SK107293A3 - Carboxylic acid derivatives, drugs containing these compounds and method of their production - Google Patents

Carboxylic acid derivatives, drugs containing these compounds and method of their production Download PDF

Info

Publication number: SK107293A3
Authority: SK; Slovakia
Prior art keywords: group; trans; piperidine; aminocarbonyl; amidinophenyl
Prior art date: 1992-10-12

Application number

SK1072-93A

Other languages

English (en)

Slovak (sk)

Inventor

Helmut Pieper

Gunter Linz

Frank Himmelsbach

Volkhard Austel

Thomas Muller

Johannes Weisenberger

Brian Guth

Original Assignee

Thomae Gmbh Dr K

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.)

1992-10-12

Filing date

1993-10-05

Publication date

1994-08-10

1993-10-05 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1994-08-10 Publication of SK107293A3 publication Critical patent/SK107293A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 88
150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 12
238000000034 method Methods 0.000 title claims abstract description 11
239000003814 drug Substances 0.000 title claims abstract description 7
238000004519 manufacturing process Methods 0.000 title claims description 13
229940079593 drug Drugs 0.000 title 1
239000000203 mixture Substances 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 30
239000002253 acid Substances 0.000 claims abstract description 21
238000002360 preparation method Methods 0.000 claims abstract description 19
150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
150000007524 organic acids Chemical class 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 5
235000005985 organic acids Nutrition 0.000 claims abstract description 4
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 301
-1 amino, amidino Chemical group 0.000 claims description 232
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 82
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 57
230000002829 reductive effect Effects 0.000 claims description 54
125000004432 carbon atom Chemical group C* 0.000 claims description 53
125000004433 nitrogen atom Chemical group N* 0.000 claims description 52
229910052757 nitrogen Inorganic materials 0.000 claims description 48
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
125000000217 alkyl group Chemical group 0.000 claims description 44
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 39
238000006243 chemical reaction Methods 0.000 claims description 35
125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 29
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 24
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
125000003884 phenylalkyl group Chemical group 0.000 claims description 22
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
239000000126 substance Substances 0.000 claims description 18
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 17
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 16
125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 claims description 16
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 15
150000003254 radicals Chemical class 0.000 claims description 15
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 13
125000004103 aminoalkyl group Chemical group 0.000 claims description 11
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 10
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
LWKZELAPNZLPPL-QAQDUYKDSA-N C1=CC(C(=N)N)=CC=C1C1CCN(C(=O)N[C@@H]2CC[C@H](CC2)C(O)=O)CC1 Chemical compound C1=CC(C(=N)N)=CC=C1C1CCN(C(=O)N[C@@H]2CC[C@H](CC2)C(O)=O)CC1 LWKZELAPNZLPPL-QAQDUYKDSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
150000001602 bicycloalkyls Chemical group 0.000 claims description 4
150000001723 carbon free-radicals Chemical class 0.000 claims description 4
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
230000007062 hydrolysis Effects 0.000 claims description 4
238000006460 hydrolysis reaction Methods 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
239000011541 reaction mixture Substances 0.000 claims description 4
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 3
YQAUKEIBOSVPCC-UHFFFAOYSA-N 2-[1-[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]piperidin-4-yl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1CCC(C(=O)N2CCC(CC(O)=O)CC2)CC1 YQAUKEIBOSVPCC-UHFFFAOYSA-N 0.000 claims description 3
SLBOMWZWZGAUKM-MQMHXKEQSA-N C(N)(=N)C=1C=CC(=NC1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound C(N)(=N)C=1C=CC(=NC1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O SLBOMWZWZGAUKM-MQMHXKEQSA-N 0.000 claims description 3
RIPTZMIGKNISGS-HZCBDIJESA-N C1C[C@@H](C(=O)O)CC[C@@H]1NC(=O)N1CCN(C=2C=CC(=CC=2)C(=N)NC(=O)OCC=2C=CC=CC=2)CC1 Chemical compound C1C[C@@H](C(=O)O)CC[C@@H]1NC(=O)N1CCN(C=2C=CC(=CC=2)C(=N)NC(=O)OCC=2C=CC=CC=2)CC1 RIPTZMIGKNISGS-HZCBDIJESA-N 0.000 claims description 3
LDOHZGIQAWHPBX-WKILWMFISA-N NC(=N)c1ccc(cc1)N1CCC(CC1)C(=O)N[C@H]1CC[C@@H](CC1)C(O)=O Chemical compound NC(=N)c1ccc(cc1)N1CCC(CC1)C(=O)N[C@H]1CC[C@@H](CC1)C(O)=O LDOHZGIQAWHPBX-WKILWMFISA-N 0.000 claims description 3
TYQAZQQMDGMCBB-WKILWMFISA-N NCC1=CC=C(C=C1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound NCC1=CC=C(C=C1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O TYQAZQQMDGMCBB-WKILWMFISA-N 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
125000004956 cyclohexylene group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000006697 (C1-C3) aminoalkyl group Chemical group 0.000 claims description 2
125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 2
RBVYHBAKPCKYHP-UHFFFAOYSA-N 2-[1-[1-(5-carbamimidoylpyridin-2-yl)piperidine-4-carbonyl]piperidin-4-yl]acetic acid Chemical compound N1=CC(C(=N)N)=CC=C1N1CCC(C(=O)N2CCC(CC(O)=O)CC2)CC1 RBVYHBAKPCKYHP-UHFFFAOYSA-N 0.000 claims description 2
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
AESKGMVEHZNWCJ-SHTZXODSSA-N C(N)(=N)C1=CC=C(C=C1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound C(N)(=N)C1=CC=C(C=C1)N1CCN(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O AESKGMVEHZNWCJ-SHTZXODSSA-N 0.000 claims description 2
DCDABPUHRPAYEK-AFARHQOCSA-N C1=CC(C(=N)N)=CC=C1N1CCN(C(=O)N(CC=2C=CC=CC=2)[C@@H]2CC[C@H](CC2)C(O)=O)CC1 Chemical compound C1=CC(C(=N)N)=CC=C1N1CCN(C(=O)N(CC=2C=CC=CC=2)[C@@H]2CC[C@H](CC2)C(O)=O)CC1 DCDABPUHRPAYEK-AFARHQOCSA-N 0.000 claims description 2
KAFLWBKBAJGLMG-WKILWMFISA-N C1CN(C=2C=CC(=CC=2)C(N)=N)CCN1C(=O)N(C)[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound C1CN(C=2C=CC(=CC=2)C(N)=N)CCN1C(=O)N(C)[C@H]1CC[C@H](C(O)=O)CC1 KAFLWBKBAJGLMG-WKILWMFISA-N 0.000 claims description 2
BGYBOGDAUCPCOC-CTYIDZIISA-N C1CN(C=2N=CC(=CC=2)C(N)=N)CCN1C(=O)N(C)[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound C1CN(C=2N=CC(=CC=2)C(N)=N)CCN1C(=O)N(C)[C@H]1CC[C@H](C(O)=O)CC1 BGYBOGDAUCPCOC-CTYIDZIISA-N 0.000 claims description 2
RGUOAVKNVGQWNY-SHTZXODSSA-N N1=CC(CN)=CC=C1N1CCN(C(=O)N[C@@H]2CC[C@H](CC2)C(O)=O)CC1 Chemical compound N1=CC(CN)=CC=C1N1CCN(C(=O)N[C@@H]2CC[C@H](CC2)C(O)=O)CC1 RGUOAVKNVGQWNY-SHTZXODSSA-N 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
230000008619 cell matrix interaction Effects 0.000 claims description 2
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 2
125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
201000010099 disease Diseases 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
MITDIHVTCDFQIP-YOCNBXQISA-N C(N)(=N)C1=CC=C(C=C1)N1CCC(CC1)C(=O)N(CCCC1=CC=CC=C1)[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound C(N)(=N)C1=CC=C(C=C1)N1CCC(CC1)C(=O)N(CCCC1=CC=CC=C1)[C@@H]1CC[C@H](CC1)C(=O)O MITDIHVTCDFQIP-YOCNBXQISA-N 0.000 claims 1
HJXGESYHYDRRHP-AQYVVDRMSA-N C(N)(=N)C1=CC=C(C=C1)N1CCC(CC1)C(=O)N(CCCCC)[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound C(N)(=N)C1=CC=C(C=C1)N1CCC(CC1)C(=O)N(CCCCC)[C@@H]1CC[C@H](CC1)C(=O)O HJXGESYHYDRRHP-AQYVVDRMSA-N 0.000 claims 1
QBVLLEPHJNOODW-QAQDUYKDSA-N NCC1=CC=C(C=C1)N1CCC(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O Chemical compound NCC1=CC=C(C=C1)N1CCC(CC1)C(=O)N[C@@H]1CC[C@H](CC1)C(=O)O QBVLLEPHJNOODW-QAQDUYKDSA-N 0.000 claims 1
150000001721 carbon Chemical group 0.000 claims 1
238000001149 thermolysis Methods 0.000 claims 1
230000002776 aggregation Effects 0.000 abstract description 5
238000004220 aggregation Methods 0.000 abstract description 5
230000002401 inhibitory effect Effects 0.000 abstract description 4
230000000144 pharmacologic effect Effects 0.000 abstract description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 297
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 112
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 100
239000000741 silica gel Substances 0.000 description 100
229910002027 silica gel Inorganic materials 0.000 description 100
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 77
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
239000002904 solvent Substances 0.000 description 67
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
238000001819 mass spectrum Methods 0.000 description 57
229910021529 ammonia Inorganic materials 0.000 description 56
239000000243 solution Substances 0.000 description 56
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
238000002844 melting Methods 0.000 description 52
230000008018 melting Effects 0.000 description 52
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000012043 crude product Substances 0.000 description 27
238000003756 stirring Methods 0.000 description 26
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
238000000354 decomposition reaction Methods 0.000 description 21
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
239000012074 organic phase Substances 0.000 description 18
239000000725 suspension Substances 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
239000013543 active substance Substances 0.000 description 14
229910052739 hydrogen Inorganic materials 0.000 description 14
239000001257 hydrogen Substances 0.000 description 14
239000008346 aqueous phase Substances 0.000 description 13
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
239000012071 phase Substances 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
239000002585 base Substances 0.000 description 11
CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 11
OHEDMAIVEXQCOZ-UHFFFAOYSA-N piperidine;dihydrochloride Chemical compound Cl.Cl.C1CCNCC1 OHEDMAIVEXQCOZ-UHFFFAOYSA-N 0.000 description 11
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 10
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229940006607 hirudin Drugs 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
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230000007574 infarction Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
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229940057948 magnesium stearate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
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238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
FWBXWAQRSCOFBZ-UHFFFAOYSA-N methyl 1-[2-[1-(4-carbamimidoylphenyl)piperidin-4-yl]ethyl]piperidine-4-carboxylate;hydrochloride Chemical compound Cl.C1CC(C(=O)OC)CCN1CCC1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 FWBXWAQRSCOFBZ-UHFFFAOYSA-N 0.000 description 1
VMKCGZVWZXLGGE-UHFFFAOYSA-N methyl 1-[2-[1-(4-cyanophenyl)piperidin-4-yl]ethyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OC)CCN1CCC1CCN(C=2C=CC(=CC=2)C#N)CC1 VMKCGZVWZXLGGE-UHFFFAOYSA-N 0.000 description 1
IVVXBJJCJPIPNF-UHFFFAOYSA-N methyl 1-[2-[1-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidin-4-yl]ethyl]piperidine-4-carboxylate Chemical compound C1=CC(C(=N)NC(=O)OC)=CC=C1N1CCC(CCN2CCC(CC2)C(=O)OC)CC1 IVVXBJJCJPIPNF-UHFFFAOYSA-N 0.000 description 1
LIUFCVWGYULRCU-UHFFFAOYSA-N methyl 1-[[1-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidin-4-yl]methyl]piperidine-4-carboxylate Chemical compound C1=CC(C(=N)NC(=O)OC)=CC=C1N1CCC(CN2CCC(CC2)C(=O)OC)CC1 LIUFCVWGYULRCU-UHFFFAOYSA-N 0.000 description 1
HTKOLQGIUNEVOZ-UHFFFAOYSA-N methyl 2-[1-[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.C1CC(CC(=O)OC)CCN1C(=O)C1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 HTKOLQGIUNEVOZ-UHFFFAOYSA-N 0.000 description 1
YVGZHVDHCBVLOY-UHFFFAOYSA-N methyl 2-[1-[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]piperidin-4-ylidene]acetate;hydrochloride Chemical compound Cl.C1CC(=CC(=O)OC)CCN1C(=O)C1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 YVGZHVDHCBVLOY-UHFFFAOYSA-N 0.000 description 1
JCXGXBDEZOZSED-UHFFFAOYSA-N methyl 2-[1-[1-(4-cyanophenyl)piperidine-4-carbonyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OC)CCN1C(=O)C1CCN(C=2C=CC(=CC=2)C#N)CC1 JCXGXBDEZOZSED-UHFFFAOYSA-N 0.000 description 1
JZKZNULSAOKOLO-UHFFFAOYSA-N methyl 2-[1-[1-(5-cyanopyridin-2-yl)piperidine-4-carbonyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OC)CCN1C(=O)C1CCN(C=2N=CC(=CC=2)C#N)CC1 JZKZNULSAOKOLO-UHFFFAOYSA-N 0.000 description 1
QTSCGCIRQIILDY-UHFFFAOYSA-N methyl 2-[1-[1-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidine-4-carbonyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OC)CCN1C(=O)C1CCN(C=2C=CC(=CC=2)C(=N)NC(=O)OC)CC1 QTSCGCIRQIILDY-UHFFFAOYSA-N 0.000 description 1
VDVFKYQBGSLDSP-UHFFFAOYSA-N methyl 2-[1-[1-[5-(aminomethyl)pyridin-2-yl]piperidine-4-carbonyl]piperidin-4-yl]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)OC)CCN1C(=O)C1CCN(C=2N=CC(CN)=CC=2)CC1 VDVFKYQBGSLDSP-UHFFFAOYSA-N 0.000 description 1
OKSBVXFEIBGKOJ-UHFFFAOYSA-N methyl 2-[1-[4-(4-carbamimidoylphenyl)piperidine-1-carbonyl]piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.C1CC(CC(=O)OC)CCN1C(=O)N1CCC(C=2C=CC(=CC=2)C(N)=N)CC1 OKSBVXFEIBGKOJ-UHFFFAOYSA-N 0.000 description 1
XWSAFTZMSSOVEB-UHFFFAOYSA-N methyl 2-[1-[4-(4-cyanophenyl)piperazine-1-carbonyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OC)CCN1C(=O)N1CCN(C=2C=CC(=CC=2)C#N)CC1 XWSAFTZMSSOVEB-UHFFFAOYSA-N 0.000 description 1
UIPVBUCQRGLHGQ-UHFFFAOYSA-N methyl 2-[1-[4-[4-(aminomethyl)phenyl]piperazine-1-carbonyl]piperidin-4-yl]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)OC)CCN1C(=O)N1CCN(C=2C=CC(CN)=CC=2)CC1 UIPVBUCQRGLHGQ-UHFFFAOYSA-N 0.000 description 1
WVKYKAMFHSAJNK-UHFFFAOYSA-N methyl 2-[1-[4-[4-(aminomethyl)phenyl]piperidine-1-carbonyl]piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.C1CC(CC(=O)OC)CCN1C(=O)N1CCC(C=2C=CC(CN)=CC=2)CC1 WVKYKAMFHSAJNK-UHFFFAOYSA-N 0.000 description 1
ZEOZSTJUTRYJAK-UHFFFAOYSA-N methyl 2-[1-[[1-(4-carbamimidoylphenyl)piperidin-4-yl]methyl]piperidin-4-yl]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)OC)CCN1CC1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 ZEOZSTJUTRYJAK-UHFFFAOYSA-N 0.000 description 1
BYPMGYWXGHNNHY-UHFFFAOYSA-N methyl 2-[1-[[1-(4-carbamimidoylphenyl)piperidin-4-yl]methyl]piperidin-4-ylidene]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(=CC(=O)OC)CCN1CC1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 BYPMGYWXGHNNHY-UHFFFAOYSA-N 0.000 description 1
QYTJTCXAGCBVJH-UHFFFAOYSA-N methyl 2-[1-[[1-(4-cyanophenyl)piperidin-4-yl]methyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OC)CCN1CC1CCN(C=2C=CC(=CC=2)C#N)CC1 QYTJTCXAGCBVJH-UHFFFAOYSA-N 0.000 description 1
BBWJWFOBFQJTAK-UHFFFAOYSA-N methyl 2-[1-[[1-(4-cyanophenyl)piperidin-4-yl]methyl]piperidin-4-ylidene]acetate Chemical compound C1CC(=CC(=O)OC)CCN1CC1CCN(C=2C=CC(=CC=2)C#N)CC1 BBWJWFOBFQJTAK-UHFFFAOYSA-N 0.000 description 1
CVIPUGLZHSRYLD-UHFFFAOYSA-N methyl 2-[1-[[1-[4-(aminomethyl)phenyl]piperidin-4-yl]methyl]piperidin-4-yl]acetate;trihydrochloride Chemical compound Cl.Cl.Cl.C1CC(CC(=O)OC)CCN1CC1CCN(C=2C=CC(CN)=CC=2)CC1 CVIPUGLZHSRYLD-UHFFFAOYSA-N 0.000 description 1
NZQAYTXAKABLBR-UHFFFAOYSA-N methyl 2-[4-[1-(5-carbamimidoylpyridin-2-yl)piperidine-4-carbonyl]piperazin-1-yl]acetate;hydrochloride Chemical compound Cl.C1CN(CC(=O)OC)CCN1C(=O)C1CCN(C=2N=CC(=CC=2)C(N)=N)CC1 NZQAYTXAKABLBR-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
QIHNJSDHEAOBSZ-UHFFFAOYSA-N methyl 2-piperidin-4-ylideneacetate Chemical compound COC(=O)C=C1CCNCC1 QIHNJSDHEAOBSZ-UHFFFAOYSA-N 0.000 description 1
ONHITUPMAULSRR-UHFFFAOYSA-N methyl 3-[2-[1-(4-carbamimidoylphenyl)piperidin-4-yl]ethylamino]propanoate;hydrochloride Chemical compound Cl.C1CC(CCNCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 ONHITUPMAULSRR-UHFFFAOYSA-N 0.000 description 1
JGMYVAUZJQQVFT-UHFFFAOYSA-N methyl 3-[[2-[1-(4-carbamimidoylphenyl)piperidin-4-yl]acetyl]-(2-phenylethyl)amino]propanoate;hydrochloride Chemical compound Cl.C1CN(C=2C=CC(=CC=2)C(N)=N)CCC1CC(=O)N(CCC(=O)OC)CCC1=CC=CC=C1 JGMYVAUZJQQVFT-UHFFFAOYSA-N 0.000 description 1
KNBRSTHVPFDTCC-UHFFFAOYSA-N methyl 3-[[2-[1-(4-carbamimidoylphenyl)piperidin-4-yl]acetyl]-methylamino]propanoate;hydrochloride Chemical compound Cl.C1CC(CC(=O)N(C)CCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 KNBRSTHVPFDTCC-UHFFFAOYSA-N 0.000 description 1
PEDLWDGRZLGZNR-UHFFFAOYSA-N methyl 3-[[2-[1-(4-carbamimidoylphenyl)piperidin-4-yl]acetyl]amino]propanoate;hydrochloride Chemical compound Cl.C1CC(CC(=O)NCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 PEDLWDGRZLGZNR-UHFFFAOYSA-N 0.000 description 1
DWEWQRVLQILBLH-UHFFFAOYSA-N methyl 3-[[2-[1-(4-cyanophenyl)piperidin-4-yl]acetyl]-(2-phenylethyl)amino]propanoate Chemical compound C1CN(C=2C=CC(=CC=2)C#N)CCC1CC(=O)N(CCC(=O)OC)CCC1=CC=CC=C1 DWEWQRVLQILBLH-UHFFFAOYSA-N 0.000 description 1
CEZLDGZVXMDBSF-UHFFFAOYSA-N methyl 3-[[2-[1-(4-cyanophenyl)piperidin-4-yl]acetyl]-methylamino]propanoate Chemical compound C1CC(CC(=O)N(C)CCC(=O)OC)CCN1C1=CC=C(C#N)C=C1 CEZLDGZVXMDBSF-UHFFFAOYSA-N 0.000 description 1
FROBUOUWXZWVDO-UHFFFAOYSA-N methyl 3-[[2-[1-[4-(aminomethyl)phenyl]piperidin-4-yl]acetyl]-methylamino]propanoate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)N(C)CCC(=O)OC)CCN1C1=CC=C(CN)C=C1 FROBUOUWXZWVDO-UHFFFAOYSA-N 0.000 description 1
XUPPSPDVBPHZEA-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)piperazin-1-yl]acetyl]-(2-phenylethyl)amino]propanoate;hydrochloride Chemical compound Cl.C1CN(C=2C=CC(=CC=2)C(N)=N)CCN1CC(=O)N(CCC(=O)OC)CCC1=CC=CC=C1 XUPPSPDVBPHZEA-UHFFFAOYSA-N 0.000 description 1
FSHXEPGKZKVMKR-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)piperazin-1-yl]acetyl]amino]propanoate;hydrochloride Chemical compound Cl.C1CN(CC(=O)NCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 FSHXEPGKZKVMKR-UHFFFAOYSA-N 0.000 description 1
UIHASLNATQHPJG-UHFFFAOYSA-N methyl 3-[[2-[4-(4-cyanophenyl)piperazin-1-yl]acetyl]-(2-phenylethyl)amino]propanoate Chemical compound C1CN(C=2C=CC(=CC=2)C#N)CCN1CC(=O)N(CCC(=O)OC)CCC1=CC=CC=C1 UIHASLNATQHPJG-UHFFFAOYSA-N 0.000 description 1
HETWGTUIIDSXCR-UHFFFAOYSA-N methyl 3-[[2-[4-(4-cyanophenyl)piperazin-1-yl]acetyl]amino]propanoate Chemical compound C1CN(CC(=O)NCCC(=O)OC)CCN1C1=CC=C(C#N)C=C1 HETWGTUIIDSXCR-UHFFFAOYSA-N 0.000 description 1
CXZIJDNQYOKWOY-UHFFFAOYSA-N methyl 3-[[2-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperazin-1-yl]acetyl]amino]propanoate Chemical compound C1CN(CC(=O)NCCC(=O)OC)CCN1C1=CC=C(C(\N)=N/C(=O)OC)C=C1 CXZIJDNQYOKWOY-UHFFFAOYSA-N 0.000 description 1
MVAUFZWNLLFQNG-UHFFFAOYSA-N methyl 4-[[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]-(2-phenylethyl)amino]butanoate;hydrochloride Chemical compound Cl.C1CN(C=2C=CC(=CC=2)C(N)=N)CCC1C(=O)N(CCCC(=O)OC)CCC1=CC=CC=C1 MVAUFZWNLLFQNG-UHFFFAOYSA-N 0.000 description 1
LKEVWJLDXPTSKQ-UHFFFAOYSA-N methyl 4-[[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]-methylamino]butanoate;hydrochloride Chemical compound Cl.C1CC(C(=O)N(C)CCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 LKEVWJLDXPTSKQ-UHFFFAOYSA-N 0.000 description 1
XBEYUCCVWNOMCF-UHFFFAOYSA-N methyl 4-[[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]-pentylamino]butanoate;hydrochloride Chemical compound Cl.C1CC(C(=O)N(CCCC(=O)OC)CCCCC)CCN1C1=CC=C(C(N)=N)C=C1 XBEYUCCVWNOMCF-UHFFFAOYSA-N 0.000 description 1
RWGPQYOUSFEHAR-UHFFFAOYSA-N methyl 4-[[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]amino]butanoate;dihydrochloride Chemical compound Cl.Cl.C1CC(C(=O)NCCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 RWGPQYOUSFEHAR-UHFFFAOYSA-N 0.000 description 1
RXAJILSCBNTQKP-UHFFFAOYSA-N methyl 4-[[1-(4-cyanophenyl)piperidine-4-carbonyl]-(3-phenylpropyl)amino]butanoate Chemical compound C1CN(C=2C=CC(=CC=2)C#N)CCC1C(=O)N(CCCC(=O)OC)CCCC1=CC=CC=C1 RXAJILSCBNTQKP-UHFFFAOYSA-N 0.000 description 1
VGEGYZUNKGPIPY-UHFFFAOYSA-N methyl 4-[[1-(4-cyanophenyl)piperidine-4-carbonyl]-methylamino]butanoate Chemical compound C1CC(C(=O)N(C)CCCC(=O)OC)CCN1C1=CC=C(C#N)C=C1 VGEGYZUNKGPIPY-UHFFFAOYSA-N 0.000 description 1
KRQJWMAIOPMZGE-UHFFFAOYSA-N methyl 4-[[1-(4-cyanophenyl)piperidine-4-carbonyl]-pentylamino]butanoate Chemical compound C1CC(C(=O)N(CCCC(=O)OC)CCCCC)CCN1C1=CC=C(C#N)C=C1 KRQJWMAIOPMZGE-UHFFFAOYSA-N 0.000 description 1
QCOLNKQNFUNOBC-UHFFFAOYSA-N methyl 4-[[1-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidine-4-carbonyl]amino]butanoate Chemical compound C1CC(C(=O)NCCCC(=O)OC)CCN1C1=CC=C(C(\N)=N/C(=O)OC)C=C1 QCOLNKQNFUNOBC-UHFFFAOYSA-N 0.000 description 1
VRXVDWLERLWWOC-UHFFFAOYSA-N methyl 4-[[1-[4-[(z)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidine-4-carbonyl]-methylamino]butanoate Chemical compound C1CC(C(=O)N(C)CCCC(=O)OC)CCN1C1=CC=C(C(=N)NC(=O)OC)C=C1 VRXVDWLERLWWOC-UHFFFAOYSA-N 0.000 description 1
OMJRFRMJSSMYLG-UHFFFAOYSA-N methyl 4-[benzyl-[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]amino]butanoate;hydrochloride Chemical compound Cl.C1CN(C=2C=CC(=CC=2)C(N)=N)CCC1C(=O)N(CCCC(=O)OC)CC1=CC=CC=C1 OMJRFRMJSSMYLG-UHFFFAOYSA-N 0.000 description 1
FDIOWFWXMGXNKY-UHFFFAOYSA-N methyl 4-[benzyl-[1-(4-cyanophenyl)piperidine-4-carbonyl]amino]butanoate Chemical compound C1CN(C=2C=CC(=CC=2)C#N)CCC1C(=O)N(CCCC(=O)OC)CC1=CC=CC=C1 FDIOWFWXMGXNKY-UHFFFAOYSA-N 0.000 description 1
GTWPGPHENPGMKV-UHFFFAOYSA-N methyl 5-[[1-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]piperidin-4-yl]amino]-5-oxopentanoate Chemical compound C1CC(NC(=O)CCCC(=O)OC)CCN1C1=CC=C(C(\N)=N/C(=O)OC)C=C1 GTWPGPHENPGMKV-UHFFFAOYSA-N 0.000 description 1
CAYZPTIEOLOEGN-UHFFFAOYSA-N methyl 5-[[4-(4-carbamimidoylphenyl)piperazine-1-carbonyl]amino]pentanoate;hydrochloride Chemical compound Cl.C1CN(C(=O)NCCCCC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 CAYZPTIEOLOEGN-UHFFFAOYSA-N 0.000 description 1
NUZKIKREZITOPO-UHFFFAOYSA-N methyl 5-[[4-(4-carbamimidoylphenyl)piperidine-1-carbonyl]-methylamino]pentanoate;hydrochloride Chemical compound Cl.C1CN(C(=O)N(C)CCCCC(=O)OC)CCC1C1=CC=C(C(N)=N)C=C1 NUZKIKREZITOPO-UHFFFAOYSA-N 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
YKFLJYAKACCWMH-UHFFFAOYSA-N methyl piperidine-1-carboxylate Chemical compound COC(=O)N1CCCCC1 YKFLJYAKACCWMH-UHFFFAOYSA-N 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004706 n-propylthio group Chemical group C(CC)S* 0.000 description 1
230000010807 negative regulation of binding Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
YSUHCFNNYZUKJK-UHFFFAOYSA-N pentan-3-yl 3-[[2-[4-(4-carbamimidoylphenyl)piperazin-1-yl]acetyl]amino]propanoate trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CC(=O)NCCC(=O)OC(CC)CC)CCN1C1=CC=C(C(N)=N)C=C1 YSUHCFNNYZUKJK-UHFFFAOYSA-N 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
239000001120 potassium sulphate Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
PLBHSDWTCDEOQC-UHFFFAOYSA-N propan-2-yl 2-[1-[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]piperidin-4-yl]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)OC(C)C)CCN1C(=O)C1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 PLBHSDWTCDEOQC-UHFFFAOYSA-N 0.000 description 1
COVRXMMBILKNFG-UHFFFAOYSA-N propan-2-yl 2-[1-[4-(4-carbamimidoylphenyl)piperazine-1-carbonyl]piperidin-4-yl]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(CC(=O)OC(C)C)CCN1C(=O)N1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 COVRXMMBILKNFG-UHFFFAOYSA-N 0.000 description 1
CDLNBWODTPSUTO-UHFFFAOYSA-N propan-2-yl 3-[[2-[4-(4-carbamimidoylphenyl)piperazin-1-yl]acetyl]amino]propanoate;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CC(=O)NCCC(=O)OC(C)C)CCN1C1=CC=C(C(N)=N)C=C1 CDLNBWODTPSUTO-UHFFFAOYSA-N 0.000 description 1
MRUXUKNJSWESLR-UHFFFAOYSA-N propan-2-yl 4-[[1-(4-carbamimidoylphenyl)piperidine-4-carbonyl]-methylamino]butanoate;dihydrochloride Chemical compound Cl.Cl.C1CC(C(=O)N(C)CCCC(=O)OC(C)C)CCN1C1=CC=C(C(N)=N)C=C1 MRUXUKNJSWESLR-UHFFFAOYSA-N 0.000 description 1
229960000856 protein c Drugs 0.000 description 1
PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
108010073863 saruplase Proteins 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
239000013049 sediment Substances 0.000 description 1
230000035939 shock Effects 0.000 description 1
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
229910001958 silver carbonate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000003826 tablet Substances 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
WSNYPQZNUKSYBI-UHFFFAOYSA-N tert-butyl 4-(2-methylsulfonyloxyethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CCOS(C)(=O)=O)CC1 WSNYPQZNUKSYBI-UHFFFAOYSA-N 0.000 description 1
QQKMRJBIMLSKQL-UHFFFAOYSA-N tert-butyl n-[1-(4-cyanophenyl)piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C1=CC=C(C#N)C=C1 QQKMRJBIMLSKQL-UHFFFAOYSA-N 0.000 description 1
CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000003868 thrombin inhibitor Substances 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
238000002834 transmittance Methods 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
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 1
229960005356 urokinase Drugs 0.000 description 1
229940019333 vitamin k antagonists Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

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Chemical & Material Sciences (AREA)
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Animal Behavior & Ethology (AREA)
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Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Diabetes (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyridine Compounds (AREA)

SK1072-93A 1992-10-12 1993-10-05 Carboxylic acid derivatives, drugs containing these compounds and method of their production SK107293A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE4234295A DE4234295A1 (de)	1992-10-12	1992-10-12	Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung

Publications (1)

Publication Number	Publication Date
SK107293A3 true SK107293A3 (en)	1994-08-10

Family

ID=6470224

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1072-93A SK107293A3 (en)	1992-10-12	1993-10-05	Carboxylic acid derivatives, drugs containing these compounds and method of their production

Country Status (19)

Country	Link
US (1)	US5442064A (fr)
EP (1)	EP0592949A3 (fr)
JP (1)	JPH06199788A (fr)
KR (1)	KR940009164A (fr)
CN (1)	CN1087904A (fr)
AU (1)	AU668765B2 (fr)
CA (1)	CA2108093A1 (fr)
CZ (1)	CZ212893A3 (fr)
DE (1)	DE4234295A1 (fr)
FI (1)	FI934460A7 (fr)
HU (1)	HU9302875D0 (fr)
IL (1)	IL107221A0 (fr)
MX (1)	MX9306303A (fr)
NO (1)	NO180232C (fr)
NZ (1)	NZ248894A (fr)
PL (1)	PL300673A1 (fr)
SK (1)	SK107293A3 (fr)
TW (1)	TW293815B (fr)
ZA (1)	ZA937502B (fr)

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GB0012362D0 (en) *	2000-05-22	2000-07-12	Aventis Pharma Ltd	Chemical compounds
CA2410567A1 (fr)	2000-05-24	2001-11-29	Eli Lilly And Company	Preparations et techniques permettant de traiter des hypercoagulations
JP2004525071A (ja)	2000-07-20	2004-08-19	ニューロジェンコーポレイション	カプサイシン受容体リガンド
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US7157462B2 (en)	2002-09-24	2007-01-02	Euro-Celtique S.A.	Therapeutic agents useful for treating pain
WO2004103954A1 (fr) *	2003-05-20	2004-12-02	Ajinomoto Co., Inc.	Derive d'amide
MY142655A (en) *	2003-06-12	2010-12-15	Euro Celtique Sa	Therapeutic agents useful for treating pain
SI1867644T1 (sl) *	2003-07-24	2009-10-31	Euro Celtique Sa	Heteroaril-tetrahidropiperidilne spojine, koristne za zdravljenje ali preprečevanje bolečine
EP1664041B1 (fr)	2003-09-22	2008-07-02	Euro-Celtique S.A.	Composes phenyl-carboxamide utiles pour traiter la douleur
PL1664016T3 (pl) *	2003-09-22	2009-04-30	Euro Celtique Sa	Środki terapeutyczne przydatne do leczenia bólu
TWI350168B (en) *	2004-05-07	2011-10-11	Incyte Corp	Amido compounds and their use as pharmaceuticals
US20060009491A1 (en) *	2004-06-24	2006-01-12	Incyte Corporation	Amido compounds and their use as pharmaceuticals
MXPA06014573A (es) *	2004-06-24	2007-03-12	Incyte Corp	Compuestos amido y su uso como farmaceuticos.
US8071624B2 (en)	2004-06-24	2011-12-06	Incyte Corporation	N-substituted piperidines and their use as pharmaceuticals
US7687665B2 (en)	2004-06-24	2010-03-30	Incyte Corporation	2-methylprop anamides and their use as pharmaceuticals
US20060122197A1 (en) *	2004-08-10	2006-06-08	Wenqing Yao	Amido compounds and their use as pharmaceuticals
US8110581B2 (en)	2004-11-10	2012-02-07	Incyte Corporation	Lactam compounds and their use as pharmaceuticals
CA2585797C (fr) *	2004-11-10	2015-01-06	Incyte Corporation	Composes de lactame et leur utilisation en temps que substances pharmaceutiques
JP2008520700A (ja) *	2004-11-18	2008-06-19	インサイト・コーポレイション	１１−βヒドロキシルステロイドデヒドロゲナーゼタイプＩの阻害剤およびその使用方法
AU2005317928B2 (en) *	2004-12-24	2010-06-10	Astrazeneca Ab	Heterocyclic compounds as CCR2b antagonists
WO2007038138A2 (fr) *	2005-09-21	2007-04-05	Incyte Corporation	Utilisation pharmaceutique de composes amido
EP1957494A2 (fr) *	2005-12-05	2008-08-20	Incyte Corporation	Composes lactames et procedes d'utilisation de ceux-ci
GB0525957D0 (en)	2005-12-21	2006-02-01	Astrazeneca Ab	Methods
WO2007084314A2 (fr) *	2006-01-12	2007-07-26	Incyte Corporation	MODULATEURS de la 11-ß HYDROXYSTEROIDE DESHYDROGENASE DE TYPE 1, LEURS COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCEDES D'UTILISATION
BRPI0707408A2 (pt) *	2006-01-31	2011-05-03	Incyte Corp	compostos de amido e seu uso como produtos farmacêuticos
WO2007101270A1 (fr) *	2006-03-02	2007-09-07	Incyte Corporation	MODULATEURS DE LA 11β-HYDROXYSTEROIDE DESHYDROGENASE DE TYPE 1, COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT ET PROCEDE D'UTILISATION DESDITS MODULATEURS
WO2007103719A2 (fr) *	2006-03-03	2007-09-13	Incyte Corporation	MODULATEURS DE LA 11-β-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1, LEURS COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION
WO2007130898A1 (fr) *	2006-05-01	2007-11-15	Incyte Corporation	URÉES TÉTRASUBSTITUÉES MODULATEURS DE LA 11-β HYDROXYL STÉROÏD DÉSHYDROGÉNASE DE TYPE 1
JP2009537564A (ja) *	2006-05-17	2009-10-29	インサイト・コーポレイション	１１−βヒドロキシルステロイドデヒドロゲナーゼタイプＩの複素環阻害剤およびそれを用いる方法
ES2293834B1 (es) *	2006-07-20	2009-02-16	Consejo Superior Investig. Cientificas	Compuesto con actividad inhibidora de las interacciones ubc13-uev, composiciones farmaceuticas que lo comprenden y sus aplicaciones terapeuticas.
WO2008133973A1 (fr) *	2007-04-27	2008-11-06	Purdue Pharma L.P.	Agents thérapeutiques utiles pour traiter la douleur
DK2142529T3 (da) *	2007-04-27	2014-02-10	Purdue Pharma Lp	Trpv1-antagonister og anvendelser deraf
AU2011226773C1 (en) *	2007-04-27	2012-07-26	Purdue Pharma L.P.	TRPV1 antagonists and uses thereof
ES2373255T3 (es) *	2007-05-04	2012-02-01	Astrazeneca Ab	Proceso para s�?ntesis de �?cidos alquilfosf�?nicos mediante iniciación de una amina y un aminóxido.
CL2008001839A1 (es) *	2007-06-21	2009-01-16	Incyte Holdings Corp	Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades.
US7946206B2 (en) *	2007-11-21	2011-05-24	Rocksmart, Llc	Quick-release system
WO2010065668A1 (fr) *	2008-12-03	2010-06-10	Presidio Pharmaceuticals, Inc.	Inhibiteurs du virus de l'hépatite c de type ns5a
US20100152197A1 (en) *	2008-12-15	2010-06-17	Astrazeneca Ab	(4-tert-butylpiperazin-2-yl)(piperazin-1-yl)methanone-n-carboxamide derivatives
CA2749163A1 (fr) *	2009-01-14	2010-07-22	The Salk Institute For Biological Studies	Methodes de criblage et composes utiles dans la protection contre les maladies amyloides
HRP20170507T1 (hr)	2011-06-22	2017-06-02	Purdue Pharma Lp	Trpv1 antagonisti uključujući dihidroksi supstituente i njihove uporabe
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US5256812A (en) *	1989-01-31	1993-10-26	Hoffmann-La Roche Inc.	Carboxamides and sulfonamides
US5084466A (en) *	1989-01-31	1992-01-28	Hoffmann-La Roche Inc.	Novel carboxamide pyridine compounds which have useful pharmaceutical utility
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DE4303840A1 (de) *	1992-10-22	1994-08-11	Thomae Gmbh Dr K	Aryliden-1-azacycloalkane und Arylalkyl-1-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung
JPH08504194A (ja) *	1992-12-01	1996-05-07	メルクエンドカンパニーインコーポレーテッド	フィブリノーゲンレセプターアンタゴニスト

1992
- 1992-10-12 DE DE4234295A patent/DE4234295A1/de not_active Withdrawn
1993
- 1993-09-10 TW TW082107457A patent/TW293815B/zh active
- 1993-10-05 SK SK1072-93A patent/SK107293A3/sk unknown
- 1993-10-07 EP EP19930116244 patent/EP0592949A3/de not_active Withdrawn
- 1993-10-08 JP JP5252019A patent/JPH06199788A/ja active Pending
- 1993-10-08 NZ NZ248894A patent/NZ248894A/en unknown
- 1993-10-08 CA CA002108093A patent/CA2108093A1/fr not_active Abandoned
- 1993-10-11 KR KR1019930021147A patent/KR940009164A/ko not_active Withdrawn
- 1993-10-11 AU AU48939/93A patent/AU668765B2/en not_active Ceased
- 1993-10-11 NO NO933647A patent/NO180232C/no unknown
- 1993-10-11 HU HU9302875A patent/HU9302875D0/hu unknown
- 1993-10-11 PL PL93300673A patent/PL300673A1/xx unknown
- 1993-10-11 CZ CZ932128A patent/CZ212893A3/cs unknown
- 1993-10-11 FI FI934460A patent/FI934460A7/fi not_active Application Discontinuation
- 1993-10-11 ZA ZA937502A patent/ZA937502B/xx unknown
- 1993-10-11 MX MX9306303A patent/MX9306303A/es unknown
- 1993-10-11 IL IL107221A patent/IL107221A0/xx unknown
- 1993-10-12 US US08/135,041 patent/US5442064A/en not_active Expired - Fee Related
- 1993-10-12 CN CN93118925A patent/CN1087904A/zh active Pending

Also Published As

Publication number	Publication date
IL107221A0 (en)	1994-01-25
JPH06199788A (ja)	1994-07-19
EP0592949A3 (en)	1994-08-10
KR940009164A (ko)	1994-05-20
CA2108093A1 (fr)	1994-04-13
EP0592949A2 (fr)	1994-04-20
NZ248894A (en)	1996-01-26
AU668765B2 (en)	1996-05-16
AU4893993A (en)	1994-04-28
FI934460A0 (fi)	1993-10-11
TW293815B (fr)	1996-12-21
FI934460A7 (fi)	1994-04-13
CN1087904A (zh)	1994-06-15
MX9306303A (es)	1994-04-29
NO180232C (no)	1997-03-12
NO933647L (no)	1994-04-13
PL300673A1 (en)	1994-05-16
ZA937502B (en)	1995-04-11
CZ212893A3 (en)	1994-04-13
NO933647D0 (no)	1993-10-11
NO180232B (no)	1996-12-02
US5442064A (en)	1995-08-15
HU9302875D0 (en)	1993-12-28
DE4234295A1 (de)	1994-04-14

Publication	Publication Date	Title
SK107293A3 (en)	1994-08-10	Carboxylic acid derivatives, drugs containing these compounds and method of their production
US5700801A (en)	1997-12-23	Piperazine derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them
US5994356A (en)	1999-11-30	Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production
US5418233A (en)	1995-05-23	Heterobiarly derivatives and pharmaceutical compositions thereof
US5922717A (en)	1999-07-13	Piperazine derivatives, medicaments comprising these compounds, their use and processes for their preparation
US5434150A (en)	1995-07-18	Condensed 5-membered heterocyclic compounds, processes for preparing them and pharmaceutical preparations containing these compounds
US5817677A (en)	1998-10-06	5-membered heterocycles, medicaments containing these compounds, their use and processes for their preparation
SK128193A3 (en)	1995-02-08	Carboxylic acids derivatives, medicaments containing these compounds and method of their production
EP0608858A1 (fr)	1994-08-03	Dérivés hétérocycliques à 5 chaînons comme inhibiteurs d'aguégation
CA2098158A1 (fr)	1993-12-12	Derives de biphenyles, compositions pharmaceutiques qui contiennent ces composes et leur mode de preparation
CA2197789A1 (fr)	1996-02-22	Derives cycliques d'uree; compositions pharmaceutiques renfermant ces coomposes et methodes de preparation
CA2129374A1 (fr)	1995-02-06	Carbonamides; compositions pharmaceutiques a base de ces composes; methode de preparation
US5489693A (en)	1996-02-06	Cyclic imino derivatives, pharmaceutical compositions containing these compounds and processes preparing them
US5607944A (en)	1997-03-04	Bicyclic heterocyclic compounds, pharmaceutical preparations containing these compounds and processes for their preparations
JP2005508874A (ja)	2005-04-07	置換ｎ−アシル−アニリン誘導体、その調製及び医薬組成物としての使用
CA2380986C (fr)	2009-10-20	Amides d'acide carboxylique, leur production et leur utilisation comme medicaments
US5958952A (en)	1999-09-28	Substituted phenylamindines, medicaments containing these compounds and process for producing them
AU5285399A (en)	2000-02-14	Substituted phenylamidines with antithrombotic action
JP2003520791A (ja)	2003-07-08	置換フェニルアミジン、これらの化合物を含む医薬組成物及びこれらの調製方法
CA2244860A1 (fr)	1997-10-16	Derives d'acides carboxyliques a effet inhibant l'agregation