KR19980052667A - Novel captosesin derivatives exhibit anticancer activity - Google Patents

Novel captosesin derivatives exhibit anticancer activity Download PDF

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KR19980052667A
KR19980052667A KR1019960071684A KR19960071684A KR19980052667A KR 19980052667 A KR19980052667 A KR 19980052667A KR 1019960071684 A KR1019960071684 A KR 1019960071684A KR 19960071684 A KR19960071684 A KR 19960071684A KR 19980052667 A KR19980052667 A KR 19980052667A
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anticancer activity
novel
present
captosesin
derivatives exhibit
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KR0183440B1 (en
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이동훈
한우석
유용상
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구형우
한솔제지 주식회사
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings

Abstract

본 발명은 항암활성을 나타내는 신규 캠토쎄신 유도체에 관한 것이다.The present invention relates to a novel camptothecin derivative exhibiting anticancer activity.

[화학식 1][Formula 1]

상기 화학식에서,In the above formula,

X 또는 Y는 서로 같거나 다른 것으로서 시아노, 니트릴, C1~ C4의 아실, C1~ C4의 카보알콕시 또는 카보아마이드기 이다.X or Y are the same or different from each other and are cyano, nitrile, C 1 to C 4 acyl, C 1 to C 4 carboalkoxy or carboamide groups.

Description

항암활성을 나타내는 신규 캠토쎄신 유도체Novel camptothecin derivatives showing anticancer activity

본 발명은 항암활성을 나타내는 신규 캠토쎄신 유도체에 관한 것이다.The present invention relates to a novel camptothecin derivative exhibiting anticancer activity.

상기 화학식에서,In the above formula,

X 또는 Y는 서로 같거나 다른 것으로서 시아노, 니트릴, C1~ C4의 아실, C1~ C4의 카보알콕시 또는 카보아마이드기 이다.X or Y are the same or different from each other and are cyano, nitrile, C 1 to C 4 acyl, C 1 to C 4 carboalkoxy or carboamide groups.

캠토쎄신(Camptothecin)은 접합퀴놀린, 피롤린, α-피리돈, 락톤환을 가지는 오중고리 알카로이드로서, 월(Wall) 등에 의해 차이니즈 트리(Chinese tree; Camptotheca acuminata Decsne.)로부터 처음 추출되었다[J. Am. Chem. Soc. 88, 3888(1966)].Camptothecin is a pentagonal alkaloid with conjugated quinoline, pyrroline, α-pyridone, and lactone ring, first extracted from Chinese tree by Camp et al., Camptotheca acuminata Decsne. Am. Chem. Soc. 88, 3888 (1966).

또한, 캠토쎄신(Camptothecin)은 세포성장과 관련된 효소중의 하나인 토포아이소머라제 I(topoisomerase I)의 작용을 저해함으로써 항암활성을 나타내는 유일한 화합물로 알려져 있다. 캠토쎄신의 항암활성은 C-20 위치의 S 배열을 갖는 α-하이드록시 락톤환에 의해 결정되는 것으로 알려져 있으며, 그 효과가 뛰어나 가장 잠재력이 큰 항암활성 물질로 각광을 받고 있고, 이에 대한 많은 연구가 진행중에 있다.Camptothecin is also known to be the only compound that exhibits anticancer activity by inhibiting the action of topoisomerase I, one of the enzymes involved in cell growth. It is known that the anticancer activity of camptothecin is determined by the α-hydroxy lactone ring having the S configuration at the C-20 position, and it has been spotlighted as the most potent anticancer active substance due to its excellent effect. Is in progress.

그러나, 캠토쎄신은 물에 대한 용해도가 매우 나빠 제제화에 문제가 있으며, 독성이 매우 심해 임상에 대한 적용에 제한이 있는 단점을 가지고 있다. 따라서, 용해도를 증가시키며 독성을 감소시킬 수 있는 새로운 치환체들을 도입하거나 모핵의 구조를 변형시킴으로써 그러한 문제점들을 해결할 수 있는 신규 캠토쎄신 유도체의 개발이 절실히 필요하다.However, camptothecin has a disadvantage in that it is very poor in solubility in water in formulating, and is very toxic and has limitations in application to the clinic. Therefore, there is an urgent need for the development of new camptothecin derivatives that can solve such problems by introducing new substituents that can increase solubility and reduce toxicity or by modifying the structure of the parent nucleus.

본 발명자들은 상기와 같은 요구에 착안하여 용해도의 증가와 독성을 낮출 수 있는 신규 캠토쎄신 유도체를 제조하고자 다각적으로 연구하였고, 그 결과 C-7위치에 새로운 치환기롤 도입함으로써 본 발명을 완성하였다.The present inventors have studied in various ways to prepare a novel camtosesin derivative which can increase the solubility and lower the toxicity in view of the above requirements, and as a result, the present invention was completed by introducing a new substituent at the C-7 position.

따라서, 본 발명은 물에 대한 용해도가 우수하여 제제화가 용이하고 독성이 낮을 뿐만 아니라 항암활성이 우수한 신규 캠포쎄신 유도체를 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a novel camphorcein derivative having excellent solubility in water, which is easy to formulate, low in toxicity, and excellent in anticancer activity.

본 발명은 다음 화학식 1로 표시되는 캠토쎄신 유도체를 그 특징으로 한다.The present invention is characterized by the camtosesin derivative represented by the following formula (1).

화학식 1Formula 1

상기 화학식에서,In the above formula,

X 또는 Y는 서로 같거나 다른 것으로서 시아노, 니트릴, C1~ C4의 아실, C1~ C4의 카보알콕시 또는 카보아마이드기 이다.X or Y are the same or different from each other and are cyano, nitrile, C 1 to C 4 acyl, C 1 to C 4 carboalkoxy or carboamide groups.

이와같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.

본 발명은 항암활성이 우수한 신규 캠토쎄신 유도체에 관한 것으로서, 상기 화학식 1로 표시되는 유도체중에서도 특히 바람직하기로는 X와 Y가 모두 시아노기인 경우이거나, 또는 X 또는 Y가 각각 C1~ C4의 카보알콕시기인 경우이다.The present invention relates to a novel camtosesin derivative having excellent anticancer activity, and particularly preferably among the derivatives represented by Formula 1, X and Y are both cyano groups, or X or Y are each C 1 to C 4 In the case of a carboalkoxy group.

망간(Ⅲ)아세테이트는 온화한 선택성을 보이는 산화제로서 카복시메틸라디칼아세트산을 형성하여 알킨에 첨가반응을 하는 것으로 알려져 있다[Chemtracts Org. Chem., 403, (1991)]. 이러한 사실에 착안하여, 본 발명에서는 망간(Ⅲ)아세테이트를 이용하여 20(S)-캠토쎄신의 C-7위치에 새로운 치환기인 활성수소화합물들을 라디칼 친전자성 치환반응을 통하여 도입하였다. 이때, 망간(Ⅲ)아세테이트는 5 ~ 20 당량을 사용하고, 반응용매로는 아세트산을 사용하며, 24시간정도 환류시키는 것이 수율면에서 바람직하다.Manganese (III) acetate is an oxidant with mild selectivity and is known to form carboxymethyl radical acetic acid and react with alkyne [Chemtracts Org. Chem., 403, (1991). In view of this fact, in the present invention, manganese (III) acetate was used to introduce active hydrogen compounds, which are new substituents at the C-7 position of 20 (S) -camptocecin, through radical electrophilic substitution reaction. In this case, manganese (III) acetate is used in the amount of 5 to 20 equivalents, acetic acid is used as the reaction solvent, and refluxing for about 24 hours is preferable in terms of yield.

상기에서 설명한 바와 같은 본 발명의 캠토쎄신 유도체는 시험관내 세포독성활성 및 생체내 항암활성 측정결과 우수한 항암활성을 가지는 것으로 밝혀졌다.As described above, the camtosesin derivative of the present invention was found to have excellent anticancer activity as a result of in vitro cytotoxic activity and in vivo anticancer activity measurement.

이와같은 본 발명을 다음의 실시에에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 이에 한정되는 것은 아니다.The present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.

실시예: 캠토쎄신 유도체(화합물번호 10)의 제조Example: Preparation of Camptocecin Derivative (Compound No. 10)

반응기에 4(S)-캠토쎄신(0.0545 mmol), 다이에틸말로네이트(82 ㎕), 망간(Ⅲ) 아세테이트(146 ㎎, 10당량) 및 아세트산(1.0 ㎖)을 넣고, 24시간동안 환류반응시켰다. 반응이 완결된 후, 반응물은 메탄올/메틸렌클로라이드(5/95 부피%)의 혼합용액으로 추출하고 감압증류 및 건조하여 잔사를 얻었다. 잔사를 실리카겔 칼럼크로마토그래피(용출용매: 톨루엔/1,4-디옥산/아세트산=90/25/4부피비)로 분리하여 목적 화합물을 얻었다.(수율 65%)4 (S) -camptocecin (0.0545 mmol), diethylmalonate (82 μl), manganese (III) acetate (146 mg, 10 equiv) and acetic acid (1.0 mL) were added to the reactor and refluxed for 24 hours. . After the reaction was completed, the reaction was extracted with a mixed solution of methanol / methylene chloride (5/95 vol.%), Distilled under reduced pressure and dried to obtain a residue. The residue was separated by silica gel column chromatography (eluent: toluene / 1,4-dioxane / acetic acid = 90/25/4 by volume) to obtain the target compound. (Yield 65%)

그 밖의 본 발명에 따른 캠토쎄신 유도체들은 상기 실시예와 동일한 제조방법에 의해 C-7 위치에 다양한 활성수소 치환기를 도입할 수 있다.Other camptothecin derivatives according to the present invention can introduce various active hydrogen substituents at the C-7 position by the same preparation method as in the above example.

본 발명에서 제조한 몇몇 화합물은 다음 표1에 나타내었다.Some compounds prepared in the present invention are shown in Table 1 below.

화합물번호Compound number XX YY 수율(%)yield(%) 1H-NMR(CDC13),δppm 1 H-NMR (CDC1 3 ), δ ppm 1One CNCN CNCN 6565 1.02(t, 3H), 1.86(q, 2H), 3.94(s, 1H), 5.23(s, 2H), 5.25∼5.26(d, 1H), 5.71∼5.75(d, 1H), 7.8∼9.01(m, 5H)1.02 (t, 3H), 1.86 (q, 2H), 3.94 (s, 1H), 5.23 (s, 2H), 5.25 to 5.26 (d, 1H), 5.71 to 5.75 (d, 1H), 7.8 to 9.01 ( m, 5H) 22 CNCN NO2 NO 2 6666 1.04(t, 3H), 1.87(q, 2H), 3.96(s, 1H), 5.23(s, 2H), 5.25∼5.27(d,1H), 5.72∼5.76(d, 1H), 7.81∼9.02(m, 5H)1.04 (t, 3H), 1.87 (q, 2H), 3.96 (s, 1H), 5.23 (s, 2H), 5.25 to 5.27 (d, 1H), 5.72 to 5.72 (d, 1H), 7.81 to 9.02 ( m, 5H) 33 CNCN CO2CH3 CO 2 CH 3 6363 1.03(t, 3H), 1.86(q, 2H), 3.76(s, 1H), 3.80(s, 3H), 5.21(s, 2H), 5.24∼5.29(d, 1H), 5.64∼5.69(d, 1H), 7.74∼8.82(m, 5H)1.03 (t, 3H), 1.86 (q, 2H), 3.76 (s, 1H), 3.80 (s, 3H), 5.21 (s, 2H), 5.24 to 5.29 (d, 1H), 5.64 to 5.69 (d, 1H), 7.74-8.82 (m, 5H) 44 CNCN CONH2 CONH 2 6262 1.03(t, 3H), 1.87(q, 2H), 3.75(s, 1H), 5.20(s, 2H), 5.23∼5.29(d, 1H), 5.63∼5.7(d, 1H), 7.5∼8.6(m, 5H)1.03 (t, 3H), 1.87 (q, 2H), 3.75 (s, 1H), 5.20 (s, 2H), 5.23 to 5.29 (d, 1H), 5.63 to 5.7 (d, 1H), 7.5 to 8.6 ( m, 5H) 55 CNCN COCH3 COCH 3 6060 1.02(t, 3H), 1.86(q, 2H), 2.31(s, 3H), 3.77(s, 1H), 5.24∼5.28(d, 1H), 5.64∼5.69(d, 1H), 7.6∼8.7(m, 5H)1.02 (t, 3H), 1.86 (q, 2H), 2.31 (s, 3H), 3.77 (s, 1H), 5.24 to 5.28 (d, 1H), 5.64 to 5.69 (d, 1H), 7.6 to 8.7 ( m, 5H) 66 CO2CH3 CO 2 CH 3 CO2CH3 CO 2 CH 3 6767 1.01(t, 3H), 1.84(q, 2H), 3.21(m, 1H), 3.85(s, 6H), 5.18(s, 2H), 5.22∼5.31(d, 1H), 5.69∼5.75(d, 1H), 7.62∼8.89(m, 5H)1.01 (t, 3H), 1.84 (q, 2H), 3.21 (m, 1H), 3.85 (s, 6H), 5.18 (s, 2H), 5.22 to 5.31 (d, 1H), 5.69 to 5.75 (d, 1H), 7.62-8.89 (m, 5H) 77 CO2CH3 CO 2 CH 3 CONH2 CONH 2 6262 1.01(t, 3H), 1.85(q, 2H), 2.29(s, 3H), 3.19(m, 1H), 5.23(s, 2H), 5.24∼5.29(d, 1H), 5.67∼5.70(d, 1H), 7.65∼8.79(m, 5H)1.01 (t, 3H), 1.85 (q, 2H), 2.29 (s, 3H), 3.19 (m, 1H), 5.23 (s, 2H), 5.24 to 5.29 (d, 1H), 5.67 to 5.70 (d, 1H), 7.65-8.79 (m, 5H) 88 COCH3 COCH 3 COCH3 COCH 3 5858 1.02(t, 3H), 1.84(q, 2H), 2.23(s, 6H), 3.22(m, 1H), 5.21(s, 2H), 5.22∼5.28(d, 1H), 5.68∼5.71(d, 1H), 7.63∼8.8(m, 5H)1.02 (t, 3H), 1.84 (q, 2H), 2.23 (s, 6H), 3.22 (m, 1H), 5.21 (s, 2H), 5.22 to 5.28 (d, 1H), 5.68 to 5.71 (d, 1H), 7.63-8.8 (m, 5H) 99 COCH3 COCH 3 CO2CH3 CO 2 CH 3 6161 1.02(t, 3H), 1.84(q, 2H), 2.21(s, 3H), 3.21(m, 1H), 3.81(s, 3H), 5.19(s, 2H), 5.22∼5.29(d, 1H), 5.67∼5.75(d, 1H), 7.61∼8.9(m, 5H)1.02 (t, 3H), 1.84 (q, 2H), 2.21 (s, 3H), 3.21 (m, 1H), 3.81 (s, 3H), 5.19 (s, 2H), 5.22 to 5.29 (d, 1H) , 5.67 to 5.75 (d, 1H), 7.61 to 8.9 (m, 5H) 1010 CO2EtCO 2 Et CO2EtCO 2 Et 6767 1.02(t, 3H), 1.21(m, 6H), 1.85(q, 2H), 3.21(m, 1H), 3,83(m, 4H), 5.19(s, 2H), 5.21∼5.30(d, 1H), 5.68∼5.74(d, 1H), 7.6∼8.9(m, 5H)1.02 (t, 3H), 1.21 (m, 6H), 1.85 (q, 2H), 3.21 (m, 1H), 3,83 (m, 4H), 5.19 (s, 2H), 5.21-5.30 (d, 1H), 5.68 to 5.74 (d, 1H), 7.6 to 8.9 (m, 5H)

실험예 1 : 시험관내 세포독성Experimental Example 1 In Vitro Cytotoxicity

세포독성 측정은 카미셀(Carmichael)의 MTT방법을 이용하였다. 다음 표2에 나타낸 세포주를 T-25 배용용기에 일정농도가 되게 지수증식기까지 배양하여 단세포 현탁액을 만든 후, 세포농도를 조정하여 96웰 배양접시에 일정량씩(100ℓ) 분주하여 37℃, 5% CO2배양기에서 24시간 배양하였다. 여기에 각 농도의 약물을 배지에 녹여 100ℓ씩 가한 후 3 ∼ 5일간 더 배양하였다. 배양이 끝나면 MTT용액을 20㎖씩 각 웰(well)에 넣어 4시간 배양한 후, 디메틸설폭사이드(DMSO)로 염료를 녹여 570nm에서 흡광도를 측정하였다. 측정한 흡광도를 다음 수학식 1에 대입하여 생존율을 측정함으로써 세포독성을 평가하였다.Cytotoxicity was measured by Carmichael's MTT method. Next, the cell lines shown in Table 2 were cultured to an exponential growth stage to a constant concentration in a T-25 incubator to make a single cell suspension. Incubated for 24 hours in a CO 2 incubator. The drug of each concentration was dissolved in the medium, and 100 l of each was added, followed by further incubation for 3-5 days. After incubation, 20 ml of MTT solution was added to each well and incubated for 4 hours. After dissolving the dye with dimethyl sulfoxide (DMSO), the absorbance was measured at 570 nm. Cytotoxicity was evaluated by measuring the survival rate by substituting the measured absorbance into the following Equation 1.

이때 한가지 농도군에 대해서는 1컬럼(8 well)을 동일한 조건으로 사용하며, 시료의 최종농도는 웰(well)당 각각 300, 100, 30 g/㎖ 씩 되도록 하였다. 대조군은 한컬럼에 약물대신에 PBS 100ℓ만을 첨가하여 100% 생존군으로 삼았다. 흡광도 측정시 사용한 표준시료(Blank)에는 세포없는 배지 100ℓ만을 가하고 PBS 또는 약물을 100ℓ 첨가하였다.In this case, 1 column (8 wells) was used under the same conditions for one concentration group, and the final concentration of the sample was 300, 100, and 30 g / ml per well, respectively. As a control group, only 100 L of PBS was added instead of the drug in one column to make a 100% survival group. Only 100 l of cell-free medium was added to the standard sample used for absorbance measurement, and 100 l of PBS or drug was added.

또한, 선별물질의 세포독성은 세포의 증식을 50% 억제할 수 있는 50% 억제농도(IC50)로 나타내었다. In addition, the cytotoxicity of the selection material was expressed as a 50% inhibitory concentration (IC 50 ) that can inhibit cell proliferation by 50%.

50% 억제농도(IC50; ㎍/㎖)50% inhibitory concentration (IC 50 ; μg / ml) 투여약물Medication SNU-5SNU-5 SNU-398SNU-398 SNU-16SNU-16 SNU-C5SNU-C5 캠토쎄신Camptosesin 4.43×10-6 4.43 × 10 -6 5.77×10-5 5.77 × 10 -5 1.03×10-5 1.03 × 10 -5 6.47×10-5 6.47 × 10 -5 화합물번호 2Compound number 2 2.29×10-4 2.29 × 10 -4 3.92×10-5 3.92 × 10 -5 8.53×10-4 8.53 × 10 -4 1.59×10-4 1.59 × 10 -4 화합물번호 10Compound number 10 3.82×10-5 3.82 × 10 -5 4.52×10-4 4.52 × 10 -4 7.89×10-4 7.89 × 10 -4 2.39×10-5 2.39 × 10 -5 (주)SNU-5: 국내위암 세포주SNU-398: 국내간암 세포주SNU-C5: 국내대장암 세포주SNU-16: 국내위암 세포주SNU-5: Domestic stomach cancer cell line SNU-398: Domestic liver cancer cell line SNU-C5: Domestic colon cancer cell line SNU-16: Domestic stomach cancer cell line

실험예 2 : 생체내 항암활성Experimental Example 2: In vivo anticancer activity

생체내 항암활성은 P388(마우스 백혈병세포주)와 3LL(마우스 폐암세포주)를 이식한 쥐에 약물을 투여하여 생존율을 조사하므로써 평가하였다.In vivo anticancer activity was evaluated by investigating the survival rate of the mice implanted with P388 (mouse leukemia cell line) and 3LL (mouse lung cancer cell line).

1) P388종양에 대한 항암효과1) Anticancer effect on P388 tumors

생체내 항암활성을 측정하는 모델로서 BDF1(7주령의 암컷, 1군 5마리)마우스에 P388 백혈병 세포 1×106개를 이식하고, 이식 24시간 후부터 본 발명의 화합물을, 그리고 양성대조로서 마이토마이신을 연일 9일간 1일 1회 복강투여하여 생존율을 조사하였으며 대조군으로서는 생리식염액 투여군을 사용하였다. 결과는 다음 표 3에 나타내었다.As a model for measuring anti-cancer activity in vivo, 1 × 10 6 P388 leukemia cells were transplanted into BDF1 (7 week old female, 5 group 1) mice, and the compounds of the present invention were used as positive controls 24 hours after transplantation. Tomycin was intraperitoneally administered once a day for 9 days a day to check the survival rate, and a saline-administered group was used as a control group. The results are shown in Table 3 below.

투여약물Medication P388 세포P388 cells 용량(㎍/마리)Dose (μg / horse) 평균생존기간(days)Average survival (days) % T/C% T / C 마이토마이신Mitomycin 4040 2626 137137 화합물번호 1Compound number 1 4040 3030 158158 화합물번호 10Compound number 10 4040 3131 163163 대조군Control -- 1919 100100

상기의 표3의 생체실험결과에 의하면,기존의 잘 알려진 항암제인 마이토마이신의 경우 P388세포에 대한 %T/C 값이 137 이었다. 반면에 본 발명에 따른 신규 유도체는 150 ∼ 165 사이의 아주 높은 값을 나타내었는 바, 이로써 본 발명의 화합물의 항암활성이 매우 우수함을 알 수 있다.According to the results of the in vivo experiment of Table 3, in the case of the well-known anticancer drug mitomycin, the% T / C value for P388 cells was 137. On the other hand, the novel derivatives according to the present invention showed a very high value between 150 and 165, which shows that the anticancer activity of the compound of the present invention is very excellent.

2) 3LL 종양에 대한 항암효과2) Anticancer effect on 3LL tumor

BDF1(7주령의 암컷, 1군 5마리)마우스에 3LL 폐암세포 1×106개를 복강에 이식하고, 이식 24시간 후부터 본 발명의 화합물을, 그리고 양성대조로서 마이토마이신을 연일 9일간 1일 1회 복강투여하여 생존율을 조사하였으며, 대조군으로서는 생리식염액 투여군을 사용하였다. 그 결과는 다음 표4에 나타내었다.1 × 10 6 3LL lung cancer cells were implanted in BDF1 (7 week old female, 5 group 1 mice) intraperitoneally, and the compound of the present invention was administered 24 hours after transplantation and mitomycin as a positive control for 9 days a day. The survival rate was examined by intraperitoneal administration once a day, and the saline administration group was used as a control. The results are shown in Table 4 below.

투여약물Medication 3LL 세포3LL cells 용량(㎍/마리)Dose (μg / horse) 평균생존기간(days)Average survival (days) % T/C% T / C 마이토마이신Mitomycin 4040 2020 139139 화합물번호 1Compound number 1 4040 2121 146146 화합물번호 10Compound number 10 4040 2222 153153 대조군Control -- 14.314.3 100100

본 발명에 따른 상기 화학식 1로 표시되는 캠토쎄신 유도체는 항암활성이 우수하므로 항암제로 매우 유용하다.The camtosesin derivative represented by Formula 1 according to the present invention is very useful as an anticancer agent because of its excellent anticancer activity.

Claims (3)

다음 화학식 1로 표시되는 것을 특징으로 하는 캠토쎄신 유도체.Kamtosesin derivative characterized by the following formula (1). 화학식 1Formula 1 상기 화학식에서,In the above formula, X 또는 Y는 서로 같거나 다른 것으로서 시아노, 니트릴, C1~ C4의 아실, C1~ C4의 카보알콕시 또는 카보아마이드기 이다.X or Y are the same or different from each other and are cyano, nitrile, C 1 to C 4 acyl, C 1 to C 4 carboalkoxy or carboamide groups. 제 1 항에 있어서, 상기 X 및 Y가 시아노기인 것을 특징으로 하는 캠토쎄신 유도체.2. The camptothecin derivative according to claim 1, wherein X and Y are cyano groups. 제 1 항에 있어서, 상기 X 또는 Y는 서로 같거나 다른 것으로서 C1~ C4의 카보알콕시기인 것을 특징으로 하는 캠토쎄신 유도체.[Claim 2] The camptothecin derivative according to claim 1, wherein X or Y is the same as or different from each other and a C 1 to C 4 carboalkoxy group.
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