JPS6391319A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPS6391319A JPS6391319A JP61236300A JP23630086A JPS6391319A JP S6391319 A JPS6391319 A JP S6391319A JP 61236300 A JP61236300 A JP 61236300A JP 23630086 A JP23630086 A JP 23630086A JP S6391319 A JPS6391319 A JP S6391319A
- Authority
- JP
- Japan
- Prior art keywords
- organic solvent
- methanol
- formula
- eluted
- chromatography
- 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.)
- Granted
Links
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 7
- -1 triterpene compound Chemical class 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 48
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 32
- 150000001875 compounds Chemical class 0.000 abstract description 19
- 239000000284 extract Substances 0.000 abstract description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 12
- 239000000741 silica gel Substances 0.000 abstract description 12
- 229910002027 silica gel Inorganic materials 0.000 abstract description 12
- 239000003960 organic solvent Substances 0.000 abstract description 11
- 239000003495 polar organic solvent Substances 0.000 abstract description 9
- 239000003463 adsorbent Substances 0.000 abstract description 8
- 230000007935 neutral effect Effects 0.000 abstract description 7
- 239000000287 crude extract Substances 0.000 abstract description 4
- 241001474374 Blennius Species 0.000 abstract description 3
- 241000206572 Rhodophyta Species 0.000 abstract description 2
- 238000005377 adsorption chromatography Methods 0.000 abstract description 2
- 238000004587 chromatography analysis Methods 0.000 abstract description 2
- 238000001640 fractional crystallisation Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 238000004810 partition chromatography Methods 0.000 abstract description 2
- 150000003648 triterpenes Chemical class 0.000 abstract description 2
- 241000978095 Laurencia obtusa Species 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 230000009102 absorption Effects 0.000 description 18
- 238000010521 absorption reaction Methods 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229910021532 Calcite Inorganic materials 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 2
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- IFHPYSVGNHWKDY-UHFFFAOYSA-N (+)-Thyrsiferol Natural products O1C(C(C)(O)C)CCC1(C)C(O)CCC(C)(O)C1OC2(C)CCC(C3(C)OC(C)(C)C(Br)CC3)OC2CC1 IFHPYSVGNHWKDY-UHFFFAOYSA-N 0.000 description 1
- IFHPYSVGNHWKDY-JXHBSGSUSA-N (1s,4s)-4-[(2r,4as,6r,8ar)-2-[(2s,5r)-5-bromo-2,6,6-trimethyloxan-2-yl]-4a-methyl-3,4,6,7,8,8a-hexahydro-2h-pyrano[3,2-b]pyran-6-yl]-1-[(2r,5r)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]pentane-1,4-diol Chemical compound O1[C@@H](C(C)(O)C)CC[C@]1(C)[C@@H](O)CC[C@](C)(O)[C@@H]1O[C@@]2(C)CC[C@H]([C@@]3(C)OC(C)(C)[C@H](Br)CC3)O[C@@H]2CC1 IFHPYSVGNHWKDY-JXHBSGSUSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 241001303909 Lensia Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 239000012670 alkaline solution Substances 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
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940072049 amyl acetate Drugs 0.000 description 1
- PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000003323 beak Anatomy 0.000 description 1
- 239000002775 capsule Substances 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
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- JPQFUHCOKXIWBB-ZCRGAIPPSA-N isoobtusol Natural products CC1(C)[C@@H](Br)[C@@H](O)CC(=C)[C@@]11C[C@H](Cl)[C@@](C)(Br)CC1 JPQFUHCOKXIWBB-ZCRGAIPPSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- JPQFUHCOKXIWBB-FWZIUSJTSA-N obtusol Chemical compound CC1(C)[C@H](Br)[C@H](O)CC(=C)[C@]11C[C@@H](Cl)[C@](C)(Br)CC1 JPQFUHCOKXIWBB-FWZIUSJTSA-N 0.000 description 1
- MJYXNLJVQSSJFM-UHFFFAOYSA-N obtusol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(CO)CCC5(C)CCC(C)C(C)C5C4=CCC3C21C MJYXNLJVQSSJFM-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- KIRZKILDCHMWNV-UHFFFAOYSA-N thyrsiferol Natural products CC(C)(O)C1CCC(C)(C1)C(O)CCC(C)(O)C2CCC3OC(CCC3(C)O2)C4(C)CCC(Br)C(C)(C)O4 KIRZKILDCHMWNV-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (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、新規なトリテルペン系化合物を有効成分とす
る抗腫瘍剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to an antitumor agent containing a novel triterpene compound as an active ingredient.
従来技術
マギレソゾは、学名をローレンシア・オプツサ（Ｌ ａ
ｕｒｅｎｃｉａ ｏｂｔｕｓａ ）という紅藻類に属す
る海藻である。The scientific name of the conventional technology Magiresozo is Laurentia optusa (L a
It is a seaweed that belongs to the red algae family (Urencia obtusa).
マギレソゾの成分の薬理効果については、あまり知られ
ておらず、現在までに、該海藻の一部の成分について、
抗菌作用を有する化合物、抗ウィルス作用を有する化合
物、抗腫瘍活性を有する化合物等が小数単離されている
。セスキテルペン系化合物であるオブツソール（ｏｂｔ
ｕｓｏｌ ） 、イソオブッソール（ｉｓｏ −ｏｂｔ
ｕｓｏｌ ） 、イソオブッソール・アセテート（１ｓ
ｏｏｂｔｕｓｏｌ ａｃｅｔａｔｅ）が抗腫瘍活性を有
する化合物として知られている［Ａ、Ｇ。Not much is known about the pharmacological effects of the ingredients in Magiresozo.
A small number of compounds having antibacterial activity, antiviral activity, antitumor activity, etc. have been isolated. Obtusol (obt) is a sesquiterpene compound.
usol), isoobassol (iso-obt)
usol), isobussol acetate (1s
oobtusol acetate) is known as a compound with antitumor activity [A, G.
ゴンザレスら、プランタメゾイカ（Ｐ Ｉａｎｔａｍｅ
ｄｉａ ）第４４巻４５頁（１９８２年）参照］。これ
らの化合物は、抗腫瘍活性が低く、実用性に乏しかった
。Gonzalez et al., Planta mezoica (P Iantame)
dia), Vol. 44, p. 45 (1982)]. These compounds had low antitumor activity and were of little practical use.
また、分子内に炭素原子のみからなる脂環式環構造を含
有しないトリテルペン系化合物は、スクアレン以外余り
知られていない。かかるトリテルペン系化合物として、
マギレソゾと同族の海藻〇−レンシア・シルシフエラ（
Ｌ ０ｒｅｎＣｉａｌｌｌ ｔｈＶｒｓｉｔｅｒａ）
から単離されたシルシフエロール（ｔｈｙｒｓｉｆｅｒ
ｏｌ ）及びその１８位の一〇Ｈ基がアセトキシル基で
置換されたシルシフエロールのアセチル誘導体であるシ
ルシフエリルアセテートが知られていル［７ラント（Ｊ
、 Ｗ、 Ｂｌｕｎｔ）ら、テトラヘドロンレターズ（
Ｔ ｅｔｒａｈｅｄｒｏｎ Ｌ ｅｔｔｅｒｓ＞ ６
９〜７２頁（１９７８）参照］、シかしながら、前記文
献によれば、シルシフエロール及びその前記アセテート
は、生物学的に不活性であるとされており、殊に抗腫瘍
活性については全く言及されていない。Further, other than squalene, there are not many triterpene compounds that do not contain an alicyclic ring structure consisting only of carbon atoms in the molecule. As such triterpene compounds,
Seaweed related to Magiresozo 〇 - Lensia circifuela (
L0renCialll thVrsitera)
thyrsiferol isolated from
ol ) and silcipheryl acetate, which is an acetyl derivative of silciferol in which the 10H group at the 18th position is substituted with an acetoxyl group, are known.
, W. Blunt) et al., Tetrahedron Letters (
T etrahedron L etters> 6
However, according to the above-mentioned literature, silciferol and its acetate are said to be biologically inactive, especially regarding antitumor activity. Not mentioned at all.
本発明者らは、既にマギレソゾより分離したシルシフェ
ロール誘導体が抗腫瘍として有用であることを開示した
（特１４昭６１−１５２６２６号公報及び６１−１５２
６８７号公報参照）。The present inventors have already disclosed that siluciferol derivatives isolated from Magiresozo are useful as antitumor agents (Japanese Patent Application Publication No. 14-152-626 and No. 61-152).
(See Publication No. 687).
発明の目的
本発明者らは、更にマギレソゾより有用な生理活性の高
い物質を得ることを目的に鋭意研究した結果、マギレソ
ゾを親水性有機溶剤で抽出処理し、シリカゲル等の活性
吸着剤に吸着させ、ベンゼン等の非極性溶剤で溶出処理
し該操作で溶出される成分を除き、次いでメタノール等
の極性溶剤で溶出することにより得られる中性抽出物か
ら顕著な抗腫瘍活性を有する新規なトリテルペン系化合
物を単離し本発明に到達した。Purpose of the Invention As a result of intensive research aimed at obtaining a substance with higher physiological activity that is more useful than Magiresozo, the present inventors extracted Magiresozo with a hydrophilic organic solvent and adsorbed it onto an active adsorbent such as silica gel. , a novel triterpene type with remarkable antitumor activity is obtained from a neutral extract obtained by elution treatment with a non-polar solvent such as benzene, removing the components eluted in this operation, and then elution with a polar solvent such as methanol. The compound was isolated and the present invention was achieved.
発明の構成及び効果
すなわち、本発明は下記式［ＩＩ
で表わされるトリテルペン系化合物を有効成分とする抗
腫瘍剤である。DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is an antitumor agent containing a triterpene compound represented by the following formula [II] as an active ingredient.
ＣＨ２
鴇
ここで、Ｒは−Ｃ−ＣＨ２−ＣＨ２−又はｌｈ
−Ｃ＝ｃ−ＣＨ２−であり、夫々、エラ／（ｅｘａ）又
はエンド（ｅｎｄｏ）の二重結合を有する異性体構造で
ある。CH2 Here, R is -C-CH2-CH2- or lh-C=c-CH2-, which is an isomeric structure having an exa or endo double bond, respectively.
本発明の前記式（Ｉ）で示され、エンド二重結合を有す
る化合物の理化学的特性は以下の通りである。The physicochemical properties of the compound of the present invention represented by the above formula (I) and having an end double bond are as follows.
理化学的特性
・融点： ６４．５〜６６℃
・マススペクトル：親イオンビーク
５７０／ ５７２ （ダブレット）
・分子式： Ｃ３０１−ｋｌ Ｏ５３ｒ（高分解マスス
ペクトル）
・比旋光度：［α］０＝＋７，８゜
・溶解性：水に難溶、メタノール、エタノール。Physical and chemical properties - Melting point: 64.5-66°C - Mass spectrum: Parent ion peak 570/572 (doublet) - Molecular formula: C301-kl O53r (high resolution mass spectrum) - Specific rotation: [α]0=+7, 8゜・Solubility: Slightly soluble in water, methanol, ethanol.
ブタノール、アセトン、クロロホルム。Butanol, acetone, chloroform.
エチルエーテル、ベンゼン、トルエン
客の通常の有機溶剤に可溶
・赤外吸収スペクトル：
３４４０、３３２０．１６４０． ９００ｍ−’に特性
吸収・核磁気共鳴（プロトン、ＣＤ（Ｊ３）δ値：１１
Ｃ１りｎ １９１ １９７ １ｄ
Ｏ−１，６２、１，ｅｓｐｐｍｍ夫々メチルのプロトン
の特性吸収、３．０８〜５．１３１）ｌ）ＩＩにメタン
のプロトンの特性吸収、 ４．８９． ５．０４ｐＤ
ｌｌにメチリデン（ＣＨ２＝）のプロトンの特性吸収、
・核磁気共鳴（Ｃ−１３，ＣＤＣＩｇ ＞δ値：１７．
７．１９．５．２０，１．２３，３．２３，７．２５．
７．３１，０゜１）Ｅｌｍに夫々メチルの炭素原子の特
性吸収（カルチット） 、２１．７．２２，１．２２．
９．２Ｂ、１．２８．３゜２９．６．３０．０．３６．
１．３７，１．３８．６ｐｐｍに夫々メチレンの炭素原
子の特性吸収（トリブレット）。Soluble in common organic solvents of ethyl ether, benzene, and toluene; infrared absorption spectra: 3440, 3320.1640. Characteristic absorption/nuclear magnetic resonance (proton, CD (J3) δ value: 11 at 900 m-'
C1 Rin 191 197 1d
Characteristic absorption of protons of methyl in O-1,62,1,esppmm, respectively, 3.08 to 5.131) l) Characteristic absorption of protons of methane in II, 4.89. 5.04pD
Characteristic absorption of protons of methylidene (CH2=) in ll, Nuclear magnetic resonance (C-13, CDCIg > δ value: 17.
7.19.5.20, 1.23, 3.23, 7.25.
7.31,0゜1) Characteristic absorption of carbon atoms of methyl (calcite) in Elm, 21.7.22, 1.22.
9.2B, 1.28.3°29.6.30.0.36.
Characteristic absorptions (triblet) of methylene carbon atoms at 1.37 and 1.38.6 ppm, respectively.
１１０．４ｐｐＨｌにメチリデンの炭素原子の特性吸収
（トリブレット） 、 ５９．０．７２．５．７８，２
．７８，８゜８６．７． １２４．７ｐ’１）Ｉｎに夫
々メチンの炭素原子の特性吸収（ダブレット） 、 ７
３，１．７４，４．７４，６゜７５．０． １３１．６
． １５１，１． ＣＤＩＩＩに夫々水素原子と結合し
ていない炭素原子の特性吸収（シングレット）
又、本発明の前記式（Ｉ）で表わされるエンド二重結合
を有する化合物の理化学特性は以下の通りである。Characteristic absorption (triblet) of the carbon atom of methylidene at 110.4 ppHl, 59.0.72.5.78,2
．． 78,8°86.7. 124.7p'1) Characteristic absorption (doublet) of each methine carbon atom in In, 7
3, 1.74, 4.74, 6°75.0. 131.6
．． 151,1. Characteristic absorption (singlet) of a carbon atom not bonded to a hydrogen atom in CDIII The physicochemical properties of the compound having an end double bond represented by the formula (I) of the present invention are as follows.
理化学特性
・融点：６９〜７０℃
・マススペクトル：親イオンビーク
５７０／ ５７２ （ダブレット）
・分子式： Ｃ５０Ｉ−ｂｌ Ｏｓ ３ｒ（高分解マス
スペクトル）
・比旋光度：［α］０＝＋６．４゜
・溶解性：水に難溶、メタノール、エタノール。Physical and chemical properties - Melting point: 69-70°C - Mass spectrum: Parent ion beak 570/572 (doublet) - Molecular formula: C50I-bl Os 3r (high resolution mass spectrum) - Specific optical rotation: [α] 0 = +6.4°・Solubility: Slightly soluble in water, methanol, ethanol.
ブタノール、アセトン、クロロホルム、エチルエーテル
、ベンゼン、トルエン等の通常の有機溶剤に可溶
・赤外吸収スペクトル：
３５５０、３５００．１１１０．１０６０ｃａ＋−’に
特性吸収・核磁気共鳴くプロトン、ＣＤＣｊｘ）δ値：
１．１９ 、 １．２０ 、 １．２２ 、 １．２７
、 １．４０ 。Soluble in common organic solvents such as butanol, acetone, chloroform, ethyl ether, benzene, toluene, etc. Infrared absorption spectrum: Characteristic absorption at 3550, 3500.1110.1060ca+-' Nuclear magnetic resonance proton, CDCjx) δ value :
1.19, 1.20, 1.22, 1.27
, 1.40.
１．６３ 、 １．６６ 、 １．６９１１１）ｆｆｌ
に夫々メチルのプロトンの特性吸収、 ３．０７〜４
，２６ ｐｐＩｌｌにメチンのプロトンの特性吸収５，
１３． ５．５：Ｌｐｐｍに夫々炭素、炭素二重結合に
結合しているプロトンの特性吸収。1.63, 1.66, 1.69111) ffl
Characteristic absorption of methyl protons, respectively, 3.07~4
, 26 Characteristic absorption of methine protons in ppIll 5,
13. 5.5: Characteristic absorption of protons bonded to carbon and carbon double bonds in Lppm, respectively.
・核磁気共鳴（Ｃ−１３，０ＤＣ第３）δ値：１２．８
，１７．７，２０．１，２０．３，２３．４，２３．７
，２５．７゜３１．１ ｐｐＩｌｌに夫々にメチルの炭
素原子の特性吸収（カルチット） 、 ２１．８．２２
．２．２３．０．２５．８゜２８．３．．３０．０．３
６．４．３７，１．３８．８ ｐｐｍに夫々メチレンの
炭素原子の特性吸収（トリブレット）。・Nuclear magnetic resonance (C-13,0DC 3rd) δ value: 12.8
,17.7,20.1,20.3,23.4,23.7
,25.7゜31.1 Characteristic absorption of methyl carbon atom (calcite) in ppIll, respectively, 21.8.22
．． 2.23.0.25.8°28.3. ．． 30.0.3
Characteristic absorption (triblet) of methylene carbon atoms at 6.4.37 and 1.38.8 ppm, respectively.
５９．０．７５．４．７７．７．７７．９．８６．６
ｐｐｍに夫々メチンの炭素原子の特性吸収（ダブレット
）、１２２．６． １２４．６１）ｌ）＋１１に夫々水
素原子と結合している二重結合の炭素原子の特性吸収（
ダブレット） 、 ７２，３．７４．４ （Ｘ ２ ）
、 ７４，９． １３１．７゜１３９．６ ｐｐｍに
夫々水素原子と結合していない炭素原子の特性吸収（シ
ングレット）
本発明の化合物は、以下に説明する方法で得ることがで
きる。59.0.75.4.77.7.77.9.86.6
Characteristic absorption (doublet) of carbon atoms of methine in ppm, respectively, 122.6. 124.61) l) Characteristic absorption of carbon atoms in double bonds bonded to hydrogen atoms at +11, respectively (
doublet), 72,3.74.4 (X 2)
, 74,9. Characteristic absorption (singlet) of carbon atoms not bonded to hydrogen atoms at 131.7° and 139.6 ppm, respectively.The compound of the present invention can be obtained by the method described below.
先ず、マギレソゾを親水性有線溶媒で抽出する。First, Magiresozo is extracted with a hydrophilic wired solvent.
溶媒としては、メタノール、エタノール、プロパツール
、ｎ−ブタノールのような低級アルコール。As a solvent, lower alcohols such as methanol, ethanol, propatool, and n-butanol are used.
アセトンのようなケトン類等があげられるが、就中低級
アルコールが好ましく、特にメタノール。Examples include ketones such as acetone, but lower alcohols are preferred, particularly methanol.
エタノールが好ましい。抽出処理は、通常マギレソゾを
親水性有機溶剤で浸漬脱水し、次いで新しい親水性有機
溶剤に交換し、１週間以上浸漬することによって好まし
く行われる。Ethanol is preferred. The extraction treatment is usually preferably carried out by immersing and dehydrating the Magiresozo in a hydrophilic organic solvent, then replacing it with a new hydrophilic organic solvent, and immersing it for one week or more.
得られる抽出物は、次いで非極性吸着剤に吸着せしめる
が、本発明では、この抽出物をあらかじめ次に記す精製
工程に付すのが好ましい。すなわち、抽出物を疎水性有
機溶剤に溶解し、水洗後、アルカリ水溶液、酸性水溶液
で洗浄するのが好ましい。ここで使用する疎水性有機溶
剤としては、例えば四塩化炭素、クロロホルム、ジクロ
ルメタンなどのハロゲン化炭化水素類、ジエチルエーテ
ルなどのエーテル類、酢酸エチル等のエステル類が挙げ
られる。アルカリ水溶液としては、水酸化ナトリウム、
水酸化カリウム、炭酸ナトリウム。The resulting extract is then adsorbed onto a non-polar adsorbent, but in the present invention it is preferable to previously subject this extract to the following purification step. That is, it is preferable to dissolve the extract in a hydrophobic organic solvent, wash with water, and then wash with an alkaline aqueous solution or an acidic aqueous solution. Examples of the hydrophobic organic solvent used here include halogenated hydrocarbons such as carbon tetrachloride, chloroform, and dichloromethane, ethers such as diethyl ether, and esters such as ethyl acetate. Examples of alkaline aqueous solutions include sodium hydroxide,
Potassium hydroxide, sodium carbonate.
アンモニアなどのアルカリ水溶液が挙げられ、酸性水溶
液としては、塩酸、硫酸、酢酸などの酸性水溶液が挙げ
られる。Examples of the aqueous alkaline solution include ammonia and the like, and examples of the acidic aqueous solution include acidic aqueous solutions such as hydrochloric acid, sulfuric acid, and acetic acid.
本発明で用いる活性吸着剤としては、例えば、シリカゲ
ル、アルミナ、活性炭、ゼオライト、セルロースなどが
挙げられる。なかでもシリカゲルが好ましい。吸着剤に
吸着せしめるに際しては、抽出物を濃縮し、次いで後述
する非極性有機溶剤に溶解して吸着するのが好ましい。Examples of the active adsorbent used in the present invention include silica gel, alumina, activated carbon, zeolite, and cellulose. Among them, silica gel is preferred. When adsorbing on an adsorbent, it is preferable to concentrate the extract and then dissolve and adsorb it in a non-polar organic solvent as described below.
マキレソゾからの抽出物を活性吸着剤に吸着せしめた後
、次いで非極性有機溶剤で溶出処理して極性有機溶剤で
溶出する成分を除去する。非極性有機溶剤としては、非
誘電率３以上の有機溶剤が好ましく、例えば、ベンゼン
、トルエン、キシレン、エチルベンゼンなどの如き芳香
族炭化水素などが挙げられ、就中、ベンゼンが好ましい
。After the extract from Makiresozo is adsorbed onto an active adsorbent, it is then eluted with a non-polar organic solvent to remove components that can be eluted with polar organic solvents. The nonpolar organic solvent is preferably an organic solvent with a dielectric constant of 3 or more, such as aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene, with benzene being particularly preferred.
非極性有機溶剤で溶出せしめる際の非極性有機溶剤の聞
は、その種類及び使用する活性吸着剤により左右される
が、例えば、活性吸着剤としてシリカゲルを用い、非極
性有機溶媒としてベンゼンを用いる場合には、シリカゲ
ルに対して約１０〜５０容量倍のベンゼンが使用される
。次いで、極性有機溶剤で溶出することによって、中性
粗抽出物が得られる。The number of non-polar organic solvents used for elution with a non-polar organic solvent depends on its type and the active adsorbent used; for example, when silica gel is used as the active adsorbent and benzene is used as the non-polar organic solvent. Benzene is used in an amount of about 10 to 50 times the volume of silica gel. A neutral crude extract is then obtained by elution with a polar organic solvent.
極性有機溶剤としては、例えば、メタノール。Examples of the polar organic solvent include methanol.
エタノール、イソプロパノール、エトキシエタノールの
如き低級アルコール類、アセトン、メチルエチルケトン
、メチルイソブチルケトンの如きケトン類、酢酸エチル
、酢酸アミルの如きエステル類、テトラヒドロフランの
如きエーテル類などが挙げられる。これらのうち、低級
アルコール類が好ましい。Examples include lower alcohols such as ethanol, isopropanol and ethoxyethanol, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, esters such as ethyl acetate and amyl acetate, and ethers such as tetrahydrofuran. Among these, lower alcohols are preferred.
かくして得られる粗抽出物は、通常の吸着クロマトグラ
フ法０分配りＯマドグラフ法等のクロマトグラフ法、分
別結晶法等を単独もしくは組合わせにより精製すること
により結晶状のシルシフエロールが得られる。The crude extract thus obtained is purified by conventional adsorption chromatography, chromatography such as 0-partition O-madograph, fractional crystallization, etc. alone or in combination to obtain crystalline silciferol.
かかる精製操作には、特に分配クロマトグラフ法を用い
ることが好ましく、オクタデシル化シリカゲル、オクチ
ル化シリカゲル、シアノプロピル化シリカゲル等の極性
の異なる充填剤を適宜用いることにより、目的の化合物
を容易に分離・精製することができる。For such purification operations, it is particularly preferable to use partition chromatography, and by appropriately using packing materials with different polarities such as octadecylated silica gel, octylated silica gel, and cyanopropylated silica gel, the target compound can be easily separated and separated. Can be purified.
かくして得られる本発明の化合物は著しい抗腫瘍活性を
有していて、好ましく抗腫瘍剤とて用いることができる
。かかる剤の形態としては、散剤。The compound of the present invention thus obtained has remarkable antitumor activity and can be preferably used as an antitumor agent. The form of such agents is powder.
乳剤、水剤、カプセル剤などで、注射薬、内服薬。Emulsions, solutions, capsules, etc., injections, and oral medications.
座薬などによって投与される。Administered via suppositories.
以下、実施例を掲げ、本発明を更に詳しく説明する。Hereinafter, the present invention will be explained in more detail with reference to Examples.
実施例１
風乾処理したマギレソゾ３ Ｋｇをメタノール２０．Ｑ
浸漬抽出操作を３回繰り返し、得られた抽出液６０文か
らメタノール留去操作により３隻の原抽出液を得た。原
抽出液をエチルエーテル３文で希釈後、該希釈液を水洗
、３Ｎの０．５Ｎ水酸化ナトリウム水溶液で洗浄、水洗
、３文の１Ｎ塩酸で洗浄、水洗の各操作を順次に行った
。しかる侵、該エチルエーテル溶液からエチルエーテル
を留去し、粘稠な液体として約５０９の中性抽出物を得
た。Example 1 3 kg of air-dried Magiresozo was mixed with 20.0 kg of methanol. Q
The immersion extraction operation was repeated three times, and three original extracts were obtained from the 60 extracts obtained by distilling off methanol. After diluting the raw extract with 3 portions of ethyl ether, the diluted solution was washed with water, 3N of 0.5N aqueous sodium hydroxide solution, water, 3 portions of 1N hydrochloric acid, and water. Ethyl ether was then distilled off from the ethyl ether solution to obtain a neutral extract of about 509 as a viscous liquid.
該中性抽出物を５００ｄのベンゼンに溶解し６０〜２０
０メツシユのシリカゲルＩ Ｋｇを充填した直径７５履
のガラスカラムに通し吸着させた。次いで、９．５．Ｑ
のベンゼンを用いて吸着成分の１部を溶出させた後、２
旦のメタノールを用いて、ベンゼン処理で溶出されなか
った吸着成分を溶出した。該メタノール溶液からメタノ
ールを留去し、濃緑色の粘稠な液体として３０９の中性
抽出物を得た。The neutral extract was dissolved in 500 d of benzene and the
The mixture was passed through a glass column with a diameter of 75 mm filled with 0.0 kg of silica gel I for adsorption. Then 9.5. Q
After eluting a part of the adsorbed components with benzene, 2
Adsorbed components that were not eluted by benzene treatment were eluted using methanol. Methanol was distilled off from the methanol solution to obtain a neutral extract of 309 as a dark green viscous liquid.
該中性粗抽出物５ｇをメタノール１０ａｅに溶解し、数
回に分けてオクタデシル化シリカゲルカラム（内径２０
ａｗ＋Ｘ２５α）に注入し、メタノール／水（７５／２
５）の溶媒系で高速液体クロマトグラフィー （ＨＰＬ
Ｃ）を行ない、腫瘍細胞に対する増殖阻害性を指標に特
に活性の高い両分を集め減圧下に濃縮乾固した。次いで
、これを９山のメタノールに溶解し、シアノプロピル化
シリカゲルカラム（内径２０ａ＊ ｘ ２ＳｃＩＲ）に
注入し、ｎ−ヘキサン／イソプロピルアルコール（９８
／２）の溶媒系でＨＰＬＣ操作を行ない、抗腫瘍活性が
高く、化合物の極性の近い２つの両分を集め、該画分を
夫々減圧下淵縮して、結晶として夫々１７ａｙ（化合物
Ａとする） 、 １５Ｒｇ（化合物Ｂとする）を得た。5 g of the neutral crude extract was dissolved in 10 ae of methanol, divided into several portions and applied to an octadecylated silica gel column (inner diameter 20
aw+X25α) and methanol/water (75/2
5) High performance liquid chromatography (HPL) using the solvent system
C) was carried out, and both components with particularly high activity were collected and concentrated to dryness under reduced pressure, using the growth inhibitory property against tumor cells as an index. This was then dissolved in 9 molar methanol, injected onto a cyanopropylated silica gel column (20a* x 2ScIR) and diluted with n-hexane/isopropyl alcohol (98
HPLC operation was performed in the solvent system of /2), and two fractions with high antitumor activity and similar polarity of the compound were collected, and the fractions were condensed under reduced pressure to form crystals of 17 ay (Compound A and Compound A). ), 15Rg (referred to as compound B) was obtained.
得られた結晶を解析し、化合物Ａは前記式（Ｉ）のエン
ド二重結合を有する化合物であり、又化合物Ｂは前記式
（Ｉ）のエンド二重結合を有する化合物であった。化合
物Ａ、Ｂの理化学的特性は前記した通りであった。The obtained crystals were analyzed, and Compound A was a compound having an end double bond of the above formula (I), and Compound B was a compound having an end double bond of the above formula (I). The physicochemical properties of Compounds A and B were as described above.
実施例２
Ｐ３８８Ｄ＋培養細胞に対する抗腫瘍活性試験（試料ｗ
４製）
実施例１で得られた化合物Ａ、Ｂ３ｊ１ｇを夫々エタノ
ール１１ｄに溶解し、希釈法により対数等間隔的に３■
／ｄ〜１１００ｎ／ｄのエタノール溶液を調製した後、
夫々の濃度の溶液を１００培容の生理食塩水で希釈し投
与溶液とした。（１％エタノール含有）
（細胞増殖性評価）
１０％牛脂児血清添加ＲＰＭ Ｉ １６４０培地で前日
に継代したマウス白血病由来の培養細胞Ｐ３８８Ｄ＋細
胞を、１ｘｉｏ’細胞／Ｉｄとなるよう調整し、該細胞
懸濁液を９６穴マイクＯプレート各穴に２００μＵ／穴
で分注した。Example 2 Antitumor activity test on P388D+ cultured cells (sample w
4) 1 g of Compounds A and B3j obtained in Example 1 were each dissolved in 11 d of ethanol, and diluted at 3× logarithmically equal intervals using a dilution method.
After preparing an ethanol solution of /d ~ 1100n/d,
Solutions of each concentration were diluted with 100 volumes of physiological saline to prepare administration solutions. (Contains 1% ethanol) (Evaluation of cell proliferation) Mouse leukemia-derived cultured P388D+ cells, which had been passaged the previous day in RPM I 1640 medium supplemented with 10% tallow serum, were adjusted to 1xio' cells/Id. The cell suspension was dispensed into each well of a 96-well Micro-O plate at 200 μU/well.
上記！ｌｌ！！製した各濃度の投与液をｍ胞＠濁液を分
注した９６穴マイクロプレートに、夫々２０μＮ／穴で
投与した。（投与濃度３Ａｔ９／ａ１２〜０，１ ｎ９
／ｄ、エタノール含有ｆｆｉ Ｏ，０９％）ブランク対
照としては、エタノール０．０９％含有生理食塩水を用
いた。the above! ll! ! The prepared administration solution at each concentration was administered at 20 μN/well into a 96-well microplate into which m cells @ suspension had been dispensed. (Dose concentration 3At9/a12~0,1 n9
/d, ffiO containing ethanol, 09%) Physiological saline containing 0.09% ethanol was used as a blank control.
次いで、該マイクロプレートを３７℃炭酸ガス培養器で
２日間培養を行ない、各穴の細胞数を測定しＰ３８８Ｄ
＋細胞に対する増殖抑制効果を評価した。Next, the microplate was cultured in a carbon dioxide incubator at 37°C for 2 days, and the number of cells in each well was measured.
The growth inhibitory effect on + cells was evaluated.
（結果） 化合物Ａ、Ｂ共ＥＤｓｏは３０ｎ９／ｄであった。(result) The EDso of both compounds A and B was 30n9/d.
Claims (1)
） （但し、式中Ｒは▲数式、化学式、表等があります▼又
は▲数式、化学式、表等があります▼である）で表わさ
れるトリテルペン系化合物を有効成分とする抗腫瘍剤。[Claims] The following formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(I
) (However, R in the formula is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼) An antitumor agent containing a triterpene compound as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61236300A JPS6391319A (en) | 1986-10-06 | 1986-10-06 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61236300A JPS6391319A (en) | 1986-10-06 | 1986-10-06 | Antitumor agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6391319A true JPS6391319A (en) | 1988-04-22 |
| JPH0442366B2 JPH0442366B2 (en) | 1992-07-13 |
Family
ID=16998750
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61236300A Granted JPS6391319A (en) | 1986-10-06 | 1986-10-06 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6391319A (en) |
-
1986
- 1986-10-06 JP JP61236300A patent/JPS6391319A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0442366B2 (en) | 1992-07-13 |
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