AP330A - Piperidine aectate derivatives. - Google Patents

Piperidine aectate derivatives. Download PDF

Info

Publication number: AP330A
Authority: AP; ARIPO
Prior art keywords: solvates; physiologically acceptable; piperazinyl; acceptable salts; formula
Prior art date: 1991-11-14

Application number

APAP/P/1992/000447A

Other languages

English (en)

Other versions

AP9200447A0 (en

Inventor

Barry Porter

Colin David Eldred

Henry Anderson Kelly

James Russell Wheatcroft

Original Assignee

Glaxo Group Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-11-14

Filing date

1992-11-13

Publication date

1994-03-30

1991-11-14 Priority claimed from GB919124221A external-priority patent/GB9124221D0/en

1992-01-16 Priority claimed from GB929201052A external-priority patent/GB9201052D0/en

1992-11-13 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1993-01-31 Publication of AP9200447A0 publication Critical patent/AP9200447A0/xx

1994-03-30 Application granted granted Critical

1994-03-30 Publication of AP330A publication Critical patent/AP330A/en

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
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150000007530 organic bases Chemical class 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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230000002093 peripheral effect Effects 0.000 description 1
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GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
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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
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QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
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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
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239000013049 sediment Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
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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
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IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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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)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Diabetes (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Hematology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

APAP/P/1992/000447A 1991-11-14 1992-11-13 Piperidine aectate derivatives. AP330A (en)

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 (zh)
JP (1)	JPH07501063A (zh)
CN (1)	CN1073169A (zh)
AP (1)	AP330A (zh)
AU (1)	AU2915892A (zh)
IL (1)	IL103746A0 (zh)
IS (1)	IS3945A (zh)
MX (1)	MX9206541A (zh)
TW (1)	TW221996B (zh)
WO (1)	WO1993010091A2 (zh)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
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 (zh) *	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
US5750754A (en) *	1993-03-29	1998-05-12	Zeneca Limited	Heterocyclic compounds
EP0691959B1 (en) *	1993-03-29	1998-07-22	Zeneca Limited	Heterocyclic derivatives 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
EP0690847A1 (en) *	1993-03-29	1996-01-10	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
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
USRE39263E1 (en) *	1994-05-04	2006-09-05	Bayer Aktiengesellschaft	Substituted aromatic thiocarboxylic acid amides and their use as herbicides
US6077813A (en)	1994-05-04	2000-06-20	Bayer Aktiengesellschaft	Substituted aromatic thiocarboxylic acid amides and their use as herbicides
TW397831B (en) *	1994-07-15	2000-07-11	Meiji Seika Kaisha	The anti-platelet-agglutination hexahydrogenated pyridine and its derivatives
US5795893A (en) *	1994-12-22	1998-08-18	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
WO1996024583A1 (en) *	1995-02-10	1996-08-15	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
WO1997002245A1 (en) *	1995-07-06	1997-01-23	Japan Tobacco Inc.	Benzamidoxime derivatives and medicinal use thereof
EP0891359A1 (de) *	1996-03-30	1999-01-20	Roche Diagnostics GmbH	Neue oxazolidinderivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
TW403745B (en) *	1996-05-30	2000-09-01	Yamanouchi Pharma Co Ltd	Novel substituted -amidinobenzene derivative and pharmaceutical compositions thereof
WO1997049698A1 (en) *	1996-06-21	1997-12-31	Glaxo Group Limited	Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders
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
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
CA2318351A1 (en) *	1997-12-26	1999-07-08	Hidemitsu Nishida	Aromatic compounds having cyclic amino or salts thereof
CA2333927A1 (en)	1998-04-01	1999-10-07	Dupont Pharmaceuticals Company	Pyrimidines and triazines as integrin antagonists
ES2300151T3 (es) *	1998-09-22	2008-06-01	Astellas Pharma Inc.	Derivados de cianofenilo.
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
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
US7635698B2 (en)	2004-12-29	2009-12-22	Millennium Pharmaceuticals, Inc.	Compounds useful as chemokine receptor antagonists
US7880002B2 (en)	2004-12-29	2011-02-01	Millennium Pharmaceuticals, Inc.	Substituted piperazinyl-pyrrolidine compounds useful as chemokine receptor antagonists
MX2007009949A (es)	2005-02-16	2007-09-26	Schering Corp	Pirazinil-piperazin-piperidinas sustituidas con heteroarilo con actividad antagonista de cxcr3.
BRPI0607946A2 (pt)	2005-02-16	2009-10-20	Schering Corp	piperazina-piperidinas substituìdas por pirazinila com atividade de antagonista cxcr3
CA2598489A1 (en)	2005-02-16	2006-08-24	Schering Corporation	Piperazine-piperidines with cxcr3 antagonist activity
CA2598456A1 (en) *	2005-02-16	2006-08-24	Schering Corporation	Heterocyclic substituted piperazines with cxcr3 antagonist activity
CN101146793A (zh)	2005-02-16	2008-03-19	先灵公司	具有cxcr3拮抗剂活性的新的杂环取代了的吡啶或苯基化合物
AU2006214378A1 (en)	2005-02-16	2006-08-24	Pharmacopeia, Inc.	Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity
WO2007011293A1 (en)	2005-07-21	2007-01-25	Astrazeneca Ab	Novel piperidine derivatives
RU2418798C2 (ru) *	2005-08-31	2011-05-20	Арикс Терапьютикс, Инк.	Способы синтеза и промежуточные соединения при синтезе стереоизомерных соединений, пригодных для лечения желудочно-кишечных расстройств и расстройств центральной нервной системы
CN101460482B (zh) *	2006-03-21	2013-03-27	默沙东公司	具有cxcr3拮抗剂活性的杂环取代的吡啶化合物
MX2009000577A (es) *	2006-07-14	2009-03-09	Schering Corp	Compuestos de piperazina sustituida heterociclica con actividad antagonista de cxcr3.
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
MA47697A (fr) *	2017-02-28	2020-01-08	Morphic Therapeutic Inc	Inhibiteurs de l'(alpha-v)(bêta-6) intégrine
MA52117A (fr)	2017-02-28	2022-04-06	Morphic Therapeutic Inc	Inhibiteurs de l'intégrine (alpha-v) (bêta-6)
FI3844162T3 (fi)	2018-08-29	2025-03-27	Morphic Therapeutic Inc	Alfa v beeta6 -integriinin estäjiä
EP4086254B1 (en)	2018-08-29	2024-12-18	Morphic Therapeutic, Inc.	Integrin inhibitors
WO2020047208A1 (en)	2018-08-29	2020-03-05	Morphic Therapeutic, Inc.	Inhibitors of (alpha-v)(beta-6) integrin

Citations (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 JP JP5508956A patent/JPH07501063A/ja active Pending
- 1992-11-10 WO PCT/EP1992/002588 patent/WO1993010091A2/en not_active Ceased
- 1992-11-10 EP EP92923116A patent/EP0612313A1/en not_active Withdrawn
- 1992-11-10 TW TW081108989A patent/TW221996B/zh active
- 1992-11-10 EP EP19920203442 patent/EP0542363A3/en not_active Withdrawn
- 1992-11-10 AU AU29158/92A patent/AU2915892A/en not_active Abandoned
- 1992-11-13 IL IL103746A patent/IL103746A0/xx unknown
- 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
- 1992-11-13 AP APAP/P/1992/000447A patent/AP330A/en active

Patent Citations (3)

* Cited by examiner, † Cited by third party
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
WO1993010091A3 (en)	1993-06-24
EP0612313A1 (en)	1994-08-31
EP0542363A3 (en)	1993-07-14
WO1993010091A2 (en)	1993-05-27
MX9206541A (es)	1993-04-01
JPH07501063A (ja)	1995-02-02
IL103746A0 (en)	1993-04-04
IS3945A (is)	1993-05-15
EP0542363A2 (en)	1993-05-19
AU2915892A (en)	1993-06-15
CN1073169A (zh)	1993-06-16
TW221996B (zh)	1994-04-01
AP9200447A0 (en)	1993-01-31

Publication	Publication Date	Title
AP330A (en)	1994-03-30	Piperidine aectate derivatives.
WO1993014077A1 (en)	1993-07-22	Piperidineacetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation
EP1181017B1 (en)	2003-04-16	Metalloprotease inhibitors
US6511993B1 (en)	2003-01-28	Metalloprotease inhibitors
EP1902046B1 (en)	2009-12-02	Piperidine derivatives useful as histamine h3 antagonists
KR20070091038A (ko)	2007-09-06	Ｇ-단백질 결합 수용체(ｇｐｒ116) 효능제 및 비만 및당뇨병을 치료하기 위한 이의 용도
EP1896453B1 (en)	2009-12-02	Carbon-linked substituted piperidines and derivatives thereof useful as histamine h3 antagonists
KR20100033541A (ko)	2010-03-30	멜라노코르틴-4 수용체 모듈레이터로서의 치환된 헤테로아릴피페리딘 유도체
CZ20031316A3 (cs)	2003-10-15	Heterocyklylalkylpiperidinové deriváty, jejich příprava a prostředky, které je obsahují
KR101665749B1 (ko)	2016-10-12	5-하이드록시피리미딘-4-카르복사미드 유도체
US7060836B2 (en)	2006-06-13	Lactams as tachykinin antagonists
TW201623260A (zh)	2016-07-01	新穎二取代１，２，４－三化合物
ZA200507795B (en)	2006-07-26	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
EP0537980A1 (en)	1993-04-21	Cyclohexaneacetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation
US20200347029A1 (en)	2020-11-05	C5a receptor modulators
EP0799223B1 (en)	1999-06-09	Piperidineacetic acid derivatives useful as fibrinogen antagonist agent
US4292321A (en)	1981-09-29	1,3,8-Triazaspirodecane-4-ones, pharmaceutical compositions thereof and method of use thereof
KR20080039990A (ko)	2008-05-07	선택적 ｃｇｒｐ 길항제, 이의 제조 방법 및 이의약제로서의 용도
US10160745B2 (en)	2018-12-25	Piperidine and azepine derivatives as prokineticin receptor modulators
TW200948801A (en)	2009-12-01	Substituierte sulfonamid-derivate
US4411904A (en)	1983-10-25	Diphenylpropanamines, compositions thereof and use thereof
KR19990087055A (ko)	1999-12-15	알레르기성 질환 치료에 유용한 신규의 치환된 n-메틸-n-(4-(피페리딘-1-일)-2-(아릴)부틸)벤즈아미드
EP1551827B1 (en)	2009-12-02	Piperidine derivatives as ccr5 inhibitors
US20080051430A1 (en)	2008-02-28	Acylated Piperidine Derivatives as Melanocortin 4-Receptor Agonists
SG173114A1 (en)	2011-08-29	Piperidine derivatives as nk3 receptor antagonists