JPS63238079A - Quinoline based compound, production thereof and anticancer agent containing said compound as active ingredient - Google Patents
Quinoline based compound, production thereof and anticancer agent containing said compound as active ingredientInfo
- Publication number
- JPS63238079A JPS63238079A JP6976687A JP6976687A JPS63238079A JP S63238079 A JPS63238079 A JP S63238079A JP 6976687 A JP6976687 A JP 6976687A JP 6976687 A JP6976687 A JP 6976687A JP S63238079 A JPS63238079 A JP S63238079A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- anticancer agent
- active ingredient
- agent containing
- production
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 239000004480 active ingredient Substances 0.000 title claims description 3
- 239000000126 substance Substances 0.000 claims description 6
- -1 quinoline compound Chemical class 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- JBEUZJVHYAAMNF-UHFFFAOYSA-N n-(4-amino-3-methoxyphenyl)methanesulfonamide Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1N JBEUZJVHYAAMNF-UHFFFAOYSA-N 0.000 claims description 2
- 238000010992 reflux Methods 0.000 abstract description 3
- OFRMASLPWOMYHN-UHFFFAOYSA-N 1-[3-methoxy-4-[[6-(2-propan-2-ylsulfonylanilino)-7H-purin-2-yl]amino]phenyl]piperidin-4-ol Chemical compound COc1cc(ccc1Nc1nc(Nc2ccccc2S(=O)(=O)C(C)C)c2[nH]cnc2n1)N1CCC(O)CC1 OFRMASLPWOMYHN-UHFFFAOYSA-N 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000003756 stirring Methods 0.000 abstract 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 5
- 229960001220 amsacrine Drugs 0.000 description 5
- 230000001093 anti-cancer Effects 0.000 description 5
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 2
- 229940093475 2-ethoxyethanol Drugs 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical group C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- XDNADZYPWVQFRI-UHFFFAOYSA-N [1]benzofuro[2,3-h]quinoline Chemical class C1=CC=NC2=C3C4=CC=CC=C4OC3=CC=C21 XDNADZYPWVQFRI-UHFFFAOYSA-N 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、新規なキノリン系化合物(さらに詳しくはベ
ンゾフラノキノリン系化合物およびベンゾチェノキノリ
ン系化合物)その製造法、ならびにそれらの化合物を有
効成分とする抗癌剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing novel quinoline compounds (more specifically, benzofuranoquinoline compounds and benzochenoquinoline compounds), and methods for making these compounds effective. The present invention relates to an anticancer agent as a component.
1972年に、ジー・ジエイ・アトウェル(G。 In 1972, G.
J、Atwell)、ピー・エフ・カイン(B、F、C
a1n)、アール・エフ・シールx (RoN、5ea
lye)らは、アクリジンの9位にアルキルアミノ基が
存在するアクリジン誘導体を合成し、それらの中のいく
つかに抗白血病作用があることを見出した。〔(J。J, Atwell), P.F. Cain (B, F, C
a1n), RF Seal x (RoN, 5ea
synthesized acridine derivatives in which an alkylamino group was present at the 9-position of acridine, and found that some of them had anti-leukemic effects. [(J.
Med、Chem、、 Vol 15 、 611
、 (1972))。Med, Chem,, Vol 15, 611
, (1972)).
さらにカインらは、アク、リジン誘導体の抗癌作用と9
位のアルキルアミノ基の種類との関係を検討した結果、
N−(4−(9−アクリジニルアミノ)−3−メトキシ
フェニルコメタンスルホンアミド(アムサクリン)が最
も有効であることを見出した。〔(B、F、 Ca1n
、 RlN、5eelye、 G、J。Furthermore, Cain et al.
As a result of examining the relationship with the type of alkylamino group in position,
We found that N-(4-(9-acridinylamino)-3-methoxyphenylcomethanesulfonamide (Amsacrine) was the most effective. [(B, F, Ca1n
, RlN, 5eelye, G,J.
Atwell;J、 !、Ied、 Chem、
Vol 17 、 9 2 2 (1974):B
、F、Ca1n、 G、J、 ^twell、
W、A、Denny; J、Med。Atwell;J,! ,Ied,Chem,
Vol 17, 9 2 2 (1974):B
,F,Ca1n,G,J,^twell,
W, A, Denny; J, Med.
Chem、 Vol 1 8 、 1 1 1 0
(1975)) 。Chem, Vol 1 8, 1 1 1 0
(1975)).
さらにCa1n等はアムサクリンの分子のアクリジン骨
格を構成している2つのベンゼン環の1つを還元したも
の、すなわち、テトラヒドロアムサクリンは抗癌活性が
低下するという報告をしている。((B、F、Ca1n
、 RoN、5eelye、 G、J、 Atwe
ll;JoMed、Chem、 Vol 17 、9
22 (1974):]。Furthermore, Caln et al. have reported that the anticancer activity of amsacrine, which is obtained by reducing one of the two benzene rings constituting the acridine skeleton of the amsacrine molecule, that is, tetrahydroamsacrine, is reduced. ((B, F, Ca1n
, RoN, 5eelye, G, J, Atwe.
ll; JoMed, Chem, Vol 17, 9
22 (1974): ].
そこで本発明者らは、前記アムサクリン分子のアクリジ
ン骨格を構成している1つのベンゼン環を、インデン環
、インドール環、及びジヒドロナフタレン環に変換した
場合に於いて、それらの化合物の抗癌活性を検討し、既
に特許出願している。Therefore, the present inventors investigated the anticancer activity of these compounds by converting one benzene ring constituting the acridine skeleton of the amsacrine molecule into an indene ring, an indole ring, and a dihydronaphthalene ring. We are considering this and have already applied for a patent.
すなわち、アムサクリン分子のアクリジン骨格の代りに
インデノキノリンをもつ新規な誘導体〔N−(4−(1
1H−インデノ [:3,2−bE キノリン−10−
イル]−3−メトキシフェニル)メタンスルホンアミド
を製造し、このものが強い抗癌作用を有することを見出
し、特許出願をしている。(特願昭61−246776
>
今回本発明者等は、さらに、アムサクリンのアクリジン
骨格の代りに、ベンゾフロキノリン又はベンゾチェノキ
ノリンをもつ新規な誘導体に着目し、それらがそれぞれ
強い抗癌活性を有することを知見し、本発明に到達した
。That is, a novel derivative [N-(4-(1
1H-indeno [:3,2-bE quinoline-10-
yl]-3-methoxyphenyl)methanesulfonamide, and found that this product has a strong anticancer effect, and has filed a patent application. (Patent application No. 61-246776
> This time, the present inventors further focused on new derivatives having benzofloquinoline or benzochenoquinoline in place of the acridine skeleton of amsacrine, and found that each of them has strong anticancer activity. invention has been achieved.
すなわち、本発明は
一般式:・
で示される化合物と、
で示される化合物、すなわち、N−(4−アミノ−3−
、’トキシフェニル)メタンスルフォンアミドとを反応
させて、
一般式
で示される化合物を得ることを特徴とする、ベンゾフロ
キノリン系又はベンゾチェノキノリン系化合物の製造方
法に関し、さらに別の態様として、本発明は一般式(1
)で示される化合物それ自体及びそれを有効成分とする
抗癌剤に関する。That is, the present invention provides a compound represented by the general formula:
, 'toxyphenyl)methanesulfonamide to obtain a compound represented by the general formula, as yet another embodiment, a method for producing a benzofloquinoline or benzochenoquinoline compound, The present invention is based on the general formula (1
) The present invention relates to the compound itself and an anticancer agent containing the compound as an active ingredient.
以下、本発明をさらに実施例により具体的に説明する。Hereinafter, the present invention will be explained in more detail with reference to Examples.
実施例I N−(4−((ベンゾフロ[3,,2−b
〕キノリン−11イル)アミノクー
3−メトキシフェニル)メタンスルホ
ンアミド (化合物4)
120−130℃
■
(B)
(C)
C2H3OCI12C1(20H
2,5時間加熱
NH302CH,・・・・・・(4)
原料(A)より、(B)を経て(C)を得る工程は、サ
ンダー、ビートの文献に従った。〔S。Example I N-(4-((Benzofuro[3,,2-b
] Quinolin-11yl) aminocou-3-methoxyphenyl) methanesulfonamide (Compound 4) 120-130°C ■ (B) (C) C2H3OCI12C1 (20H heated for 2.5 hours in NH302CH,... (4) Raw material The process of obtaining (C) from (A) via (B) was according to the literature by Sander and Beat. [S.
5under、 N、P、Peet; J、)Iete
rocyclic Chem、、 15 。5under, N, P, Peet; J,) Iete
cyclic Chem,, 15.
そのようにして得られた化合物(C)587mgおよび
N−(4−アミノ−3−メトキシフェニル)メタンスル
ホンアミド500 mgを2−エトキシエタノール5m
j2に混合し、この混合物を2.5時間加熱還流下に攪
拌した。冷浸、10%水酸化カリウム水溶液でアルカリ
性としたのち、クロロホルムで抽出、クロロホルム層を
水洗、乾燥後、溶媒を留去した。残渣をアルミナカラム
クロマトで精製すると、480 mg (収率48%)
の目的物(化合物4)が得られた。587 mg of the compound (C) thus obtained and 500 mg of N-(4-amino-3-methoxyphenyl)methanesulfonamide were added to 5 m of 2-ethoxyethanol.
The mixture was stirred under heating and reflux for 2.5 hours. After cooling and making alkaline with a 10% aqueous potassium hydroxide solution, extraction was performed with chloroform. The chloroform layer was washed with water, dried, and the solvent was distilled off. Purification of the residue with alumina column chromatography yielded 480 mg (yield 48%)
The desired product (compound 4) was obtained.
m、p、 230℃。m, p, 230℃.
’ H−N M R(CDC*3 +DMSロー
ds)。'H-NMR (CDC*3 + DMS load ds).
δ:3.00(3H,S)、 3.83(3H,S)、
6.74−7.24(3)i。δ: 3.00 (3H, S), 3.83 (3H, S),
6.74-7.24(3)i.
m)、 7.24−8.00(6H,m)、 8.12
−8.58(3H,m)。m), 7.24-8.00 (6H, m), 8.12
-8.58 (3H, m).
9.34−9.62(1)1. br) 。9.34-9.62 (1) 1. br) .
MSm/jl!:433 (M”) 。MSm/jl! :433 (M”).
実施例2 N−(4−[(ベンゾチェノ〔3,2−6
〕キノリン−11−イル〉アミノ〕−3−メトキシフェ
ニル)メタンスル
ホンアミド ・・・・・・(化合物5)■
120℃1.5時間加熱
■
(ロ)
NH5O2CH3・・・・・・(5〕
原料(P)より、(Q)を経て(R)を得る工程は、ゲ
ルリッツァ一、ウニバーの文献に従った。Example 2 N-(4-[(benzocheno[3,2-6
[Quinoline-11-yl>amino]-3-methoxyphenyl) methanesulfonamide......(Compound 5) ■ Heating at 120°C for 1.5 hours■ (B) NH5O2CH3... (5) The process of obtaining (R) from raw material (P) via (Q) was in accordance with the literature by Gerlitzer and Univer.
[K、 G′0rlitzer、 J、Weber;
Arch Pharm、314 。[K, G'0rlitzer, J, Weber;
Arch Pharm, 314.
76、(1980)]
そのようにして得られた11−クロロベンゾチェノ[:
3.2−b)キノリン(化合物R)1.0g及びN−(
4−アミノ−3−メトキシフェニル)メタンスルホンア
ミド0.8gを2−エトキシエタノール15m1に溶か
し、この混合物を15時間加熱還流下に攪拌した。冷浸
、結晶を濾取し、10%水酸化カリウム溶液に溶かし、
クロロホルムで抽出した。クロロホルム層は水洗乾燥後
溶媒を留去し、残渣をアセトンより再結晶した。76, (1980)] 11-chlorobenzocheno[:
3.2-b) 1.0 g of quinoline (compound R) and N-(
0.8 g of 4-amino-3-methoxyphenyl)methanesulfonamide was dissolved in 15 ml of 2-ethoxyethanol, and the mixture was stirred under heating under reflux for 15 hours. Cooling, filter the crystals, dissolve in 10% potassium hydroxide solution,
Extracted with chloroform. The chloroform layer was washed with water and dried, the solvent was distilled off, and the residue was recrystallized from acetone.
0.8g(収率48%)のく化合物5)を得る。0.8 g (yield 48%) of compound 5) is obtained.
m、p、 265−266.5 ℃(分解)。m, p, 265-266.5°C (decomposed).
元素分析値、 C,61,42、H,4J5 ; N、
9.28゜’ H−N M R(DMSO−d、)δ
;3.13(3H,S)、 3.68(31(、S)、
6.87−8.82(IIH,m)、 8.91−9
.21(IH,br)、 9.80−10.08(lt
l、 br)。Elemental analysis value, C, 61, 42, H, 4J5; N,
9.28゜'H-NMR(DMSO-d,)δ
;3.13(3H,S), 3.68(31(,S),
6.87-8.82 (IIH, m), 8.91-9
.. 21 (IH, br), 9.80-10.08 (lt
l, br).
Msm/1 :449 (M”) 。Msm/1:449 (M”).
製剤例1(注射、点滴剤)
前記化合物(4)及び(5)の120 mgを含有する
ように10%塩酸0.36+++j!を加えて、バイア
ルに無菌的に分配し、密封して保存した。Formulation Example 1 (injection, infusion) 10% hydrochloric acid 0.36+++j! containing 120 mg of the compounds (4) and (5). and aseptically dispensed into vials, sealed and stored.
使用直後に、0.85%生理的食塩水19.6+y+1
を添加、静脈内注射剤とした。Immediately after use, 0.85% physiological saline 19.6+y+1
was added to form an intravenous injection.
1日、20mj!を症状に応じて静脈内注射又は点滴で
投与した。20mj a day! was administered by intravenous injection or drip depending on the symptoms.
試験例1 抗腫瘍試験
1) K B−細胞増殖抑制作用
癌化細胞腫のKB−細胞をin vitroの浮遊培養
の系に移し、前記化合物(4)及び(5)の薬効を、同
化合物を夫々添加しない場合を対照として比較した。Test Example 1 Antitumor Test 1) KB-cell proliferation inhibitory effect KB-cells of carcinomatoma were transferred to an in vitro suspension culture system, and the medicinal effects of the compounds (4) and (5) were evaluated by A comparison was made with the case where each was not added as a control.
実験系
細 胞:KB細胞(derived from a
humanepidermoid carcinoma
of themouth)
培 地:Bagles minimal essen
tial medi−um(MEM)−10% cal
f serum培 養:37℃、炭酸ガスインキュ
ベーター(5%CD□)
実験方法:day OKB細胞を2X10’/n+I
1mediumに希釈。3mj2を
60 +nm Plastic dishに植える。2
dishes per
dose 1evel
day l Drugをfinal 濃度100、
30.10.3.1 μg/m1になる様に加える。Experimental cells: KB cells (derived from a
humanepidermoid carcinoma
of the mouth) Medium: Bagles minimal essen
tial medium (MEM)-10% cal
f Serum culture: 37℃, carbon dioxide gas incubator (5% CD□) Experimental method: day OKB cells 2X10'/n+I
Dilute to 1 medium. Plant 3mj2 in a 60+nm plastic dish. 2
dishes per dose 1 level day l Drug final concentration 100,
30.10.3. Add so that it becomes 1 μg/ml.
day 4 細胞をdish面よりトリプシンを用
いはがし、細胞
数をコールタ−カウンタ
ーで計測する。Day 4 Peel the cells from the dish surface using trypsin, and count the number of cells using a Coulter counter.
判定基準
NCI (USA)の規定を準用し、対象に比較し、実
質50−%のgrowth 1nbition を示
す濃度(EDso) を求める。このEDs。が合成
物 4μg7mfl以下
天然物 20μg/m1以下
である物質を、有効物質とする。Judgment Criteria By applying the provisions of the NCI (USA), the concentration (EDso) that shows substantially 50% growth is determined by comparison with the control. This EDs. A substance in which the amount is 4 μg/ml or less for a synthetic product and 20 μg/ml or less for a natural product is considered to be an effective substance.
尚、KB−細胞増殖抑制効果は、生存細胞数をコールタ
−カウンターで求め、対照(化合物(4)及び(5))
を加えないもの)と比較して50%増殖抑制を示す薬物
濃度を求め、ED、。とじた。In addition, the KB cell proliferation inhibitory effect was determined by determining the number of viable cells using a Coulter counter, and comparing the control (compounds (4) and (5)) with
Determine the drug concentration that shows 50% growth inhibition compared to that without addition of ED. Closed.
結果を以下に示す。The results are shown below.
抗癌試験結果
(1) K B−細胞増殖抑制効果
P−388担癌マウスをin vivoの系において、
前記各化合物の薬効を、同化合物を添加しない場合を対
象として比較した。Anticancer test results (1) KB-cell proliferation inhibitory effect P-388 tumor-bearing mice were tested in an in vivo system.
The medicinal efficacy of each of the above compounds was compared with the case where the same compound was not added.
実験系
動 物:CDF、?ウス(6mice/group
)腫 瘍:P388
移植細胞数: l Q” cells/mouse移植
部位 :i、p。Experimental animal: CDF, ? 6mice/group
) Tumor: P388 Number of transplanted cells: l Q” cells/mouse Transplant site: i, p.
薬剤投与臼:day 1.5、又はdayl〜9薬剤投
与量:day 1.5の場合はLDso又は400mg
/ kg / dayを最高とし、day1〜9の場
合はMLD、。又は200
mg / kg / dayを最高とし、day1〜9
の場合は’A L D s o又は200mg / k
g / dayを最高とし、その%、スの3dose
1evels 。Drug administration mortar: day 1.5, or dayl~9 Drug dosage: LDso or 400mg in case of day 1.5
/ kg / day as the highest, and MLD for days 1 to 9. Or 200 mg/kg/day as the maximum, days 1 to 9
For 'ALDso or 200mg/k
g/day as the highest, its %, 3dose of
1 level.
判定基準
無処置群の生存日数に対する投与群の生存日数の比(T
/C%)が、合成物では120%、天然物では130%
以上の場合、有効(P)とする。無処置群の生存日数は
、約10日(median survivaltime
) が通例。尚、T/C0%と記載されている場合は
、day 5までに3匹以上のマウスが毒性のために
死亡したことを示す。Judgment Criteria Ratio of survival days of treated group to survival days of untreated group (T
/C%) is 120% for synthetic products and 130% for natural products.
In the above cases, it is considered valid (P). The survival time of the untreated group was approximately 10 days (median survival time).
) is customary. In addition, when T/C0% is described, it indicates that 3 or more mice died by day 5 due to toxicity.
Claims (3)
ホンアミドとを反応させて、 一般式 ▲数式、化学式、表等があります▼・・・・・・(1) (ただし、XはOまたはSを表わす) で示される化合物を得ることを特徴とする、キノリン系
化合物の製造方法。(2) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(2) (However, X represents O or S) A compound represented by and N-(4-amino-3 -Methoxyphenyl) methanesulfonamide to form a compound represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(1) (However, X represents O or S) A method for producing a quinoline compound, the method comprising: obtaining a quinoline compound;
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6976687A JPS63238079A (en) | 1987-03-24 | 1987-03-24 | Quinoline based compound, production thereof and anticancer agent containing said compound as active ingredient |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6976687A JPS63238079A (en) | 1987-03-24 | 1987-03-24 | Quinoline based compound, production thereof and anticancer agent containing said compound as active ingredient |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63238079A true JPS63238079A (en) | 1988-10-04 |
Family
ID=13412247
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP6976687A Pending JPS63238079A (en) | 1987-03-24 | 1987-03-24 | Quinoline based compound, production thereof and anticancer agent containing said compound as active ingredient |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63238079A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5217961A (en) * | 1988-12-27 | 1993-06-08 | Mect Corporation | Condensed quinoline system N-glycosides |
US7354927B2 (en) | 2004-09-07 | 2008-04-08 | Wyeth | 6H-[1]benzopyrano[4,3-b]quinolines and their use as estrogenic agents |
-
1987
- 1987-03-24 JP JP6976687A patent/JPS63238079A/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5217961A (en) * | 1988-12-27 | 1993-06-08 | Mect Corporation | Condensed quinoline system N-glycosides |
US7354927B2 (en) | 2004-09-07 | 2008-04-08 | Wyeth | 6H-[1]benzopyrano[4,3-b]quinolines and their use as estrogenic agents |
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