JPH0159272B2 - - Google Patents
Info
- Publication number
- JPH0159272B2 JPH0159272B2 JP3076881A JP3076881A JPH0159272B2 JP H0159272 B2 JPH0159272 B2 JP H0159272B2 JP 3076881 A JP3076881 A JP 3076881A JP 3076881 A JP3076881 A JP 3076881A JP H0159272 B2 JPH0159272 B2 JP H0159272B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- triazin
- phenyl
- methylthio
- methyl
- 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 triazine compound Chemical class 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 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
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000001760 anti-analgesic effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- IRFQKISACZBIOF-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-phenylazanium;iodide Chemical compound I.CSC(N)=NC1=CC=CC=C1 IRFQKISACZBIOF-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- GFZDPFFFELGNRG-UHFFFAOYSA-N ethyl n-ethoxycarbonylmethanimidate Chemical compound CCOC=NC(=O)OCC GFZDPFFFELGNRG-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- LSNSJCKGQREPDW-UHFFFAOYSA-N methyl 3-amino-3-oxopropanoate Chemical compound COC(=O)CC(N)=O LSNSJCKGQREPDW-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- OERQZVLFGBLJSS-UHFFFAOYSA-N methyl n'-phenylcarbamimidate Chemical compound COC(N)=NC1=CC=CC=C1 OERQZVLFGBLJSS-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明はトリアジン化合物に関する。[Detailed description of the invention] The present invention relates to triazine compounds.
本発明のトリアジン化合物は、新規化合物であ
り、下記一般式(1)で表わされる。 The triazine compound of the present invention is a new compound and is represented by the following general formula (1).
（式中R1は置換基としてハロゲン原子、低級ア
ルキル基若しくは低級アルコキシ基を有すること
のあるフエニル基を、R2は低級アルキル基を、
R3は水素原子又は低級アルキル基を、Ｘは酸素
原子又はイオウ原子を意味する。）
本発明の上記一般式(1)で表わされるトリアジン
化合物、すなわち１―アリール―ｓ―トリアジン
―２（1H）―オン誘導体は、利尿作用、抗菌作
用、抗炎症作用、鎮痛作用等を有し、利尿剤、抗
菌剤、抗炎症剤、鎮痛剤として有用である。 (In the formula, R 1 is a phenyl group that may have a halogen atom, lower alkyl group, or lower alkoxy group as a substituent, R 2 is a lower alkyl group,
R 3 represents a hydrogen atom or a lower alkyl group, and X represents an oxygen atom or a sulfur atom. ) The triazine compound represented by the above general formula (1) of the present invention, that is, the 1-aryl-s-triazin-2(1H)-one derivative, has diuretic, antibacterial, anti-inflammatory, analgesic, etc. It is useful as a diuretic, antibacterial, anti-inflammatory, and analgesic.
上記一般式(1)中R1で定義されるフエニル基の
有し得る置換基である低級アルキル基およびR2、
R3で定義される低級アルキル基としては、炭素
数１〜６の直鎖状あるは分枝状のアルキル基例え
ばメチル、エチル、プロピル、ブチル、ペンチ
ル、ヘキシル基等を例示できる。またR1で定義
されるフエニル基の有し得る置換基である低級ア
ルコキシ基としては、炭素数１〜６のアルコキシ
基例えばメトキシ、エトキシ、プロポキシ、ブト
キシ、ペンチルオキシ、ヘキシルオキシ基等を、
及びハロゲン原子としては弗素、塩素、臭素、沃
素を挙げることができる。 A lower alkyl group that is a substituent that the phenyl group defined as R 1 in the above general formula (1) and R 2 ,
Examples of the lower alkyl group defined as R3 include linear or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, and hexyl groups. Further, as the lower alkoxy group which is a substituent that the phenyl group defined as R 1 may have, alkoxy groups having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy groups, etc.
Examples of the halogen atom include fluorine, chlorine, bromine, and iodine.
本発明のトリアジン化合物の具体例を次に示
す。 Specific examples of the triazine compounds of the present invention are shown below.
６―メチルチオ―１―フエニル―ｓ―トリアジ
ン―２（1H）―オン（化合物１）
６―エチルチオ―１―フエニル―ｓ―トリアジ
ン―２（1H）―オン（化合物２）
６―イソプロピルチオ―１―フエニル―ｓ―ト
リアジン―２（1H）―オン（化合物３）
６―メチルチオ―４―メチル―１―フエニル―
ｓ―トリアジン―２（1H）―オン（化合物４）
６―メチルチオ―４―ヘキシル―１―フエニル
―ｓ―トリアジン―２（1H）―オン（化合物
５）
６―ブチルチオ―４―メチル―１―フエニル―
ｓ―トリアジン―２（1H）―オン（化合物６）
６―メチルチオ―１―（４―クロルフエニル）
―ｓ―トリアジン―２（1H）―オン（化合物
７）
６―メチルチオ―１―（４―メチルフエニル）
―ｓ―トリアジン―２（1H）―オン（化合物
８）
６―メチルチオ―１―（４―メトキシフエニ
ル）―ｓ―トリアジン―２（1H）―オン（化合
物９）
６―エチルチオ―４―エチル―１―（４―エト
キシフエニル）―ｓ―トリアジン―２（1H）―
オン（化合物10）
６―ヘキシルチオ―４―メチル―１―（４―ク
ロルフエニル）―ｓ―トリアジン―２（1H）―
オン（化合物11）
６―メチルチオ―４―プロピル―１―（４―ブ
ロモフエニル）―ｓ―トリアジン―２（1H）―
オン（化合物12）
６―メチルチオ―４―イソプロピル―１―（４
―フルオロフエニル）―ｓ―トリアジン―２
（1H）―オン（化合物13）
６―メトキシ―１―フエニル―ｓ―トリアジン
―２（1H）―オン（化合物14）
６―メトキシ―４―メチル―１―フエニル―ｓ
―トリアジン―２（1H）―オン（化合物15）
６―メトキシ―１―（４―クロルフエニル）―
ｓ―トリアジン―２（1H）―オン（化合物16）
６―プロポキシ―１―フエニル―ｓ―トリアジ
ン―２（1H）―オン（化合物17）
６―エトキシ―１―（４―メチルフエニル）―
ｓ―トリアジン―２（1H）―オン（化合物18）
６―メトキシ―１―（４―メトキシフエニル）
―ｓ―トリアジン―２（1H）―オン（化合物）
６―メトキシ―４―メチル―１―（４―クロル
フエニル）―ｓ―トリアジン―２（1H）―オン
（化合物20）
６―メトキシ―４―ブチル―１―（４―メチル
フエニル）―ｓ―トリアジン―２（1H）―オン
（化合物21）
本発明の一般式(1)で表わされるトリアジン化合
物は、例えば下記反応行程式に示す如き方法によ
り製造することができる。6-Methylthio-1-phenyl-s-triazin-2(1H)-one (Compound 1) 6-ethylthio-1-phenyl-s-triazin-2(1H)-one (Compound 2) 6-isopropylthio-1 -Phenyl-s-triazin-2(1H)-one (compound 3) 6-methylthio-4-methyl-1-phenyl-
s-triazin-2(1H)-one (compound 4) 6-methylthio-4-hexyl-1-phenyl-s-triazin-2(1H)-one (compound 5) 6-butylthio-4-methyl-1- Phenyl
s-triazin-2(1H)-one (compound 6) 6-methylthio-1-(4-chlorophenyl)
-s-triazin-2(1H)-one (compound 7) 6-methylthio-1-(4-methylphenyl)
-s-triazin-2(1H)-one (compound 8) 6-methylthio-1-(4-methoxyphenyl)-s-triazin-2(1H)-one (compound 9) 6-ethylthio-4-ethyl -1-(4-ethoxyphenyl)-s-triazine-2(1H)-
(Compound 10) 6-hexylthio-4-methyl-1-(4-chlorophenyl)-s-triazine-2(1H)-
(Compound 11) 6-methylthio-4-propyl-1-(4-bromophenyl)-s-triazine-2(1H)-
(Compound 12) 6-methylthio-4-isopropyl-1-(4
-fluorophenyl)-s-triazine-2
(1H)-one (compound 13) 6-methoxy-1-phenyl-s-triazin-2(1H)-one (compound 14) 6-methoxy-4-methyl-1-phenyl-s
-triazin-2(1H)-one (compound 15) 6-methoxy-1-(4-chlorophenyl)-
s-triazin-2(1H)-one (compound 16) 6-propoxy-1-phenyl-s-triazin-2(1H)-one (compound 17) 6-ethoxy-1-(4-methylphenyl)-
s-triazin-2(1H)-one (compound 18) 6-methoxy-1-(4-methoxyphenyl)
-s-triazin-2(1H)-one (compound) 6-methoxy-4-methyl-1-(4-chlorophenyl)-s-triazin-2(1H)-one (compound 20) 6-methoxy-4- Butyl-1-(4-methylphenyl)-s-triazin-2(1H)-one (Compound 21) The triazine compound represented by the general formula (1) of the present invention can be produced, for example, by a method as shown in the following reaction scheme. can do.
〈反応行程式〉
（各式中R1、R2、R3およびＸは上記に同じ。Ｙ
およびＺは同一または相異なつて低級アルキル基
を意味する。）
即ち本発明化合物は、一般式(2)で表わされる公
知化合物と一般式(3)で表わされる公知化合物とを
反応させることにより製造される。上記反応は通
常適当な溶媒中で、または無溶媒下に行なわれ
る。溶媒としては反応に関与しない限り特に限定
はなく広く各種のものを利用できる。一般には例
えばベンゼン、トルエン、キシレン等の芳香族炭
化水素類、テトラヒドロフラン、ジオキサン等の
エーテル類、ジメチルホルムアミド、ジメチルス
ルホキシド等の非プロトン性極性溶媒類、プロパ
ノール、ブタノール等のアルコール類等が１種単
独でまたは２種以上混合して好ましく使用でき
る。<Reaction equation> (In each formula, R 1 , R 2 , R 3 and X are the same as above.Y
and Z are the same or different and mean a lower alkyl group. ) That is, the compound of the present invention is produced by reacting a known compound represented by general formula (2) with a known compound represented by general formula (3). The above reaction is usually carried out in a suitable solvent or without a solvent. There are no particular limitations on the solvent as long as it does not participate in the reaction, and a wide variety of solvents can be used. In general, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as tetrahydrofuran and dioxane, aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide, and alcohols such as propanol and butanol are used alone. It can be preferably used alone or in combination of two or more.
一般式(2)で示される化合物と、一般式(3)で示さ
れる化合物の使用割合は適宜選択すればよいが、
一般に等モル量を使用するのが有利である。反応
温度も適宜選択すればよいが、一般に50℃から溶
媒の還流温度程度までとされ、この範囲の温度に
おいて反応は有利に進行する。反応時間は短かく
通常約0.5〜10時間で反応は完結する。 The ratio of the compound represented by general formula (2) and the compound represented by general formula (3) may be selected as appropriate;
It is generally advantageous to use equimolar amounts. Although the reaction temperature may be selected as appropriate, it is generally from 50° C. to about the reflux temperature of the solvent, and the reaction proceeds advantageously at a temperature within this range. The reaction time is short, and the reaction is usually completed in about 0.5 to 10 hours.
本発明の一般式(1)で示されるトリアジン化合物
は通常の分離手段例えば抽出、再結晶、カラムク
ロマトグラフイー等により単離可能である。 The triazine compound represented by the general formula (1) of the present invention can be isolated by conventional separation means such as extraction, recrystallization, column chromatography, etc.
以下本発明のトリアジン化合物の製造例を実施
例として挙げる。 Examples of the production of the triazine compound of the present invention will be given below as examples.
実施例 １
６―メチルチオ―１―フエニル―ｓ―トリアジ
ン―２（1H）―オン（化合物１）の合成
Ｓ―メチル―Ｎ―フエニルイソチオ尿素ヨウ化
水素酸塩14.7ｇを水50mlに溶解後水酸化カリウム
2.8ｇを水20mlで溶解した溶液で中和し、塩化メ
チレン70mlで抽出した。塩化メチレン濃縮残渣に
エチル―Ｎ―エトキシカルボニルホルムイミデイ
ト7.2ｇを加えて、トルエン30ml中３時間還流し
た。冷却後析出物を取し、ベンゼンより再結晶
して６―メチルチオ―１―フエニル―ｓ―トリア
ジン―２（1H）―オン6.6ｇを得た（収率60％）。Example 1 Synthesis of 6-methylthio-1-phenyl-s-triazin-2(1H)-one (compound 1) Hydroxylation after dissolving 14.7 g of S-methyl-N-phenylisothiourea hydroiodide in 50 ml of water. potassium
It was neutralized with a solution of 2.8 g dissolved in 20 ml of water and extracted with 70 ml of methylene chloride. 7.2 g of ethyl-N-ethoxycarbonylformimidate was added to the methylene chloride concentration residue, and the mixture was refluxed in 30 ml of toluene for 3 hours. After cooling, the precipitate was collected and recrystallized from benzene to obtain 6.6 g of 6-methylthio-1-phenyl-s-triazin-2(1H)-one (yield 60%).
融点 162〜163℃
元素分析値 C10H9N3OSとして
計算値（％）：C54.78；H4.14；N19.16
実測値（％）：C54.95；H4.16；N19.13
実施例 ２
４―メチル―６―メチルチオ―１―フエニル―
ｓ―トリアジン―２（1H）―オン（化合物４）
の合成
Ｓ―メチル―Ｎ―フエニルイソチオ尿素ヨウ化
水素酸塩29.4ｇと水酸化カリウム5.6ｇより、実
施例１と同様の処理にて得た残渣にエチル―Ｎ―
メトキシカルボニルアセトイミデイト16ｇを加
え、トルエン25ml中で３時間還流する。冷却後析
出物を取し、エタノール―エーテルより再結晶
して４―メチル―６―メチルチオ―１―フエニル
―ｓ―トリアジン―２（1H）―オン13.1ｇを得た
（収率56％）。 Melting point 162-163℃ Elemental analysis value C 10 H 9 N 3 Calculated value as OS (%): C54.78; H4.14; N19.16 Actual value (%): C54.95; H4.16; N19.13 Example 2 4-methyl-6-methylthio-1-phenyl-
s-triazin-2(1H)-one (compound 4)
Synthesis of ethyl-N-
Add 16 g of methoxycarbonylacetimidate and reflux in 25 ml of toluene for 3 hours. After cooling, the precipitate was collected and recrystallized from ethanol-ether to obtain 13.1 g of 4-methyl-6-methylthio-1-phenyl-s-triazin-2(1H)-one (yield 56%).
融点 170〜171℃
元素分析値 C11H11N3OSとして
計算値（％）：C56.63；H4.75；N18.01
実測値（％）：C56.82；H4.80；N17.96
実施例 ３
６―メトキシ―４―メチル―１―フエニル―ｓ
―トリアジン―２（1H）―オン（化合物15）の
合成
Ｏ―メチル―Ｎ―フエニルイソ尿素３ｇとエチ
ル―Ｎ―メトキシカルボニルアセトイミデイト３
ｇとをトルエン５ml中４時間還流し、冷却後エー
テルを加えて析出物を取し、エタノール―エー
テルより再結晶して６―メトキシ―４―メチル―
１―フエニル―ｓ―トリアジン―２（1H）―オン
2.8ｇを得た（収率62％）。 Melting point 170-171℃ Elemental analysis value C 11 H 11 N 3 Calculated value as OS (%): C56.63; H4.75; N18.01 Actual value (%): C56.82; H4.80; N17.96 Example 3 6-methoxy-4-methyl-1-phenyl-s
-Synthesis of triazin-2(1H)-one (compound 15) O-methyl-N-phenylisourea 3g and ethyl-N-methoxycarbonylacetimidate 3
refluxed in 5 ml of toluene for 4 hours, and after cooling, ether was added to remove the precipitate, which was recrystallized from ethanol-ether to give 6-methoxy-4-methyl-
1-phenyl-s-triazin-2(1H)-one
2.8g was obtained (yield 62%).
融点 182〜184℃
元素分析値 C11H11N3O2として
計算値（％）：C60.82；H5.10；N19.34
実測値（％）：C61.16；H5.23；N19.23
適当な出発物質を用い、上記実施例１〜３と同
様にして、化合物２、３、５〜14及び16〜21を得
た。之等各化合物はその融点、元素分析値及びそ
の他の各種機器分析データーにより同定される。 Melting point 182-184℃ Elemental analysis value Calculated value (%) as C 11 H 11 N 3 O 2 : C60.82; H5.10; N19.34 Actual value (%): C61.16; H5.23; N19. 23 Compounds 2, 3, 5-14 and 16-21 were obtained in the same manner as in Examples 1-3 above using appropriate starting materials. Each of these compounds is identified by its melting point, elemental analysis value, and other various instrumental analysis data.
上記で得られた化合物につき、急性カラゲニン
浮腫試験法〔日本薬理学雑誌、56，575（1960）〕
に準じてラツトのカラゲニン足浮腫（抗炎症作
用）を、またKosterらの方法〔Fed.Pro.、18、
412（1959）〕に準じてマウスの酢酸ストレツチン
グ（鎮痛作用）を調べた。その結果、本発明化合
物が、コントロール（薬剤無投与）の場合に比
べ、50％以上の抗炎症作用及び鎮痛作用を有して
いることが確認された。 Acute carrageenan edema test method [Japanese Pharmacological Journal, 56 , 575 (1960)] for the compound obtained above.
carrageenan paw edema (anti-inflammatory effect) in rats according to the method of Koster et al. [Fed.Pro., 18 ,
412 (1959)], acetic acid stretching (analgesic effect) in mice was investigated. As a result, it was confirmed that the compound of the present invention had anti-inflammatory and analgesic effects that were 50% or more compared to the control (no drug administered).
Claims (1)
アルキル基若しくは低級アルコキシ基を有するこ
とのあるフエニル基を、R2は低級アルキル基を、
R3は水素原子又は低級アルキル基を、Ｘは酸素
原子又はイオウ原子を意味する。） で表わされるトリアジン化合物。[Claims] 1. General formula (In the formula, R 1 is a phenyl group that may have a halogen atom, lower alkyl group, or lower alkoxy group as a substituent, R 2 is a lower alkyl group,
R 3 represents a hydrogen atom or a lower alkyl group, and X represents an oxygen atom or a sulfur atom. ) A triazine compound represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3076881A JPS57144268A (en) | 1981-03-03 | 1981-03-03 | Triazine compound and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3076881A JPS57144268A (en) | 1981-03-03 | 1981-03-03 | Triazine compound and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57144268A JPS57144268A (en) | 1982-09-06 |
| JPH0159272B2 true JPH0159272B2 (en) | 1989-12-15 |
Family
ID=12312857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3076881A Granted JPS57144268A (en) | 1981-03-03 | 1981-03-03 | Triazine compound and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57144268A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2869127C (en) * | 2012-03-30 | 2020-06-09 | Nissan Chemical Industries, Ltd. | Triazinone compound and t-type calcium channel inhibitor |
-
1981
- 1981-03-03 JP JP3076881A patent/JPS57144268A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57144268A (en) | 1982-09-06 |
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