ZA200503870B - Novel 2,4-diamino-1,3,5-triazine derivative - Google Patents
Novel 2,4-diamino-1,3,5-triazine derivative Download PDFInfo
- Publication number
- ZA200503870B ZA200503870B ZA200503870A ZA200503870A ZA200503870B ZA 200503870 B ZA200503870 B ZA 200503870B ZA 200503870 A ZA200503870 A ZA 200503870A ZA 200503870 A ZA200503870 A ZA 200503870A ZA 200503870 B ZA200503870 B ZA 200503870B
- Authority
- ZA
- South Africa
- Prior art keywords
- group
- optionally substituted
- alkyl group
- hydrogen atom
- heterocyclic
- Prior art date
Links
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical class NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 title description 6
- -1 dihydrotriazine compound Chemical class 0.000 claims description 137
- 125000004432 carbon atom Chemical group C* 0.000 claims description 97
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 85
- 125000000623 heterocyclic group Chemical group 0.000 claims description 60
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- VXMDOKODOQETRU-UHFFFAOYSA-N 2-[(4-amino-2,5-dihydro-1H-1,3,5-triazin-6-ylidene)-methylazaniumyl]acetate Chemical group C\[N+](CC([O-])=O)=C1\NCN=C(N)N1 VXMDOKODOQETRU-UHFFFAOYSA-N 0.000 claims description 36
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 32
- 125000001624 naphthyl group Chemical group 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 25
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 24
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001326 naphthylalkyl group Chemical group 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- 230000000844 anti-bacterial effect Effects 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 11
- 239000000645 desinfectant Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 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 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000004599 antimicrobial Substances 0.000 claims description 3
- 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 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002421 anti-septic effect Effects 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- 125000006178 methyl benzyl group Chemical group 0.000 claims 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims 1
- 125000004803 chlorobenzyl group Chemical group 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000006286 dichlorobenzyl group Chemical group 0.000 claims 1
- 229940050410 gluconate Drugs 0.000 claims 1
- 125000006289 hydroxybenzyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 39
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 230000000078 anti-malarial effect Effects 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 3
- 125000004995 haloalkylthio group Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- QXBVNDNLFDDQSX-UHFFFAOYSA-N 1,4-dihydro-1,3,5-triazine-2,6-diamine Chemical class NC1=NC(N)=NCN1 QXBVNDNLFDDQSX-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108010059993 Vancomycin Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000000507 anthelmentic effect Effects 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000003167 anti-vitamin Effects 0.000 description 2
- 239000003430 antimalarial agent Substances 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- QMNFFXRFOJIOKZ-UHFFFAOYSA-N cycloguanil Chemical compound CC1(C)N=C(N)N=C(N)N1C1=CC=C(Cl)C=C1 QMNFFXRFOJIOKZ-UHFFFAOYSA-N 0.000 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 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 description 2
- 125000004992 haloalkylamino group Chemical group 0.000 description 2
- 125000004664 haloalkylsulfonylamino group Chemical group 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229960003165 vancomycin Drugs 0.000 description 2
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 2
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- ZBPANFPFKDRDTA-UHFFFAOYSA-N 1-(4-chlorophenyl)-2h-1,3,5-triazine-4,6-diamine Chemical compound NC1=NC(N)=NCN1C1=CC=C(Cl)C=C1 ZBPANFPFKDRDTA-UHFFFAOYSA-N 0.000 description 1
- RLKGBZALMDTISP-UHFFFAOYSA-N 1-phenyl-2h-1,3,5-triazine-4,6-diamine Chemical class NC1=NC(N)=NCN1C1=CC=CC=C1 RLKGBZALMDTISP-UHFFFAOYSA-N 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- CXIUWTTYUPDMGW-UHFFFAOYSA-N 4,4-dimethyl-1h-1,3,5-triazine Chemical compound CC1(C)NC=NC=N1 CXIUWTTYUPDMGW-UHFFFAOYSA-N 0.000 description 1
- HVJCIXRGJVRSOY-UHFFFAOYSA-N 4,4-dimethyl-1h-1,3,5-triazine-2,6-diamine Chemical class CC1(C)NC(N)=NC(N)=N1 HVJCIXRGJVRSOY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- LGTCEMHLJHTOGU-UHFFFAOYSA-N 6,6-dimethyl-1-(3-phenylpropyl)-1,3,5-triazine-2,4-diamine Chemical class CC1(C)N=C(N)N=C(N)N1CCCC1=CC=CC=C1 LGTCEMHLJHTOGU-UHFFFAOYSA-N 0.000 description 1
- VMVKLCXTXSSZSI-UHFFFAOYSA-N 6,6-dimethyl-1-phenyl-1,3,5-triazine-2,4-diamine Chemical class CC1(C)N=C(N)N=C(N)N1C1=CC=CC=C1 VMVKLCXTXSSZSI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- LUTSRLYCMSCGCS-BWOMAWGNSA-N [(3s,8r,9s,10r,13s)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC=C3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 LUTSRLYCMSCGCS-BWOMAWGNSA-N 0.000 description 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229950004734 cycloguanil Drugs 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 125000005280 halo alkyl sulfonyloxy group Chemical group 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
- 125000006137 n-hexyl sulfonyl group Chemical group 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
- 125000006129 n-pentyl sulfonyl group Chemical group 0.000 description 1
- 125000004712 n-pentylthio group Chemical group C(CCCC)S* 0.000 description 1
- 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000005936 piperidyl group Chemical group 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
- 230000002265 prevention Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 229960005385 proguanil Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
‘ ® 1
SPECIFICATION
NOVEL 2,4-DIAMINO-1,3,5-TRIAZINE DERIVATIVE
The present invention relates to anovel antibacterial agent and a novel 2,4-diamino-1,3,5-triazine derivative.
Many infectious diseases have been overcome by development of various Dbactericides/disinfectants, antibiotics, and synthetic antibacterial agents, and the average life span of human beings has been considerably extended. On the other hand, however, many bacteria resistant to these drugs appear and, at the same time, in elderly people, so-called opportunistic infection with bacteria which are usually weak in their a infectious power has been increased due to a cause such as reduction in immunity, and increase in hospital infection and population infection in other facilities has become a great social problem. Especially in recent years, infectious diseaseswhichcannotbe treatedby conventional drugs, including those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) or, nowadays those caused by vancomycin-resistant MRSA, multiple drug-resistant Pseudomonas aeruginosa, pneumococcus and
Serratia bacteria, have increased rapidly, and development of effective methods of preventing or treating such diseases is now keenly desired.
Since the discovery of 4,6-diamino-1-(p-chlorophenyl)-
i
Qo 2 1,2- dihydro-2,2-dimethyl-s-triazine (Cycloguanil) which is an active metabolite of an anti-malaria agent Proguanil fifty several years ago (Journal of Pharmacology 1947, Vol.2, pP.-161-168; British H.C.Carrington et al., Nature 1951, Vol. 168, p.1080), various patent applications or study reports have been made.
For example, E. J. Modest et al., Journal of the American
Chemical Society 1952, Vol. 74, p. 855-856 describes anti-vitamin activity and anti-malaria activity of 4,6-diamino-2,2- dimethyl-s-triazine derivatives. E.J.Modest et al., Journal of Organic Chemistry 1956, Vol.21, p.1-13, p.14-20 describes 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazines regarding anti-vitamin, anti-malaria, anti-cancer and anti-coccidium activities. USP No. 5,565,451 describes the use of 1-(3-phenylpropyl)-2,4-diamino-6,6-dimethyl-1,6- dihydro-1,3,5-triazines as an insecticide. EP No. 0504290 describes that 4,6-diamino-1,2-dihydro-1-phenyl-s-triazines have an action of inhibiting growth of Pneumocystic carinii.
WO 01/53276 describes the use of 1-p-chlorophenyl-4,6-diamino- 1,2-dihydro-1,3,5-triazine and the like as an anthelmintic (anti-malaria agent etc.). However, the aforementioned known references do not refer to antibacterial activity at all.
USP No. 3,682,912 describes 4,6-diamino-1,2-dihydro- 1,3,5-triazine derivatives as a compound having antibacterial activity in addition to anti-malaria activity, and USP No. 3,723,429 describes 4,6-diamino-1,2-dihydro-1,3,5-triazine derivatives as an anti-malaria/antibacterial active compound.
However, since compounds described in these known references have all a substituent at position 1 of the 1,2-dihydro-1,3,5-
(
CY 3 triazine ring using -0O- as an intervening group, they are different compounds from those of the present invention, and no data of antibacterial activity are described therein.
USP No. 3,287,365 describes a compound represented by the following formula (4) having herbicidal activity in Working
Example 5, but antibacterial activity thereof is not described at all. i
QP d @
USP No. 3,287,366 describes a compound represented by the following formula (5) having herbicidal activity in Working
Example 3, but nothing is known about antibacterial activity thereof.
N N_NH
HC ~~ NG Y 2
HN x N 5)
HsC CHj
Andre Rosowskyetal., Antimicrobial Agents and Chemotherapy 1995, Vol.39, p.79-86 describes a compound represented by the following formula (6) as a dehydrofolate reductase inhibitor (anthelmintic (anti-malaria)). However, the aforementioned known reference does not describe antibacterial activity of the same compound at all.
CHj3
Segal
N N (6) «Ci
(
An object of the present invention is to provide a novel antibacterial agent containing, as an active ingredient, a 2,4-diamino-1,3,5-triazine derivative or a pharmacologically acceptable salt thereof. Another object of the present invention is to provide novel 2,4-diamino-1,3,5-triazine derivatives or pharmacologically acceptable salts thereof.
In order to attain the aforementioned objects, the present inventors have created novel triazine derivatives and investigated physiological activity thereof and, as a result, found that 2,4-diamino-1,3,5-triazine derivatives or pharmacologically acceptable salts thereof have a wide range of strong growth inhibiting effect and bactericidal effect against Gram-positive and Gram-negative bacteria. Based on these findings, the present invention has been completed.
That is, the present invention relates to: 1) An antibacterial agent, which comprises, as an active ingredient, a compound represented by the following general formula (1):
RIHN oN. NHR,
PRT wm
R; R, (wherein R; represents (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group,
f each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R; is a hydrogen atom, R;’ represents (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (v) acycloalkyl group or a cycloalkyl-alkyl group, each of which is substituted, said groups (i) to (v) being substituted at position 1 of the dihydrotriazine ring, or (b) when R; is other than a hydrogen atom, R;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring;
R; represents a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms;
R; and R, represent that R; is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, andR, is a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R; and R; are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkyl spirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a pharmacologically acceptable salt thereof,
( ° ; 2) The antibacterial agent according to the above 1), wherein any one of R; and R; is an optionally substituted alkyl group of 7 to 16 carbon atoms, 3) A compound represented by the general formula (la):
RyHN_ N NHR, oh hd
N<6Ns
KT aa
Rs; R, (wherein R; represents (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R, is a hydrogen atom, R,’ represents (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, (v) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted, said groups (i) to (v) being substituted at position 1 of the dihydrotriazine ring, or (b) when R; is other than a hydrogen atom, R;’' represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring;
R,; represents an optionally substituted alkyl group of 7 to 16 carbon atoms;
Rj; and R, represent that R; is a hydrogen atom or an optionally substituted alkyl groupof 1 to 3 carbonatoms, andR, is ahydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R; and Ry are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkyl spirocycloalkane group: and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a salt thereof, 4) The compound according to the above 3), wherein R; is (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) an optionally substituted naphthyl group, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted: (a) when R; is a hydrogen atom, R;’' is (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, or (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, said groups
; o . (i) to (iv) being substituted at position 1 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof, 5) The compound according to the above 3), wherein R,; is a phenyl group or a phenylalkyl group, or an alkyl group of 1 to 16 carbon atoms, each of which is optionally substituted;
R; is an optionally substituted alkyl group of 1 to 3 carbon atoms; and Rs is an optionally substituted alkyl group of 1 to 16 carbon atoms, or a tautomer thereof or a salt thereof, 6) A compound represented by the following general formula (1b):
Ry HN N NH, na
Neg Ns
Kav
Rs; Rs (wherein R;; represents (i) a hydrogen atom, (ii) an optionally substituted phenyl group, (iii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iv) a heterocyclic group or a heterocyclic alkyl group, each of which is optionally substituted, or (v) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R;; is a hydrogen atom, R;;’ represents (i) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (ii) a heterocyclic group or a heterocyclic alkyl group, each of which is optionally substituted, (iii) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (iv) a cycloalkyl group or a cycloalkyl-alkyl group, each of
® 9 which is optionally substituted, said groups (i) to (iv) being substituted at position 1 of the dihydrotriazine ring, or (b) when R;; is other than a hydrogen atom, R;;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 5S 3 of the dihydrotriazine ring;
R; and R,; represent that R; is a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, and R; is a hydrogen atom or an alkyl group of 1 to 16 carbon atoms, or R; and R; are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkylspirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3, provided that at least one of R;;’ and Ry; is an optionally substituted alkyl group of 7 to 16 carbon atoms), or a tautomer thereof or a salt thereof, 7) The compound according to the above 6), wherein R;; is an optionally substituted phenyl group, or a tautomer thereof or a salt thereof, 8) A compound represented by the following general formula (1c):
H
HN. N NH(CH) CH,
PX ao
H,C CH, (whereinnrepresentsanintegerof13tol5),oratautomer thereof or a salt thereof, 9) A compound represented by the following general formula
PS 10
Ry2HN 5 N NHR,
XT a
Rs R, (wherein R;, represents a hydrogen atom, or a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, the last three groups being optionally substituted, (a) when R;», is a hydrogen atom, R,;,’' represents an optionally substituted heterocyclic group, an optionally substituted heterocyclic alkyl group or an optionally substituted heterocyclic aminoalkyl group, said groups being substituted at position 1 of the dihydrotriazine ring, or (b) when R;, is other than a hydrogen atom, R;, represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring;
R; represents a hydrogen atom, or an optionally substituted alkyl group of 1 to 16 carbon atoms;
R; and Ry represent that R; is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, andR; is ahydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or Rj; and Ry, are taken together with the adjacent carbon atomtoformaspirocycloalkane grouporanalkylspirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a salt thereof, 10) A bactericidal/disinfectant agent, which comprises, as an active ingredient, a compound represented by the general formula (1) as defined in the above 1), or a tautomer thereof
® 11 or a pharmacologically acceptable salt thereof, 11) An antiseptic/preservative agent for cosmetics, which comprises, as an active ingredient, a compound represented by the general formula (1) as defined in the above 1}, or a tautomer thereof or a pharmacologically acceptable salt thereof, 12) Amethodof treatingorpreventingbacterial infectious diseases, which comprises administering a therapeutically effective amount of a compound represented by the general formula (1) as defined in the above 1), or a tautomer thereof or a pharmacologically acceptable salt thereof to mammals, birds or fish in need of treatment or prevention of bacterial infectious diseases, and 13) Use of a compound represented by the general formula (1) as defined in the above 1), or a tautomer thereof or a pharmacologically acceptable salt thereof for preparation of a medicament for treating or preventing bacterial infectious diseases.
Since the compounds (1) which are an active ingredient of the present invention have strong antibacterial activity and bactericidal activity, they are extremely useful as antibacterial agents or bactericides/disinfectants.
The compounds used in the present invention represented by the formula (1), and the compounds represented by the formulae (la), (1b) and (1d) will be explained in detail below.
Each substituent in the formula (1) will be explained.
The substituent R; is (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iv) a heterocyclic group, a heterocyclic alkyl group, or a heterocyclic aminoalkyl group, each of which is optionally substituted, (v) an 5S optionally substituted alkyl group of 1 to 16 carbon atoms or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted.
Herein, examples of the "phenylalkyl group” include a group in which a linear or branched alkyl group of 1 to 6 carbon atoms is attached to a phenyl group, and preferable examples include benzyl, l1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl and 3-phenylpropyl.
Examples of the "naphthyl group” include l-naphthyl and 2-naphthyl.
Examples of the "naphthylalkyl group” include a group in which a linear or branched alkyl group of 1 to 6 carbon atoms is attached to a naphthyl group, and preferable examples include l-naphthylmethyl, 2-naphthylmethyl, l1-naphthylethyl and 2-naphthylethyl.
Examples of the "heterocyclic group” include a 3 to 6 -membered heterocyclic group containing 1 to 3 atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, to which a benzene ring may be fused, and examples include pyridyl such as 2-pyridyl, 3-pyridyl and 4-pyridyl; pyrazinyl:; furyl such as 2-furyl; thiazolyl such as 2-thiazolyl; piperidyl such as l-piperidyl; piperazyl such as l-piperazyl; tetrahydrofuryl; 2-oxotetrahydrofuryl; thienyl; pyrrolyl; pyrrolidinyl; oxazolyl; imidazolyl; isooxazolyl; isothiazolyl; pyrazolyl: tetrahydropyranyl; 2-oxotetrahydropyranyl; pyrimidinyl;
® 13 pyridazinyl; morpholinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; quinolyl such as 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl and 8-quinolyl; and isoquinolyl such as 1l-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl and 5-isoquinolyl.
Examples of the “heterocyclic alkyl group” include a group in which a linear or branched alkyl group of 1 to 6 carbon atoms is attached to the aforementioned heterocyclic group, and preferable examples include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-pyridylethyl, 3-pyridylethyl, 4-pyridylethyl, pyrazinylmethyl, pyrazinylethyl, 2-furylmethyl, 2-furylethyl, 2-thiazolylmethyl, 2-thiazolylethyl, 4-piperidylmethyl, 2-quinolylmethyl, 3-quinolylmethyl, 4-quinolylmethyl, 5-quinolylmethyl, 8-quinolylmethyl, l-isoquinolylmethyl, 3-isoquinolylmethyl, 4-isoquinolylmethyl and 5-isoquinolylmethyl.
Examples of the "heterocyclic aminoalkyl group” include a group in which a linear or branched alkyl group of 1 to 12 carbon atoms is attached to a heterocyclic amino group, and preferable examples include a 4-amino-dihydro-1,3,5-triazin- 2-ylamino group, a 4-alkylamino-dihydro-1,3,5-triazin-2-ylamino group and a 4-phenylalkylamino-dihydro-1,3,5-triazin-2~ylamino group.
Examples of the "alkyl group of 1 to 16 carbon atoms” include a linear or branched alkyl group, and preferable examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-hexyl, n-heptyl, n-octyl, tert-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, and n-hexadecyl.
Examples of the "cycloalkyl group” include a cycloalkyl
® 14 group of 3 to 6 carbon atoms, and examples include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
Examples of the “cycloalkyl-alkyl group” include a group in which a linear or branched alkyl group of 1 to 6 carbon atoms is attached to the aforementioned cycloalkyl group, and preferable examples include cyclohexylmethyl, l-cyclohexylethyl and 2-cyclohexylethyl.
A benzene ring of the phenyl group or the phenylalkyl group; a naphthalene ring of the naphthyl group or the naphthylalkyl group; a heterocyclic ring of the heterocyclic group, the heterocyclic alkyl group or the heterocyclic aminoalkyl group; an alkyl group of 1 to 16 carbon atoms; a cycloalkyl group of the cycloalkyl group or of the cycloalkyl-alkyl group may have a substituent. Examples of such substituents include a halogen atom, a hydroxy group, a nitro group, a cyano group, a C;-¢ alkyl group, a C;.¢ haloalkyl group, a Ci.¢ cycloalkyl group, a Cg-10 aryl group, a Cg¢-10 aryloxy group, a C;.¢ alkoxy group, a C;-.¢ haloalkoxy group, aCi.¢cycloalkyloxy group, aC;.7alkanoyl group, a carboxyl group, a carbamoyl group, a C;.; alkoxycarbonyl group, a C;_y haloalkoxycarbonyl group, a C;.;; aryloxycarbonyl group, a C;_; cycloalkyloxycarbonyl group, an amino group, a C;.¢ alkylamino group, a C;.¢ haloalkylamino group, di-C;.¢ alkylamino group, a
C:;.7 alkanoylamino group, a cyclic amino group, a CC, alkylaminocarbonyl group, amercapto group, asulfonicacidgroup, a sulfonamido group, a C;.¢ alkylthio group, a C,.¢ haloalkylthio group, a Ci.¢alkylsulfonyl group, a C;.shaloalkylsulfonyl group, a C;.¢ alkylsulfonyloxy group, a C;.¢ haloalkylsulfonyloxy group, a C,.s alkylslfonylamino group, and a C;.¢ haloalkylsulfonylamino group. About 1 to 6, preferably 1 to 3, substituent(s) may be
® 15 attached to the same or different chemically acceptable arbitrary positions.
Examples of the "halogen atom” include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
The "C,.¢ alkyl group” may be linear or branched, and examples thereof include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl and isohexyl.
Examples of the "C;.¢ haloalkylgroup” include chloromethyl, bromomethyl, 1l-chloroethyl and trifluoromethyl.
Examples of the "Cj3.¢ cycloalkyl group” include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
Examples of the "C¢_,0 aryl group” include phenyl andnaphthyl, preferably phenyl.
Examples of the "Cq.;0 aryloxy group” include phenyloxy and naphthyloxy, preferably phenyloxy.
Examples of the "C,.¢ alkoxy group” include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy and isobutoxy.
Examples of the "C;.¢ haloalkoxy group” include trifluoromethoxy.
Examples of the "Cs3.s cycloalkyloxy group” include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy and cyclohexyloxy.
Examples of the "C;,_; alkanoyl group” include formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl and hexanoyl.
Examples of the "C,.; alkoxycarbonyl group” include a group which is made through ester bond formation between a linear or branched alkyl group of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and a carboxyl group, and examples include
® 16 methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-propoxycarbonyl and isobutoxycarbonyl.
Examples of the "C,.; haloalkoxycarbonyl group” include chloromethoxycarbonyl, bromomethoxycarbonyl and (1-chloro)ethoxycarbonyl.
Examples of the "C,.; cycloalkyloxycarbonyl group” include cyclopropoxycarbonyl and cyclopentyloxycarbonyl.
Examples of the "C;.11 aryloxycarbonyl group” include phenyloxycarbonyl and naphthaleneoxycarbonyl.
Examples of the "C;_¢alkylamino group” include methylamino, ethylamino, n-propylamino, isopropylamino, sec-butylamino and n-pentylamino.
Examples of the "di-C;.¢ alkylamino group” include dimethylamino, diethylamino and methylethylamino.
Examples of the "C;.¢ haloalkylamino group” include trifluoromethylamino.
Examples of the "C,.; alkanoylamino group” include a substituent in which an amino group is attached to the aforementioned C;.; alkanoyl group.
Examples of the "cycloamino group” include a morpholino group.
Examples of the "C,_; alkylamino carbonyl group” include a substituent in which a carbonyl group is attached to the aforementioned C;.¢ alkylamino group.
Examples of the "C,.¢ alkylthio group” include methylthio, ethylthio, n-propylthio, isospropylthio, sec-butylthio and n-pentylthio.
Examples of the "C;.4 haloalkylthio group” include trifluoromethylthio.
® 17
Examples of the "C,;.¢ alkylsulfonyl group” include methanesulfonyl, ethanesulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, sec-pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, n-hexylsulfonyl and isohexylsulfonyl.
Examples of the "C,.s haloalkylsulfonyl group” include chloromethylsulfonyl and trifluoromethylsulfonyl.
Examples of the "C;.¢ alkylsulfonylamino group” or the “C;_¢ haloalkylsulfonylamino group” include a substituent in which an amino group is attached to the "C;_.¢ haloalkylsulfonyl group” or the "C,.s haloalkylsulfonyl group”.
As the substituent R;, (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) an alkyl group of 1 to 16 carbon atoms or (iv) a cycloalkyl-alkyl group is preferable. As a phenylalkyl group, benzyl group or 2-phenylethyl group is more preferable.
Examples of the substituent on the benzene ring of a phenyl group or a phenylalkyl group include a halogen atom, more preferably a fluorine atom and a chlorine atom; a hydroxy group; a C;_s alkyl group, more preferably methyl or t-butyl; a C,.¢ haloalkyl group, more preferably trifluoromethyl; a C,.¢ alkoxy group, more preferably methoxy; a C;.¢ haloalkoxy group, more preferably trifluoromethoxy. More preferable examples of the substituent
R; include phenyl, benzyl, 4-chlorophenyl, 2,4-difluorophenyl, 2,3,4-trifluorophenyl, 4-t-butylphenyl, 4 -methoxyphenyl, 2-methoxy-4-t-butylphenyl, 4-trifluoromethoxyphenyl, 4-hydroxybenzyl, 3,4-dichlorobenzyl, 2,3,4-trichlorobenzyl, 4-methylbenzyl, 4-trifluoromethylbenzyl, 4-methoxybenzyl,
® 18 3,4-dimethoxybenzyl, 2-(4-methoxyphenyl)-ethyl, ethyl, isopropyl, n-hexyl, n-heptyl, n-octyl, n-tetradecyl, and cyclohexylmethyl. (a) When R; is hydrogen, then the substituent R;’ represents (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (v) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted, said group (i) to (v) being substituted at position 1 of the dihydrotriazine ring. These substituents areas described for the aforementioned substituent
Ry. (b) When R; is other than hydrogen, then the substituent
R;’' represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring.
The substituents R;, and R; each represents a hydrogen atom or anoptionally substituted alkyl group of 1 to 16 carbon atoms.
Herein, the alkyl group of 1 to 16 carbon atoms may be linear or branched, and examples include those exemplified for the aforementioned R;. When R; is hydrogen, at least one of R; and
Ry is preferably an optionally substituted alkyl group of 6 to 16 carbon atoms, more preferably an alkyl group of 12 to 16 carbon atoms, most preferably an alkyl group of 13 to 15 carbon atoms.
In the present invention, more preferably, at least one of R; and Ry; is an alkyl group of 6 to 16 carbon atoms, preferably 7 to 16 carbon atoms, and the other is hydrogen or an alkyl group
® 19 of 1 to 6 carbon atoms. More preferably, at least one of R; and R; is a linear alkyl group of 7 to 13 carbon atoms, more preferably 8 to 12 carbon atoms, and the other is hydrogen or methyl.
The substituent Ryrepresentsahydrogenatomoranoptionally substituted alkyl group of 1 to 3 carbon atoms. Herein, an alkyl group of 1 to 3 carbon atoms may be linear or branched, and examples include methyl, ethyl, propyl and isopropyl. In addition, the alkyl group of 1 to 3 carbon atoms may form a ring such as a cyclopropyl group.
Regarding R; and Rs, R; and R; may be taken together with the carbon atom to which they are attached to form a spirocycloalkane group or an alkylspirocycloalkane group. In this case, it is preferable that R; is an optionally substituted alkyl group of 6 to 16 carbon atoms, preferably 7 to 16 carbon atoms. Regarding the spirocycloalkane, the number of carbon atoms which constitute the ring is 3 to 16, preferably 3 to 12, more preferably 3 to 8, still more preferably 4 to 6. Examples of the "alkylspirocycloalkane” include those having one or more substituent(s), in which a replaceable number of alkyl groups of 1 to 6 carbon atoms are attached to chemically acceptable arbitrary position(s) of the aforementioned spirocycloalkane.
When the substituents R,, R; and R; are an alkyl group, the aforementioned alkyl group may have a substituent. Examples of the substituent of such alkyl group include a halogen atom, a C,.¢ alkoxy group, aC;_salkylthio group, a C;.¢haloalkoxy group, a C;.¢ haloalkylthio group, a hydroxy group, an amino group, a
Ci1-.¢ alkylamino group, a di-C,;_¢-alkylamino group, a Ci. alkanoylamino group, a formyl group, a C:.¢ alkoxycarbonyl group,
® 20
Ci.shaloalkoxycarbonyl group, a carbamoyl group, amercapto group and a cyano group. The substitution position of substituent(s) isnot particularly limitedas faras it ischemically acceptable, and the number of substituents may bewithin a replaceable number range, and is preferably 1 to 6.
In addition, when R; and R, are not the same, and R; and
R, are not the same, there are two kinds of optical isomers of the carbon atom at position 6 of the dihydrotriazine ring, and any isomer is included in the scope of the aforementioned compound.
In the compound represented by the aforementioned general formula (1), a double bond represented by the dashed line is located at positions between 2 and 3, when R; is hydrogen and
R;’ is substituted at position 1 of the dihydrotriazine ring, or adoublebondis located at positions between 1 and 2 or between 2 and 3, when the position 1 of the dihydrotriazine ring is unsubstituted. However, in the compounds represented by the general formula (1), there are several other tautomers, and a double bond can be moved depending on its environment. The present invention includes all of these tautomers.
Each group in the formula (la) will be explained below.
The substituents R; and R;’ in the formula (la) are as explained for the aforementioned formula (1).
In the present invention, it is preferable that the substituent R; is (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) an optionally substituted naphthyl group, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (v)
® 21 an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted, and (a) When R; is hydrogen, then R;’' is (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, or (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms (more preferably 7 to 16 carbon atoms), each of which is optionally substituted, said groups (i) to (iv) being substituted at position 1 of the dihydrotriazine ring.
R,; represents an optionally substituted alkyl group of 7 to 16 carbon atoms. Examples of the "alkyl group of 7 to 16 carbon atoms” include a linear or branched alkyl group of 7 to 16 carbon atoms, and preferably such alkyl groups include, for example, n-heptyl, n-octyl, tert-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, and n-hexadecyl. The optionally substituted alkyl group of 7 to 16 carbon atoms may have the same substituents as those explained for the aforementioned formula (1).
The substituents R;andR,;in the formula (la) are as explained for the aforementioned formula (1) and, in the formula (1b), it is preferable that the substituent R; is an optionally substituted alkyl group of 1 to 3 carbon atoms, and R; is an optionally substituted alkyl group of 1 to 16 carbon atoms.
The dashed line in the formula (la) is as explained for the aforementioned formula (1).
® 22
Each group in the formula (1b) will be explained below.
The substituent R;; represents (i) a hydrogen atom, (ii) an optionally substituted phenyl group, (iii) a naphthyl group or a naphthylalkyl group, eachof whichisoptionally substituted, (iv) a heterocyclic group or a heterocyclic alkyl group, each of which is optionally substituted, or (v) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted. These groups may be the same as respective groups explained for the aforementioned R;, respectively. In the present invention, it is preferable that the R;; is an optionally substituted phenyl group. (a) When R;; is hydrogen, then the substituent R;,’ represents (i) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (ii) a heterocyclic group or a heterocyclicalkyl group, eachofwhichisoptionallysubstituted, (iii) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (iv) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted, said groups (i) to (iv) being substituted at position 1 of the dihydrotriazine ring.
These groups may be the same as those explained for the aforementioned R,’. (b) When R;; is other than hydrogen, then the substituent
R;;’' represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring.
The substituents R;andR, in the formula (1b) are as explained for the aforementioned formula (1).
The dashed line in the formula (1b) is as explained for the aforementioned formula (1).
In the formula (1b), at least one of R;; and R, is an optionally
® 23 substituted alkyl group of 7 to 16 carbon atoms. The "optionally substituted alkyl group of 7 to 16 carbon atoms” is the same as the group explained for the aforementioned formula (la).
Each group in the formula (1d) will be explained below.
The substituent R;, in the formula (1d) represents a hydrogen atom, or a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, the last three groups of which are optionally substituted. (a) When R,, is hydrogen, then the substituent R;,’' in the formula (1d) represents a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted and is attached to position 1 of the dihydrotriazine ring, or (b) when R;, is other than hydrogen,
R;.’' represents a hydrogen atom attached to the nitrogen atom atpositionlor3ofthedihydrotriazinering. The “heterocyclic group, heterocyclic alkyl group or heterocyclic aminoalkyl group, each of which is optionally substituted” in the aforementioned substituents R;, and R,;,’' are as explained in the aforementioned formula (1).
The substituents R,, R; and R;, in the formula (14) are as explained for the aforementioned formula (1). The dashed line in the formula (1d) is also as explained for the aforementioned formula (1).
The aforementioned compounds (1) may form a salt. Examples of such salt include salts with an organic acid such as formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric
® 24 ’ acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid: salts with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid, and boric acid. The aforementioned acid addition salt is prepared by adopting a normal salt forming method such as by (a) mixing the aforementioned compound (1) and an acid directly, (b) dissolving one of them in a solvent or a hydrous solvent, and mixing them, or (c) placing the compound (1) and an acid in a solvent or a hydrous solvent, and mixing them.
When the aforementioned compound (1) has an acidic group such as a carboxyl group and a sulfonic acid group, the compound (1) becomes a zwitterion salt, and such salt may be an alkali metal salt such as sodium salt and potassium salt, an alkaline earth metal salt such as calcium salt and magnesium salt, and a salt with an inorganic base such as aluminum salt and ammonium salt; a base addition salt such as salt with an organic base such as trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine and N, N’'-dibenzylethylenediamine. In addition, the salt of the aforementioned compound (1) may be a salt with a basic amino acid such as arginine, lysine and ornithine; a salt with an acidic amino acid such as aspartic acid.
The salt of the aforementioned compound (1) is preferably a pharmacologically acceptable salt, more preferably an acid addition salt, still more preferably acetate, hydrochloride,
® » hydrobromide, methanesulfonate, malonate or oxalate.
When the aforementioned compound (1) is used as an external agent or a bactericide/disinfectant, the compound (1) may form a stable coordinated compound with a metal such as Ag, Mn and
Zn.
Then, a process for preparing the compound (1) which is an active ingredient of the present invention will be explained.
The compound (1) or a salt thereof can be prepared, for example, as follows:
Preparation method 1 ' H H H
NaN(CN), PY No RNH: NNN,
R1aNH> —_— Ra hd CN —— Ria hd hi R,' 7 8 NH 10 NH NH 9 11
HoN N NHR,' hg he R;aNH N NHR,’ 13 he NY
N N '
Ry” x N_ NH 14" 2 fh x
PR 3 Rg Ra R,
Rj R,
H
A BE eM 14 —— Se 14°
R3 Ry Rs Ry (wherein R,’ represents an optionally substituted alkyl group of 1 to 16 carbon atoms, R;, represents the aforementioned R; or R;;, and other all symbols are the same as defined above)
A process forpreparing a compound represented by the general formula (1) wherein R, is an alkyl group (R,’) of 1 to 16 carbon atoms is shown in Preparationmethod1l. According to the present
Claims (6)
1. An external bactericidal/disinfectant agent, which comprises, as an active ingredient, a dihydrotriazine compound represented by the following general formula (1): RiHN_ N. NHR, RX Te N 6 Ns Kw Rs Ry (wherein Ry represents (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) a naphthyl group or a naphthylalkyl group, each of which is opticnally substituted, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminocalkyl group, each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R; is a hydrogen atom, R;’ represents (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (v) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is substituted, said groups (i) to (v) being substituted at position 1 of the dihydrotriazine ring, or (b) when R; is other than a hydrogen atom, R;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring; R, represents a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms; R; and Rg; represent that Rs; 1s a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, and Amended sheet: 9 May 2006 v yo Rs is a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R; and R; are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkyl spirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a pharmacologically acceptable salt thereof.
2. The external bactericidal/disinfectant agent according toclaiml, wherein any one of R; and Ry is an optionally substituted alkyl group of 7 to 16 carbon atoms.
3. The external bactericidal/disinfectant agent according to claim ll, wherein R; is an optionally substituted phenylalkyl group; Ry; is a hydrogen atom; R3 is a hydrogen atom; R; is an alkyl group of 7 to 16 carbon atoms; and Ry’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring.
4. The external bactericidal/disinfectant agent according to claim 1, wherein R; is a hydrogen atom; R; is a hydrogen atom; R; is a hydrogen atom; Rg is an alkyl group of 7 to 16 carbon atoms; and R;’ 1s an optionally substituted phenyl group substituted at position 1 of the dihydrotriazine ring.
5. A dihydrotriazine compound represented by the general formula (la): RyHN 5 N NHR, i T
N 6. Ns KT qa Rs; Ry (wherein R; represents (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) a naphthyl group or a naphthylalkyl group, each of which Amended sheet: 9 May 2006 is optionally substituted, (iv) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R; is a hydrogen atom, R;’ represents (1) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (ii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, (Vv) a cycloalkyl group or a cycloalkyl-alkyl group, each of which 1S is optionally substituted, said groups (i) to (v) being substituted at position 1 of the dihydrotriazine ring, or (b) when R; is other than a hydrogen atom, R;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring; Ry; represents an optionally substituted alkyl group of 7 to 16 carbon atoms; R; and R; represent that R; is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, and Rs; is a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R; and Ry are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkyl spirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a salt thereof.
6. The dihydrotriazine compound according to claim 5, wherein R; is (i) a hydrogen atom, (ii) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (iii) an optionally substituted naphthyl group, (iv) a heterocyclic group, a heterocyclic alkyl group or a Amended sheet: 9 May 2006
¢ 112 heterocyclic aminoalkyl group, each of which is optionally substituted, (v) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (vi) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted; (a) when R; is a hydrogen atom, Ri’ is (i) a phenyl group or a phenylalkyl group, each of which is optionally substituted, (11) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iii) a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, each of which is optionally substituted, or (iv) an optionally substituted alkyl group of 1 to 16 carbon atoms, said groups (1) to (iv) being substituted at position 1 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
7. The dihydrotriazine compound according to claim 5, wherein R; is a phenyl group or a phenylalkyl group, or an alkyl group of 1 to 16 carbon atoms, each of which is optionally substituted; R; is an optionally substituted alkyl group of 1 to 3 carbon atoms; and Rg is an optionally substituted alkyl group of 1 to 16 carbon atoms, or a tautomer thereof or a salt thereof.
8. The dihydrotriazine compound according to claim 5, wherein R; is a phenyl group or a phenylalkyl group, each of which is optionally substituted by one to three substituents selected from the group consisting of fluoro, chloro, hydroxy, methyl, trifluoromethyl and methoxy; Rz; is n-octyl, n-nonyl or n-decyl; Rs and R; are each methyl; and R;’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
9. The dihydrotriazine compound according to claim 5, wherein R; is a phenyl group, a benzyl group or a 2-phenylethyl Amended sheet: 9 May 2006
¢ 113 group, each of which is optionally substituted by one to three substituents selected from the group consisting of fluoro, chloro, hydroxy, methyl, trifluoromethyl and methoxy; Rp; is n-octyl, n-nonyl or n-decyl; R; and Ry are each methyl; and R;’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
10. The dihydrotriazine compound according to claim 5, wherein R; is phenyl, chlorophenyl, benzyl, methylbenzyl, methoxybenzyl, hydroxybenzyl, chlorobenzyl, dichlorobenzyl or 2-phenylethyl; Ry; is n-octyl, n-nonyl or n-decyl; Ri; and Ry are each methyl; and Ry’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
11. The dihydrotriazine compound according to claim 5, wherein R; is methylbenzyl; R,; 1s n-octyl; Ri; and Ry; are each methyl; and Ry’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
12. The dihydrotriazine compound according to claim 5, which is 4-octylamino-3, 6~dihydro-6, 6-dimethyl-2-(4'- methylbenzylamino)-1,3,5-triazine gluconate, or a tautomer thereof or a salt thereof.
13. The dihydrotriazine compound according to claim 5, wherein R; is an alkyl group of 1 to 16 carbon atoms or a cycloalkyl-alkyl group, and R;’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
14. The dihydrotriazine compound according to claim 5, wherein R; is n-butyl, n-hexyl, n-heptyl or cyclohexylmethyl; Ry; is n-heptyl or n-octyl; Rs; and Rs; are each methyl; and R;’ Amended sheet: 9 May 2006
' na is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
15. The dihydrotriazine compound according to claim 5, wherein R; is a naphthyl group, a heterocyclic group or a heterocyclic alkyl group; Ry; is n-octyl, n-nonyl, n-decyl, n-undecyl or n-dodecyl; Rj; and Rs; are each methyl; and Ry’ is a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring, or a tautomer thereof or a salt thereof.
le. A dihydrotriazine compound represented by the following general formula (lc): ) 3
HN. 5, N NH(CH),CH, hi Te ) 5 XT 0) H,C CH, (wherein n represents an integer of 13 to 15), or a tautomer thereof or a salt thereof.
17. The external bactericidal/disinfectant agent according to claim 1, which comprises, as an active ingredient, the dihydrotriazine compound as defined in any one of claims 5to 16, or a tautomer thereof or a pharmacologically acceptable salt thereof.
18. The external Dbactericidal/disinfectant agent according to claim 1, which comprises, as an active ingredient, a dihydrotriazine compound represented by the following general formula (1b): Amended sheet: 9 May 2006 y 1s RHN N_ NH, Ry 1 T
N 6. Ns Kab) R; Ry (wherein Rj; represents (i) a hydrogen atom, (ii) an optionally substituted phenyl group, (iii) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (iv) a heterocyclic group or a heterocyclic alkyl group, each of which is optionally substituted, or (v) a cycloalkyl group or a cycloalkyl~alkyl group, each of which is optionally substituted; (a) when Rj; is a hydrogen atom, Rij; represents (i) a naphthyl group or a naphthylalkyl group, each of which is optionally substituted, (ii) a heterocyclic group or a heterocyclic alkyl group, each of which 1s optionally substituted, (iii) an optionally substituted alkyl group of 1 to 16 carbon atoms, or (iv) a cycloalkyl group or a cycloalkyl-alkyl group, each of which is optionally substituted, said groups (i) to (iv) being substituted at position 1 of the dihydrotriazine ring, or (b) when Rj; is other than a hydrogen atom, R;;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring; R; and Ry represent that Rs is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, and Rs; is a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R; and Rs; are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkylspirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3, provided that at least one of Ry; and Rg is an optionally substituted alkyl group of 7 to 16 carbon atoms), or a tautomer thereof or a salt thereof. Amended sheet: 9 May 2006
£ 116
19. The external bactericidal/disinfectant agent according to claim 1, which comprises, as an active ingredient, a dihydrotriazine compound represented by the following general formula (1d): RizHN 5 N. NHR, TK ad) Rs Ry (wherein Rj; represents a hydrogen atom, or a heterocyclic group, a heterocyclic alkyl group or a heterocyclic aminoalkyl group, the last three groups being optionally substituted, (a) when Rj; is a hydrogen atom, Ri’ represents an optionally substituted heterocyclic group, an optionally substituted heterocyclic alkyl group or an optionally substituted heterocyclic aminoalkyl group, said groups being substituted at position 1 of the dihydrotriazine ring, or (b) when Ry; is other than a hydrogen atom, R;;’ represents a hydrogen atom attached to the nitrogen atom at position 1 or 3 of the dihydrotriazine ring; R,; represents a hydrogen atom, or an optionally substituted alkyl group of 1 to 16 carbon atoms; R; and R; represent that Riz is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms, and Ry is a hydrogen atom or an optionally substituted alkyl group of 1 to 16 carbon atoms, or R;3 and Rs; are taken together with the adjacent carbon atom to form a spirocycloalkane group or an alkylspirocycloalkane group; and the dashed line indicates that the position of a double bond is either between 1 and 2 or between 2 and 3), or a tautomer thereof or a salt thereof.
20. An antiseptic/preservative agent for cosmetics, which comprises, as an active ingredient, the dihydrotriazine compound represented by the general formula (1) as defined in claiml, or a tautomer thereof or a pharmacologically acceptable Amended sheet: 9 May 2006 h 17 salt thereof.
Amended sheet: 9 May 2006
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002365927 | 2002-12-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200503870B true ZA200503870B (en) | 2007-03-28 |
Family
ID=35925146
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200503870A ZA200503870B (en) | 2002-12-17 | 2005-05-13 | Novel 2,4-diamino-1,3,5-triazine derivative |
| ZA200603660A ZA200603660B (en) | 2002-12-17 | 2006-05-09 | Novel 2,4-diamino-1,3,5-triazine derivative |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200603660A ZA200603660B (en) | 2002-12-17 | 2006-05-09 | Novel 2,4-diamino-1,3,5-triazine derivative |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN100551916C (en) |
| ZA (2) | ZA200503870B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102008007314A1 (en) * | 2008-02-02 | 2009-08-06 | Merck Patent Gmbh | Process for the preparation of 3,6-dihydro-1,3,5-triazine derivatives |
| CN107033093B (en) * | 2017-06-07 | 2019-09-03 | 浙江工业大学 | N- substituted sulphonamide compound and the preparation method and application thereof |
| CN114591256B (en) * | 2022-02-15 | 2024-02-20 | 上海奥萝拉医药科技有限公司 | Directional synthesis method of dihydrotriazine |
-
2003
- 2003-12-16 CN CNB2003801062895A patent/CN100551916C/en not_active Expired - Lifetime
-
2005
- 2005-05-13 ZA ZA200503870A patent/ZA200503870B/en unknown
-
2006
- 2006-05-09 ZA ZA200603660A patent/ZA200603660B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1726199A (en) | 2006-01-25 |
| ZA200603660B (en) | 2007-07-25 |
| CN100551916C (en) | 2009-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HUT62861A (en) | Composition with fungicidal activity, comprising carboxylic acid anilide derivative as active ingredient, its application, as well as process for producing the active ingredients | |
| MY132405A (en) | Quinazoline derivatives | |
| NO991423L (en) | Quinoline derivatives that inhibit the effect of growth factors such as VEGF | |
| CA2344290A1 (en) | Quinazoline derivatives | |
| ME01312B (en) | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors | |
| EP3273937A1 (en) | Synergistic compositions of dehydroacetic acid and methods for reducing yellowing in various end-user compositions | |
| JP2019537597A (en) | Synergistic antimicrobial composition | |
| ZA200503870B (en) | Novel 2,4-diamino-1,3,5-triazine derivative | |
| KR101027366B1 (en) | Novel 2,4-diamino-1,3,5-triazine derivative | |
| US4980176A (en) | Preservative compositions and uses thereof | |
| ZA200108943B (en) | Pesticidal triazine derivatives. | |
| DE69315836D1 (en) | PYRAZOLPYRIDINE FOR TREATING ANEMIA | |
| DE60216610D1 (en) | Use of fused pyrazole compounds for the manufacture of a medicament for the treatment of hypertension | |
| AU597626B2 (en) | Preservative compositions and uses thereof | |
| JPH05194361A (en) | Monobiguanide derivative and disinfectant containing the same derivative | |
| US20110207926A1 (en) | Novel dihydrotriazine derivative | |
| JPH04308562A (en) | Bisguanide derivative and disinfectant containing the same derivative | |
| EP1541562A4 (en) | Novel uracil derivatives and medicinal use thereof | |
| NL8203824A (en) | IGNITION BRAKING, DISINFECTIVE AND ANTIBACTERIAL COMPOUND. | |
| Paulus | Pyridine Derivatives and Related Compounds (Benzopyridines= Quinolines) | |
| NL9101389A (en) | Method for preparing a bactericide, and preparation obtained with the aid of this method | |
| TH65076A (en) | Dehelogino compounds |