JPH0338523A - Antimicrobial agent - Google Patents
Antimicrobial agentInfo
- Publication number
- JPH0338523A JPH0338523A JP17535789A JP17535789A JPH0338523A JP H0338523 A JPH0338523 A JP H0338523A JP 17535789 A JP17535789 A JP 17535789A JP 17535789 A JP17535789 A JP 17535789A JP H0338523 A JPH0338523 A JP H0338523A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- methoxy
- methyl
- benzimidazole
- antimicrobial agent
- 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.)
- Pending
Links
- 239000004599 antimicrobial Substances 0.000 title abstract 4
- -1 pyrimidine compound Chemical class 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 241000894006 Bacteria Species 0.000 abstract description 14
- 241000589876 Campylobacter Species 0.000 abstract description 7
- 239000003826 tablet Substances 0.000 abstract description 4
- 208000035473 Communicable disease Diseases 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 3
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 239000008187 granular material Substances 0.000 abstract description 2
- SZLHMAGNHFWTJH-UHFFFAOYSA-N 2-[(5-benzyl-4-methoxy-6-methylpyrimidin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=NC(CSC=2NC3=CC=CC=C3N=2)=NC(C)=C1CC1=CC=CC=C1 SZLHMAGNHFWTJH-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 14
- 241000590002 Helicobacter pylori Species 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 208000007882 Gastritis Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 229960001699 ofloxacin Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 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
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- 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 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 229960005412 bacampicillin hydrochloride Drugs 0.000 description 1
- IWVTXAGTHUECPN-ANBBSHPLSA-N bacampicillin hydrochloride Chemical compound [H+].[Cl-].C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OC(C)OC(=O)OCC)=CC=CC=C1 IWVTXAGTHUECPN-ANBBSHPLSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000009036 growth inhibition Effects 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
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000011140 intestinal infectious disease Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([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
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 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
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は抗菌剤、とりわけキャンピロバクター属細菌に
対してより優れた抗菌作用を有する抗菌剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an antibacterial agent, particularly an antibacterial agent having superior antibacterial activity against Campylobacter bacteria.
特開平１−１３２５８１号公報には胃酸分泌抑制作用を
有し、胃および十二指腸潰瘍などの治療薬として有用な
ピリ果ジン化合物が開示されている。JP-A-1-132581 discloses a pyrifruitdine compound that has a gastric acid secretion suppressing effect and is useful as a therapeutic agent for gastric and duodenal ulcers.
（発明が解決しようとする課題）
ダラム陰性の微好気性細菌であるキャンピロバクター（
Ｃａｍｐｙｌｏｂａｃｔｅｒ）属細菌は家畜に下痢や流
産などを起こす菌として発見された。ヒトにおいては細
菌性腸炎を起こすものとしてＣａ＋ａｐｙｌｏｂａｃｔ
ｅｒｊｅｊｕｎｌ、 Ｃａｓ＋ｐｙｌｏｂａｃｔｅｒ
ｃｏｌｔなどが知られている。(Problem to be solved by the invention) Campylobacter, a Durham-negative microaerobic bacterium (
Bacteria of the genus Campylobacter were discovered as bacteria that cause diarrhea and miscarriage in livestock. In humans, Ca+ apylobact causes bacterial enteritis.
erjejunl, Cas+pylobacter
colt etc. are known.
一方、１９８３年にＷａｒｒｅｎとＭａｒｓｈａｌｌに
より、胃炎とＣａｍｐｙｌｏｂａｃｔｅｒ ｐｙｌｏｒ
ｉ（キャンピロバクター・ピロリ−）感染との関連が報
告されて以来、多くの研究、報告がなされてきた。事実
、慢性胃炎および胃・十二指腸潰瘍に合併する前庭部胃
炎組織からキャンピロバクター・ピロリ−が高頻度に検
出されている。On the other hand, in 1983, Warren and Marshall identified gastritis and Campylobacter pylor.
Since the association with Campylobacter pylori (Campylobacter pylori) infection was reported, many studies and reports have been made. In fact, Campylobacter pylori is frequently detected in antral gastritis tissue associated with chronic gastritis and gastric/duodenal ulcers.
現在のところ、上記病変とキャンピロバクター・ピロリ
−による感染との関連が明らかにされてはいないが、本
閑の排除を目的にオフロキサシン、塩酸バカンビシリン
などの抗生物質を患者に投与することが試みられている
。しかしながら、塩酸バカンピシリン投与での除菌効果
は５０％であり、また、本菌はオフロキサシンに対する
耐性を獲得しやすいといわれているように、未だ十分な
効果を上げるに至っていない。このような実情から、キ
ャンピロバクター・ピロリ−などによる細菌感染の治療
に用いうる有用な抗菌剤の開発が望まれている。At present, the relationship between the above-mentioned lesions and Campylobacter pylori infection has not been clarified, but attempts have been made to administer antibiotics such as ofloxacin and bacambicillin hydrochloride to patients in order to eliminate this disease. It is being However, the eradication effect of bacampicillin hydrochloride is only 50%, and as it is said that this bacterium tends to acquire resistance to ofloxacin, sufficient efficacy has not yet been achieved. Under these circumstances, there is a desire for the development of useful antibacterial agents that can be used to treat bacterial infections caused by Campylobacter pylori and the like.
上記課題を解決するために、本発明者らは種々研究を重
ねてきたところ、従来その胃酸分泌抑制作用に基づいて
抗潰瘍剤として知られている前記公報に記載の化合物群
が意外にもキャンピロバクター属細菌に対して優れた抗
菌作用を有することを見出して、本発明を完成するに至
った。In order to solve the above problems, the present inventors have conducted various studies and found that the group of compounds described in the above publication, which have been known as anti-ulcer agents based on their gastric acid secretion suppressing effects, surprisingly The present invention was completed based on the discovery that it has an excellent antibacterial effect against bacteria of the genus Pylobacter.
すなわち、本発明は一般式
（）
により表わされるピリミジン化合物またはソノ酸付加塩
を活性成分として含有することを特徴とする抗菌剤に関
する。That is, the present invention relates to an antibacterial agent characterized by containing a pyrimidine compound represented by the general formula () or a sonoacid addition salt as an active ingredient.
式中、Ｒ１は水素、ハロゲン（塩素、臭素、フッ素、ヨ
ウ素）、アルキル（メチル、エチル、プロピル、イソプ
ロピル、ブチル、イソブチル、ペンチル、ヘキシル、オ
クチルなど）、アルコキシ（メトキシ、エトキシ、プロ
ポキシ、イソプロポキシ、ブトキシ、イソブトキシ、ペ
ンチルオキシ、ヘキシルオキシ、オクチルオキシなど）
、アルコキシカルボニル（メトキシカルボニル、エトキ
シカルボニル、プロポキシカルボニル、イソプロポキシ
カルボニル、ブトキシカルボニル、イソブトキシカルボ
ニル、ヘキシルオキシカルボニルなど）、トリフルオロ
メチルを、Ｘは−Ｓ−−Ｓ○を、Ｒ２はアルキル（前記
と同義）を、Ｒ３は水素、アルキル（前記と同義）、置
換していてもよいアラルキル、置換していてもよいヘテ
ロアラルキル（置換基としては、１〜３個のハロゲン、
アルキル、アルコキシ、ニトロ、アミノ、水酸基などが
あげられ、ベンジル、２−クロロベンジル、２−メチル
ベンジル、２−メトキシベジル、２ニトロベンジル、２
−アミノベンジル、２−ヒドロキシベンジル、２．４−
ジクロロベンジル、３．４．５−トリメトキシベンジル
、２−フェニルエチル、ｌ−フェニルエチル、２− （
３−フルオロフェニル）エチル、３−フェニルプロピル
、３−（４−メチルフェニル）プロピル、３−ピリジル
メチル、２−（２−ピリジル）エチル、３−（４−ピリ
ジル）プロピルなど）を、Ｒ４は水素、アルキル（前記
と同義）を示す。In the formula, R1 is hydrogen, halogen (chlorine, bromine, fluorine, iodine), alkyl (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, octyl, etc.), alkoxy (methoxy, ethoxy, propoxy, isopropoxy) , butoxy, isobutoxy, pentyloxy, hexyloxy, octyloxy, etc.)
, alkoxycarbonyl (methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, hexyloxycarbonyl, etc.), trifluoromethyl, X is -S--S○, R2 is alkyl (the above ), R3 is hydrogen, alkyl (same definition as above), optionally substituted aralkyl, optionally substituted heteroaralkyl (substituents include 1 to 3 halogens,
Alkyl, alkoxy, nitro, amino, hydroxyl groups, etc. include benzyl, 2-chlorobenzyl, 2-methylbenzyl, 2-methoxybenzyl, 2-nitrobenzyl,
-aminobenzyl, 2-hydroxybenzyl, 2.4-
Dichlorobenzyl, 3.4.5-trimethoxybenzyl, 2-phenylethyl, l-phenylethyl, 2-(
R4 is Indicates hydrogen and alkyl (same meaning as above).
本発明の抗菌剤は特にダラム陰性菌、とりわけ微好気性
細菌、就中キャンピロバクター・ピロリ−に代表される
キャンピロバクター属の菌に対して有効である。従って
、本発明はヒトを含む哺乳動物の感染症の予防および治
療法を提供し、その方法は有効量の一般式（＋）により
表わされる化合物、またはその酸付加塩を投与すること
を特徴とする。The antibacterial agent of the present invention is particularly effective against Durham-negative bacteria, especially microaerophilic bacteria, especially Campylobacter genus bacteria represented by Campylobacter pylori. Therefore, the present invention provides a method for preventing and treating infectious diseases in mammals including humans, which method is characterized by administering an effective amount of a compound represented by general formula (+) or an acid addition salt thereof. do.
本発明の一般式Ｎ）の化合物には種々の異性体が存在し
うる。本発明はこれら異性体の１種またはそれら異性体
の混合物を含む。The compounds of general formula N) according to the invention may exist in various isomers. The present invention includes one of these isomers or a mixture of these isomers.
一般式（１）の化合物の酸付加塩としては、塩酸塩、臭
化水素酸塩、ヨウ化水素酸塩、硫酸塩、硝酸塩、リン酸
塩、酢酸塩、クエン酸塩、マレイン酸塩、フマール酸塩
、マロン酸塩、リンゴ酸塩、酒石酸塩などがあげられる
。Acid addition salts of the compound of general formula (1) include hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, acetate, citrate, maleate, fumarate. Examples include acid salts, malonates, malates, and tartrates.
一般式（１）の化合物またはその酸付加塩は公知の方法
、たとえば特開平１−１３２５８１号公報に記載の方法
によって製造することができる。The compound of general formula (1) or its acid addition salt can be produced by a known method, for example, the method described in JP-A-1-132581.
本発明に含まれる化合物としては以下の化合物が例示さ
れるが、本発明はこれらに限定されるものではない。The following compounds are exemplified as compounds included in the present invention, but the present invention is not limited thereto.
（１） ２−（５−ベンジル−４−メトキシ−６−
メチル−２−ピリミジニル〉メチルチオ−ＩＨ−ベンズ
イミダゾール
（２） ２−（５−ベンジル−４−メトキシ−６−
メチル−２−ピリくジニル）メチルスルフィニル＝ｌＨ
−ベンズイ藁ダゾール
（３） ２−（４−メトキシ−６−メチル−２ピリ
ミジニル）メチルチオ−Ｉ Ｈ−ベンズイミダゾール
（４） ２−（４−メトキシ−６−メチル−２ピリ
ミジニル）メチルスルフィニル−ＩＨ−ベンズイミダゾ
ール
（５） ２−（４−メトキシ−６−メチル−５−（
３−ピリジルメチル）−２−ピリミジニル）メチルチオ
−Ｌ Ｈ−ベンズイミダゾール（６） ２−（４−
メトキシ−６−メチル−５−（３−ピリジルメチル〉−
２−ピリミジニル）メチルスルフィニル−ＩＨ−ベンズ
イミダゾール（７） ２−（４−メトキシ−６−メ
チル−５−ペンチル−２−ピリミジニル）メチルチオ−
Ｌ Ｈ＝ベンズイξダゾール
（８） ２−（４−メトキシ−６−メチル−５−ペン
チル−２−ピリミジニル）メチルスルフィニル−ＩＨ−
ベンズイミダゾール
（９） ２−（４−メトキシ−２−ピリミジニル）
メチルチオ−ＩＨ−ベンズイごダゾール（１０）
２−（４−メトキシ−２−ピリ雫ジニル）メチルスルフ
ィニル−ＩＨ−ベンズイミダゾール
（１１） ２− （４−メトキシ−５，６−ジメチ
ル−２−ピリミジニル）メチルチオ−ＩＨ−ベンズイミ
ダゾール
（１２） ２−（４−メトキシ−５，６−ジメチル
−２−ピリミジニル）メチルスルフィニル−ＩＨ−ペン
ズイミダゾール
（１３） ２−（５−ベンジル−４−メトキシ６−
メチル−２−ピリごジニル）メチルチオ−５−クロロ−
ＩＨ−ベンズイミダゾール
（１４） ２〜（５−ベンジル−４−メトキシ−６
−メチル−２−ピリミジニル）メチルスルフィニル−５
−クロロ−ＩＨ−ベンズイミダゾール（１５） ２
−（４−メトキシ−６−メチル−２−ピリもジニル）メ
チルチオ−５−メチル〜ＩＨ−ベンズイξダゾール
（１６） ２−（４−メトキシ−６−メチル−２ピ
リξジニル）メチルスルフィニル−５−メチル−Ｌ Ｈ
−ベンズイミダゾール
（１７） ５−メトキシ−２−（４−メトキシ６−
メチル−５−（３−ピリジルメチル）−２−ピリミジニ
ル）メチルチオ−ＩＨ−ベンズイミダゾール
（１８） ５−メトキシ−２−（４−メトキシ−６
−メチル−５−（３−ピリジルメチル）−２−ピリミジ
ニル）メチルスルフィニル−１！（−ベンズイミダゾー
ル
（１９） ２−（４−メトキシ−６−メチル−５＝
ベンチルー２−ピリミジニル）メチルチオ−５−メトキ
シカルボニル−Ｌ Ｈ−ベンズイミダゾール
（２０） ２− （４−メトキシ−６−メチル−５
−ベンチルー２−ピリ處ジニル）メチルスルフィニル−
５−メトキシカルボニル−ＩＨ−ベンズイミダゾール
（２１） ２−（４−メトキシ−２−ピリミジニル
）メチルチオ−５−トリフルオロメチル−ＩＨ−ペンズ
イミダゾール
（２２） ２−（４−メトキシル２−ピリミジニル
）メチルスルフィニル−５−トリフルオロメチル−１Ｈ
−ペンズイミダゾール
（２３） ４−ブロモ−２−（４−メトキシ−５，６
−ジメチル−２−ピリミジニル）メチルチオ−ＩＨ−ベ
ンズイミダゾール
（２４） ４−ブロモ−２−（４−メトキシ−５，６
−ジメチル−２−ピリくジニル）メチルスルフィニル−
ＬＨ−ベンズイミダゾール〔作用および効果〕
本発明の抗菌剤は、待にダラム陰性菌、とりわけ微好気
性細菌、就中キャンピロバクター・ピロリ−に代表され
るキャンピロバクター属の菌に対して有効である。従っ
て、本発明はヒトを含む哺乳動物の感染症の予防および
治療に使用される。(1) 2-(5-benzyl-4-methoxy-6-
Methyl-2-pyrimidinyl〉Methylthio-IH-benzimidazole (2) 2-(5-benzyl-4-methoxy-6-
Methyl-2-pyridinyl)methylsulfinyl = lH
-benzistradazole (3) 2-(4-methoxy-6-methyl-2pyrimidinyl)methylthio-I H-benzimidazole (4) 2-(4-methoxy-6-methyl-2pyrimidinyl)methylsulfinyl-IH- Benzimidazole (5) 2-(4-methoxy-6-methyl-5-(
3-pyridylmethyl)-2-pyrimidinyl)methylthio-L H-benzimidazole (6) 2-(4-
Methoxy-6-methyl-5-(3-pyridylmethyl〉-
2-pyrimidinyl)methylsulfinyl-IH-benzimidazole (7) 2-(4-methoxy-6-methyl-5-pentyl-2-pyrimidinyl)methylthio-
L H=benziξdazole (8) 2-(4-methoxy-6-methyl-5-pentyl-2-pyrimidinyl)methylsulfinyl-IH-
Benzimidazole (9) 2-(4-methoxy-2-pyrimidinyl)
Methylthio-IH-benzigodazole (10)
2-(4-methoxy-2-pyrimidinyl)methylsulfinyl-IH-benzimidazole (11) 2-(4-methoxy-5,6-dimethyl-2-pyrimidinyl)methylthio-IH-benzimidazole (12) 2 -(4-methoxy-5,6-dimethyl-2-pyrimidinyl)methylsulfinyl-IH-penzimidazole (13) 2-(5-benzyl-4-methoxy6-
Methyl-2-pyrigodinyl)methylthio-5-chloro-
IH-benzimidazole (14) 2-(5-benzyl-4-methoxy-6
-methyl-2-pyrimidinyl)methylsulfinyl-5
-chloro-IH-benzimidazole (15) 2
-(4-Methoxy-6-methyl-2-pyridinyl)methylthio-5-methyl~IH-benziξdazole (16) 2-(4-methoxy-6-methyl-2pyridinyl)methylsulfinyl-5 -Methyl-L H
-Benzimidazole (17) 5-methoxy-2-(4-methoxy6-
Methyl-5-(3-pyridylmethyl)-2-pyrimidinyl)methylthio-IH-benzimidazole (18) 5-methoxy-2-(4-methoxy-6
-Methyl-5-(3-pyridylmethyl)-2-pyrimidinyl)methylsulfinyl-1! (-benzimidazole (19) 2-(4-methoxy-6-methyl-5=
Benzi-2-pyrimidinyl) methylthio-5-methoxycarbonyl-L H-benzimidazole (20) 2- (4-methoxy-6-methyl-5
-Bench-2-pyridinyl)methylsulfinyl-
5-methoxycarbonyl-IH-benzimidazole (21) 2-(4-methoxy-2-pyrimidinyl)methylthio-5-trifluoromethyl-IH-penzimidazole (22) 2-(4-methoxyl2-pyrimidinyl)methylsulfinyl -5-trifluoromethyl-1H
-Penzimidazole (23) 4-bromo-2-(4-methoxy-5,6
-dimethyl-2-pyrimidinyl)methylthio-IH-benzimidazole (24) 4-bromo-2-(4-methoxy-5,6
-dimethyl-2-pyridinyl)methylsulfinyl-
LH-benzimidazole [Action and effect] The antibacterial agent of the present invention is effective against Durham-negative bacteria, especially microaerophilic bacteria, and especially Campylobacter genus bacteria represented by Campylobacter pylori. It is. Therefore, the present invention can be used for the prevention and treatment of infectious diseases in mammals, including humans.
本発明の抗菌剤を、たとえば細菌感染症治療・予防剤と
して使用する場合には、通常薬学的に許容されうる担体
とともに化合物（１）自体（すなわち、遊離塩基）、ま
たはその塩を活性成分として含有する薬学的製剤の形態
で、賦形剤、担体、希釈剤、溶解補助剤などの添加剤と
混合してカプセル剤、錠剤（ｔｌ衣錠、フィルムコート
錠も含む）、顆粒剤、注射剤、点滴用剤などの剤型とし
て投与することができる。投与量は経口投与の場合、成
人１日当たり約０．Ｏｌ〜３０■／ｋｉｒ、好ましくは
０．１〜４ ｓｇ／ｋｇであるが、患者の症状、年齢、
耐薬性などによって変わりうるちのであることは言うま
でもない。When the antibacterial agent of the present invention is used, for example, as an agent for treating or preventing bacterial infections, compound (1) itself (i.e., free base) or a salt thereof is usually used as an active ingredient together with a pharmaceutically acceptable carrier. In the form of pharmaceutical preparations, it can be mixed with excipients, carriers, diluents, solubilizing agents, and other additives to produce capsules, tablets (including TL-coated tablets and film-coated tablets), granules, and injections. , it can be administered in the form of an infusion, etc. In the case of oral administration, the dosage is approximately 0.0 mg per day for adults. Ol to 30 sg/kir, preferably 0.1 to 4 sg/kg, but depending on the patient's symptoms, age,
Needless to say, this will vary depending on drug resistance and other factors.
実験例１
本発明の有効成分のキャンピロバクター・ピロリ−に対
する試験管内抗菌活性を下記の寒天平板希釈法によって
求めた。Experimental Example 1 The in vitro antibacterial activity of the active ingredient of the present invention against Campylobacter pylori was determined by the agar plate dilution method described below.
５％馬血清を用い、３７℃徽好気性条件下で７２時間培
養した試験菌をプルセラ・ブロスで希釈し、菌数約１０
’個／ｍｌの菌液を作製した。２倍希釈濃度系列の被検
化合物を含有した寒天平板上に、ミクロプランタ−を使
用して希釈菌液をスポット接種し、ｌＯ％二酸二酸化炭
素下℃で２日間培養した後、最小発育阻止濃度（Ｍ Ｉ
Ｃ）を測定した。Using 5% horse serum, the test bacteria were cultured for 72 hours under aerobic conditions at 37°C and diluted with Pulsella broth to obtain a bacterial count of approximately 10.
A bacterial solution was prepared at a concentration of '5 cells/ml. Using a micro planter, the diluted bacterial solution was spot inoculated onto an agar plate containing a 2-fold diluted concentration series of the test compound, and after culturing for 2 days at ℃ under 10% diacid and carbon dioxide, minimal growth inhibition was achieved. Concentration (M I
C) was measured.
その結果を第１表に示す。The results are shown in Table 1.
一以下余白一
第
表
試験化合物
化合物（３）
化合物〈７）
ＭＩＣ（μ ｇ／１ｌ）
３．１３
０．１０
以上の薬理データから、本発明化合物は優れた抗菌作用
を有し、抗菌剤などの医薬として有用である。1 Margin below 1 Table Test Compound Compound (3) Compound <7) MIC (μg/1l) 3.13 0.10 From the above pharmacological data, the compound of the present invention has excellent antibacterial activity and is suitable for use as an antibacterial agent. It is useful as a medicine.
本発明抗菌剤の実施例を以下に示すが、本発明はこれら
実施例に限定されるものではない。Examples of the antibacterial agent of the present invention are shown below, but the present invention is not limited to these Examples.
製剤例
化合物（１） ３０．０■乳に
！ ５０．０■コー
ンスタ、−チ １５．５■微結晶
セルロース ２０．０■タルク
４．０■ステアリン酸マグ
ネシウム ０．５■１２０．０■
化合物（１〉、乳糖、コーンスターチおよび微結晶セル
ロースを練合機にとり混合した後、５％コーンスターチ
糊液を加え造粒し乾燥する。２４メツシユの篩を通し整
粒し、タルクおよびステアリン酸マグネシウムを混合し
、直径７關の杵を用いて１錠１２０■の錠剤とする。Formulation Example Compound (1) 30.0■For milk! 50.0 ■ Corn star, -chi 15.5 ■ Microcrystalline cellulose 20.0 ■ Talc
4.0 ■ Magnesium stearate 0.5 ■ 120.0 ■ Compound (1), lactose, cornstarch and microcrystalline cellulose are mixed in a kneader, then 5% cornstarch paste is added, granulated and dried.24 The mixture is sized through a mesh sieve, mixed with talc and magnesium stearate, and made into 120 square tablets using a 7-inch diameter pestle.
Claims (1)
を活性成分として含有することを特徴とする抗菌剤。 式中、Ｒ＾１は水素、ハロゲン、アルキル、アルコキシ
、アルコキシカルボニル、トリフルオロメチルを、Ｘは
−Ｓ−、−ＳＯ−を、Ｒ＾２はアルキルを、Ｒ＾３は水
素、アルキル、置換していてもよいアラルキル、置換し
ていてもよいヘテロアラルキルを、Ｒ＾４は水素、アル
キルを示す。(1) An antibacterial agent characterized by containing a pyrimidine compound represented by the general formula (numerical formula, chemical formula, table, etc.) or an acid addition salt thereof as an active ingredient. In the formula, R^1 is hydrogen, halogen, alkyl, alkoxy, alkoxycarbonyl, trifluoromethyl, X is -S-, -SO-, R^2 is alkyl, R^3 is hydrogen, alkyl, substituted R^4 represents an optionally substituted aralkyl or an optionally substituted heteroaralkyl, and R^4 represents hydrogen or alkyl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17535789A JPH0338523A (en) | 1989-07-05 | 1989-07-05 | Antimicrobial agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17535789A JPH0338523A (en) | 1989-07-05 | 1989-07-05 | Antimicrobial agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0338523A true JPH0338523A (en) | 1991-02-19 |
Family
ID=15994660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17535789A Pending JPH0338523A (en) | 1989-07-05 | 1989-07-05 | Antimicrobial agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0338523A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294661A (en) * | 2015-07-27 | 2016-02-03 | 西南大学 | 5-fluorouracil benzimidazole compound, preparation method and application thereof |
-
1989
- 1989-07-05 JP JP17535789A patent/JPH0338523A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294661A (en) * | 2015-07-27 | 2016-02-03 | 西南大学 | 5-fluorouracil benzimidazole compound, preparation method and application thereof |
| CN105294661B (en) * | 2015-07-27 | 2017-10-24 | 西南大学 | 5 fluorouracil benzimidazoles compounds and its preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK79599A3 (en) | 8-cyano-1-cyclopropyl-6-fluoro-7-(2-oxa-5,8- -diazabicyclo[4.3.0]non-8-yl)-1,4-dihydro-4-oxo-3-quinolone carboxylic acid, the use thereof and medicaments comprising the same | |
| TW201434467A (en) | Antituberculous therapeutic drugs and kit containing the same | |
| US6242424B1 (en) | Moenomycin and its derivatives for the production of pharmaceuticals, and pharmaceuticals containing moenomycin or its derivatives | |
| US6740667B2 (en) | Antimicrobial agent | |
| JPH0930970A (en) | Antimicrobial agent | |
| JPH06503806A (en) | Pharmaceutical composition containing 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridyl)methylsulfinyl]benzimidazole and anti-Helicobacter agent for treating gastrointestinal diseases | |
| JPH0348680A (en) | Antimicrobial agent | |
| IL99471A (en) | Pharmaceutical compositions for treating helicobacter bacteria infections containing 5-fluoromethoxy-2-(3,4-dimethoxy-2-pyridyl)methylsulphinyl)-1h-benzimidazole and salts thereof in combination with an antimicrobial agent | |
| KR20200026118A (en) | Composition for eradicating helicobacter pylori | |
| JPH0338523A (en) | Antimicrobial agent | |
| CN102120030B (en) | Medicament of ilaprazole chemical structure and application thereof | |
| AU727594B2 (en) | Acyl urea compounds for the treatment of coccidioidomycosis in warm-blooded animals | |
| CA2290549C (en) | Anti-helicobacter pylori pharmaceutical composition | |
| JP2798588B2 (en) | Antibacterial agent | |
| CA1285226C (en) | Compositions containing a 2,4-diamino-pyrimidine and sulphadimidine | |
| JPH03161440A (en) | Antibacterial agent | |
| JP3490146B2 (en) | Anti-Helicobacter pylori agent | |
| JPH11189529A (en) | Anti-helicobacter pylori agent | |
| JPH0352812A (en) | Antimicrobial agent | |
| JP2002265354A (en) | Anti-helicobacter pylori agent composition | |
| US11905259B1 (en) | 2-(benzo[d]oxazol-2-yl)-N′-(4-(dimethylamino)benzoyloxy)acetimidamide as an antimicrobial compound | |
| JP3964476B2 (en) | Peptic ulcer treatment | |
| EA017028B1 (en) | Antibacterial composition | |
| RU2741764C2 (en) | Lysobactin for use in treatment of bovine mastitis | |
| JPH0920668A (en) | Antibacterial agent for helicobacter pylori as slightly aerobic gram-negative bacillus |