AP330A - Piperidine aectate derivatives. - Google Patents
Piperidine aectate derivatives. Download PDFInfo
- Publication number
- AP330A AP330A APAP/P/1992/000447A AP9200447A AP330A AP 330 A AP330 A AP 330A AP 9200447 A AP9200447 A AP 9200447A AP 330 A AP330 A AP 330A
- Authority
- AP
- ARIPO
- Prior art keywords
- solvates
- physiologically acceptable
- piperazinyl
- acceptable salts
- formula
- Prior art date
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 328
- 150000003839 salts Chemical class 0.000 claims abstract description 125
- 239000012453 solvate Substances 0.000 claims abstract description 103
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
- 239000011737 fluorine Substances 0.000 claims abstract description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 104
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 8
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- PWIBJZBXBPVCAM-UHFFFAOYSA-N 2-[4-[4-(4-methanehydrazonoylphenyl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound C1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 PWIBJZBXBPVCAM-UHFFFAOYSA-N 0.000 claims description 2
- ONPCDIAVSPPJPN-UHFFFAOYSA-N 2-[4-[4-[4-[(ethoxycarbonylhydrazinylidene)methyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound C1=CC(C=NNC(=O)OCC)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 ONPCDIAVSPPJPN-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- TUZXZKLQIBAYHZ-UHFFFAOYSA-N tert-butyl 2-[4-[4-(4-methanehydrazonoyl-2-methylphenyl)piperazin-1-yl]piperidin-1-yl]acetate Chemical compound CC1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(=O)OC(C)(C)C)CC2)CC1 TUZXZKLQIBAYHZ-UHFFFAOYSA-N 0.000 claims description 2
- OKOSKHISHNRDHB-UHFFFAOYSA-N tert-butyl 2-[4-[4-(4-methanehydrazonoylphenyl)piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2C=CC(C=NN)=CC=2)CC1 OKOSKHISHNRDHB-UHFFFAOYSA-N 0.000 claims description 2
- OSYLNIVYXONDEI-UHFFFAOYSA-N tert-butyl 2-[4-[4-(6-methanehydrazonoylpyridin-3-yl)piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2C=NC(C=NN)=CC=2)CC1 OSYLNIVYXONDEI-UHFFFAOYSA-N 0.000 claims description 2
- ANCNTBUSBUODCH-UHFFFAOYSA-N tert-butyl 2-[4-[4-[4-[(diethoxyphosphorylhydrazinylidene)methyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1=CC(C=NNP(=O)(OCC)OCC)=CC=C1N1CCN(C2CCN(CC(=O)OC(C)(C)C)CC2)CC1 ANCNTBUSBUODCH-UHFFFAOYSA-N 0.000 claims description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- XVOUMQNXTGKGMA-OWOJBTEDSA-N (E)-glutaconic acid Chemical compound OC(=O)C\C=C\C(O)=O XVOUMQNXTGKGMA-OWOJBTEDSA-N 0.000 claims 1
- OHBXIRUZXOFBAZ-UHFFFAOYSA-N 2-[4-[4-(4-methanehydrazonoyl-2-methylphenyl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound CC1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 OHBXIRUZXOFBAZ-UHFFFAOYSA-N 0.000 claims 1
- GYBKMCAZLRWJHI-UHFFFAOYSA-N 2-[4-[4-(5-methanehydrazonoylpyridin-2-yl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound N1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 GYBKMCAZLRWJHI-UHFFFAOYSA-N 0.000 claims 1
- OXDSCIXIPQDVJW-UHFFFAOYSA-N 2-[4-[4-(6-methanehydrazonoylpyridin-3-yl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound C1=NC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 OXDSCIXIPQDVJW-UHFFFAOYSA-N 0.000 claims 1
- LPUGHCBDVBQVMO-UHFFFAOYSA-N 2-[4-[4-[4-[(diethylphosphorylhydrazinylidene)methyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound C1=CC(C=NNP(=O)(CC)CC)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 LPUGHCBDVBQVMO-UHFFFAOYSA-N 0.000 claims 1
- CQLQOTNRCDRHNQ-UHFFFAOYSA-N 2-[4-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound C1=CC(C(N)=NC(=O)OC)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 CQLQOTNRCDRHNQ-UHFFFAOYSA-N 0.000 claims 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 229940072107 ascorbate Drugs 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 229940001447 lactate Drugs 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- REGWVSTWPUXKJS-UHFFFAOYSA-N methyl 2-piperidin-1-ylacetate Chemical compound COC(=O)CN1CCCCC1 REGWVSTWPUXKJS-UHFFFAOYSA-N 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Chemical class 0.000 claims 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims 1
- 229960001860 salicylate Drugs 0.000 claims 1
- 229940086735 succinate Drugs 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims 1
- 229910021653 sulphate ion Inorganic materials 0.000 claims 1
- 229940095064 tartrate Drugs 0.000 claims 1
- ABMKZZPZLHESEG-UHFFFAOYSA-N tert-butyl 2-[4-[4-(2-bromo-4-methanehydrazonoylphenyl)piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2C(=CC(C=NN)=CC=2)Br)CC1 ABMKZZPZLHESEG-UHFFFAOYSA-N 0.000 claims 1
- LTJCGYZHVZQHTN-UHFFFAOYSA-N tert-butyl 2-[4-[4-(4-methanehydrazonoylphenyl)-2-methylpiperazin-1-yl]piperidin-1-yl]acetate Chemical compound CC1CN(C=2C=CC(C=NN)=CC=2)CCN1C1CCN(CC(=O)OC(C)(C)C)CC1 LTJCGYZHVZQHTN-UHFFFAOYSA-N 0.000 claims 1
- DSZNMOPZHUMIGZ-UHFFFAOYSA-N tert-butyl 2-[4-[4-[4-(n'-hydroxycarbamimidoyl)phenyl]piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2C=CC(=CC=2)C(\N)=N\O)CC1 DSZNMOPZHUMIGZ-UHFFFAOYSA-N 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 1
- KQTIIICEAUMSDG-UHFFFAOYSA-N tricarballylic acid Chemical compound OC(=O)CC(C(O)=O)CC(O)=O KQTIIICEAUMSDG-UHFFFAOYSA-N 0.000 claims 1
- 210000001772 blood platelet Anatomy 0.000 abstract description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract description 6
- 102000008946 Fibrinogen Human genes 0.000 abstract description 4
- 108010049003 Fibrinogen Proteins 0.000 abstract description 4
- 150000001242 acetic acid derivatives Chemical class 0.000 abstract description 4
- 229940012952 fibrinogen Drugs 0.000 abstract description 4
- 230000001419 dependent effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000000543 intermediate Substances 0.000 description 95
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000007787 solid Substances 0.000 description 84
- 239000002904 solvent Substances 0.000 description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- 239000000243 solution Substances 0.000 description 51
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 238000010992 reflux Methods 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- -1 ptoluenesulphonates Chemical class 0.000 description 29
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 239000000377 silicon dioxide Substances 0.000 description 23
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 229910052681 coesite Inorganic materials 0.000 description 19
- 229910052906 cristobalite Inorganic materials 0.000 description 19
- 229910052682 stishovite Inorganic materials 0.000 description 19
- 229910052905 tridymite Inorganic materials 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 238000001819 mass spectrum Methods 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 239000003054 catalyst Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 12
- 239000005695 Ammonium acetate Substances 0.000 description 12
- 229940043376 ammonium acetate Drugs 0.000 description 12
- 235000019257 ammonium acetate Nutrition 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 9
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 9
- 150000001409 amidines Chemical group 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
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Classifications
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- 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
-
- 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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919124221A GB9124221D0 (en) | 1991-11-14 | 1991-11-14 | Chemical compounds |
| GB929201052A GB9201052D0 (en) | 1992-01-16 | 1992-01-16 | Chemical compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9200447A0 AP9200447A0 (en) | 1993-01-31 |
| AP330A true AP330A (en) | 1994-03-30 |
Family
ID=26299862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1992/000447A AP330A (en) | 1991-11-14 | 1992-11-13 | Piperidine aectate derivatives. |
Country Status (10)
| Country | Link |
|---|---|
| EP (2) | EP0612313A1 (OSRAM) |
| JP (1) | JPH07501063A (OSRAM) |
| CN (1) | CN1073169A (OSRAM) |
| AP (1) | AP330A (OSRAM) |
| AU (1) | AU2915892A (OSRAM) |
| IL (1) | IL103746A0 (OSRAM) |
| IS (1) | IS3945A (OSRAM) |
| MX (1) | MX9206541A (OSRAM) |
| TW (1) | TW221996B (OSRAM) |
| WO (1) | WO1993010091A2 (OSRAM) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4127404A1 (de) | 1991-08-19 | 1993-02-25 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| TW257757B (OSRAM) * | 1993-03-03 | 1995-09-21 | Boehringer Mannheim Gmbh | |
| DE4309285A1 (de) * | 1993-03-23 | 1994-09-29 | Boehringer Ingelheim Kg | Heterocyclen enthaltende Amidinderivate, ihre Herstellung und Verwendung |
| EP0690847A1 (en) * | 1993-03-29 | 1996-01-10 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| ES2159798T3 (es) * | 1993-03-29 | 2001-10-16 | Astrazeneca Ab | Derivados heterociclicos como inhibidores de la agregacion plaquetaria. |
| US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
| JPH06340619A (ja) * | 1993-05-03 | 1994-12-13 | Bristol Myers Squibb Co | グアニジニルまたはアミジニル置換メチルアミノ複素環トロンビン抑制剤 |
| GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| WO1995030661A1 (de) * | 1994-05-04 | 1995-11-16 | Bayer Aktiengesellschaft | Substituierte aromatische thiocarbonsäureamide und ihre verwendung als herbizide |
| USRE39263E1 (en) * | 1994-05-04 | 2006-09-05 | Bayer Aktiengesellschaft | Substituted aromatic thiocarboxylic acid amides and their use as herbicides |
| CN1134695A (zh) * | 1994-07-15 | 1996-10-30 | 明治制果株式会社 | 具有血小板凝聚抑制作用的新颖化合物 |
| WO1996019475A1 (en) * | 1994-12-22 | 1996-06-27 | Smithkline Beecham Corporation | Fibrinogen receptor antagonists |
| ZA951822B (en) * | 1994-12-23 | 1996-09-26 | Glaxo Group Ltd | Chemical compounds |
| FR2728901B1 (fr) * | 1994-12-28 | 1997-03-28 | Sanofi Sa | Derives de phenyl-4-thiazoles substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
| IL116893A (en) * | 1995-02-10 | 2000-02-29 | Yamanouchi Pharma Co Ltd | Piperazine derivatives and pharmaceutical compositions containing them |
| AU4633296A (en) * | 1995-02-10 | 1996-08-27 | Yamanouchi Pharmaceutical Co., Ltd. | Novel benzamidine derivatives and medicinal composition thereof |
| US5889006A (en) * | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| DE19516483A1 (de) | 1995-05-05 | 1996-11-07 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| GB9511989D0 (en) * | 1995-06-13 | 1995-08-09 | Glaxo Group Ltd | Chemical compounds |
| AU6318896A (en) * | 1995-07-06 | 1997-02-05 | Japan Tobacco Inc. | Benzamidoxime derivatives and medicinal use thereof |
| PL329053A1 (en) * | 1996-03-30 | 1999-03-01 | Roche Diagnostics Gmbh | Novel derivatives of oxazolydine, method of obtaining them and therapeutic agents containing such compounds |
| TW403745B (en) * | 1996-05-30 | 2000-09-01 | Yamanouchi Pharma Co Ltd | Novel substituted -amidinobenzene derivative and pharmaceutical compositions thereof |
| AR008245A1 (es) * | 1996-06-21 | 1999-12-29 | Glaxo Group Ltd | Derivados de acido acetico, uso de los mismos en la fabricacion de un agente terapeutico y proceso para preparar dichos derivados |
| AU3261097A (en) * | 1996-06-21 | 1998-01-14 | Glaxo Group Limited | Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders |
| DE19643331A1 (de) * | 1996-10-21 | 1998-04-23 | Thomae Gmbh Dr K | 1-(4-Piperidinyl)-piperidinylene, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19652919A1 (de) * | 1996-12-19 | 1998-06-25 | Solvay Pharm Gmbh | Piperazinophenyl- und Piperazinophenyloxy-carbonsäure-Derivate sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| AR013693A1 (es) * | 1997-10-23 | 2001-01-10 | Uriach & Cia Sa J | Nuevas piperidinas y piperazinas como inhibidores de la agregacion plaquetaria |
| WO1999033805A1 (en) * | 1997-12-26 | 1999-07-08 | Mochida Pharmaceutical Co., Ltd. | Aromatic compounds having cyclic amino or salts thereof |
| JP2003504301A (ja) | 1998-04-01 | 2003-02-04 | ブリストル−マイヤーズ スクイブ ファーマ カンパニー | インテグリンアンタゴニスト |
| ATE384048T1 (de) * | 1998-09-22 | 2008-02-15 | Astellas Pharma Inc | Cyanophenyl-derivate |
| US6204282B1 (en) | 1998-11-30 | 2001-03-20 | Schering Corporation | Benzimidazole compounds that are vitronectin receptor antagonists |
| KR20040013090A (ko) | 2001-07-02 | 2004-02-11 | 아스트라제네카 아베 | 케모킨 수용체 활성의 조절자로서 유용한 피페리딘 유도체 |
| GB0120461D0 (en) | 2001-08-22 | 2001-10-17 | Astrazeneca Ab | Novel compounds |
| GB0122503D0 (en) | 2001-09-18 | 2001-11-07 | Astrazeneca Ab | Chemical compounds |
| SE0200844D0 (sv) * | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| SE0200843D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| SE0300957D0 (sv) | 2003-04-01 | 2003-04-01 | Astrazeneca Ab | Chemical compounds |
| WO2006071875A1 (en) | 2004-12-29 | 2006-07-06 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| US7635698B2 (en) | 2004-12-29 | 2009-12-22 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| US7868005B2 (en) | 2005-02-16 | 2011-01-11 | Schering Corporation | Pyrazinyl substituted piperazine-piperidines with CXCR3 antagonist activity |
| MX2007010068A (es) | 2005-02-16 | 2007-10-10 | Schering Corp | Piperazino-piperidinas con actividad antagonista de cxcr3. |
| AU2006216941B2 (en) | 2005-02-16 | 2009-12-03 | Pharmacopeia, Llc | Heteroaryl substituted pyrazinyl-piperazine-piperidines with CXCR3 antagonist activity |
| AU2006214477A1 (en) | 2005-02-16 | 2006-08-24 | Pharmacopeia, Inc. | Heterocyclic substituted piperazines with CXCR3 antagonist activity |
| JP2008530218A (ja) | 2005-02-16 | 2008-08-07 | シェーリング コーポレイション | Ｃｘｃｒ３アンタゴニスト活性を有する、ピリジルおよびフェニルで置換されたピペラジン−ピペリジン |
| MX2007010067A (es) | 2005-02-16 | 2007-12-07 | Schering Corp | Compuestos heterociclicos novedosos sustituidos con piridina o fenilo con actividad antagonista de cxcr3. |
| WO2007011293A1 (en) | 2005-07-21 | 2007-01-25 | Astrazeneca Ab | Novel piperidine derivatives |
| CA2620379C (en) * | 2005-08-31 | 2015-02-24 | Aryx Therapeutics, Inc. | Synthetic methods and intermediates for stereoisomeric compounds useful for the treatment of gastrointestinal and central nervous system disorders |
| JP2009530383A (ja) | 2006-03-21 | 2009-08-27 | シェーリング コーポレイション | Ｃｘｃｒ３拮抗活性を有する、新規ヘテロ環ピリジン置換体 |
| WO2008008453A1 (en) * | 2006-07-14 | 2008-01-17 | Schering Corporation | Heterocyclic substituted piperazine compounds with cxcr3 antagonist activity |
| DE102007038250A1 (de) | 2007-08-13 | 2009-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neues Herstellverfahren |
| WO2010081851A1 (en) | 2009-01-14 | 2010-07-22 | Genoscience Pharma | Piperidin-4-ylpiperazine compounds for the treatment of hcv infection |
| US11046685B2 (en) * | 2017-02-28 | 2021-06-29 | Morphic Therapeutic, Inc. | Inhibitors of (α-v)(β-6) integrin |
| IL316954A (en) * | 2017-02-28 | 2025-01-01 | Morphic Therapeutic Inc | (Alpha-V)(beta-6)integrin inhibitors |
| CN112805001B (zh) | 2018-08-29 | 2024-07-23 | 莫菲克医疗股份有限公司 | 抑制αvβ6整联蛋白 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4433152A (en) * | 1981-05-25 | 1984-02-21 | Nippon Chemiphar Co., Ltd. | Amidinopiperidine derivatives |
| US4514416A (en) * | 1981-02-27 | 1985-04-30 | Torii & Co. Ltd. | Amidine compound, process for producing same and anti-complement agent comprising same |
| EP0236164A1 (fr) * | 1986-01-24 | 1987-09-09 | Sanofi | Dérivés des N alpha-arylsulfonylaminoacyl p-amidino-phénylalaninamides, leur procédé de préparation, leur application comme médicaments et leurs intermédiaires de synthèse |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9122016D0 (en) * | 1991-10-16 | 1991-11-27 | Glaxo Group Ltd | Chemical compounds |
-
1992
- 1992-11-10 TW TW081108989A patent/TW221996B/zh active
- 1992-11-10 JP JP5508956A patent/JPH07501063A/ja active Pending
- 1992-11-10 EP EP92923116A patent/EP0612313A1/en not_active Withdrawn
- 1992-11-10 EP EP19920203442 patent/EP0542363A3/en not_active Withdrawn
- 1992-11-10 WO PCT/EP1992/002588 patent/WO1993010091A2/en not_active Ceased
- 1992-11-10 AU AU29158/92A patent/AU2915892A/en not_active Abandoned
- 1992-11-13 IS IS3945A patent/IS3945A/is unknown
- 1992-11-13 CN CN92114388A patent/CN1073169A/zh active Pending
- 1992-11-13 IL IL103746A patent/IL103746A0/xx unknown
- 1992-11-13 MX MX9206541A patent/MX9206541A/es unknown
- 1992-11-13 AP APAP/P/1992/000447A patent/AP330A/en active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4514416A (en) * | 1981-02-27 | 1985-04-30 | Torii & Co. Ltd. | Amidine compound, process for producing same and anti-complement agent comprising same |
| US4433152A (en) * | 1981-05-25 | 1984-02-21 | Nippon Chemiphar Co., Ltd. | Amidinopiperidine derivatives |
| EP0236164A1 (fr) * | 1986-01-24 | 1987-09-09 | Sanofi | Dérivés des N alpha-arylsulfonylaminoacyl p-amidino-phénylalaninamides, leur procédé de préparation, leur application comme médicaments et leurs intermédiaires de synthèse |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1993010091A2 (en) | 1993-05-27 |
| MX9206541A (es) | 1993-04-01 |
| EP0542363A2 (en) | 1993-05-19 |
| TW221996B (OSRAM) | 1994-04-01 |
| WO1993010091A3 (en) | 1993-06-24 |
| IL103746A0 (en) | 1993-04-04 |
| JPH07501063A (ja) | 1995-02-02 |
| CN1073169A (zh) | 1993-06-16 |
| AP9200447A0 (en) | 1993-01-31 |
| EP0542363A3 (en) | 1993-07-14 |
| IS3945A (is) | 1993-05-15 |
| AU2915892A (en) | 1993-06-15 |
| EP0612313A1 (en) | 1994-08-31 |
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