JPH0215551B2 - - Google Patents
Info
- Publication number
- JPH0215551B2 JPH0215551B2 JP8845781A JP8845781A JPH0215551B2 JP H0215551 B2 JPH0215551 B2 JP H0215551B2 JP 8845781 A JP8845781 A JP 8845781A JP 8845781 A JP8845781 A JP 8845781A JP H0215551 B2 JPH0215551 B2 JP H0215551B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- lower alkyl
- alkyl group
- oxo
- salt
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- -1 benzoxazepine-7-carboxylic acid Chemical compound 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 1
- 229960001732 pipemidic acid Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
本発明は一般式
（式中、ＺはＯ，ＳまたはNR3を、R1および
R2はそれぞれＨまたは低級アルキル基を、Ｒは
ヒドロキシ基，低級アルキル基，低級アルコキシ
基，アミノ基，低級アルキルアミノ基，ヒドロキ
シ低級アルキル基またはオキソ基で置換されてい
ることもある環状アミノ基を表わす。ｎは０，１
または２である。ここで、R3はＨまたは低級ア
ルキル基を表わす。ただし、Ｚ＝０でｎ＝１のと
き、R1＝Ｈを除く。）で表わされる１，８−環状
置換キノリンカルボン酸誘導体に関するものであ
る。
ここで、低級アルキル基はメチル，エチル，ｎ
−プロピル，イソプロピル等があげられる。環状
アミノ基としては、ピロリジニル，ピペリジニ
ル，モルホリニル，ピペラジニルの如き５，６員
環の基があげられる。これらの環状アミノ基はヒ
ドロキシ基，低級アルキル基，低級アルコキシ
基，アミノ基，低級アルキルアミノ基，ヒドロキ
シ低級アルキル基，オキソ基がその環に置換する
こともあり得る。更に詳しい置換基Ｒの例として
１−ピペラジニル，４−メチル−１−ピペラジニ
ル，１−ピロリジニル等を挙げることができる。
ｎが０のときは（ ）内が存在しないことを意
味する。
また、塩としては塩酸，硫酸，メタンスルホン
酸の如き、無機酸もしくは有機酸との塩あるいは
カルボン酸のナトリウム塩やカリウム塩が具体例
としてあげられる。
次に、本発明の化合物の製造法の例を反応式で
示して説明する。
（式中、Ｚ，R1，R2，ｎ，Ｒは前記に同じ。）
すなわち、化合物（）をジメチルスルホキシ
ド，スルホラン，ジメチルホルムアミド，ヘキサ
メチル燐酸アミド，水の如き極性溶媒中でアミン
類（RH）と室温ないし200℃，好ましくは70〜
150℃で30分間ないし48時間加熱することによつ
て化合物（）が得られる。ＺがNH（R3＝Ｈ）
の場合はこれをアルキル化し、ついで加水分解す
ることによつてR3が低級アルキル基である化合
物が得られる。
本発明の一般式（）で表わされる化合物およ
びその塩は緑膿菌を含むグラム陰性菌およびグラ
ム陽性菌に対して広域な抗菌スペクトルを示し、
医薬品としての使用が期待できる。例えば、医薬
品として使用されているピペミド酸を対照として
試験管内抗菌試験における最小発育阻止濃度を測
定した結果を次表に示したが、優れた抗菌活性を
示す。なお、試験方法は、日本化学療法学会指定
の方法に準じた。
The present invention is based on the general formula (In the formula, Z is O, S or NR 3 , R 1 and
R 2 is H or a lower alkyl group, and R is a cyclic amino group which may be substituted with a hydroxy group, a lower alkyl group, a lower alkoxy group, an amino group, a lower alkylamino group, a hydroxy lower alkyl group, or an oxo group. represents. n is 0,1
Or 2. Here, R 3 represents H or a lower alkyl group. However, when Z=0 and n=1, R 1 =H is excluded. ) This relates to a 1,8-cyclic substituted quinoline carboxylic acid derivative represented by: Here, lower alkyl groups are methyl, ethyl, n
-Propyl, isopropyl, etc. Examples of the cyclic amino group include 5- and 6-membered ring groups such as pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl. The ring of these cyclic amino groups may be substituted with a hydroxy group, lower alkyl group, lower alkoxy group, amino group, lower alkylamino group, hydroxy lower alkyl group, or oxo group. More detailed examples of the substituent R include 1-piperazinyl, 4-methyl-1-piperazinyl, and 1-pyrrolidinyl. When n is 0, it means that the part in parentheses does not exist. Specific examples of the salt include salts with inorganic or organic acids such as hydrochloric acid, sulfuric acid, and methanesulfonic acid, and sodium and potassium salts of carboxylic acids. Next, an example of a method for producing the compound of the present invention will be explained using a reaction formula. (In the formula, Z, R 1 , R 2 , n, and R are the same as above.) That is, the compound () is mixed with amines (RH ) and room temperature to 200℃, preferably 70~
Compound () is obtained by heating at 150°C for 30 minutes to 48 hours. Z is NH (R 3 = H)
In the case of , a compound in which R 3 is a lower alkyl group can be obtained by alkylating it and then hydrolyzing it. The compound represented by the general formula () and its salt of the present invention exhibits a broad antibacterial spectrum against Gram-negative bacteria and Gram-positive bacteria including Pseudomonas aeruginosa,
It is expected to be used as a medicine. For example, the following table shows the results of measuring the minimum inhibitory concentration in an in vitro antibacterial test using pipemidic acid, which is used as a pharmaceutical, as a control, and shows excellent antibacterial activity. The test method was in accordance with the method specified by the Japanese Society of Chemotherapy.
【表】【table】
【表】【table】
Claims (1)
R2はそれぞれＨまたは低級アルキル基を、Ｒは
ヒドロキシ基，低級アルキル基，低級アルコキシ
基，アミノ基，低級アルキルアミノ基，ヒドロキ
シ低級アルキル基またはオキソ基で置換されてい
ることもある環状アミノ基を表わす。ｎは０，１
または２である。ここで、R3はＨまたは低級ア
ルキル基を表わす。ただし、Ｚ＝０でｎ＝１のと
き、R1＝Ｈを除く。）で表わされる化合物および
その塩。 ２ 10−フルオロ−11−（４−メチル−１−ピペ
ラジニル）−８−オキソ−２，３−ジヒドロ−
4H，8H−ピリド［１，２，３−ef］［１，５］
ベンゾオキサゼピン−７−カルボン酸またはその
塩である特許請求の範囲第１項記載の化合物。 ３ ９−フルオロ−１，３−ジメチル−７−オキ
ソ−10−（１−ピロリジニル）−２，３−ジヒドロ
−1H，7H−ピリド［１，２，３−de］キノキサ
リン−６−カルボン酸またはその塩である特許請
求の範囲第１項記載の化合物。 ４ ９−フルオロ−７−オキソ−10−（１−ピロ
リジニル）−２，３−ジヒドロ−7H−ピリド
［１，２，３−de］［１，４］ベンゾチアジン−
６−カルボン酸またはその塩である特許請求の範
囲第１項記載の化合物。[Claims] 1. General formula (In the formula, Z is O, S or NR 3 , R 1 and
R 2 is H or a lower alkyl group, and R is a cyclic amino group which may be substituted with a hydroxy group, a lower alkyl group, a lower alkoxy group, an amino group, a lower alkylamino group, a hydroxy lower alkyl group, or an oxo group. represents. n is 0,1
Or 2. Here, R 3 represents H or a lower alkyl group. However, when Z=0 and n=1, R 1 =H is excluded. ) and its salts. 2 10-Fluoro-11-(4-methyl-1-piperazinyl)-8-oxo-2,3-dihydro-
4H,8H-pyrido[1,2,3-ef][1,5]
The compound according to claim 1, which is benzoxazepine-7-carboxylic acid or a salt thereof. 3 9-fluoro-1,3-dimethyl-7-oxo-10-(1-pyrrolidinyl)-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxylic acid or The compound according to claim 1, which is a salt thereof. 4 9-Fluoro-7-oxo-10-(1-pyrrolidinyl)-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzothiazine-
The compound according to claim 1, which is 6-carboxylic acid or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8845781A JPS57203085A (en) | 1981-06-09 | 1981-06-09 | 1,8-cyclic substituted quinoline derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8845781A JPS57203085A (en) | 1981-06-09 | 1981-06-09 | 1,8-cyclic substituted quinoline derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57203085A JPS57203085A (en) | 1982-12-13 |
| JPH0215551B2 true JPH0215551B2 (en) | 1990-04-12 |
Family
ID=13943316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8845781A Granted JPS57203085A (en) | 1981-06-09 | 1981-06-09 | 1,8-cyclic substituted quinoline derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57203085A (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5976091A (en) * | 1982-10-22 | 1984-04-28 | Otsuka Pharmaceut Co Ltd | Pyrido (1,2,3-de)(1,4)benzothiazine derivative |
| IT1173374B (en) * | 1984-02-24 | 1987-06-24 | Mediolanum Farmaceutici Srl | PYRID-BENZOTHIAZINIC DERIVATIVES WITH HIGH ANTIMICROBIAL ACTIVITY |
| US4571396A (en) * | 1984-04-16 | 1986-02-18 | Warner-Lambert Company | Antibacterial agents |
| DE3543513A1 (en) * | 1985-12-10 | 1987-06-11 | Bayer Ag | ENANTIOMER-PURE 1,8-BRIDGED 4-CHINOLON-3-CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THE MEDICINAL PRODUCTS CONTAINING THEM AND THEIR USE FOR THE PRODUCTION OF MEDICINAL PRODUCTS |
| IT1196429B (en) * | 1986-07-01 | 1988-11-16 | Mediolanum Farmaceutici Srl | PROCESS FOR THE PREPARATION OF PYRID BENZOTIAZINS FOR ANTIBACTERIAL ACTIVITY AND THEIR SALTS WITH SULPHONIC ACIDS |
| IT1222833B (en) * | 1987-10-06 | 1990-09-12 | Mediolanum Farmaceutici Srl | PYROID BENZOTHIAZINIC DERIVATIVES EQUIPPED WITH HIGH ANTIBACTERIAL ACTIVITY AND HIGH TISSUE BIO AVAILABILITY |
| US5175160A (en) * | 1988-08-09 | 1992-12-29 | Daiichi Pharmaceutical Co., Ltd. | Antimicrobial agent for animals |
| CA2081891C (en) * | 1990-05-02 | 1999-03-16 | Daniel T. Chu | Quinolizinone type compounds |
| CN111170941B (en) * | 2018-11-12 | 2023-07-25 | 江西农业大学 | Preparation method of 1-cyclopropyl-6,7-difluoro-8-methoxyfluoroquinolone-3-carboxylate |
-
1981
- 1981-06-09 JP JP8845781A patent/JPS57203085A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57203085A (en) | 1982-12-13 |
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