CA1270828A - Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant - Google Patents

Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant

Info

Publication number: CA1270828A
Authority: CA; Canada
Prior art keywords: compound; formula; salt; phenyl; alkyl
Prior art date: 1985-05-16
Legal status (The legal status 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 status listed.): Expired - Fee Related

Application number

CA000481718A

Other languages

English (en)

Inventor

Osamu Nakaguti

Norihiko Shimazaki

Yoshio Kawai

Masashi Hashimoto

Michie Nakatuka

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Fujisawa Pharmaceutical Co Ltd

Original Assignee

Fujisawa Pharmaceutical Co 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.)

1985-05-16

Filing date

1985-05-16

Publication date

1990-06-26

1985-05-16 Application filed by Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd

1985-05-16 Priority to CA000481718A priority Critical patent/CA1270828A/fr

1990-06-26 Application granted granted Critical

1990-06-26 Publication of CA1270828A publication Critical patent/CA1270828A/fr

2007-06-26 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 5
150000003349 semicarbazides Chemical class 0.000 title abstract description 10
238000000034 method Methods 0.000 title description 30
238000002360 preparation method Methods 0.000 title description 15
150000003839 salts Chemical class 0.000 claims abstract description 63
125000000217 alkyl group Chemical group 0.000 claims abstract description 40
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 22
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
125000001424 substituent group Chemical group 0.000 claims abstract description 13
125000003342 alkenyl group Chemical group 0.000 claims abstract description 11
229910052736 halogen Inorganic materials 0.000 claims abstract description 11
150000002367 halogens Chemical class 0.000 claims abstract description 10
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
125000003282 alkyl amino group Chemical group 0.000 claims abstract 4
125000001475 halogen functional group Chemical group 0.000 claims abstract 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
-1 perhydro-pyridazinediyl Chemical group 0.000 claims description 140
150000001875 compounds Chemical class 0.000 claims description 88
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 41
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000001624 naphthyl group Chemical group 0.000 claims description 6
CVLVBUFROJFLOJ-UHFFFAOYSA-N n-(4-fluorophenyl)-3,6-dihydro-1h-pyridazine-2-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1NCC=CC1 CVLVBUFROJFLOJ-UHFFFAOYSA-N 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
MANYYWKFGKYTJD-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(2-fluorophenyl)urea Chemical compound FC1=CC=CC=C1NC(=O)NN1CC=CCC1 MANYYWKFGKYTJD-UHFFFAOYSA-N 0.000 claims description 2
QLKVZMVKRVEBCR-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(4-fluorophenyl)urea Chemical compound C1=CC(F)=CC=C1NC(=O)NN1CC=CCC1 QLKVZMVKRVEBCR-UHFFFAOYSA-N 0.000 claims description 2
MIKNMKOITYLRQS-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-phenylurea Chemical compound C=1C=CC=CC=1NC(=O)NN1CCC=CC1 MIKNMKOITYLRQS-UHFFFAOYSA-N 0.000 claims description 2
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000005942 tetrahydropyridyl group Chemical group 0.000 claims 4
238000004519 manufacturing process Methods 0.000 claims 1
125000003118 aryl group Chemical group 0.000 abstract description 31
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 10
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 8
230000003110 anti-inflammatory effect Effects 0.000 abstract description 8
125000003545 alkoxy group Chemical group 0.000 abstract description 6
229920006395 saturated elastomer Polymers 0.000 abstract description 6
125000006529 (C3-C6) alkyl group Chemical group 0.000 abstract description 3
239000000730 antalgic agent Substances 0.000 abstract description 3
239000002260 anti-inflammatory agent Substances 0.000 abstract description 3
125000006526 (C1-C2) alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 32
101150041968 CDC13 gene Proteins 0.000 description 26
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
238000004458 analytical method Methods 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
239000002904 solvent Substances 0.000 description 20
239000000203 mixture Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000002253 acid Substances 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
238000006722 reduction reaction Methods 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 10
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
238000012360 testing method Methods 0.000 description 10
SZCMIMLOFSGXQX-UHFFFAOYSA-N 3,6-dihydro-2h-pyridin-1-amine;hydrochloride Chemical compound Cl.NN1CCC=CC1 SZCMIMLOFSGXQX-UHFFFAOYSA-N 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
210000002683 foot Anatomy 0.000 description 8
239000003638 chemical reducing agent Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000010531 catalytic reduction reaction Methods 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 4
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
208000002193 Pain Diseases 0.000 description 4
230000002411 adverse Effects 0.000 description 4
230000000202 analgesic effect Effects 0.000 description 4
239000002585 base Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
125000000623 heterocyclic group Chemical group 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
230000036407 pain Effects 0.000 description 4
SXDBGLYQTCIBQF-UHFFFAOYSA-N phenyl n-(3,6-dihydro-2h-pyridin-1-yl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NN1CCC=CC1 SXDBGLYQTCIBQF-UHFFFAOYSA-N 0.000 description 4
229910052697 platinum Inorganic materials 0.000 description 4
229910052701 rubidium Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
238000010792 warming Methods 0.000 description 4
YNOXSGADSYWZCU-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-naphthalen-1-ylurea Chemical compound C=1C=CC2=CC=CC=C2C=1NC(=O)NN1CCC=CC1 YNOXSGADSYWZCU-UHFFFAOYSA-N 0.000 description 3
IBLRZZNLVRIYEZ-UHFFFAOYSA-N 3-(3,6-dihydro-2h-pyridin-1-yl)-1-methyl-1-phenylurea Chemical compound C=1C=CC=CC=1N(C)C(=O)NN1CCC=CC1 IBLRZZNLVRIYEZ-UHFFFAOYSA-N 0.000 description 3
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 3
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
206010030113 Oedema Diseases 0.000 description 3
206010030124 Oedema peripheral Diseases 0.000 description 3
241000700159 Rattus Species 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
125000001118 alkylidene group Chemical group 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
229910017052 cobalt Inorganic materials 0.000 description 3
239000010941 cobalt Substances 0.000 description 3
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
DAIWVKYHHYGEOQ-UHFFFAOYSA-N n-(4-fluorophenyl)diazinane-1-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1NCCCC1 DAIWVKYHHYGEOQ-UHFFFAOYSA-N 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 3
NDRLPYIMWROJBG-UHFFFAOYSA-M pyridin-1-ium-1-amine;iodide Chemical compound [I-].N[N+]1=CC=CC=C1 NDRLPYIMWROJBG-UHFFFAOYSA-M 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000010998 test method Methods 0.000 description 3
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
VIHGJMNRYVZUGL-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-(3,6-dihydro-2h-pyridin-1-yl)urea Chemical compound FC1=CC(F)=CC=C1NC(=O)NN1CC=CCC1 VIHGJMNRYVZUGL-UHFFFAOYSA-N 0.000 description 2
ZVVLNLWEMPIEAF-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(2-methoxyphenyl)urea Chemical compound COC1=CC=CC=C1NC(=O)NN1CC=CCC1 ZVVLNLWEMPIEAF-UHFFFAOYSA-N 0.000 description 2
JQCLLRBBJNHOSW-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(3-fluorophenyl)urea Chemical compound FC1=CC=CC(NC(=O)NN2CC=CCC2)=C1 JQCLLRBBJNHOSW-UHFFFAOYSA-N 0.000 description 2
KMEAHKAZGYDTNY-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(4-methoxyphenyl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NN1CC=CCC1 KMEAHKAZGYDTNY-UHFFFAOYSA-N 0.000 description 2
UAGOQWLXGKBBBB-UHFFFAOYSA-N 1-(3,6-dihydro-2h-pyridin-1-yl)-3-(4-methylphenyl)urea Chemical compound C1=CC(C)=CC=C1NC(=O)NN1CC=CCC1 UAGOQWLXGKBBBB-UHFFFAOYSA-N 0.000 description 2
IDVVUNHQASPRJU-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-(3,6-dihydro-2h-pyridin-1-yl)urea Chemical compound C1=CC(Cl)=CC=C1NC(=O)NN1CC=CCC1 IDVVUNHQASPRJU-UHFFFAOYSA-N 0.000 description 2
MKRNJSRJRQXJLC-UHFFFAOYSA-O 1-(4-fluorophenyl)-3-(2h-pyridin-1-ium-1-ylidene)urea Chemical compound C1=CC(F)=CC=C1NC(=O)N=[N+]1C=CC=CC1 MKRNJSRJRQXJLC-UHFFFAOYSA-O 0.000 description 2
WEOAYCNZAKLIKJ-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)urea Chemical compound C1=CC(F)=CC=C1NC(=O)NN1CC=C(C=2C=CC=CC=2)CC1 WEOAYCNZAKLIKJ-UHFFFAOYSA-N 0.000 description 2
URUQQWIPEJLQGL-UHFFFAOYSA-N 1-(benzylamino)-3-(4-fluorophenyl)urea Chemical compound C1=CC(F)=CC=C1NC(=O)NNCC1=CC=CC=C1 URUQQWIPEJLQGL-UHFFFAOYSA-N 0.000 description 2
CCFSHBGKTBJKCM-UHFFFAOYSA-N 1-[di(propan-2-yl)amino]-3-(4-fluorophenyl)urea Chemical compound CC(C)N(C(C)C)NC(=O)NC1=CC=C(F)C=C1 CCFSHBGKTBJKCM-UHFFFAOYSA-N 0.000 description 2
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
101150008415 CALCA gene Proteins 0.000 description 2
101100087530 Caenorhabditis elegans rom-1 gene Proteins 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
101100305983 Mus musculus Rom1 gene Proteins 0.000 description 2
108010058846 Ovalbumin Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
238000000692 Student's t-test Methods 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
239000012964 benzotriazole Substances 0.000 description 2
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
235000010418 carrageenan Nutrition 0.000 description 2
229920001525 carrageenan Polymers 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
230000008030 elimination Effects 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
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239000012280 lithium aluminium hydride Substances 0.000 description 1
ANAFTYVSHCSQPP-UHFFFAOYSA-N lithium;trimethoxyalumane Chemical compound [Li].CO[Al](OC)OC ANAFTYVSHCSQPP-UHFFFAOYSA-N 0.000 description 1
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
159000000003 magnesium salts Chemical class 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
229910052987 metal hydride Inorganic materials 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
DTJXCICNTACJLZ-UHFFFAOYSA-N methyl 4-(3,6-dihydro-2h-pyridin-1-ylcarbamoylamino)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1NC(=O)NN1CC=CCC1 DTJXCICNTACJLZ-UHFFFAOYSA-N 0.000 description 1
LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
MGNPLIACIXIYJE-UHFFFAOYSA-N n-fluoroaniline Chemical compound FNC1=CC=CC=C1 MGNPLIACIXIYJE-UHFFFAOYSA-N 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229910000480 nickel oxide Inorganic materials 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
229910003445 palladium oxide Inorganic materials 0.000 description 1
JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
GUDQJEHEASOACG-UHFFFAOYSA-N phenyl N-(2H-pyridin-1-ium-1-ylidene)carbamate Chemical compound C1C=CC=C[N+]1=NC(=O)OC1=CC=CC=C1 GUDQJEHEASOACG-UHFFFAOYSA-N 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
PWOHALINKDREHF-UHFFFAOYSA-N phenyl n-(2,4-difluorophenyl)carbamate Chemical compound FC1=CC(F)=CC=C1NC(=O)OC1=CC=CC=C1 PWOHALINKDREHF-UHFFFAOYSA-N 0.000 description 1
NJIQKGRTBWUWSX-UHFFFAOYSA-N phenyl n-[2-(dimethylamino)phenyl]carbamate Chemical compound CN(C)C1=CC=CC=C1NC(=O)OC1=CC=CC=C1 NJIQKGRTBWUWSX-UHFFFAOYSA-N 0.000 description 1
ONMIXKXTPKQWAZ-UHFFFAOYSA-N phenyl n-[4-(dimethylamino)phenyl]carbamate Chemical compound C1=CC(N(C)C)=CC=C1NC(=O)OC1=CC=CC=C1 ONMIXKXTPKQWAZ-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000000047 product Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229950011008 tetrachloroethylene Drugs 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
239000011135 tin Substances 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
208000004371 toothache Diseases 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000481718A 1985-05-16 1985-05-16 Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant Expired - Fee Related CA1270828A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000481718A CA1270828A (fr)	1985-05-16	1985-05-16	Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000481718A CA1270828A (fr)	1985-05-16	1985-05-16	Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant

Publications (1)

Publication Number	Publication Date
CA1270828A true CA1270828A (fr)	1990-06-26

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Application Number	Title	Priority Date	Filing Date
CA000481718A Expired - Fee Related CA1270828A (fr)	1985-05-16	1985-05-16	Derives de semicarbazide, procede de preparation et composes pharmaceutiques les contenant

Country Status (1)

Country	Link
CA (1)	CA1270828A (fr)

1985
- 1985-05-16 CA CA000481718A patent/CA1270828A/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1992-12-28	MKLA	Lapsed

Publication	Publication Date	Title
US2927924A (en)	1960-03-08	Novel phenethyl-substituted piperazines
EP0260817A1 (fr)	1988-03-23	Quinazolinediones et pyridopyrimidinediones
CA2133077A1 (fr)	1993-10-28	Composes azacycliques
US4742057A (en)	1988-05-03	Antiallergic thiazole compounds
PL113082B1 (en)	1980-11-29	Method of guanidine derivatives preparation
JPS6320231B2 (fr)	1988-04-26
IE880721L (en)	1988-09-12	Thiazoles
HU198033B (en)	1989-07-28	Process for production of n-benzhydril-diaz-cycloalkilalcane-anilides and medical preparatives containing these compounds as active substance
SK282002B6 (sk)	2001-10-08	Deriváty hydroxámovej kyseliny, medziprodukty a spôsob ich výroby, ich použitie a liečivá na ich báze
GB1588166A (en)	1981-04-15	Nitrogen-containing heterocyclic compounds
CA2090027A1 (fr)	1992-03-01	Derives de la pyrimidine et medicaments
JPH05148228A (ja)	1993-06-15	新規１，４−二置換ピペリジン、その製法と治療用途
NZ226089A (en)	1990-06-26	Pyrimidinylamino derivatives of substituted piperidine; pharmaceutical compositions and processes of preparation
US4725608A (en)	1988-02-16	Semicarbazide derivatives, processes for preparation thereof and pharmaceutical composition comprising the same
EP0359389A1 (fr)	1990-03-21	Agents antiarythmiques
US4945096A (en)	1990-07-31	Treatment of a depressive state with 2-[(4-piperidyl)methyl]-1,2,3,4-tetrahydroisoquinoline derivates
US5250528A (en)	1993-10-05	New aminopiperazine derivatives
US4322533A (en)	1982-03-30	1H-Indole-2,3-dione derivatives
EP0436734B1 (fr)	1995-10-11	Nouveaux derives d'aminopiperazine
US4293549A (en)	1981-10-06	Quinolinyl guanidines having antiinflammatory, analgesic or antipyretic activity
EP0279598B1 (fr)	1993-09-15	Composés arylpipérazinyl-alcoylène-phényl-hétérocycliques
US4241072A (en)	1980-12-23	Substituted ureas and processes for their preparation
US4435396A (en)	1984-03-06	Antiulcer 2-guanidino-4-(2-substituted-amino-4-imidazolyl)thiazoles and process therefor
KR20010024258A (ko)	2001-03-26	포스포리파제 저해제로 사용되는9,10-디히드로-9,10-에타노안트라센 유도체
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