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
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 7
- ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 238000011321 prophylaxis Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 4
- 150000005751 4-halopyridines Chemical class 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 229920000881 Modified starch Polymers 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 239000012223 aqueous fraction Substances 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000006244 carboxylic acid protecting group Chemical group 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 4
- FTMVNUGLWHCBJK-UHFFFAOYSA-N piperidin-1-ium;2,2,2-trifluoroacetate Chemical class C1CCNCC1.OC(=O)C(F)(F)F FTMVNUGLWHCBJK-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical group OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- PDRWPUKZQFXVFL-UHFFFAOYSA-N 2-[4-[4-(2-bromo-4-methanehydrazonoylphenyl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound BrC1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 PDRWPUKZQFXVFL-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000008364 bulk solution Substances 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000005748 halopyridines Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 150000004885 piperazines Chemical class 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- 229960000103 thrombolytic agent Drugs 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- GJFNRSDCSTVPCJ-UHFFFAOYSA-N 1,8-bis(dimethylamino)naphthalene Chemical compound C1=CC(N(C)C)=C2C(N(C)C)=CC=CC2=C1 GJFNRSDCSTVPCJ-UHFFFAOYSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical class C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- ZBUSEZWKXFKLCT-UHFFFAOYSA-N 2-(4-oxopiperidin-1-yl)acetic acid Chemical compound OC(=O)CN1CCC(=O)CC1 ZBUSEZWKXFKLCT-UHFFFAOYSA-N 0.000 description 1
- BGJZCYCOXKUIEC-UHFFFAOYSA-N 2-(4-piperazin-1-ylpiperidin-1-yl)acetic acid Chemical compound C1CN(CC(=O)O)CCC1N1CCNCC1 BGJZCYCOXKUIEC-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BZAZBWRSURFHHA-UHFFFAOYSA-N 2-[4-(4-benzylpiperazin-1-yl)piperidin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCC1N1CCN(CC=2C=CC=CC=2)CC1 BZAZBWRSURFHHA-UHFFFAOYSA-N 0.000 description 1
- VWRXJCFTFVCYIK-UHFFFAOYSA-N 2-[4-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]piperidin-1-yl]acetic acid Chemical compound CC1=C(C=CC(=C1)C#N)N2CCN(CC2)C3CCN(CC3)CC(=O)O VWRXJCFTFVCYIK-UHFFFAOYSA-N 0.000 description 1
- XURZPQYOXATOKI-UHFFFAOYSA-N 2-[4-[4-(4-methanehydrazonoylphenyl)-2-methylpiperazin-1-yl]piperidin-1-yl]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1CN(C=2C=CC(C=NN)=CC=2)CCN1C1CCN(CC(O)=O)CC1 XURZPQYOXATOKI-UHFFFAOYSA-N 0.000 description 1
- HIVZPBYKMRWFRE-UHFFFAOYSA-N 2-[4-[4-(4-methanehydrazonoylphenyl)piperazin-1-yl]piperidin-1-yl]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C=NN)=CC=C1N1CCN(C2CCN(CC(O)=O)CC2)CC1 HIVZPBYKMRWFRE-UHFFFAOYSA-N 0.000 description 1
- ZURODFFXTNEYAZ-UHFFFAOYSA-N 2-[4-[4-[4-[(benzoylhydrazinylidene)methyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CN(CC(=O)O)CCC1N1CCN(C=2C=CC(C=NNC(=O)C=3C=CC=CC=3)=CC=2)CC1 ZURODFFXTNEYAZ-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- GVHPLDVGHPHBFM-UHFFFAOYSA-N 4-[4-(4-cyanophenyl)piperazin-1-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1N1CCN(C=2C=CC(=CC=2)C#N)CC1 GVHPLDVGHPHBFM-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 1
- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- FOWOXWLATUAFNQ-UHFFFAOYSA-N 4-oxopiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(=O)CC1 FOWOXWLATUAFNQ-UHFFFAOYSA-N 0.000 description 1
- DJJNYEXRPRQXPD-UHFFFAOYSA-N 4-piperazin-1-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCNCC1 DJJNYEXRPRQXPD-UHFFFAOYSA-N 0.000 description 1
- PRNRUOJLUPUJDN-UHFFFAOYSA-N 4-piperidin-4-ylpiperidine Chemical compound C1CNCCC1C1CCNCC1 PRNRUOJLUPUJDN-UHFFFAOYSA-N 0.000 description 1
- MQKBVVIPCLTENX-UHFFFAOYSA-N 4-piperidin-4-ylpiperidine;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1C1CCNCC1 MQKBVVIPCLTENX-UHFFFAOYSA-N 0.000 description 1
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
- FAEOEJIIPHVFLT-UHFFFAOYSA-N 4-pyridin-4-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=NC=C1 FAEOEJIIPHVFLT-UHFFFAOYSA-N 0.000 description 1
- DMSHUVBQFSNBBL-UHFFFAOYSA-N 5-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=C(C#N)N=C1 DMSHUVBQFSNBBL-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- RAUFBAREPZPWEF-UHFFFAOYSA-N FC(C(=O)O)(F)F.NN=CC1=CC(=C(C=C1)N1CCN(CC1)C1CCN(CC1)CC(=O)O)Br Chemical compound FC(C(=O)O)(F)F.NN=CC1=CC(=C(C=C1)N1CCN(CC1)C1CCN(CC1)CC(=O)O)Br RAUFBAREPZPWEF-UHFFFAOYSA-N 0.000 description 1
- PWIUIGOOFAVDAP-UHFFFAOYSA-N FC(C(=O)O)(F)F.NN=CC1=CC=C(C=N1)N1CCN(CC1)C1CCN(CC1)CC(=O)O Chemical compound FC(C(=O)O)(F)F.NN=CC1=CC=C(C=N1)N1CCN(CC1)C1CCN(CC1)CC(=O)O PWIUIGOOFAVDAP-UHFFFAOYSA-N 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 229940122331 Fibrinogen antagonist Drugs 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- DEEXGVAXMJQWFX-UHFFFAOYSA-N OC1=C(C(=O)OCCCC)C=CC=C1.OC1=C(C(=O)OCCC)C=CC=C1 Chemical compound OC1=C(C(=O)OCCCC)C=CC=C1.OC1=C(C(=O)OCCC)C=CC=C1 DEEXGVAXMJQWFX-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- 206010050902 Postoperative thrombosis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038908 Retinal vein thrombosis Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000000320 amidine group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- NMEGSGKCIWQRDB-UHFFFAOYSA-N butyl 2-bromoacetate Chemical compound CCCCOC(=O)CBr NMEGSGKCIWQRDB-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000013171 endarterectomy Methods 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000006203 ethylation Effects 0.000 description 1
- 238000006200 ethylation reaction Methods 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 150000003903 lactic acid esters Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- VOZUUIODSDMFDF-UHFFFAOYSA-N tert-butyl 2-[4-[4-(5-methanehydrazonoylpyridin-2-yl)piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2N=CC(C=NN)=CC=2)CC1 VOZUUIODSDMFDF-UHFFFAOYSA-N 0.000 description 1
- JZXKPSCJKUEPFG-UHFFFAOYSA-N tert-butyl 2-[4-[4-[4-[(benzoylhydrazinylidene)methyl]phenyl]piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2C=CC(C=NNC(=O)C=3C=CC=CC=3)=CC=2)CC1 JZXKPSCJKUEPFG-UHFFFAOYSA-N 0.000 description 1
- YDQGKUJOXTYOOT-UHFFFAOYSA-N tert-butyl 2-[4-[4-[5-[(e)-n'-hydroxycarbamimidoyl]pyridin-2-yl]piperazin-1-yl]piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1CCN(C=2N=CC(=CC=2)C(\N)=N/O)CC1 YDQGKUJOXTYOOT-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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)
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 (enrdf_load_html_response) * | 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 |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
| TW276254B (enrdf_load_html_response) * | 1993-03-29 | 1996-05-21 | Zeneca Ltd | |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
| AU692439B2 (en) * | 1993-03-29 | 1998-06-11 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
| 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 |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| 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 |
| AU709070B2 (en) * | 1994-07-15 | 1999-08-19 | Meiji Seika Kabushiki Kaisha | Novel compounds with platelet aggregation inhibitor activity |
| EP0801650A4 (en) * | 1994-12-22 | 1998-05-06 | Smithkline Beecham Corp | 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 |
| AU4633296A (en) * | 1995-02-10 | 1996-08-27 | Yamanouchi Pharmaceutical Co., Ltd. | Novel benzamidine derivatives and medicinal composition thereof |
| IL116893A (en) * | 1995-02-10 | 2000-02-29 | Yamanouchi Pharma Co Ltd | Piperazine derivatives and pharmaceutical compositions containing them |
| 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 |
| BR9708475A (pt) * | 1996-03-30 | 1999-04-13 | Boehringer Mannheim Gmbh | Derivados oxazolidina processos para sua produção e agentes farmacéuticos contendo estes compostos |
| 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 |
| AU1692399A (en) * | 1997-12-26 | 1999-07-19 | Mochida Pharmaceutical Co., Ltd. | Aromatic compounds having cyclic amino or salts thereof |
| AU3213799A (en) | 1998-04-01 | 1999-10-18 | Du Pont Pharmaceuticals Company | Integrin antagonists |
| WO2000017163A1 (fr) * | 1998-09-22 | 2000-03-30 | Yamanouchi Pharmaceutical Co., Ltd. | Derives de cyanophenyle |
| US6204282B1 (en) | 1998-11-30 | 2001-03-20 | Schering Corporation | Benzimidazole compounds that are vitronectin receptor antagonists |
| JP3857270B2 (ja) | 2001-07-02 | 2006-12-13 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性のモジュレーターとして有用なピペリジン誘導体 |
| GB0120461D0 (en) | 2001-08-22 | 2001-10-17 | Astrazeneca Ab | Novel compounds |
| GB0122503D0 (en) | 2001-09-18 | 2001-11-07 | Astrazeneca Ab | Chemical compounds |
| SE0200843D0 (sv) * | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
| SE0200844D0 (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 |
| CA2598459A1 (en) | 2005-02-16 | 2006-08-24 | Schering Corporation | Novel heterocyclic substituted pyridine or phenyl compounds with cxcr3 antagonist activity |
| EP1848710B1 (en) | 2005-02-16 | 2013-10-16 | Merck Sharp & Dohme Corp. | Heterocyclic substituted piperazines with cxcr3 antagonist activity |
| US7763616B2 (en) | 2005-02-16 | 2010-07-27 | Schering Corporation | Piperazine-piperidines with CXCR3 antagonist activity |
| US7776862B2 (en) | 2005-02-16 | 2010-08-17 | Schering Corporation | Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity |
| CN101189225A (zh) | 2005-02-16 | 2008-05-28 | 先灵公司 | 具有cxcr3拮抗剂活性的杂芳基取代的吡嗪基-哌嗪-哌啶 |
| JP2008530220A (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、ピラジニルで置換されたピペラジン−ピペリジン |
| EP1912941B1 (en) | 2005-07-21 | 2012-11-14 | AstraZeneca AB | 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 |
| EP1996577B1 (en) * | 2006-03-21 | 2016-02-10 | Merck Sharp & Dohme Corp. | Heterocyclic substituted pyridine compounds with cxcr3 antagonist activity |
| JP2009543782A (ja) * | 2006-07-14 | 2009-12-10 | 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している新規の複素環置換ピペラジン化合物 |
| 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 |
| SG11201907820SA (en) * | 2017-02-28 | 2019-09-27 | Morphic Therapeutic Inc | Inhibitors of (alpha-v)(beta-6) integrin |
| EP4147698A1 (en) | 2017-02-28 | 2023-03-15 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| MA51066A (fr) | 2018-08-29 | 2020-10-14 | Morphic Therapeutic Inc | Inhibiteurs d'intégrine |
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 EP EP92923116A patent/EP0612313A1/en not_active Withdrawn
- 1992-11-10 AU AU29158/92A patent/AU2915892A/en not_active Abandoned
- 1992-11-10 WO PCT/EP1992/002588 patent/WO1993010091A2/en not_active Application Discontinuation
- 1992-11-10 EP EP19920203442 patent/EP0542363A3/en not_active Withdrawn
- 1992-11-10 JP JP5508956A patent/JPH07501063A/ja active Pending
- 1992-11-13 IL IL103746A patent/IL103746A0/xx unknown
- 1992-11-13 AP APAP/P/1992/000447A patent/AP330A/en active
- 1992-11-13 IS IS3945A patent/IS3945A/is unknown
- 1992-11-13 CN CN92114388A patent/CN1073169A/zh active Pending
- 1992-11-13 MX MX9206541A patent/MX9206541A/es unknown
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 |
|---|---|
| EP0542363A3 (en) | 1993-07-14 |
| AU2915892A (en) | 1993-06-15 |
| JPH07501063A (ja) | 1995-02-02 |
| MX9206541A (es) | 1993-04-01 |
| CN1073169A (zh) | 1993-06-16 |
| AP9200447A0 (en) | 1993-01-31 |
| IS3945A (is) | 1993-05-15 |
| WO1993010091A3 (en) | 1993-06-24 |
| IL103746A0 (en) | 1993-04-04 |
| TW221996B (enrdf_load_html_response) | 1994-04-01 |
| WO1993010091A2 (en) | 1993-05-27 |
| EP0542363A2 (en) | 1993-05-19 |
| EP0612313A1 (en) | 1994-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AP330A (en) | Piperidine aectate derivatives. | |
| WO1993014077A1 (en) | Piperidineacetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation | |
| EP1181017B1 (en) | Metalloprotease inhibitors | |
| US6511993B1 (en) | Metalloprotease inhibitors | |
| EP1902046B1 (en) | Piperidine derivatives useful as histamine h3 antagonists | |
| EP1896453B1 (en) | Carbon-linked substituted piperidines and derivatives thereof useful as histamine h3 antagonists | |
| KR20070091038A (ko) | Ｇ-단백질 결합 수용체(ｇｐｒ116) 효능제 및 비만 및당뇨병을 치료하기 위한 이의 용도 | |
| KR20100033541A (ko) | 멜라노코르틴-4 수용체 모듈레이터로서의 치환된 헤테로아릴피페리딘 유도체 | |
| KR101665749B1 (ko) | 5-하이드록시피리미딘-4-카르복사미드 유도체 | |
| CZ20031316A3 (cs) | Heterocyklylalkylpiperidinové deriváty, jejich příprava a prostředky, které je obsahují | |
| US7060836B2 (en) | Lactams as tachykinin antagonists | |
| TW201623260A (zh) | 新穎二取代１，２，４－三化合物 | |
| ZA200507795B (en) | 4-(4-Heterocyclylalkoxy)phenyl)-1-(heterocyclyl-carbonyl) piperidine derivatives and related compounds as histamine H3 antagonists for the treatment of neurological diseases such as Alzheimer's | |
| US11739070B2 (en) | C5A receptor modulators | |
| KR20080039990A (ko) | 선택적 ｃｇｒｐ 길항제, 이의 제조 방법 및 이의약제로서의 용도 | |
| EP0537980A1 (en) | Cyclohexaneacetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation | |
| US4292321A (en) | 1,3,8-Triazaspirodecane-4-ones, pharmaceutical compositions thereof and method of use thereof | |
| EP0799223B1 (en) | Piperidineacetic acid derivatives useful as fibrinogen antagonist agent | |
| US10160745B2 (en) | Piperidine and azepine derivatives as prokineticin receptor modulators | |
| TW200948801A (en) | Substituierte sulfonamid-derivate | |
| US4411904A (en) | Diphenylpropanamines, compositions thereof and use thereof | |
| KR19990087055A (ko) | 알레르기성 질환 치료에 유용한 신규의 치환된 n-메틸-n-(4-(피페리딘-1-일)-2-(아릴)부틸)벤즈아미드 | |
| EP1551827B1 (en) | Piperidine derivatives as ccr5 inhibitors | |
| US20080051430A1 (en) | Acylated Piperidine Derivatives as Melanocortin 4-Receptor Agonists | |
| SG173114A1 (en) | Piperidine derivatives as nk3 receptor antagonists |