SK245992A3 - Hydantoin derivatives - Google Patents

Hydantoin derivatives Download PDF

Info

Publication number: SK245992A3
Authority: SK; Slovakia
Prior art keywords: formula; dioxoimidazolidin; alkyl; aryl; mmol
Prior art date: 1991-08-08

Application number

SK2459-92A

Other languages

English (en)

Slovak (sk)

Inventor

Wolfgang Konig

Gerhard Zoller

Melitta Just

Bernd Jablonka

Original Assignee

Cassella 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.)

1991-08-08

Filing date

1992-08-07

Publication date

2000-09-12

1992-08-07 Application filed by Cassella Ag filed Critical Cassella Ag

2000-09-12 Publication of SK245992A3 publication Critical patent/SK245992A3/sk

Links

150000001469 hydantoins Chemical class 0.000 title claims abstract description 15
229940053195 antiepileptics hydantoin derivative Drugs 0.000 title claims abstract description 8
238000000034 method Methods 0.000 claims abstract description 24
208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 5
238000002360 preparation method Methods 0.000 claims abstract description 3
230000002401 inhibitory effect Effects 0.000 claims abstract 3
-1 hydroxy, carboxy Chemical group 0.000 claims description 84
150000001875 compounds Chemical class 0.000 claims description 58
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
150000001413 amino acids Chemical group 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
150000002148 esters Chemical class 0.000 claims description 13
235000001014 amino acid Nutrition 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 11
150000002431 hydrogen Chemical group 0.000 claims description 10
238000009833 condensation Methods 0.000 claims description 9
230000005494 condensation Effects 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
108010016626 Dipeptides Proteins 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
108090000765 processed proteins & peptides Proteins 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical group OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 claims description 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
102000004196 processed proteins & peptides Human genes 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
210000000988 bone and bone Anatomy 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000000524 functional group Chemical group 0.000 claims description 3
210000002997 osteoclast Anatomy 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
125000003275 alpha amino acid group Chemical group 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000005518 carboxamido group Chemical group 0.000 claims description 2
239000012634 fragment Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
239000004474 valine Substances 0.000 claims description 2
125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 60
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
239000000243 solution Substances 0.000 description 31
229960000583 acetic acid Drugs 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
239000000126 substance Substances 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
239000000706 filtrate Substances 0.000 description 19
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 15
238000003756 stirring Methods 0.000 description 14
238000010992 reflux Methods 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
239000000047 product Substances 0.000 description 12
150000003254 radicals Chemical group 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
229940024606 amino acid Drugs 0.000 description 10
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
YKPKXMAVLXBQDT-UHFFFAOYSA-N ethyl 2-(carbamoylamino)acetate Chemical compound CCOC(=O)CNC(N)=O YKPKXMAVLXBQDT-UHFFFAOYSA-N 0.000 description 9
239000000203 mixture Substances 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
229920005654 Sephadex Polymers 0.000 description 8
239000012507 Sephadex™ Substances 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
239000000725 suspension Substances 0.000 description 8
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 7
125000004093 cyano group Chemical group *C#N 0.000 description 7
239000002198 insoluble material Substances 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
229960004295 valine Drugs 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000012071 phase Substances 0.000 description 6
239000011736 potassium bicarbonate Substances 0.000 description 6
235000015497 potassium bicarbonate Nutrition 0.000 description 6
229910000028 potassium bicarbonate Inorganic materials 0.000 description 6
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 6
229940086066 potassium hydrogencarbonate Drugs 0.000 description 6
WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 6
150000007513 acids Chemical class 0.000 description 5
239000000969 carrier Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
150000002168 ethanoic acid esters Chemical class 0.000 description 5
DUVOZUPPHBRJJO-UHFFFAOYSA-N ethyl 2-isocyanatoacetate Chemical compound CCOC(=O)CN=C=O DUVOZUPPHBRJJO-UHFFFAOYSA-N 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
230000000638 stimulation Effects 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
239000000825 pharmaceutical preparation Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
SUNPBNUXHMRMDW-VIFPVBQESA-N 2-[(4s)-4-[(4-nitrophenyl)methyl]-2,5-dioxoimidazolidin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=O)N[C@H]1CC1=CC=C([N+]([O-])=O)C=C1 SUNPBNUXHMRMDW-VIFPVBQESA-N 0.000 description 3
VTFNYAJUXHSOIR-UHFFFAOYSA-N 2-[4-[(4-cyanophenyl)methylidene]-2,5-dioxoimidazolidin-1-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=O)NC1=CC1=CC=C(C#N)C=C1 VTFNYAJUXHSOIR-UHFFFAOYSA-N 0.000 description 3
WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
108090000190 Thrombin Proteins 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
238000006243 chemical reaction Methods 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
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
229940012952 fibrinogen Drugs 0.000 description 3
229940091173 hydantoin Drugs 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000001629 suppression Effects 0.000 description 3
239000003826 tablet Substances 0.000 description 3
229960004072 thrombin Drugs 0.000 description 3
238000011282 treatment Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
FQTJZLUYYAUJSV-UHFFFAOYSA-N 2-(3-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid Chemical compound CN1CC(=O)N(CC(O)=O)C1=O FQTJZLUYYAUJSV-UHFFFAOYSA-N 0.000 description 2
CWQJAQGYEOIBMN-RGMNGODLSA-N 2-[(4s)-4-(4-aminobutyl)-2,5-dioxoimidazolidin-1-yl]acetic acid;hydrochloride Chemical compound Cl.NCCCC[C@@H]1NC(=O)N(CC(O)=O)C1=O CWQJAQGYEOIBMN-RGMNGODLSA-N 0.000 description 2
UFSBXYSZYLLVER-AXDSSHIGSA-N 2-[(4s)-4-[(diaminomethylideneamino)-(4-nitrophenyl)methyl]-2,5-dioxoimidazolidin-1-yl]acetic acid Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(N=C(N)N)[C@@H]1NC(=O)N(CC(O)=O)C1=O UFSBXYSZYLLVER-AXDSSHIGSA-N 0.000 description 2
REMALCFAAVFCKO-RGMNGODLSA-N 2-[(4s)-4-[3-(diaminomethylideneamino)propyl]-3-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid;hydrochloride Chemical compound Cl.CN1[C@@H](CCCNC(N)=N)C(=O)N(CC(O)=O)C1=O REMALCFAAVFCKO-RGMNGODLSA-N 0.000 description 2
LZCZCVOELMEXCK-UHFFFAOYSA-N 2-[4-[(4-cyanophenyl)methylidene]-3-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid Chemical compound CN1C(=O)N(CC(O)=O)C(=O)C1=CC1=CC=C(C#N)C=C1 LZCZCVOELMEXCK-UHFFFAOYSA-N 0.000 description 2
INCUIQXISBCGAM-JTQLQIEISA-N 3-[(4s)-4-[3-[[amino(nitramido)methylidene]amino]propyl]-2,5-dioxoimidazolidin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2C([C@H](CCCNC(=N)N[N+]([O-])=O)NC2=O)=O)=C1 INCUIQXISBCGAM-JTQLQIEISA-N 0.000 description 2
SOSBACKXIXFAHB-QMMMGPOBSA-N 3-[acetyl-[(4s)-4-[3-(diaminomethylideneamino)propyl]-2,5-dioxoimidazolidin-1-yl]amino]propanoic acid Chemical compound OC(=O)CCN(C(=O)C)N1C(=O)N[C@@H](CCCNC(N)=N)C1=O SOSBACKXIXFAHB-QMMMGPOBSA-N 0.000 description 2
OBTKOWGJCLQKMO-UHFFFAOYSA-N 4-[(2,5-dioxoimidazolidin-4-ylidene)methyl]benzonitrile Chemical compound N1C(=O)NC(=O)C1=CC1=CC=C(C#N)C=C1 OBTKOWGJCLQKMO-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
108010049003 Fibrinogen Proteins 0.000 description 2
102000008946 Fibrinogen Human genes 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical class NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
238000005684 Liebig rearrangement reaction Methods 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000007536 Thrombosis Diseases 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
230000037396 body weight Effects 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
235000008504 concentrate Nutrition 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
PFYJFSBYXRULHC-UHFFFAOYSA-N ethyl 3-(carbamoylamino)benzoate Chemical compound CCOC(=O)C1=CC=CC(NC(N)=O)=C1 PFYJFSBYXRULHC-UHFFFAOYSA-N 0.000 description 2
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
239000012535 impurity Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
239000003094 microcapsule Substances 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
238000005897 peptide coupling reaction Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
239000006187 pill Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
239000002904 solvent Substances 0.000 description 2
VRQDPNKOUPEWOC-UHFFFAOYSA-N spiro[bicyclo[2.2.2]octane-3,3'-piperidine] Chemical compound C1CCNCC21C(CC1)CCC1C2 VRQDPNKOUPEWOC-UHFFFAOYSA-N 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
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125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 description 1
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
229960002768 dipyridamole Drugs 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
BRABADKXISRCSH-UHFFFAOYSA-N ethyl 2-(carbamoylamino)acetate hydrochloride Chemical compound CCOC(=O)CNC(=O)N.Cl BRABADKXISRCSH-UHFFFAOYSA-N 0.000 description 1
BTKSUULMJNNXHG-UHFFFAOYSA-N ethyl 2-(methylamino)acetate Chemical compound CCOC(=O)CNC BTKSUULMJNNXHG-UHFFFAOYSA-N 0.000 description 1
GFUIEEHBCUMVOF-UHFFFAOYSA-N ethyl N-(methylcarbamoyl)carbamate hydrochloride Chemical compound Cl.C(C)OC(=O)NC(NC)=O GFUIEEHBCUMVOF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
PIHPSKJRLDSJPX-UHFFFAOYSA-N ethyl n-carbamoylcarbamate Chemical compound CCOC(=O)NC(N)=O PIHPSKJRLDSJPX-UHFFFAOYSA-N 0.000 description 1
239000003925 fat Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
238000002825 functional assay Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
125000006277 halobenzyl group Chemical group 0.000 description 1
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
239000007943 implant Substances 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000000297 inotrophic effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000005438 isoindazolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
HSSZGHOHMLQSFH-LURJTMIESA-N methyl (2s)-5-(diaminomethylideneamino)-2-(methylamino)pentanoate Chemical compound COC(=O)[C@@H](NC)CCCNC(N)=N HSSZGHOHMLQSFH-LURJTMIESA-N 0.000 description 1
SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
FLZZNZJENFNFOJ-UHFFFAOYSA-N methyl n'-nitrocarbamimidothioate Chemical compound CSC(N)=N[N+]([O-])=O FLZZNZJENFNFOJ-UHFFFAOYSA-N 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
IYJMSDVSVHDVGT-PEQKVOOWSA-N metildigoxin Chemical compound O1[C@H](C)[C@@H](OC)[C@@H](O)C[C@@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O IYJMSDVSVHDVGT-PEQKVOOWSA-N 0.000 description 1
229960003746 metildigoxin Drugs 0.000 description 1
IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
229960002237 metoprolol Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 1
229960004027 molsidomine Drugs 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229960003642 nicergoline Drugs 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229960004738 nicotinyl alcohol Drugs 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000001777 nootropic effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum 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
CQYBNXGHMBNGCG-RNJXMRFFSA-N octahydroindole-2-carboxylic acid Chemical compound C1CCC[C@H]2N[C@H](C(=O)O)C[C@@H]21 CQYBNXGHMBNGCG-RNJXMRFFSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
229960004570 oxprenolol Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
229960002035 penbutolol Drugs 0.000 description 1
CYXKNKQEMFBLER-UHFFFAOYSA-N perhexiline Chemical compound C1CCCNC1CC(C1CCCCC1)C1CCCCC1 CYXKNKQEMFBLER-UHFFFAOYSA-N 0.000 description 1
229960000989 perhexiline Drugs 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
229960004526 piracetam Drugs 0.000 description 1
229950002220 pirlindole Drugs 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
VNUORQWNUXXHLX-UHFFFAOYSA-N pyrazolidine-3-carboxylic acid Chemical compound OC(=O)C1CCNN1 VNUORQWNUXXHLX-UHFFFAOYSA-N 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
ZLQMRLSBXKQKMG-UHFFFAOYSA-N rauniticine Natural products COC(=O)C1=CC2CC3N(CCc4c3[nH]c5ccccc45)CC2C(C)O1 ZLQMRLSBXKQKMG-UHFFFAOYSA-N 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
229960004940 sulpiride Drugs 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
CAJUTDZNFURUCA-NSHDSACASA-N tert-butyl 3-[acetyl-[(4s)-4-[3-(diaminomethylideneamino)propyl]-2,5-dioxoimidazolidin-1-yl]amino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(C(=O)C)N1C(=O)N[C@@H](CCCN=C(N)N)C1=O CAJUTDZNFURUCA-NSHDSACASA-N 0.000 description 1
ZJXHVYSDMUKUCA-UHFFFAOYSA-N tert-butyl 3-aminopropanoate Chemical compound CC(C)(C)OC(=O)CCN ZJXHVYSDMUKUCA-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000006227 trimethylsilylation reaction Methods 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229960001722 verapamil Drugs 0.000 description 1
229960002726 vincamine Drugs 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1

Classifications

- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/96—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
- 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
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
- 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
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- 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
- C07K5/1019—Tetrapeptides with the first amino acid being basic
- 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
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Crystallography & Structural Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Hematology (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Peptides Or Proteins (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK2459-92A 1991-08-08 1992-08-07 Hydantoin derivatives SK245992A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE4126277A DE4126277A1 (de)	1991-08-08	1991-08-08	Hydantoinderivate

Publications (1)

Publication Number	Publication Date
SK245992A3 true SK245992A3 (en)	2000-09-12

Family

ID=6437942

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK2459-92A SK245992A3 (en)	1991-08-08	1992-08-07	Hydantoin derivatives

Country Status (16)

Country	Link
US (1)	US5389614A (fr)
EP (1)	EP0530505B1 (fr)
JP (1)	JP3293885B2 (fr)
KR (1)	KR100242621B1 (fr)
AT (1)	ATE128985T1 (fr)
CA (1)	CA2075590C (fr)
CZ (1)	CZ289929B6 (fr)
DE (2)	DE4126277A1 (fr)
DK (1)	DK0530505T3 (fr)
ES (1)	ES2081000T3 (fr)
GR (1)	GR3018557T3 (fr)
HU (1)	HU218922B (fr)
IL (1)	IL102759A (fr)
SK (1)	SK245992A3 (fr)
TW (1)	TW204345B (fr)
ZA (1)	ZA925934B (fr)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4009506A1 (de) *	1990-03-24	1991-09-26	Hoechst Ag	Hydantoinderivate
DE4213634A1 (de) *	1992-04-24	1993-10-28	Cassella Ag	2,4-Dioxo-imidazolidin-Derivate
DE4224414A1 (de) *	1992-07-24	1994-01-27	Cassella Ag	Phenylimidazolidin-derivate, ihre Herstellung und ihre Verwendung
DE4228717A1 (de) *	1992-08-28	1994-03-03	Cassella Ag	Imidazolidin-Derivate
DE4308034A1 (de) *	1993-03-13	1994-09-15	Cassella Ag	Neue Heterocyclen, ihre Herstellung und ihre Verwendung
DE4309867A1 (de) *	1993-03-26	1994-09-29	Cassella Ag	Neue Harnstoffderivate, ihre Herstellung und Verwendung
DE4427979A1 (de) *	1993-11-15	1996-02-15	Cassella Ag	Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung
US5849736A (en) *	1993-11-24	1998-12-15	The Dupont Merck Pharmaceutical Company	Isoxazoline and isoxazole fibrinogen receptor antagonists
US5563158A (en) *	1993-12-28	1996-10-08	The Dupont Merck Pharmaceutical Company	Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
DE19515177A1 (de) *	1995-04-28	1996-10-31	Cassella Ag	Hydantoinderivate als Zwischenprodukte für pharmazeutische Wirkstoffe
ZA963391B (en) *	1995-05-24	1997-10-29	Du Pont Merck Pharma	Isoxazoline fibrinogen receptor antagonists.
JP3895792B2 (ja)	1995-12-08	2007-03-22	プロスケリア・エス・ア・エス	骨形成促進剤
ES2171768T3 (es)	1996-03-20	2002-09-16	Hoechst Ag	Inhibidores de la resorcion osea y antagonistas de receptores de vitronectina.
DE19622489A1 (de)	1996-06-05	1997-12-11	Hoechst Ag	Salze des 3-(2-(4-(4-(Amino-imino-methyl)-phenyl)-4- methyl-2,5-dioxo-imidazolidin-1-yl)-acetylamino)-3- phenyl-propionsäure-ethylesters
DE19647380A1 (de) *	1996-11-15	1998-05-20	Hoechst Ag	5-Ring-Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten
US5859190A (en) *	1997-02-04	1999-01-12	Trega Biosciences, Inc.	Combinatorial libraries of hydantoin and thiohydantoin derivatives, methods of making the libraries and compounds therein
KR19990012061A (ko) *	1997-07-26	1999-02-25	성재갑	파네실 전이효소 저해제로 유용한 하이덴토인 유도체
US6384061B1 (en) *	1997-07-26	2002-05-07	Lg Chemical Ltd.	Hydantoin compounds and methods related thereto
DE19741235A1 (de) *	1997-09-18	1999-03-25	Hoechst Marion Roussel De Gmbh	Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE19741873A1 (de) *	1997-09-23	1999-03-25	Hoechst Marion Roussel De Gmbh	Neue 5-Ring-Heterocyclen, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE19751251A1 (de)	1997-11-19	1999-05-20	Hoechst Marion Roussel De Gmbh	Substituierte Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmezeutische Präparate
DE19821483A1 (de) *	1998-05-14	1999-11-18	Hoechst Marion Roussel De Gmbh	Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE19922462A1 (de)	1999-05-17	2000-11-23	Aventis Pharma Gmbh	Spiro-imidazolidinderivate, ihre Herstellung ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE10111877A1 (de)	2001-03-10	2002-09-12	Aventis Pharma Gmbh	Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
DE10137595A1 (de) *	2001-08-01	2003-02-13	Aventis Pharma Gmbh	Neue Imidazolidinderivate, ihre Herstellung und ihre Verwendung
CN1659136A (zh) *	2002-04-18	2005-08-24	弗吉尼亚大学专利基金会	新的钠通道阻滞剂
TW200519105A (en) *	2003-10-20	2005-06-16	Lg Life Science Ltd	Novel inhibitors of DPP-IV, methods of preparing the same, and pharmaceutical compositions containing the same as an active agent
JP5199108B2 (ja) *	2005-11-14	2013-05-15	ユニヴァーシティーオブサザンカリフォルニア	インテグリン結合小分子
EP3180335B1 (fr)	2014-08-11	2021-05-05	Angion Biomedica Corporation	Inhibiteurs de cytochrome p450 et leurs utilisations
CN107531631B (zh)	2014-12-31	2021-09-03	安吉昂生物医药公司	用于治疗疾病的方法和药剂

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4683291A (en) *	1985-10-28	1987-07-28	Scripps Clinic And Research Foundation	Platelet binding inhibitors
US4857508A (en) *	1987-12-03	1989-08-15	Monsanto Company	Novel platelet-aggregation inhibitor peptide derivatives
US5053393A (en) *	1988-07-20	1991-10-01	Monsanto Company	Novel platelet-aggregation inhibitor
DE4009506A1 (de) *	1990-03-24	1991-09-26	Hoechst Ag	Hydantoinderivate
GB9007751D0 (en) *	1990-04-05	1990-06-06	Ciba Geigy Ag	Novel platelet-aggregation inhibitors

1991
- 1991-08-08 DE DE4126277A patent/DE4126277A1/de not_active Withdrawn
1992
- 1992-07-31 DE DE59203976T patent/DE59203976D1/de not_active Expired - Lifetime
- 1992-07-31 ES ES92113086T patent/ES2081000T3/es not_active Expired - Lifetime
- 1992-07-31 DK DK92113086.0T patent/DK0530505T3/da active
- 1992-07-31 AT AT92113086T patent/ATE128985T1/de not_active IP Right Cessation
- 1992-07-31 EP EP92113086A patent/EP0530505B1/fr not_active Expired - Lifetime
- 1992-08-01 TW TW081106140A patent/TW204345B/zh active
- 1992-08-04 US US07/924,745 patent/US5389614A/en not_active Expired - Lifetime
- 1992-08-07 SK SK2459-92A patent/SK245992A3/sk unknown
- 1992-08-07 CZ CS19922459A patent/CZ289929B6/cs not_active IP Right Cessation
- 1992-08-07 CA CA002075590A patent/CA2075590C/fr not_active Expired - Lifetime
- 1992-08-07 JP JP21180192A patent/JP3293885B2/ja not_active Expired - Lifetime
- 1992-08-07 ZA ZA925934A patent/ZA925934B/xx unknown
- 1992-08-07 KR KR1019920014163A patent/KR100242621B1/ko not_active Expired - Fee Related
- 1992-08-07 IL IL102759A patent/IL102759A/xx not_active IP Right Cessation
- 1992-08-07 HU HU9202583A patent/HU218922B/hu not_active IP Right Cessation
1995
- 1995-12-28 GR GR950403687T patent/GR3018557T3/el unknown

Also Published As

Publication number	Publication date
EP0530505B1 (fr)	1995-10-11
CA2075590C (fr)	2003-01-07
HU218922B (hu)	2000-12-28
US5389614A (en)	1995-02-14
IL102759A0 (en)	1993-01-31
DE59203976D1 (de)	1995-11-16
JPH05213895A (ja)	1993-08-24
CA2075590A1 (fr)	1993-02-09
AU2089292A (en)	1993-03-11
DK0530505T3 (da)	1996-02-12
EP0530505A3 (en)	1993-12-29
ATE128985T1 (de)	1995-10-15
CZ245992A3 (en)	1993-12-15
KR100242621B1 (ko)	2000-03-02
HUT61779A (en)	1993-03-01
HU9202583D0 (en)	1992-10-28
IL102759A (en)	1997-06-10
AU651716B2 (en)	1994-07-28
CZ289929B6 (cs)	2002-04-17
JP3293885B2 (ja)	2002-06-17
EP0530505A2 (fr)	1993-03-10
KR930004274A (ko)	1993-03-22
ES2081000T3 (es)	1996-02-16
GR3018557T3 (en)	1996-03-31
ZA925934B (en)	1993-04-28
DE4126277A1 (de)	1993-02-11
TW204345B (fr)	1993-04-21

Publication	Publication Date	Title
KR100242621B1 (ko)	2000-03-02	히단토인유도체, 이의 제조방법 및 이를 포함하는 약제학적 조성물
US5397796A (en)	1995-03-14	2,4-dioxoimidazolidine compounds and compositions, and processes for administering same
US5554594A (en)	1996-09-10	Imidazolidine derivatives
US5424293A (en)	1995-06-13	Phenylimidazolidine derivatives and their use
KR100278532B1 (ko)	2001-01-15	4-옥소-2-티옥소이미다졸리딘 유도체, 이의 제조방법 및 이를 포함하는 약제학적 제제
DE4308034A1 (de)	1994-09-15	Neue Heterocyclen, ihre Herstellung und ihre Verwendung
CA2169643A1 (fr)	1995-05-26	Heterocycles substitues a 5 noyaux, leur preparation et leur utilisation
US5681838A (en)	1997-10-28	Substituted amino compounds, their preparation and their use as inhibitors of thrombocyte-aggregation
CA2154477C (fr)	2007-04-10	Derives de substitution amines; leur preparation et leur utilisation comme inhibiteurs de l'agregation des thrombocytes