JPH0219110B2 - - Google Patents
Info
- Publication number
- JPH0219110B2 JPH0219110B2 JP57036001A JP3600182A JPH0219110B2 JP H0219110 B2 JPH0219110 B2 JP H0219110B2 JP 57036001 A JP57036001 A JP 57036001A JP 3600182 A JP3600182 A JP 3600182A JP H0219110 B2 JPH0219110 B2 JP H0219110B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- ring
- atom
- alkyl
- formula
- Prior art date
- 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
Links
- -1 2-bromo-2,2-difluoroethyl group Chemical group 0.000 claims description 108
- 150000001875 compounds Chemical class 0.000 claims description 81
- 229910052757 nitrogen Inorganic materials 0.000 claims description 73
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 69
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 67
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 67
- 125000004434 sulfur atom Chemical group 0.000 claims description 58
- 229910052717 sulfur Inorganic materials 0.000 claims description 48
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 44
- 239000002253 acid Substances 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- 150000002357 guanidines Chemical class 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000003277 amino group Chemical group 0.000 claims description 27
- 229910052731 fluorine Inorganic materials 0.000 claims description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 238000003780 insertion Methods 0.000 claims description 21
- 230000037431 insertion Effects 0.000 claims description 21
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 21
- 229910021529 ammonia Inorganic materials 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 19
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- 125000003031 C5-C7 cycloalkylene group Chemical group 0.000 claims description 17
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
- 239000012458 free base Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 238000009830 intercalation Methods 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 125000003386 piperidinyl group Chemical group 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 8
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 8
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 150000001450 anions Chemical class 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- IYORMIDQABQCIM-UHFFFAOYSA-N 5-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]triazol-2-yl]pentanamide Chemical compound NC(=O)CCCCN1N=CC(NC(N)=NCC(F)(F)F)=N1 IYORMIDQABQCIM-UHFFFAOYSA-N 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- YUCPFMOAOKYIGN-UHFFFAOYSA-N 4-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]pyrimidin-2-yl]sulfanylbutanamide Chemical compound NC(=O)CCCSC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 YUCPFMOAOKYIGN-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 4
- 125000004780 2-chloro-2,2-difluoroethyl group Chemical group [H]C([H])(*)C(F)(F)Cl 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000003852 triazoles Chemical group 0.000 claims description 4
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- PWEFPAVXAWLQAG-UHFFFAOYSA-N 4-[4-[[n'-(2,2,3,3-tetrafluoropropyl)carbamimidoyl]amino]pyrimidin-2-yl]oxybutanamide Chemical compound NC(=O)CCCOC1=NC=CC(NC(N)=NCC(F)(F)C(F)F)=N1 PWEFPAVXAWLQAG-UHFFFAOYSA-N 0.000 claims description 3
- HCVDXBYWVYEVNY-UHFFFAOYSA-N 5-[3-[[n'-(2-chloro-2,2-difluoroethyl)carbamimidoyl]amino]pyrazol-1-yl]pentanamide Chemical compound NC(=O)CCCCN1C=CC(NC(N)=NCC(F)(F)Cl)=N1 HCVDXBYWVYEVNY-UHFFFAOYSA-N 0.000 claims description 3
- UBUDLKUOZYUGJO-UHFFFAOYSA-N 6-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]triazol-2-yl]hexanamide Chemical compound NC(=O)CCCCCN1N=CC(NC(N)=NCC(F)(F)F)=N1 UBUDLKUOZYUGJO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 3
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical group C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 2
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical group C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005838 1,3-cyclopentylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:2])C([H])([H])C1([H])[*:1] 0.000 claims description 2
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 2
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 2
- 125000004781 2,2-dichloro-2-fluoroethyl group Chemical group [H]C([H])(*)C(F)(Cl)Cl 0.000 claims description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000004779 2-chloro-2-fluoroethyl group Chemical group [H]C([H])(*)C([H])(F)Cl 0.000 claims description 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
- ALCSGJCIESECFD-UHFFFAOYSA-N 5-[3-[[amino(2,2,2-trifluoroethylimino)methyl]amino]-1-pyrazolyl]pentanamide Chemical compound NC(=O)CCCCN1C=CC(NC(N)=NCC(F)(F)F)=N1 ALCSGJCIESECFD-UHFFFAOYSA-N 0.000 claims description 2
- QPJRPJSFAQIYQC-UHFFFAOYSA-N 5-[3-[[n'-(2,2,3,3-tetrafluoropropyl)carbamimidoyl]amino]pyrazol-1-yl]pentanamide Chemical compound NC(=O)CCCCN1C=CC(NC(N)=NCC(F)(F)C(F)F)=N1 QPJRPJSFAQIYQC-UHFFFAOYSA-N 0.000 claims description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 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 2
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004979 cyclopentylene group Chemical group 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- ZUKSLMGYYPZZJD-UHFFFAOYSA-N ethenimine Chemical group C=C=N ZUKSLMGYYPZZJD-UHFFFAOYSA-N 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000006353 oxyethylene group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 10
- 125000003545 alkoxy group Chemical group 0.000 claims 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims 1
- OIWIYLWZIIJNHU-UHFFFAOYSA-N 1-sulfanylpyrazole Chemical group SN1C=CC=N1 OIWIYLWZIIJNHU-UHFFFAOYSA-N 0.000 claims 1
- CGYUBCDWVYXKFR-UHFFFAOYSA-N 5-[4-[[n'-(2,2,3,3-tetrafluoropropyl)carbamimidoyl]amino]triazol-2-yl]pentanamide Chemical compound NC(=O)CCCCN1N=CC(NC(N)=NCC(F)(F)C(F)F)=N1 CGYUBCDWVYXKFR-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- RMBGGQZGADTQLW-UHFFFAOYSA-N acetylene prop-1-ene Chemical group C#C.CC=C RMBGGQZGADTQLW-UHFFFAOYSA-N 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
- 239000000203 mixture Substances 0.000 description 153
- 239000000243 solution Substances 0.000 description 117
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 101
- 235000019439 ethyl acetate Nutrition 0.000 description 86
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 75
- 238000002844 melting Methods 0.000 description 65
- 230000008018 melting Effects 0.000 description 65
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- 239000007858 starting material Substances 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 43
- 239000007787 solid Substances 0.000 description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- 239000003921 oil Substances 0.000 description 27
- 239000000284 extract Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 23
- 229940101209 mercuric oxide Drugs 0.000 description 21
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 20
- GOXVPASJCHROBY-UHFFFAOYSA-N 1,1,1-trifluoro-2-isothiocyanatoethane Chemical compound FC(F)(F)CN=C=S GOXVPASJCHROBY-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 17
- 239000011976 maleic acid Substances 0.000 description 17
- 229960001340 histamine Drugs 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 15
- 238000009835 boiling Methods 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 241000282472 Canis lupus familiaris Species 0.000 description 10
- 229950001902 dimevamide Drugs 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
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- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 229910000464 lead oxide Inorganic materials 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- RNUMHXXTMMCVJT-UHFFFAOYSA-N methyl 3-(2-chloroacetyl)cyclopentane-1-carboxylate Chemical compound COC(=O)C1CCC(C(=O)CCl)C1 RNUMHXXTMMCVJT-UHFFFAOYSA-N 0.000 description 1
- UIRVFIRFYRFBDI-UHFFFAOYSA-N methyl 3-(4-nitrotriazol-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2N=C(C=N2)[N+]([O-])=O)=C1 UIRVFIRFYRFBDI-UHFFFAOYSA-N 0.000 description 1
- FFQSAYKBXUMYIR-UHFFFAOYSA-N methyl 3-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CC(C=2N=C(NC(N)=NCC(F)(F)F)SC=2)=C1 FFQSAYKBXUMYIR-UHFFFAOYSA-N 0.000 description 1
- UTWBBVDVDINNKS-UHFFFAOYSA-N methyl 3-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]cyclopentane-1-carboxylate Chemical compound C1C(C(=O)OC)CCC1C1=CSC(NC(N)=NCC(F)(F)F)=N1 UTWBBVDVDINNKS-UHFFFAOYSA-N 0.000 description 1
- KVAFNEXCJDVTEM-UHFFFAOYSA-N methyl 3-[4-(2,2,2-trifluoroethylcarbamothioylamino)triazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2N=C(NC(=S)NCC(F)(F)F)C=N2)=C1 KVAFNEXCJDVTEM-UHFFFAOYSA-N 0.000 description 1
- QKHNSKAMPMHMJS-UHFFFAOYSA-N methyl 5-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]pentanoate Chemical compound COC(=O)CCCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 QKHNSKAMPMHMJS-UHFFFAOYSA-N 0.000 description 1
- SRNORCARENZRSA-UHFFFAOYSA-N methyl n'-(2,2,2-trifluoroethyl)carbamimidothioate;hydroiodide Chemical compound I.CSC(=N)NCC(F)(F)F SRNORCARENZRSA-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- BLRFTGPKVXNCID-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]triazol-2-yl]benzamide Chemical compound N1=C(NC(N)=NCC(F)(F)F)C=NN1C1=CC=CC(C(=O)NCCO)=C1 BLRFTGPKVXNCID-UHFFFAOYSA-N 0.000 description 1
- DGHHMNUFNNACRT-UHFFFAOYSA-N n-methyl-3-[[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]methylsulfanyl]propanamide Chemical compound CNC(=O)CCSCC1=CSC(NC(N)=NCC(F)(F)F)=N1 DGHHMNUFNNACRT-UHFFFAOYSA-N 0.000 description 1
- QGNJGYJVWCAINQ-UHFFFAOYSA-N n-methyl-4-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]butanamide Chemical compound CNC(=O)CCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 QGNJGYJVWCAINQ-UHFFFAOYSA-N 0.000 description 1
- OGVQRIXBLLFSQD-UHFFFAOYSA-N n-methyl-4-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]pyrimidin-2-yl]sulfanylbutanamide Chemical compound CNC(=O)CCCSC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 OGVQRIXBLLFSQD-UHFFFAOYSA-N 0.000 description 1
- YSHZWAMGXKOALB-UHFFFAOYSA-N n-methyl-5-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]pentanamide Chemical compound CNC(=O)CCCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 YSHZWAMGXKOALB-UHFFFAOYSA-N 0.000 description 1
- DGPLPCOEPRHNDX-UHFFFAOYSA-N n-methyl-5-[4-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]pyrimidin-2-yl]sulfanylpentanamide Chemical compound CNC(=O)CCCCSC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 DGPLPCOEPRHNDX-UHFFFAOYSA-N 0.000 description 1
- HPHQYKQDRYQULT-UHFFFAOYSA-N n-phenyl-4-[6-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]pyrazin-2-yl]sulfanylbutanamide Chemical compound FC(F)(F)CN=C(N)NC1=CN=CC(SCCCC(=O)NC=2C=CC=CC=2)=N1 HPHQYKQDRYQULT-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical class O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960005439 propantheline bromide Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000005496 tempering Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8107273 | 1981-03-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57159769A JPS57159769A (en) | 1982-10-01 |
| JPH0219110B2 true JPH0219110B2 (ja) | 1990-04-27 |
Family
ID=10520235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57036001A Granted JPS57159769A (en) | 1981-03-09 | 1982-03-09 | Guanidine derivative, manufacture and pharmaceutical composition containing same for gastric secretion inhibition |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS57159769A (ja) |
| KR (1) | KR830009059A (ja) |
| CS (1) | CS241503B2 (ja) |
| HU (1) | HU187565B (ja) |
| PL (3) | PL138734B1 (ja) |
| SU (2) | SU1272978A3 (ja) |
| ZA (1) | ZA821568B (ja) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0543116U (ja) * | 1991-11-08 | 1993-06-11 | æå åŠå·¥æ¥æ ªåŒäŒç€Ÿ | å åŠè£ 眮ã«ãããå æ€åºã»ã³ãµã®é èšæ§é |
-
1982
- 1982-03-05 PL PL1982239277A patent/PL138734B1/pl unknown
- 1982-03-05 PL PL1982239276A patent/PL139920B1/pl unknown
- 1982-03-05 SU SU823411500A patent/SU1272978A3/ru active
- 1982-03-05 PL PL1982239275A patent/PL138525B1/pl unknown
- 1982-03-08 CS CS821570A patent/CS241503B2/cs unknown
- 1982-03-09 JP JP57036001A patent/JPS57159769A/ja active Granted
- 1982-03-09 KR KR1019820001014A patent/KR830009059A/ko unknown
- 1982-03-09 HU HU82715A patent/HU187565B/hu unknown
- 1982-03-09 ZA ZA821568A patent/ZA821568B/xx unknown
- 1982-10-26 SU SU823506256A patent/SU1233799A3/ru active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0543116U (ja) * | 1991-11-08 | 1993-06-11 | æå åŠå·¥æ¥æ ªåŒäŒç€Ÿ | å åŠè£ 眮ã«ãããå æ€åºã»ã³ãµã®é èšæ§é |
Also Published As
| Publication number | Publication date |
|---|---|
| PL239277A1 (en) | 1983-10-10 |
| PL239275A1 (en) | 1983-10-10 |
| ZA821568B (en) | 1983-01-26 |
| SU1233799A3 (ru) | 1986-05-23 |
| CS157082A2 (en) | 1985-08-15 |
| PL239276A1 (en) | 1983-10-10 |
| KR830009059A (ko) | 1983-12-17 |
| PL138525B1 (en) | 1986-09-30 |
| CS241503B2 (en) | 1986-03-13 |
| SU1272978A3 (ru) | 1986-11-23 |
| HU187565B (en) | 1986-01-28 |
| PL139920B1 (en) | 1987-03-31 |
| JPS57159769A (en) | 1982-10-01 |
| PL138734B1 (en) | 1986-10-31 |
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