JPH05310736A - Ellipticine derivative, its production and its synthetic intermediate - Google Patents

Abstract

PURPOSE:To provide the new ellipticine derivative having an excellent antitumor action and reduced in the side actions and toxicity. CONSTITUTION:A compound of formula I [R<1> is H, OH, lower alkoxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, lower alkylaminocarbonyloxy; R<2> is alkyl, lower alkenyl, lower alkynyl or heterocyclic group which may have a substituent selected from lower alkoxy, halogen, CN, OH, amino, cyclic alkyl, phenyl and -CO-R<2> (R<2>' is phenyl, heterocyclic ring group, lower alkenyl, lower alkyl, OH, lower alkoxy, cyclic alkyl, amino); R<3> is H, lower alkyl; X is the anion of an inorganic acid or organic acid], e.g. 2- phenylcarbonylmethoxy-9-hydroxyellipticinium bromide. The compound is obtained by reacting a compound of formula II with a compound of formula: R<2>X.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel ellipticine derivative useful as an antitumor agent, a process for producing the same, and a synthetic intermediate thereof.

[0002]

2. Description of the Related Art It is known that 2-methyl-9-hydroxyellipticinium acetate can be used as an antitumor agent, for example, a therapeutic agent for breast cancer (Merck Index, 10th Edition, p. 512). However, this compound has a drawback in that it does not have a sufficient drug effect, such as no life prolonging effect in mice transplanted with Lewis lung cancer, and that it has strong side effects such as tachycardia and toxicity.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides a novel ellipticine derivative which has an excellent antitumor effect and has few side effects and toxicity.

[0004]

The present invention relates to an ellipticine derivative represented by the following general formula (I) and a method for producing the same.

[Chemical 5] [In the formula, R ¹ represents a hydrogen atom, a hydroxyl group, a lower alkoxy group,
Optionally substituted lower alkylcarbonyloxy group, lower alkoxycarbonyloxy group or lower alkylaminocarbonyloxy group; R ² represents lower alkoxy group, halogen atom, cyano group, hydroxyl group, optionally substituted amino group, cyclic An alkyl group, a phenyl group, and a compound represented by the formula: —CO—R ² ′ (wherein R ² ′ may be a substituted phenyl group, a heterocyclic group, a lower alkenyl group, an optionally substituted lower alkyl group, A hydroxyl group, an optionally substituted lower alkoxy group, a cyclic alkyl group or an optionally substituted amino group), which may have a substituent selected from the group represented by the following: an alkyl group; a lower alkenyl group; a lower alkynyl A group or an optionally substituted heterocyclic group; R ³ is a hydrogen atom or a lower alkyl group;
X is an anion of an inorganic acid or an organic acid]

The ellipticine derivative of the present invention has an excellent antitumor action and is a useful pharmaceutical compound as an antitumor agent.

In the object compound (I) of the present invention, R ¹
When is a lower alkylcarbonyloxy group which may be substituted, specific examples thereof include an unsubstituted lower alkylcarbonyloxy group, a lower alkoxy group-substituted lower alkylcarbonyloxy group, a lower alkoxy-lower alkoxy group-substituted lower alkylcarbonyl group. An oxy group is mentioned. When R ² is an optionally substituted alkyl group, specific examples of the substituent on the alkyl group include, for example, a cycloalkyl group such as cyclopropyl, a halogen atom such as fluorine, a mono- or di-lower alkylamino group. Group, a lower alkoxy group, a phenyl group, a cyano group, a hydroxyl group, or a group represented by the formula: —CO—R ² ′.
When R ² 'is an optionally substituted phenyl group, specific examples thereof include an unsubstituted phenyl group, a halogen-substituted phenyl group such as 4-chlorophenyl, a lower alkoxy group-substituted phenyl group such as 4-methoxyphenyl, and the like. Examples thereof include lower alkoxy-lower alkoxy group-substituted phenyl groups such as 4- (methoxyethoxy) phenyl and hydroxyl group-substituted phenyl groups such as 4-hydroxyphenyl group.
Specific examples of the case where R ² 'is a heterocyclic group include, for example,
Examples thereof include nitrogen-containing, oxygen-containing or sulfur-containing 5- or 6-membered heterocyclic groups such as thienyl, furyl and pyridyl. When R ² ′ is an optionally substituted lower alkyl group, specific examples thereof include an unsubstituted lower alkyl group, a lower alkoxy group-substituted lower alkyl group, a lower alkoxy-lower alkoxy group-substituted lower alkyl group, Examples of lower alkylcarbonyloxy group-substituted lower alkyl group and hydroxyl group-substituted lower alkyl group, and specific examples of the optionally substituted lower alkoxy group include unsubstituted lower alkoxy group and lower alkoxy group-substituted lower alkoxy group. Group, lower alkoxy-lower alkoxy group and substituted lower alkoxy group. A specific example of the case where R ² 'is a cyclic alkyl group is a cyclopropyl group. Further, when R ² 'is an optionally substituted amino group, specific examples thereof include an unsubstituted amino group, a mono- or di-lower alkylamino group (a lower alkyl group of the mono- or di-lower alkylamino group). Is a lower alkoxy group,
A lower alkoxycarbonyl group, a phenyl group, an oxo group-substituted 5-membered heterocyclic group such as a 2-oxopyrrolidino group, and may be substituted with 1 to 2 groups selected from a phenyl lower alkylaminocarbonyl group), Lower alkoxycarbonylphenyl group-substituted amino groups such as 4-ethoxycarbonylphenylamino group can be mentioned.
When R ² is a heterocyclic group which may be substituted, specific examples thereof include 2-oxo-tetrahydrofuran-3-yl and 2 ′, 3 ′, 4′-triacetylarabinosyl. Examples thereof include an oxygen-containing 5- or 6-membered heterocyclic group such as a tetrahydrofuryl group or a tetrahydropyranyl group which may be substituted with an oxo group or a lower alkylcarbonyloxy group. The anion of the inorganic acid or organic acid of X may be any kind as long as it is pharmacologically acceptable, and examples thereof include hydrobromic acid such as hydrogen bromide, hydrogen iodide and hydrogen chloride, Lower alkanoic acid such as acetic acid, lower methylsulfonic acid such as methylsulfonic acid and nonafluoro-1-butanesulfonic acid which may be substituted with a halogen atom, lower alkoxysulfonic acid such as monomethylsulfuric acid, phenylsulfonic acid, toluenesulfonic acid And a group obtained by removing one hydrogen atom from phenylsulfonic acid which may be substituted with a lower alkyl group such as

Among the object compounds (I) of the present invention, the compound which is preferable in terms of efficacy is represented by the general formula (I) in which R ² is of the formula: —CH ₂
-CO-R ² "[wherein, R ^2" is a phenyl group, a lower alkoxy group, a substituted phenyl group, a lower alkyl group, a hydroxyl-substituted lower alkyl group or a lower alkoxy-substituted lower alkyl group]
Is a compound.

The object compound (I) of the present invention can be administered orally or parenterally, and may be administered in an appropriate manner such as tablets, granules, capsules, powders and injections by a conventional method. It can be used as a pharmaceutical material.

The dose of the object compound (I) of the present invention varies depending on the administration method, age, weight and condition of the patient.
Usually, it is preferably about 0.1 to 10 mg / kg per day, especially about 1 to 2 mg / kg.

The object compound (I) of the present invention has the general formula (I
I):

[Chemical 6] [Wherein, R ¹ and R ³ have the same meanings as described above], and a raw material compound represented by the general formula (III): R ² X (III) [wherein, X is an anion of an inorganic acid or an organic acid, R ² has the same meaning as above], and can be produced. The reaction between the starting compound (II) and the compound (III) can be carried out in a suitable solvent. Any solvent can be used as long as it does not adversely influence the reaction, and examples thereof include dimethylformamide and hexamethylphosphoramide.
As X, any group obtained by removing one hydrogen atom from an inorganic acid or an organic acid can be used, and specific examples thereof include a halogen atom, a lower alkylcarbonyloxy group, a lower alkylsulfonyloxy group, and a halogenated lower alkylsulfonyl group. Examples thereof include an oxy group, a lower alkoxysulfonyloxy group, a phenylsulfonyloxy group, and a lower alkyl group-substituted phenylsulfonyloxy group. The reaction suitably proceeds under cooling to heating (for example, 20 to 50 ° C.).

The starting compound (II) of the present invention is a novel compound and can be produced, for example, by the following method. (I) Of the starting compound (II) of the present invention, a compound of the general formula (I
Ia):

[Chemical 7] [Wherein R ¹¹ is a hydrogen atom or a lower alkoxy group, R 11
³ has the same meaning as above], and a compound represented by the general formula (IV):

[Chemical 8] A compound represented by the formula [wherein R ¹¹ and R ³ are as defined above] is subjected to an oxidation reaction according to a conventional method in the presence of a suitable oxidizing agent (eg, metachloroperbenzoic acid). ..

(Ii) The starting compound (II) of the present invention
Of the general formula (II-b) in which R ¹ is a hydroxyl group:

[Chemical 9] The compound represented by the formula [wherein R ³ has the same meaning as defined above] is the compound of the general formula (II-a) obtained in (i) above, wherein R ¹¹ is a lower alkoxy group. According to a conventional method, it can be obtained by subjecting to a dealkylation reaction in the presence of a suitable dealkylating agent (for example, boron tribromide).

(Iii) Furthermore, in the starting compound (II) of the present invention, R ¹ is of the formula: —OCOR ¹² [wherein R ¹² is an optionally substituted lower alkyl group,
A lower alkoxy group or a lower alkylamino group] represented by the general formula (II-c):

[Chemical 10] [Wherein R ¹² , R ³ and X have the same meanings as defined above] can be obtained by reacting the compound represented by the general formula (II-b) obtained in the above (ii).
A compound of formula (V): R ¹² COOH (V) [wherein R ¹² has the same meaning as defined above] or a reactive derivative thereof (eg, an acid halide such as an acid chloride, etc.) ) Are reacted in the presence or absence of a dehydrating agent or a deoxidizing agent (for example, potassium carbonate) according to a conventional method.

In the present specification, an alkyl group having 1 to 12 carbon atoms, particularly 1 to 10 carbon atoms is a lower alkyl group (or lower alkyl), a lower alkoxy group (or lower alkoxy), a lower alkenyl group, a lower alkyl group. The alkynyl group is preferably one having 1 to 6 carbon atoms, especially 1 to 4 carbon atoms, and the cyclic alkyl group is preferably one having 3 to 6 carbon atoms, especially 3 carbon atoms.

[0015]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples.

Example 1 (1) 11.7 g of 9-methoxy ellipticine was suspended in 400 ml of acetone, and 18.3 g of m-chloroperbenzoic acid was added little by little under stirring with cooling. Mix at the same temperature for 3
After stirring for 0 minutes, stirring is continued for another 20 hours at room temperature. The reaction solution is concentrated under reduced pressure to about 1/3, 500 ml of isopropyl ether is added to the residue, and the mixture is stirred for 1 hour. The precipitated powder was collected by filtration, washed with a mixed solution of acetone / isopropyl ether, and dried to obtain 10.88 g of a yellow powder of 9-methoxyelepticin-2-oxide (yield: 88.
%). mp:> 270 ° C. Mass (m / z): 292 (M ⁺ ), 276 (M ⁺ −)
O) NMR (DMSO-d ₆ ) δ: 2.76 (3H, s),
3.07 (3H, s), 3.90 (3H, s), 7.2
0 (1H, dd, J = 8.8, 2.5Hz), 7.48
(1H, d, J = 8.8Hz), 7.82 (1H, d,
J = 2.5 Hz), 8.02, 8.05 (each 1H,
d, J = 7.3 Hz), 9.12 (1 H, s), 11.
28 (1H, s) (2) 614 mg of this product is suspended in 6 ml of dimethylformamide, 1.15 g of bromacetone is added with stirring, and the mixture is stirred at room temperature for 3 hours. 60 ml of methylene chloride was added to the reaction solution, and the precipitated powder was collected by filtration, washed with methylene chloride, and dried to give 2- (2-oxopropoxy) -9-methoxyellipticinium bromide red powder 370 mg.
(Yield: 41%) is obtained. mp:> 270 ° C. Mass (m / z): 349 (M ⁺ -Br) NMR (DMSO-d ₆ ) δ: 2.19 (3H, s),
2.77 (3H, s), 3.24 (3H, s), 3.9
3 (3H, s), 5.65 (2H, s), 7.27,
7.54 (1H, d, J = 8.8Hz, respectively), 7.79
(1H, s), 8.42, 8.79 (1H, d, J respectively)
= 7.3 Hz), 10.34 (1H, s), 12.05
(1H, s)

Examples 2 to 4 9-methoxy ellipticine obtained in Example 1- (1)
The compound shown in Table 1 below is obtained by reacting 2-oxide with the corresponding starting compound in the same manner as in Example- (2).

[Table 1]

Example 5 (1) 9.41 g of 9-methoxy ellipticine-2-oxide obtained in Example 1- (1) was added to 250 m of methylene chloride.
The mixture was suspended in 1 and a solution of 20.2 g of boron tribromide in 80 ml of methylene chloride was added dropwise to the mixture at -78 ° C with stirring. Remove the cooling bath, continue stirring for 1.5 hours, and then-
Cool to 78 ° C. and add 35 ml of methanol dropwise. The cooling bath is removed, and the mixture is left standing for 1 hour as it is, concentrated under reduced pressure, 150 ml of methanol is added to the residue, and potassium acetate is added at 0 ° C. or lower with stirring to neutralize. The mixture is concentrated under reduced pressure,
100 ml of water was added to the residue, and the precipitated powder was collected by filtration, washed with water and dried to obtain 7.82 g (yield: 87%) of a dark yellow powder of 9-hydroxyelepticin-2-oxide. mp:> 270 ° C. Mass (m / z): 278 (M ⁺ ) NMR (DMSO-d ₆ ) δ: 2.75 (3H, s),
3.03 (3H, s), 7.05 (1H, dd, J =
2, 8.3 Hz), 7.39 (1H, d, J = 8.3H
z), 7.73 (1H, d, J = 2Hz), 8.01,
8.06 (1H, d, J = 7.3Hz, respectively), 9.10
(1H, s), 9.15 (1H, s), 11.13 (1
H, s) (2) 557 mg of this product was added to 10 ml of dimethylformamide.
Then, 1.1 g of bromacetone is added with stirring and the mixture is stirred at room temperature for 3 hours. Then, by treating in the same manner as in Example 1- (2), 2- (2-oxopropoxy) -9-
Hydroxyellipticinium bromide red powder 67
2 mg (yield: 81%) are obtained. mp:> 270 ° C. Mass (m / z): 335 (M ⁺ -Br) NMR (DMSO-d ₆ ) δ: 2.18 (3H, s),
2.79 (3H, s), 3.22 (3H, s), 5.6
4 (2H, s), 7.14 (1H, dd, J = 2.4,
8.8Hz), 7.48 (1H, d, J = 8.8H
z), 7.55 (1H, d, J = 2.4 Hz), 8.4
3, 8.79 (1H, dd, J = 2, 7.8H, respectively)
z), 9.40 (1H, s), 10.31 (1H, d,
J = 2Hz), 11.99 (1H, s)

Examples 6 to 60 The following Table 2 was obtained by carrying out a reaction treatment in the same manner as in Example 5.
To obtain the compounds described in

[0020]

[Table 2]

[0021]

[Table 3]

[0022]

[Table 4]

[0023]

[Table 5]

[0024]

[Table 6]

[0025]

[Table 7]

[0026]

[Table 8]

[0027]

[Table 9]

[0028]

[Table 10]

[0029]

[Table 11]

[0030]

[Table 12]

[0031]

[Table 13]

[0032]

[Table 14]

[0033]

[Table 15]

[0034]

[Table 16]

Example 61 (1) 3.90 g of 9-hydroxy ellipticine-2-oxide obtained in Example 5- (1) and anhydrous potassium carbonate 1
Add 9.34 g to 50 ml of dimethylformamide and add 1
While stirring at 0 to 15 ° C, 4.0 g of acetyl chloride was added dropwise, and the mixture was reacted at room temperature for 5 hours with stirring. The insoluble matter was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (solvent: chloroform / methanol / dimethylformamide) to give 9-acetoxy ellipticine-2-oxide yellow powder (2.06 g). (Yield: 46%) is obtained. mp: 260 to 260.5 ° C. (decomposition) Mass (m / z): 321 (MH ⁺ ) NMR (DMSO-d ₆ ) δ: 2.34 (3H, s),
2.79 (3H, s), 2.89 (3H, s), 7.3
0 (1H, d, J = 8.8Hz), 7.54 (1H,
d, J = 8.8 Hz), 8.01 (1H, d, J = 7.
8 Hz), 8.06 (1H, s), 8.09 (1H, d
d, J = 2, 7.8 Hz), 9.11 (1H, d, J =
2Hz), 11.48 (1H, s) (2) This product 426mg, bromoacetyl bromide 0.7
By reacting 3 g in the same manner as in Example 1- (2), 379 mg (yield: 62%) of yellow powder of 2- (2-oxopropoxy) -9-acetoxy ellipticinium bromide was obtained. mp: 183-185 ° C. (decomposition) Mass (m / z): 377 (M ⁺ -Br) NMR (DMSO-d ₆ ) δ: 2.18 (3H, s),
2.37 (3H, s), 2.83 (3H, s), 3.2
5 (3H, s), 5.66 (2H, s), 7.43 (1
H, dd, J = 2, 8.3 Hz), 7.65 (1H,
d, J = 8.3 Hz), 8.19 (1H, d, J = 2H)
z), 8.49 (1H, d, J = 7.8Hz), 8.8
5 (1H, dd, J = 2, 7.8 Hz), 10.40
(1H, s), 12.29 (1H, s)

Examples 62 to 71 The following Table 17 was obtained by carrying out the reaction treatment in the same manner as in Example 61.
To obtain the compound described in.

[0037]

[Table 17]

[0038]

[Table 18]

[0039]

[Table 19]

[0040]

[Table 20]

Example 72 (1) 2.09 g of a known compound, 6-methyl-9-methoxy ellipticine, and 3.1 g of m-chloroperbenzoic acid.
Was treated in the same manner as in Example 1- (1) to give 6
1.90 g (yield: 86%) of yellow powder of -methyl-9-methoxy ellipticine-2-oxide is obtained. Mass (m / z): 307 (MH ⁺ ) NMR (DMSO-d ₆ ) δ: 2.95 (6H, s),
3.89 (3H, s), 4.04 (3H, s), 7.2
2 (1H, dd, J = 2, 8.8Hz), 7.49 (1
H, d, J = 8.8 Hz), 7.72 (1H, d, J =
2Hz), 8.05 (2H, s), 9.11 (1H,
s) (2) By subjecting 400 mg of this product and 0.72 g of bromoacetone to a reaction treatment in the same manner as in Example 1- (2), 2-
370 mg (yield: 64%) of a red powder of (2-oxopropoxy) -6-methyl-9-methoxyellipticinium bromide is obtained. mp:> 270 ° Mass (m / z): 363 (M ⁺ -Br) NMR (DMSO-d ₆ ) δ: 2.18 (3H, s),
3.06 (3H, s), 3.23 (3H, s), 3.9
3 (3H, s), 4.19 (3H, s), 5.65 (2
H, s), 7.35 (1H, d, J = 8 Hz), 7.7
1 (1H, d, J = 8Hz), 7.84 (1H, s),
8.57 (1H, d, J = 7.3 Hz), 8.81 (1
H, d, J = 7.3 Hz), 10.37 (1 H, s)

Example 73 (1) Example 7 2- (1) The 6-methyl-9-methoxy ellipticine-2-oxide (1.52 g) and boron tribromide (3.13 g) were used in Example 5- ( By the same reaction treatment as in 1), 0.81 g of yellow powder of 6-methyl-9-hydroxyelepticin-2-oxide (yield: 56
%). Mass (m / z): 293 (NH ⁺ ) NMR (DMSO-d ₆ ) δ: 2.97 (6H, s),
4.05 (3H, s), 7.09 (1H, dd, J =
2, 8.8 Hz), 7.45 (1H, d, J = 8.8H
z), 7.72 (1H, d, J = 2Hz), 8.09
(2H, s), 9.12 (1H, s), 9.23 (1
H, br) (2) By subjecting this product (413 mg) and bromoacetone (0.77 g) to a reaction treatment in the same manner as in Example 5- (2), 2-
(2-oxopropoxy) -6-methyl-9-hydroxy ellipticinium bromide red powder 469 mg
(Yield: 77%) is obtained. ^{Mass (m / z): 349} (M + -Br) NMR (DMSO-d 6) δ: 2.18 (3H, s),
3.05 (3H, s), 3.17 (3H, s), 4.1
5 (3H, s), 5.64 (2H, s), 7.18 (1
H, dd, J = 2, 8.8 Hz), 7.58 (1H,
d, J = 8.8 Hz), 7.76 (1H, d, J = 2H)
z), 8.55 (1H, d, J = 7.8Hz), 8.8
0 (1H, dd, J = 1.5, 8.8Hz), 9.48
(1H, s), 10.31 (1H, d, J = 1.5H
z)

Example 74 By reacting the corresponding starting material compound in the same manner as in Example 73, a red powder of 2- (aminocarbonylmethoxy) -6-methyl-9-hydroxyelepticinium bromide was obtained in a yield of 85%. Get at. Mass (m / z): 350 (M ⁺ -Br) NMR (DMSO-d ₆ ) δ: 3.09 (3H, s),
3.21 (3H, s), 4.19 (3H, s), 5.2
7 (2H, s), 7.21 (1H, d, J = 8.8H
z), 7.63 (1H, d, J = 8.8 Hz), 7.8
1 (1H, s), 8.60 (1H, d, J = 7.8H
z), 8.90 (1H, d, J = 7.8Hz), 9.5
2 (1H, s), 10.42 (1H, s)

[0044]

The ellipticine derivative (I) of the present invention has excellent antitumor activity and is useful as an antitumor agent.
For example, a mouse having a leukemia cell P388 of the ellipticine derivative of the present invention, a mouse colon cancer colon 26 cell, and a mouse Lewis lung cancer cell transplanted has a significant antitumor effect and life prolonging effect. Furthermore, an inhibitory effect on phosphorylation of p53 gene product, which is considered to be the cause of canceration of normal cells, is observed in human colon cancer cells and the like. In addition, the ellipticine derivative (I) of the present invention has excellent features that it has weak side effects on the circulatory system such as tachycardia and low toxicity. For example, in mice 2-phenylcarbonylmethoxy-9-hydroxy ellipticinium bromide or 2- (2-oxopropoxy) -9-
Hydroxyelepticinium bromide 40mg / kg
Was administered intravenously once a day for 7 days and observed for a further 7 days, but no death was observed.

Claims (5)

[Claims] 1. A compound represented by the general formula (I): [In the formula, R ¹ represents a hydrogen atom, a hydroxyl group, a lower alkoxy group,
Optionally substituted lower alkylcarbonyloxy group, lower alkoxycarbonyloxy group or lower alkylaminocarbonyloxy group; R ² represents lower alkoxy group, halogen atom, cyano group, hydroxyl group, optionally substituted amino group, cyclic Alkyl group, phenyl group and formula: —CO—R ² ′ (wherein R ² ′ may be a substituted phenyl group, a heterocyclic group, a lower alkenyl group, an optionally substituted lower alkyl group, a hydroxyl group , An optionally substituted lower alkoxy group, a cyclic alkyl group or an optionally substituted amino group), which may have a substituent selected from the group represented by the following; an lower alkenyl group; a lower alkynyl group Or an optionally substituted heterocyclic group; R ³ is a hydrogen atom or a lower alkyl group; X
Is an anion of an inorganic acid or an organic acid]. 2. R ¹ is a hydrogen atom, a hydroxyl group, a lower alkoxy group, a lower alkylcarbonyloxy group, a lower alkoxy group-substituted lower alkylcarbonyloxy group, a lower alkoxy-lower alkoxy group-substituted lower alkylcarbonyloxy group, a lower alkoxycarbonyloxy group. Group or a lower alkylaminocarbonyloxy group, R ² is a lower alkoxy group, a halogen atom, a cyano group, a hydroxyl group, an amino group,
A mono- or di-lower alkylamino group, a cyclic alkyl group, a phenyl group and a formula: —CO—R ² ′ [in the formula, R ² ′
Is a phenyl group, a lower alkoxy group-substituted phenyl group, a lower alkoxy-lower alkoxy group-substituted phenyl group, a hydroxyl group-substituted phenyl group, a halogen-substituted phenyl group, a nitrogen-containing, oxygen-containing or sulfur-containing 5- or 6-membered heterocyclic group, a lower alkenyl group , Lower alkyl group, lower alkoxy group substituted lower alkyl group, lower alkoxy-lower alkoxy group substituted lower alkyl group, lower alkylcarbonyloxy group substituted lower alkyl group, hydroxyl group substituted lower alkyl group, hydroxyl group, lower alkoxy group, lower alkoxy group substituted Lower alkoxy group, lower alkoxy-lower alkoxy group-substituted lower alkoxy group, cyclic alkyl group, amino group, mono- or di-lower alkylamino group (the lower alkyl group of the mono- or di-lower alkylamino group is a lower alkoxy group, a lower alkoxy group, Alkoxycarbonyl group A phenyl group, an oxo group-substituted 5-membered nitrogen-containing heterocyclic group, and a phenyl lower alkylaminocarbonyl group, which may be substituted with 1 to 2 groups). The compound according to claim 1, which is an alkyl group which may be possessed; a lower alkenyl group; an oxygen-containing 5- or 6-membered heterocyclic group which may be substituted with a lower alkynyl group, an oxo group or a lower alkylcarbonyloxy group. 3. R ² has the formula: —CH ₂ —CO—R ² ″ (wherein R ² ″ is a phenyl group, a lower alkoxy group-substituted phenyl group, a lower alkyl group, a hydroxyl group-substituted lower alkyl group or a lower alkoxy group. The compound according to claim 1, which is a group represented by a substituted lower alkyl group). 4. General formula (II): [Wherein R ¹ is a hydrogen atom, a hydroxyl group, a lower alkoxy group,
An optionally substituted lower alkylcarbonyloxy group, a lower alkoxycarbonyloxy group or a lower alkylaminocarbonyloxy group, and R ³ is a hydrogen atom or a lower alkyl group] is a compound represented by the general formula (III): R ² X (III) [In the formula, R ² is a lower alkoxy group, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, a cyclic alkyl group, a phenyl group and a formula: —CO—R ² ′ (wherein ,
R ² 'is an optionally substituted phenyl group, heterocyclic group,
Lower alkenyl group, optionally substituted lower alkyl group, hydroxyl group, optionally substituted lower alkoxy group,
A cyclic alkyl group or an optionally substituted amino group) an alkyl group which may have a substituent selected from the group represented by; a lower alkenyl group; a lower alkynyl group or an optionally substituted heterocyclic group, X is an anion of an inorganic acid or an organic acid], and is reacted with a compound represented by the general formula (I): [Wherein R ¹ , R ² , R ³ and X have the same meanings as described above], and a method for producing an ellipticine derivative. 5. A compound represented by the general formula (II): [In the formula, R ¹ represents a hydrogen atom, a hydroxyl group, a lower alkoxy group,
A lower alkylcarbonyloxy group, a lower alkoxycarbonyloxy group or a lower alkylaminocarbonyloxy group which may be substituted, and R ³ is a hydrogen atom or a lower alkyl group].