N (1z)-1-diazobutane Chemical compound CCCC=[N+]=[N-] PFJVIOBMBDFBCJ-UHFFFAOYSA-N 0.000 description 1
KLKJDOXPPVLZCE-UHFFFAOYSA-N (2,3,4,5,6-pentachlorophenyl) 2-bromoacetate Chemical compound ClC1=C(Cl)C(Cl)=C(OC(=O)CBr)C(Cl)=C1Cl KLKJDOXPPVLZCE-UHFFFAOYSA-N 0.000 description 1
XDACDXSGGOZUSP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,2-dimethyl-5-oxopyrrolidin-1-yl)acetate Chemical compound CC1(C)CCC(=O)N1CC(=O)ON1C(=O)CCC1=O XDACDXSGGOZUSP-UHFFFAOYSA-N 0.000 description 1
SIFCHNIAAPMMKG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) acetate Chemical compound CC(=O)ON1C(=O)CCC1=O SIFCHNIAAPMMKG-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
UUKVLPJLKBAKPH-VIFPVBQESA-N (2s)-n-ethyl-2-[[2-[[2-(2-oxopyrrolidin-1-yl)acetyl]amino]acetyl]amino]propanamide Chemical compound CCNC(=O)[C@H](C)NC(=O)CNC(=O)CN1CCCC1=O UUKVLPJLKBAKPH-VIFPVBQESA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 1
RFMDTFSTIGPYJH-UHFFFAOYSA-N 2-(2-methyl-5-oxopyrrolidin-1-yl)acetic acid Chemical compound CC1CCC(=O)N1CC(O)=O RFMDTFSTIGPYJH-UHFFFAOYSA-N 0.000 description 1
JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
ORVPLCFGJRUYEP-UHFFFAOYSA-N 2-[4-(4-chlorophenoxy)phenyl]-2-(2-oxopyrrolidin-1-yl)acetic acid Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1C(C(=O)O)N1CCCC1=O ORVPLCFGJRUYEP-UHFFFAOYSA-N 0.000 description 1
OPVYKLRIWIQUIJ-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)-2-oxopyrrolidin-1-yl]acetic acid Chemical compound C1C(=O)N(CC(=O)O)CC1C1=CC=C(F)C=C1 OPVYKLRIWIQUIJ-UHFFFAOYSA-N 0.000 description 1
DJGACOXTAHQLTD-UHFFFAOYSA-N 2-amino-n-(2-amino-2-oxoethyl)acetamide Chemical compound NCC(=O)NCC(N)=O DJGACOXTAHQLTD-UHFFFAOYSA-N 0.000 description 1
STKDNPSTDGMVNC-UHFFFAOYSA-N 2-amino-n-[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]acetamide;hydrochloride Chemical compound Cl.NCC(=O)NCC(=O)NCC(N)=O STKDNPSTDGMVNC-UHFFFAOYSA-N 0.000 description 1
WPQFDWRECNZHMC-UHFFFAOYSA-N 2-amino-n-[2-[[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-2-oxoethyl]acetamide;hydrochloride Chemical compound Cl.NCC(=O)NCC(=O)NCC(=O)NCC(N)=O WPQFDWRECNZHMC-UHFFFAOYSA-N 0.000 description 1
OSDGRTQLKGQBSD-UHFFFAOYSA-N 2-amino-n-[2-[[2-[[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]acetamide;hydrochloride Chemical compound Cl.NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(N)=O OSDGRTQLKGQBSD-UHFFFAOYSA-N 0.000 description 1
WKNMKGVLOWGGOU-UHFFFAOYSA-N 2-aminoacetamide;hydron;chloride Chemical compound Cl.NCC(N)=O WKNMKGVLOWGGOU-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
SBMUNILHNJLMBF-UHFFFAOYSA-N 2-chloro-1,3,2$l^{5}-dioxaphospholane 2-oxide Chemical compound ClP1(=O)OCCO1 SBMUNILHNJLMBF-UHFFFAOYSA-N 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
ZDPTZLODCLLVDN-UHFFFAOYSA-N 4-(1-ethoxyethoxy)pyrrolidin-2-one Chemical compound CCOC(C)OC1CNC(=O)C1 ZDPTZLODCLLVDN-UHFFFAOYSA-N 0.000 description 1
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
DNGJVDGPCGXBFF-UHFFFAOYSA-N 4-methyl-n-(methyldiazenyl)aniline Chemical compound CN=NNC1=CC=C(C)C=C1 DNGJVDGPCGXBFF-UHFFFAOYSA-N 0.000 description 1
AGDYKCPGMDASQO-UHFFFAOYSA-N 4-methyl-n-(propan-2-yldiazenyl)aniline Chemical compound CC(C)N=NNC1=CC=C(C)C=C1 AGDYKCPGMDASQO-UHFFFAOYSA-N 0.000 description 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
NFDWHRSBPFSPQO-UHFFFAOYSA-N 4-naphthalen-1-ylpyrrolidin-2-one Chemical compound C1NC(=O)CC1C1=CC=CC2=CC=CC=C12 NFDWHRSBPFSPQO-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
UUTGCNVYKLQLRV-UHFFFAOYSA-N 5,5-dimethylpyrrolidin-2-one Chemical compound CC1(C)CCC(=O)N1 UUTGCNVYKLQLRV-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
KMZWFGHTRHOUOQ-UHFFFAOYSA-N 6-diazo-4-phenylcyclohexa-2,4-dien-1-ol Chemical compound [N-]=[N+]=C1C(O)C=CC(C=2C=CC=CC=2)=C1 KMZWFGHTRHOUOQ-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
244000186140 Asperula odorata Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
241001474374 Blennius Species 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 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
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
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 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-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
206010012289 Dementia Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
238000006228 Dieckmann condensation reaction Methods 0.000 description 1
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
235000008526 Galium odoratum Nutrition 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
108010008488 Glycylglycine Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
206010020651 Hyperkinesia Diseases 0.000 description 1
208000000269 Hyperkinesis Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
238000006612 Kolbe reaction Methods 0.000 description 1
238000000023 Kugelrohr distillation Methods 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
238000003612 Meerwein-Ponndorf-Verley reduction reaction Methods 0.000 description 1
208000026139 Memory disease Diseases 0.000 description 1
241000699673 Mesocricetus auratus Species 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
WBNQDOYYEUMPFS-UHFFFAOYSA-N N-nitrosodiethylamine Chemical compound CCN(CC)N=O WBNQDOYYEUMPFS-UHFFFAOYSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
NXJGKTAQQLSVNS-UHFFFAOYSA-N O=C(CN(CC(C1)C2=CC=CC3=CC=CC=C23)C1=O)ON(C(CC1)=O)C1=O Chemical compound O=C(CN(CC(C1)C2=CC=CC3=CC=CC=C23)C1=O)ON(C(CC1)=O)C1=O NXJGKTAQQLSVNS-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
101100316117 Rattus norvegicus Unc50 gene Proteins 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 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
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
241000219793 Trifolium Species 0.000 description 1
241000209140 Triticum Species 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays 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
FIAINKIUSZGVGX-DKWTVANSSA-N [(2s)-1-amino-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.C[C@H](N)C(N)=O FIAINKIUSZGVGX-DKWTVANSSA-N 0.000 description 1
MJMLTDMBILNUMS-UHFFFAOYSA-M [Na+].CC1(CCC(N1C(C(=O)[O-])C)=O)C Chemical compound [Na+].CC1(CCC(N1C(C(=O)[O-])C)=O)C MJMLTDMBILNUMS-UHFFFAOYSA-M 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000001785 acacia senegal l. willd gum Substances 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
238000006136 alcoholysis reaction Methods 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
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000001339 alkali metal compounds Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000005037 alkyl phenyl group Chemical group 0.000 description 1
125000005103 alkyl silyl group Chemical group 0.000 description 1
125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
230000002862 amidating effect Effects 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000005110 aryl thio group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
230000008901 benefit Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
239000012964 benzotriazole Substances 0.000 description 1
KMOIKAVWPAEPPK-LLVKDONJSA-N benzyl N-[2-[[(2R)-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamate Chemical compound C(C)NC([C@H](NC(CNC(=O)OCC1=CC=CC=C1)=O)C)=O KMOIKAVWPAEPPK-LLVKDONJSA-N 0.000 description 1
ZUUYPZVICLRSKZ-VIFPVBQESA-N benzyl n-[2-[[(2s)-1-amino-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamate Chemical compound NC(=O)[C@H](C)NC(=O)CNC(=O)OCC1=CC=CC=C1 ZUUYPZVICLRSKZ-VIFPVBQESA-N 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
239000000872 buffer Substances 0.000 description 1
SIIVGPQREKVCOP-UHFFFAOYSA-N but-1-en-1-ol Chemical compound CCC=CO SIIVGPQREKVCOP-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide 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
239000002775 capsule Substances 0.000 description 1
150000001714 carbamic acid halides Chemical class 0.000 description 1
150000001715 carbamic acids Chemical class 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000005517 carbenium group Chemical group 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
TXHWYSOQHNMOOU-UHFFFAOYSA-N chloro(diethoxy)phosphane Chemical compound CCOP(Cl)OCC TXHWYSOQHNMOOU-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
239000008139 complexing agent Substances 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
229920001577 copolymer Chemical group 0.000 description 1
239000010949 copper Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
150000001912 cyanamides Chemical class 0.000 description 1
125000004122 cyclic group Chemical group 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
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 description 1
PVCINRPAXRJLEP-UHFFFAOYSA-N dichloro(ethoxy)phosphane Chemical compound CCOP(Cl)Cl PVCINRPAXRJLEP-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
RDXABLXNTVBVML-UHFFFAOYSA-N diethoxyphosphanyl diethyl phosphite Chemical compound CCOP(OCC)OP(OCC)OCC RDXABLXNTVBVML-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
BQBCQNOOSARBQY-UHFFFAOYSA-N ethyl 2-(2,2-dimethyl-5-oxopyrrolidin-1-yl)acetate Chemical compound CCOC(=O)CN1C(=O)CCC1(C)C BQBCQNOOSARBQY-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
150000002222 fluorine compounds Chemical class 0.000 description 1
UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
229940043257 glycylglycine Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
125000004997 halocarbonyl group Chemical group 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-O hydron;1,2-oxazole Chemical compound C=1C=[NH+]OC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-O 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-O hydron;1,3-oxazole Chemical compound C1=COC=[NH+]1 ZCQWOFVYLHDMMC-UHFFFAOYSA-O 0.000 description 1
150000002443 hydroxylamines Chemical class 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
150000002463 imidates Chemical class 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
125000001261 isocyanato group Chemical group *N=C=O 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
150000002561 ketenes Chemical class 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
210000000867 larynx Anatomy 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
150000002642 lithium compounds Chemical class 0.000 description 1
HTBVGZAVHBZXMS-UHFFFAOYSA-N lithium;tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Li].[Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] HTBVGZAVHBZXMS-UHFFFAOYSA-N 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
235000009973 maize Nutrition 0.000 description 1
230000006993 memory improvement Effects 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
238000001465 metallisation Methods 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000002780 morpholines Chemical class 0.000 description 1
201000003152 motion sickness Diseases 0.000 description 1
RJSCZBRDRBIRHP-UHFFFAOYSA-N n,n-diethylprop-1-yn-1-amine Chemical compound CCN(CC)C#CC RJSCZBRDRBIRHP-UHFFFAOYSA-N 0.000 description 1
BPOZIJBDYFHEJR-UHFFFAOYSA-N n-(ethyldiazenyl)-4-methylaniline Chemical compound CCN=NNC1=CC=C(C)C=C1 BPOZIJBDYFHEJR-UHFFFAOYSA-N 0.000 description 1
VZUGBLTVBZJZOE-KRWDZBQOSA-N n-[3-[(4s)-2-amino-1,4-dimethyl-6-oxo-5h-pyrimidin-4-yl]phenyl]-5-chloropyrimidine-2-carboxamide Chemical compound N1=C(N)N(C)C(=O)C[C@@]1(C)C1=CC=CC(NC(=O)C=2N=CC(Cl)=CN=2)=C1 VZUGBLTVBZJZOE-KRWDZBQOSA-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
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
239000002664 nootropic agent Substances 0.000 description 1
230000001777 nootropic effect Effects 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
238000011302 passive avoidance test Methods 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
QQBPIHBUCMDKFG-UHFFFAOYSA-N phenazopyridine hydrochloride Chemical group Cl.NC1=NC(N)=CC=C1N=NC1=CC=CC=C1 QQBPIHBUCMDKFG-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000004714 phosphonium salts Chemical group 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000000049 pigment Substances 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical group O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 1
150000003242 quaternary ammonium salts Chemical group 0.000 description 1
238000013102 re-test Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
239000011435 rock Substances 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003334 secondary amides Chemical class 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
229950011008 tetrachloroethylene Drugs 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003560 thiocarbamic acids Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
210000003437 trachea Anatomy 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
238000005809 transesterification reaction Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
150000004654 triazenes 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
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
QDNCLIPKBNMUPP-UHFFFAOYSA-N trimethyloxidanium Chemical compound C[O+](C)C QDNCLIPKBNMUPP-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Pain & Pain Management (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)

DD84259604A 1983-01-27 1984-01-25 Verfahren zur herstellung neuer substituierter pyrrolidinderivate DD215539A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH45483		1983-01-27

Publications (1)

Publication Number	Publication Date
DD215539A5 true DD215539A5 (de)	1984-11-14

Family

ID=4187392

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD84259604A DD215539A5 (de)	1983-01-27	1984-01-25	Verfahren zur herstellung neuer substituierter pyrrolidinderivate

Country Status (12)

Country	Link
EP (1)	EP0115473A3 (fi)
JP (1)	JPS59141544A (fi)
KR (1)	KR840007570A (fi)
AU (1)	AU2383984A (fi)
DD (1)	DD215539A5 (fi)
DK (1)	DK35984A (fi)
FI (1)	FI840261A (fi)
GR (1)	GR81747B (fi)
IL (1)	IL70791A0 (fi)
NO (1)	NO840311L (fi)
PT (1)	PT78008B (fi)
ZA (1)	ZA84595B (fi)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5021568A (en) *	1988-04-22	1991-06-04	Shipov Alexandr G	Lactam-1-acetic acid carbalkoxymethyl esters and method for preparing same

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IT1190378B (it) *	1985-06-21	1988-02-16	Isf Spa	Derivati pirrolidonici
JP2997488B2 (ja) *	1989-12-25	2000-01-11	興研株式会社	腫瘍細胞増殖抑制剤
CA3231236A1 (en) *	2021-09-30	2023-04-06	Protinhi B.V.	Protease inhibitors

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AT360980B (de) *	1976-01-14	1981-02-10	Pliva Pharm & Chem Works	Verfahren zur herstellung von n-alkylamiden des 2-oxo-1-pyrrolidins
GB1539817A (en) *	1976-10-22	1979-02-07	Ucb Sa	N-substituted lactams
US4254107A (en) *	1979-11-27	1981-03-03	Merck & Co., Inc.	Long-lasting agonists of enkephalin

1984
- 1984-01-23 EP EP84810041A patent/EP0115473A3/de not_active Withdrawn
- 1984-01-23 FI FI840261A patent/FI840261A/fi not_active Application Discontinuation
- 1984-01-25 GR GR73620A patent/GR81747B/el unknown
- 1984-01-25 DD DD84259604A patent/DD215539A5/de unknown
- 1984-01-25 PT PT78008A patent/PT78008B/pt unknown
- 1984-01-26 ZA ZA84595A patent/ZA84595B/xx unknown
- 1984-01-26 AU AU23839/84A patent/AU2383984A/en not_active Abandoned
- 1984-01-26 NO NO840311A patent/NO840311L/no unknown
- 1984-01-26 JP JP59011111A patent/JPS59141544A/ja active Pending
- 1984-01-26 DK DK35984A patent/DK35984A/da not_active Application Discontinuation
- 1984-01-26 IL IL70791A patent/IL70791A0/xx unknown
- 1984-01-26 KR KR1019840000340A patent/KR840007570A/ko not_active Application Discontinuation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5021568A (en) *	1988-04-22	1991-06-04	Shipov Alexandr G	Lactam-1-acetic acid carbalkoxymethyl esters and method for preparing same

Also Published As

Publication number	Publication date
DK35984A (da)	1984-07-28
ZA84595B (en)	1984-11-28
EP0115473A2 (de)	1984-08-08
PT78008B (en)	1986-06-18
PT78008A (en)	1984-02-01
NO840311L (no)	1984-07-30
FI840261A0 (fi)	1984-01-23
KR840007570A (ko)	1984-12-08
GR81747B (fi)	1984-12-12
FI840261A (fi)	1984-07-28
IL70791A0 (en)	1984-04-30
AU2383984A (en)	1984-08-02
JPS59141544A (ja)	1984-08-14
EP0115473A3 (de)	1987-01-21
DK35984D0 (da)	1984-01-26

Publication	Publication Date	Title
EP0184550B1 (de)	1992-03-18	5-Amino-4-hydroxyvalerylamid-Derivate
DE69400798T2 (de)	1997-03-13	Urethane und Urea zur Induktion der Cytokin-Produktion
EP0119161B1 (de)	1989-06-28	Gewisse Benzazocinon- und Benzazoninon-Derivate, Verfahren zu ihrer Herstellung, pharmazeutische Präparate enthaltend diese Verbindungen, sowie ihre therapeutische Verwendung
EP0197478B1 (de)	1990-09-19	Neue Diphosphonsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
CH676988A5 (fi)	1991-03-28
CH677672A5 (fi)	1991-06-14
DD217807A5 (de)	1985-01-23	Verfahren zur herstellung neuer substituierter tetrapeptide
DE3508251A1 (de)	1986-09-11	Dipeptide
EP0169812B1 (de)	1989-08-23	Phosphatidylverbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung
DD216005A5 (de)	1984-11-28	Verfahren zur herstellung von pyrrolidinonderivaten
DE3628650A1 (de)	1987-09-24	Renininhibitoren, verfahren zur herstellung und ihre verwendung
DD283807A5 (de)	1990-10-24	Verfahren zur herstellung von cycloalkyl-substituierten glutaramid-derivaten
EP0144290A2 (de)	1985-06-12	Substituierte Aethylendiaminderivate
DD215539A5 (de)	1984-11-14	Verfahren zur herstellung neuer substituierter pyrrolidinderivate
EP0233837A2 (de)	1987-08-26	Saccharidderivate und Verfahren zu ihrer Herstellung
DE69221473T2 (de)	1998-01-22	Bis-naphthalimide, die amide und thioamide als linker enthalten als krebsmittel
DE60010711T2 (de)	2005-06-09	Amido-spiropiperidine promovieren die freisetzung von wachstumshormonen
EP0462949A1 (en)	1991-12-27	1-alkyl-3-(acylamino)-epsilon-caprolactames as enhancers of learning and memory and pharmaceutical compositions containing same
EP0174912A2 (de)	1986-03-19	Phosphorverbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung
DE69018816T2 (de)	1995-11-16	Aminosäurederivate.
DE69027460T2 (de)	1996-10-10	Peptidderivate und deren pharmazeutische Verwendung
DE69205073T2 (de)	1996-03-07	3-Acylamino-2-pyrrolidinone zur Verbesserung der Lernfähigkeit und des Gedächtnisses und diese enthaltende pharmazeutische Zubereitungen.
EP0403828A1 (de)	1990-12-27	Renininhibitorische Peptide, Verfahren zur ihrer Herstellung und ihre Verwendung in Arzneimitteln
EP0391850B1 (de)	1994-09-28	Ungesättigte Aminodicarbonsäurederivate
DE3222779C2 (fi)	1991-01-03

DD215539A5 - Verfahren zur herstellung neuer substituierter pyrrolidinderivate - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (1)

Publications (1)

Family

ID=4187392

Family Applications (1)

Country Status (12)

Cited By (1)

Families Citing this family (3)

Family Cites Families (3)

Cited By (1)

Also Published As

Similar Documents