JPH0419965B2 - - Google Patents
Info
- Publication number
- JPH0419965B2 JPH0419965B2 JP2603084A JP2603084A JPH0419965B2 JP H0419965 B2 JPH0419965 B2 JP H0419965B2 JP 2603084 A JP2603084 A JP 2603084A JP 2603084 A JP2603084 A JP 2603084A JP H0419965 B2 JPH0419965 B2 JP H0419965B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- naphthylmethyl
- add
- naphthylmethylamine
- bis
- 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
- 229940121375 antifungal agent Drugs 0.000 claims description 5
- 239000003429 antifungal agent Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- GKMOEOCCICICGF-UHFFFAOYSA-N 1-naphthalen-1-yl-n-(naphthalen-1-ylmethyl)methanamine Chemical class C1=CC=C2C(CNCC=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 GKMOEOCCICICGF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 239000000243 solution Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- -1 N-methyl-N-(2-naphthylmethyl)-1-naphthylmethylamine Chemical compound 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000000843 anti-fungal effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- RUHJZSZTSCSTCC-UHFFFAOYSA-N 2-(bromomethyl)naphthalene Chemical compound C1=CC=CC2=CC(CBr)=CC=C21 RUHJZSZTSCSTCC-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- ZDYZHECSPYIYSS-UHFFFAOYSA-N n-methyl-1-naphthalen-1-yl-n-(naphthalen-1-ylmethyl)methanamine Chemical compound C1=CC=C2C(CN(CC=3C4=CC=CC=C4C=CC=3)C)=CC=CC2=C1 ZDYZHECSPYIYSS-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- XMWGTKZEDLCVIG-UHFFFAOYSA-N 1-(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1 XMWGTKZEDLCVIG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 229960004022 clotrimazole Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- BVJVHPKFDIYQOU-UHFFFAOYSA-N methyl(naphthalen-1-ylmethyl)azanium;chloride Chemical compound Cl.C1=CC=C2C(CNC)=CC=CC2=C1 BVJVHPKFDIYQOU-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- MQRIUFVBEVFILS-UHFFFAOYSA-N n-methyl-1-naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CNC)=CC=CC2=C1 MQRIUFVBEVFILS-UHFFFAOYSA-N 0.000 description 1
- QMUNJWWRHIBJGY-UHFFFAOYSA-N n-methyl-1-naphthalen-2-yl-n-(naphthalen-2-ylmethyl)methanamine Chemical compound C1=CC=CC2=CC(CN(CC=3C=C4C=CC=CC4=CC=3)C)=CC=C21 QMUNJWWRHIBJGY-UHFFFAOYSA-N 0.000 description 1
- NEXZCFUBZJBRCP-UHFFFAOYSA-N naphthalen-1-ylmethylazanium;chloride Chemical compound Cl.C1=CC=C2C(CN)=CC=CC2=C1 NEXZCFUBZJBRCP-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Description
本発明は新規な抗真菌剤に関する。
本発明者らは種々の有機化合物についてその薬
理活性を検討する間に、一般式
（式中、メチレン基はナフタレン環の１位又は
２位に結合する）
で表わされるビス（ナフチルメチル）アミン誘導
体又はその塩が抗真菌剤として効力が優れ、しか
も毒性及び副作用の極めて少ないことを見出し本
発明に至つた。
一般式（）で表わされる化合物はＮ−メチル
−ビス（１−ナフチルメチル）アミン、Ｎ−メチ
ル−Ｎ−（２−ナフチルメチル）−１−ナフチルメ
チルアミン及びＮ−メチル−ビス（２−ナフチル
メチル）アミンがあげられるが、これらは例えば
１−（クロロメチル）ナフタレン（）とメチル
アミン（）を縮合させてＮ−メチル−ビス（１
−ナフチルメチル）アミン（）を、またＮ−メ
チル−１−ナフチルメチルアミン（）と２−
（ブロモメチル）ナフタレン（）を縮合させて
Ｎ−メチル−Ｎ−（２−ナフチルメチル）−１−ナ
フチルメチルアミンをそれぞれ製造できる
（Chemische Berichte 56巻2165〜2172頁1923年
参照）。
一般式（）の化合物の塩としては、例えば塩
酸塩、臭化水素酸塩、硫酸塩及び硝酸塩などの無
機酸、また酢酸塩、修酸塩、ベンゼンスルホン酸
塩及びメタンスルホン酸塩などの有機酸塩があ
る。
一般式（）の化合物は前記の如く既知化合物
であるが、それの薬理作用については報告されて
おらず、医薬としての用途は全く未知の状態であ
つたが、本発明者らが薬理作用を研究したとこ
ろ、後に示すように優れた抗真菌作用を有するこ
とを見出し本発明に至つた。
一般式（）の化合物は試験管内試験にて、各
種の真菌に0.05〜100μｇ／mlの濃度で抗真菌活性
を有し、また動物試験においても強い抗真菌活性
を有することが確認された。
本発明化合物は例えば液剤、軟膏剤及びクリー
ム剤などの抗真菌剤として常套な剤形にて局所投
与に適する。本化合物の使用濃度は化合物の種
類、投与法及び剤形等によつて異なるが、一般的
には0.05〜10％の濃度、更に好ましくは0.1〜５
％の濃度で用いるのが好ましい。
〔参考例 １〕
Ｎ−メチル−ビス（１−ナフチルメチル）アミ
ン塩酸塩の製法
メチルアミン塩酸塩13.4ｇ、ジメチルホルムア
ミド300ml、炭酸ナトリウム78.4ｇの混合物に１
−クロロメチルナフタリン68ｇを滴加し、50℃に
て29時間反応させる。沈殿物を濾別後、濾液を減
圧下濃縮する。得られた油状物をベンゼンで希釈
し、水洗する。ベンゼン溶液に濃塩酸を加え析出
する結晶を濾取し、エタノールより再結晶して白
色結晶49ｇを得る。
融点 219〜220℃（遊離塩基の融点87〜88℃）
元素分析値
C23H21N・HClとして
計算値（％）：Ｃ 79.41 Ｈ 6.37 Ｎ 4.03
実測値（％）：Ｃ 79.50 Ｈ 6.40 Ｎ 4.01
〔参考例 ２〕
Ｎ−メチル−Ｎ−（２−ナフチルメチル）−１−
ナフチルメチルアミン塩酸塩の製法
Ｎ−メチル−１−ナフチルメチルアミン20.5
ｇ、炭酸ナトリウム15.3ｇ、ジメチルホルムアミ
ド140ml及び２−（ブロモメチル）ナフタレン30.2
ｇの混合物を50℃で20時間反応させる。得られた
沈殿物を濾別後、濾液を減圧下濃縮する。油状物
をベンゼンで希釈し、水洗する。ベンゼン溶液に
濃塩酸を加え析出する結晶を濾取し、エタノール
より再結晶して白色結晶30.5ｇを得る。
融点 230.5〜231.5℃（遊離塩基の融点144〜145
℃）
元素分析値
C23H21N・HClとして
計算値（％）：Ｃ 79.41 Ｈ 6.37 Ｎ 4.03
実測値（％）：Ｃ 79.51 Ｈ 6.39 Ｎ 4.02
〔試験例 １〕 抗菌試験
各種の真菌を用いた最小阻止濃度（μｇ／ml）
を第１表に示す。
The present invention relates to a novel antifungal agent. While investigating the pharmacological activities of various organic compounds, the present inventors discovered the general formula (In the formula, the methylene group is bonded to the 1st or 2nd position of the naphthalene ring.) The bis(naphthylmethyl)amine derivative or its salt represented by the following formula has excellent efficacy as an antifungal agent, and has extremely low toxicity and side effects. Heading This led to the present invention. The compounds represented by the general formula () include N-methyl-bis(1-naphthylmethyl)amine, N-methyl-N-(2-naphthylmethyl)-1-naphthylmethylamine and N-methyl-bis(2-naphthylmethyl)amine. For example, N-methyl-bis(1
-naphthylmethyl)amine () and N-methyl-1-naphthylmethylamine () and 2-
(Bromomethyl)naphthalene () can be condensed to produce N-methyl-N-(2-naphthylmethyl)-1-naphthylmethylamine, respectively (see Chemische Berichte, Vol. 56, pp. 2165-2172, 1923). Salts of the compound of general formula () include inorganic acids such as hydrochloride, hydrobromide, sulfate and nitrate, and organic acids such as acetate, oxalate, benzenesulfonate and methanesulfonate. There are acid salts. Although the compound of general formula () is a known compound as mentioned above, its pharmacological action has not been reported and its use as a medicine was completely unknown. As a result of research, it was discovered that it has excellent antifungal activity, as will be shown later, leading to the present invention. It was confirmed that the compound of general formula () has antifungal activity against various fungi at a concentration of 0.05 to 100 μg/ml in in vitro tests, and also has strong antifungal activity in animal tests. The compounds of the invention are suitable for topical administration in the usual dosage forms for antifungal agents, such as solutions, ointments and creams. The concentration of this compound to be used varies depending on the type of compound, administration method, dosage form, etc., but generally the concentration is 0.05 to 10%, more preferably 0.1 to 5%.
It is preferred to use a concentration of %. [Reference Example 1] Process for producing N-methyl-bis(1-naphthylmethyl)amine hydrochloride Add 1 to a mixture of 13.4 g of methylamine hydrochloride, 300 ml of dimethylformamide, and 78.4 g of sodium carbonate.
- Add 68 g of chloromethylnaphthalene dropwise and react at 50°C for 29 hours. After filtering off the precipitate, the filtrate is concentrated under reduced pressure. The resulting oil is diluted with benzene and washed with water. Add concentrated hydrochloric acid to the benzene solution, collect the precipitated crystals by filtration, and recrystallize from ethanol to obtain 49 g of white crystals. Melting point 219-220℃ (free base melting point 87-88℃) Elemental analysis value C 23 H 21 As N・HCl Calculated value (%): C 79.41 H 6.37 N 4.03 Actual value (%): C 79.50 H 6.40 N 4.01 [Reference example 2] N-methyl-N-(2-naphthylmethyl)-1-
Method for producing naphthylmethylamine hydrochloride N-methyl-1-naphthylmethylamine 20.5
g, sodium carbonate 15.3 g, dimethylformamide 140 ml and 2-(bromomethyl)naphthalene 30.2 g.
The mixture of g is reacted at 50°C for 20 hours. After filtering off the obtained precipitate, the filtrate is concentrated under reduced pressure. Dilute the oil with benzene and wash with water. Add concentrated hydrochloric acid to the benzene solution, collect the precipitated crystals by filtration, and recrystallize from ethanol to obtain 30.5 g of white crystals. Melting point 230.5-231.5℃ (free base melting point 144-145
℃) Elemental analysis value C 23 H 21 As N・HCl Calculated value (%): C 79.41 H 6.37 N 4.03 Actual value (%): C 79.51 H 6.39 N 4.02 [Test Example 1] Antibacterial test Using various fungi Minimum inhibitory concentration (μg/ml)
are shown in Table 1.
【表】
なお、対照として用いたクロトリマゾールは下
記の構造を有する抗真菌活性物質である。
〔試験例 ２〕
ハートレイ系モルモツト雄（体重600〜700ｇ）
の背部４ケ所を４cm2ずつ抜毛し、軽くサンドペー
パーで擦過した後、モルモツトから逆培養した２
代目の毛瘡白癬菌（１感染当り１×105胞子）を
感染させた。感染後48時間後から、エタノールで
溶解した被検化合物0.2mlを１日１回計10回塗布
した。最終治療の２日後にモルモツトを屠殺し、
各感染面より10個の組織片をシクロヘキシミド及
びカナマイシン含有サブロ−平均培地に置き、27
℃で７日間培養し、白癬菌の有無を判定し、下記
の式から抑制率を算出し、得られた結果を第２表
に示す。
抑制率＝（１−生育組織片数／逆培養組織片数）
×100[Table] Clotrimazole, which was used as a control, is an antifungal active substance having the following structure. [Test Example 2] Male Hartley Guinea Motu (weight 600-700g)
The hair was removed from the back of the guinea pig in 4 cm2 portions, and the hair was lightly rubbed with sandpaper.
The cells were infected with the third generation of Trichophyton trichophyton (1×10 5 spores per infection). Starting 48 hours after infection, 0.2 ml of the test compound dissolved in ethanol was applied once a day for a total of 10 times. Two days after the final treatment, the guinea pigs were sacrificed.
Ten tissue pieces from each infected surface were placed in Sabouraud's medium containing cycloheximide and kanamycin.
The samples were cultured at ℃ for 7 days, the presence or absence of Trichophyton was determined, and the inhibition rate was calculated from the following formula. The obtained results are shown in Table 2. Suppression rate = (1 - number of grown tissue pieces/number of reverse cultured tissue pieces)
×100
【表】
〔試験例 ３〕 急性毒性試験
ICR系雄性マウス５週令（体重26〜28ｇ）を試
験に供した。Ｎ−メチル−ビス（１−ナフチルメ
チル）アミン塩酸塩及びＮ−メチル−Ｎ−（２−
ナフチルメチル）−１−ナフチルメチルアミン塩
酸塩を各々0.5％メチルセルロースで懸濁し、濃
度を調整して0.1ml／10ｇの体重相応量を経口投
与した。各投与群とも１群５匹とし、投与後７日
間観察した。
各化合物を4000mg／Kgまで投与したが死亡例は
無く、また投与後の一般症状においても何等変化
は認められなかつた。
〔実施例 １〕 液剤
200mlのマクロゴール400をエタノール750mlに
溶かし、これにＮ−メチル−Ｎ−（２−ナフチル
メチル）−１−ナフチルメチルアミン塩酸塩５ｇ
を加えて溶かす。さらにエタノールにて全量を
1000mlとし、液剤として供する。
〔実施例 ２〕 軟膏剤
白色ワセリン400ｇ、セタノール180ｇ、パラオ
キシ安息香酸プロピル１ｇ及びセスキオレイン酸
ソルビタン50ｇを水浴上にて80℃に保ちながら溶
かし、次いでＮ−メチル−Ｎ−（２−ナフチルメ
チル）−１−ナフチルメチルアミン塩酸塩５ｇを
加えて溶かす。一方、パラオキシ安息香酸メチル
１ｇに水を加え80℃に加温し溶かした液を前述の
液に徐々に加え混合する。冷却後軟膏剤として供
する。[Table] [Test Example 3] Acute toxicity test ICR male mice of 5 weeks old (body weight 26-28 g) were subjected to the test. N-methyl-bis(1-naphthylmethyl)amine hydrochloride and N-methyl-N-(2-
Naphthylmethyl)-1-naphthylmethylamine hydrochloride was each suspended in 0.5% methylcellulose, the concentration was adjusted, and an amount of 0.1 ml/10 g corresponding to the body weight was orally administered. There were 5 animals in each administration group, and the animals were observed for 7 days after administration. Each compound was administered up to 4000 mg/Kg, but there were no deaths, and no changes were observed in general symptoms after administration. [Example 1] Solution Dissolve 200 ml of Macrogol 400 in 750 ml of ethanol, and add 5 g of N-methyl-N-(2-naphthylmethyl)-1-naphthylmethylamine hydrochloride to this solution.
Add and dissolve. Further, remove the entire amount with ethanol.
Make the volume 1000ml and serve as a liquid. [Example 2] Ointment 400 g of white petrolatum, 180 g of cetanol, 1 g of propyl paraoxybenzoate and 50 g of sorbitan sesquioleate were dissolved on a water bath while maintaining the temperature at 80°C, and then N-methyl-N-(2-naphthylmethyl) was dissolved. -Add and dissolve 5 g of 1-naphthylmethylamine hydrochloride. On the other hand, add water to 1 g of methyl paraoxybenzoate, heat to 80°C, and dissolve the solution. Gradually add the solution to the above-mentioned solution and mix. After cooling, serve as an ointment.
Claims (1)
２位に結合する） で表わされるビス（ナフチルメチル）アミン誘導
体又はその塩を有効成分とする抗真菌剤。[Claims] 1. General formula (In the formula, the methylene group is bonded to the 1st or 2nd position of the naphthalene ring.) An antifungal agent containing a bis(naphthylmethyl)amine derivative or a salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2603084A JPS60172919A (en) | 1984-02-16 | 1984-02-16 | Antifungal agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2603084A JPS60172919A (en) | 1984-02-16 | 1984-02-16 | Antifungal agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60172919A JPS60172919A (en) | 1985-09-06 |
| JPH0419965B2 true JPH0419965B2 (en) | 1992-03-31 |
Family
ID=12182303
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2603084A Granted JPS60172919A (en) | 1984-02-16 | 1984-02-16 | Antifungal agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60172919A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6145A (en) * | 1984-06-09 | 1986-01-06 | Kaken Pharmaceut Co Ltd | Naphthylmethylamine derivative and antifungal containing the same |
| EP2052609A1 (en) | 2007-10-24 | 2009-04-29 | Bayer CropScience AG | Herbicide combination |
| DE102008037621A1 (en) | 2008-08-14 | 2010-02-18 | Bayer Cropscience Ag | Herbicide combination with dimethoxytriazinyl-substituted difluoromethanesulfonylanilides |
-
1984
- 1984-02-16 JP JP2603084A patent/JPS60172919A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60172919A (en) | 1985-09-06 |
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