SK284471B6 - Substituované päťčlenné heterocykly, spôsob ich výroby, ich medicínske použitie, farmaceutický prostriedok s ich obsahom a spôsob jeho výroby - Google Patents
Substituované päťčlenné heterocykly, spôsob ich výroby, ich medicínske použitie, farmaceutický prostriedok s ich obsahom a spôsob jeho výroby Download PDFInfo
- Publication number
- SK284471B6 SK284471B6 SK585-96A SK58596A SK284471B6 SK 284471 B6 SK284471 B6 SK 284471B6 SK 58596 A SK58596 A SK 58596A SK 284471 B6 SK284471 B6 SK 284471B6
- Authority
- SK
- Slovakia
- Prior art keywords
- methyl
- group
- phenyl
- carbon atoms
- amino
- Prior art date
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- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 230000027455 binding Effects 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 6
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims abstract description 5
- 210000002997 osteoclast Anatomy 0.000 claims abstract description 5
- 239000003112 inhibitor Substances 0.000 claims abstract description 4
- -1 nitro, methylenedioxy Chemical group 0.000 claims description 120
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000001721 carbon Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 9
- 239000013543 active substance Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 208000007536 Thrombosis Diseases 0.000 claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 230000017531 blood circulation Effects 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 150000003841 chloride salts Chemical class 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- 230000002776 aggregation Effects 0.000 abstract description 4
- 238000004220 aggregation Methods 0.000 abstract description 4
- 201000009030 Carcinoma Diseases 0.000 abstract 1
- 210000001772 blood platelet Anatomy 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 119
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 102
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 100
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 81
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Substances 0.000 description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 62
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 47
- 229960000583 acetic acid Drugs 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 46
- 239000000126 substance Substances 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 29
- 239000002244 precipitate Substances 0.000 description 26
- 239000001120 potassium sulphate Substances 0.000 description 25
- 238000000746 purification Methods 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 239000012362 glacial acetic acid Substances 0.000 description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- 229960005261 aspartic acid Drugs 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 14
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 14
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 229940012952 fibrinogen Drugs 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 7
- 108010049003 Fibrinogen Proteins 0.000 description 7
- 102000008946 Fibrinogen Human genes 0.000 description 7
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 7
- 229910052939 potassium sulfate Inorganic materials 0.000 description 7
- 235000011151 potassium sulphates Nutrition 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 6
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 5
- 239000005695 Ammonium acetate Substances 0.000 description 5
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- 229940043376 ammonium acetate Drugs 0.000 description 5
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- XSOHXMFFSKTSIT-UHFFFAOYSA-N 1-adamantylmethanamine Chemical compound C1C(C2)CC3CC2CC1(CN)C3 XSOHXMFFSKTSIT-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
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- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
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- 210000004623 platelet-rich plasma Anatomy 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- 238000009835 boiling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
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- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
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- IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 2
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- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
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- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
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- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
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- LVIYQYZFXDAWQD-UHFFFAOYSA-N methyl 2-hydrazinylacetate Chemical compound COC(=O)CNN LVIYQYZFXDAWQD-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 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
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- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- NSETWVJZUWGCKE-UHFFFAOYSA-N propylphosphonic acid Chemical compound CCCP(O)(O)=O NSETWVJZUWGCKE-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- ZLQMRLSBXKQKMG-UHFFFAOYSA-N rauniticine Natural products COC(=O)C1=CC2CC3N(CCc4c3[nH]c5ccccc45)CC2C(C)O1 ZLQMRLSBXKQKMG-UHFFFAOYSA-N 0.000 description 1
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- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07K5/021—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)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
-
- 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
-
- 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
-
- 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4338944A DE4338944A1 (de) | 1993-11-15 | 1993-11-15 | Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung |
| DE4427979A DE4427979A1 (de) | 1993-11-15 | 1994-08-08 | Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung |
| PCT/EP1994/003491 WO1995014008A1 (de) | 1993-11-15 | 1994-10-24 | Substituierte 5-ring-heterocyclen, ihre herstellung und ihre verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK58596A3 SK58596A3 (en) | 1997-05-07 |
| SK284471B6 true SK284471B6 (sk) | 2005-04-01 |
Family
ID=25931237
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK585-96A SK284471B6 (sk) | 1993-11-15 | 1994-10-24 | Substituované päťčlenné heterocykly, spôsob ich výroby, ich medicínske použitie, farmaceutický prostriedok s ich obsahom a spôsob jeho výroby |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5981492A (cs) |
| EP (1) | EP0729460B1 (cs) |
| JP (1) | JP3813983B2 (cs) |
| KR (1) | KR100402192B1 (cs) |
| CN (1) | CN1069316C (cs) |
| AT (1) | ATE217615T1 (cs) |
| AU (1) | AU693811B2 (cs) |
| CA (1) | CA2169643A1 (cs) |
| CY (1) | CY2385B1 (cs) |
| CZ (1) | CZ292573B6 (cs) |
| DE (2) | DE4427979A1 (cs) |
| DK (1) | DK0729460T3 (cs) |
| ES (1) | ES2176261T3 (cs) |
| FI (1) | FI113265B (cs) |
| HU (1) | HU223806B1 (cs) |
| IL (1) | IL111622A (cs) |
| PL (1) | PL180906B1 (cs) |
| PT (1) | PT729460E (cs) |
| RU (1) | RU2151143C1 (cs) |
| SK (1) | SK284471B6 (cs) |
| TW (1) | TW326040B (cs) |
| WO (1) | WO1995014008A1 (cs) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4427979A1 (de) | 1993-11-15 | 1996-02-15 | Cassella Ag | Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung |
| DE19515177A1 (de) * | 1995-04-28 | 1996-10-31 | Cassella Ag | Hydantoinderivate als Zwischenprodukte für pharmazeutische Wirkstoffe |
| 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 |
| DE19624604A1 (de) * | 1996-06-20 | 1998-01-02 | Hoechst Ag | Verfahren zur Herstellung chiraler, nicht racemischer (4-Aryl-2,5-dioxoimidazolidin-1-yl)essigsäuren |
| DE19629816A1 (de) | 1996-07-24 | 1998-01-29 | Hoechst Ag | Neue Cycloalkyl-Derivate als Inhibitoren der Knochenresorption und Vitronectinrezeptor-Antagonisten |
| DE19629817A1 (de) * | 1996-07-24 | 1998-01-29 | Hoechst Ag | Neue Imino-Derivate als Inhibitoren der Knochenresorption und Vitronectinrezeptor-Antagonisten |
| DE19647381A1 (de) * | 1996-11-15 | 1998-05-20 | Hoechst Ag | Neue Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| KR100697959B1 (ko) * | 1996-11-15 | 2007-07-09 | 훽스트 게엠베하 | 백혈구부착의억제제및vla-4길항제로서의헤테로사이클 |
| DE19647380A1 (de) * | 1996-11-15 | 1998-05-20 | Hoechst Ag | 5-Ring-Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| PL323130A1 (en) | 1996-11-15 | 1998-05-25 | Hoechst Ag | Application of heterocyclic compounds in production of a pharmaceutic agent, novel heterocyclic compounds and pharmaceutic agent as such |
| 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 |
| US6624187B1 (en) * | 2000-06-12 | 2003-09-23 | Health Research, Inc. | Long wave length absorbing bacteriochlorin alkyl ether analogs |
| 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 |
| JP2007514742A (ja) * | 2003-12-18 | 2007-06-07 | アストラゼネカ アクチボラグ | トロンビンの阻害薬として有用な新規５，６−ジヒドロピリジン−２−オン化合物 |
| CN107383147A (zh) * | 2017-07-14 | 2017-11-24 | 广东食品药品职业学院 | 一种β‑谷甾醇与依帕司他偶联物及其制备方法和用途 |
| WO2019200202A1 (en) * | 2018-04-12 | 2019-10-17 | Morphic Therapeutic, Inc. | Antagonists of human integrin (alpha4)(beta7) |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| BR112022007284A2 (pt) | 2019-10-16 | 2022-07-05 | Morphic Therapeutic Inc | Inibição de integrina humana alpha-4 beta-7 |
| CN117800921B (zh) * | 2024-02-28 | 2024-06-11 | 南京市鸿舜医药科技有限公司 | 一种咪唑烷二酮类hdac抑制剂、制备方法及应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3300510A (en) * | 1964-03-06 | 1967-01-24 | American Home Prod | Hydantoins |
| DE2714655A1 (de) * | 1977-04-01 | 1978-10-05 | Bayer Ag | Verfahren zur herstellung von hydantoinen |
| EP0006352A1 (en) * | 1978-06-15 | 1980-01-09 | Beecham Group Plc | Hydantoins and thiohydantoins, process for their preparation and pharmaceutical compositions containing them |
| GB2032419B (en) * | 1978-09-05 | 1983-01-19 | Wellcome Found | Hydantoin prostaglandin analogues |
| CA2008116C (en) * | 1989-02-23 | 2001-11-20 | Thomas Weller | Glycine derivatives |
| DE4009506A1 (de) * | 1990-03-24 | 1991-09-26 | Hoechst Ag | Hydantoinderivate |
| WO1992019595A1 (en) * | 1991-05-07 | 1992-11-12 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| DE4126277A1 (de) * | 1991-08-08 | 1993-02-11 | Cassella Ag | Hydantoinderivate |
| DE4207254A1 (de) * | 1992-03-07 | 1993-09-09 | Cassella Ag | 4-oxo-2-thioxoimidazolidin-derivate |
| 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 |
| DE4301747A1 (de) * | 1993-01-23 | 1994-07-28 | Cassella Ag | Substituierte Aminoverbindungen, ihre Herstellung und ihre Verwendung |
| 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 |
-
1994
- 1994-08-08 DE DE4427979A patent/DE4427979A1/de not_active Withdrawn
- 1994-10-24 WO PCT/EP1994/003491 patent/WO1995014008A1/de active IP Right Grant
- 1994-10-24 EP EP94930215A patent/EP0729460B1/de not_active Expired - Lifetime
- 1994-10-24 RU RU96113118/04A patent/RU2151143C1/ru not_active IP Right Cessation
- 1994-10-24 SK SK585-96A patent/SK284471B6/sk unknown
- 1994-10-24 PL PL94314306A patent/PL180906B1/pl not_active IP Right Cessation
- 1994-10-24 DK DK94930215T patent/DK0729460T3/da active
- 1994-10-24 DE DE59410120T patent/DE59410120D1/de not_active Expired - Lifetime
- 1994-10-24 CA CA002169643A patent/CA2169643A1/en not_active Abandoned
- 1994-10-24 AT AT94930215T patent/ATE217615T1/de not_active IP Right Cessation
- 1994-10-24 CN CN94194043A patent/CN1069316C/zh not_active Expired - Fee Related
- 1994-10-24 PT PT94930215T patent/PT729460E/pt unknown
- 1994-10-24 AU AU79397/94A patent/AU693811B2/en not_active Ceased
- 1994-10-24 ES ES94930215T patent/ES2176261T3/es not_active Expired - Lifetime
- 1994-10-24 CZ CZ19961162A patent/CZ292573B6/cs not_active IP Right Cessation
- 1994-10-24 HU HU9601300A patent/HU223806B1/hu not_active IP Right Cessation
- 1994-10-24 KR KR1019960702512A patent/KR100402192B1/ko not_active Expired - Fee Related
- 1994-10-24 US US08/640,895 patent/US5981492A/en not_active Expired - Lifetime
- 1994-10-24 JP JP51417695A patent/JP3813983B2/ja not_active Expired - Fee Related
- 1994-11-14 IL IL11162294A patent/IL111622A/xx not_active IP Right Cessation
- 1994-12-13 TW TW083111713A patent/TW326040B/zh active
-
1996
- 1996-05-14 FI FI962043A patent/FI113265B/fi not_active IP Right Cessation
-
1999
- 1999-07-28 US US09/362,363 patent/US6191282B1/en not_active Expired - Fee Related
-
2003
- 2003-11-11 CY CY0300083A patent/CY2385B1/xx unknown
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