JPS58121278A - Isoquinolinesulfonic acid amide derivative - Google Patents

Abstract

NEW MATERIAL:The isoquinolinesulfonic acid amide derivative of formulaI(m and n are integer of 0-9; R1 is H, 1-10C alkyl or aryl; R2 and R3 are H, 1- 10C alkyl, aryl, aralkyl, or bonded together directly or through O atom forming a heterocyclic group with adjacent N atom) and its acid addition salt. EXAMPLE:N-(4-Aminobutyl)-5-isoquinolinesulfonic acid amide. USE:A vasodilator, cerebral circulation improving agent, remedy for stenocardia, preventive and remedy for thrombosis of the celebral and cardiac vessel. It has strong smooth muscle relaxing and blood flow rate increasing activities. PROCESS:The compound of formulaIis prepared e.g. by reacting the 5-isoquinolinesulfonic acid chloride of formula II with the compound of formula III (e.g. 1,2-diaminoethane, 1,4-diaminobutane, etc.) in the presence of an acid acceptor such as sodium bicarbonate, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (I) R1 (wherein m and n are integers of 9 to 9, R2 represents a hydrogen atom, an alkyl group or an aryl group having 1 to 10 carbon atoms, R,,R,Fi water atom, C1-C10 alkyl group, aryl group, aralkyl group, or FiR.

Birds are bonded directly or through oxygen atoms, and adjacent N
The present invention relates to inquinoline sulfonic acid amide derivatives and acid addition salts thereof, which represent a group that forms a complex IN with the inquinoline sulfonic acid amide derivatives.

Examples of R8 include hydrogen, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, reduced-butyl group, n-pentyl group, cyclopentyl group, n-hexyl group, and cyclohexyl group. group, phenyl group, vignetting, mino group, ethylamino group, n-propylamino group, isopropylamino group, n-butylamino group, imbutylamino group, n-hexylamino group, cyclohexylamino group, dimethylamino group , diethylamino group, di-n-butylamino group, N-methyl-N-cyclopentylamino group, N-methyl-N-cyclohexylamino group, N-methyl-N-phenylamino group, N-methyl-N-benzylamino group group, N-ethyl-N-benzylamino group, N-inpropyl-N-pe/dylamino group, pyrrolidino group, -piperidino group, and morpholino group.

Specifically, examples include the following compounds.

(31N-(2-7minoethyl)-5-isoquinolinesulfonic acid amide (21N-(S-aminopropyl)-5
-Inquinoline sulfonic acid amide 131 N-(4-aminobutyl)-5-Inquinoline sulfonic acid amide 14
1N-(4-7minohexyl)-5-isoquinolinesulfonic acid amide (53N-(8-aminooctyl)-5-
Inquinoline sulfonic acid amide (61N-(10-aminodecyl)-5-inquinoline sulfonic acid amide (7)
N-(2-amino-1-methylethyl)-5-inquinolinesulfonic acid amide (8!IN-(1-7minomethylglobil)-5-inquinolinsulfonic acid amide (9)
N-(1-7minomethylbutyl)-5-isoquinolinesulfone 127mide (IIN-(1-aminomethylpentyl)-5-inquinolinesulfonic acid amide (IIN-(
2-7minoprovir)-5-isoquinoline sulfonic acid amide 63N-(2-7minobutyl)-5-inoquinori/
Sulfonic acid amide a3N-(2-amino-3-methylbutyl)-5-isoquinoline sulfonic acid amide a4N-(
2-7minohexyl)-5-isoquinoline sulfone 12
mido(1'9N-(1-phenylethyl)-5-isoquinolinesulfonic acid amide (15N-(2-phenylethyl)-5-inquinolinesulfonic acid amide a?)N-(
2-Methylaminoethyl)-5-quinolinsulfonic acid amide alN-(2-ethylaminoethyl)-5-isoquinolinesulfonic acid amide (L field N-(2-improhyvaminoethyl)-5-isoquinol/sulfonic acid Amide N-(2-n-butylaminoethyl)-5-isoquinolinesulfonic acid amide C21) N-[2-(N-methyl-N-benzylamino)ethyl-5-isoquinolinesulfonic acid amide (ffiN-(2- (N-Ethyl-N-benzylamino)ethyl-5-isoquinolinesulfonamide (c)N-(2-(N-inpropyl-N-benzylamino)ethyl]-5-iaquinolinesulfonamide C70) N- C2-(N-n-butyl-N-benzylamino)ethyl]-5-inquinolinesulfonic acid amide (c) N-(3-dimethylaminopropyl)-5-isoquinolinesulfonic acid amide (to) N-(3 -diethylaminopropyl)-5-isoquinoline sulfonic acid amide@
N-(3-di-n-butylaminopropyl)-5-isoquinolinesulfonic acid amide C! 19N-(3-piveridinoglovir)-5-inquinoline sulfonic acid amide (c)N-(3-morpholinoglovir)-5-isoquinoli/
Sulfonic acid amide (7)N-(5-(N-methyl-N-
cyclohexylamino)propyl]--5-inquinolinesulfonic acid amide ogN-(3-(N-methyl-N-phenylamino)propyl]-5-isoquinolinesulfonic acid amide 33N-(3-(N-methyl- N-Benzylamino)propyl-5-inquinoline sulfonic acid amide The present invention also provides an acid addition salt of the isoquinoline derivative represented by the general formula (I).This salt is a pharmaceutically acceptable non-toxic salt. Salts of inorganic acids such as salt-acids, hydrobromic acid, phosphoric acid, sulfuric acid, and acetic acid, citric acid, tartaric acid, lactic acid, succinic acid, fumaric acid, maleic acid,
Organic acids such as meta/sulfonic acid and p-toluenesulfonic acid can be mentioned.

The isoquinoline sulfonic acid amide derivative represented by the general formula (I) provided by the present invention can be synthesized, for example, according to the following formula.

(In the formula, R1, R1, R, Fi represents the same meaning as above.) That is, 5-isoquinolinesulfonic acid chloride 9
It can be obtained by reacting 0D with a compound represented by the general formula (IID).

Examples of compounds represented by the formula (song) include 1,2-diaminoethane, 1,3-diaminopro-I, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diamithexane, 1,8-diaminooctane, 1.10
-diaminodecane, 2-(N-methyl-N-benzylamino)ethylamine, 2-(N-benzylamino)ethylamine, 2-(N-isopropyl-
N-benzylamino)ethylamine, 2-(N-n-butyl-N-benzylamino)ethylamine 5-dimethylaminopropylamine, 3-diethylamine clobylamine, 3-(di-n-propylamine)propylamine, 5-(diimpropylamino)propylamine, 3
-(di-n-butylamino) clobylamine, S-(diisobutylamino)propylamine, 5-(N-methyl-N-cyclohexylamino) clobylamine, 3-(
N-methyl-N-phenylamino)propylamide, 3
- (N-1f-N-benzylamino)propylamine, 3-piperidinopropylamine, 5-bipridinoglobylamine, 3-morpholinopropylamine, and the like.

An acid acceptor may be present in this reaction.

Acid acceptors include alkali metal compounds such as sodium bicarbonate, sodium hydroxide, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydride, sodium methylate, and organic compounds such as pyridine, trimethylamine, triethylamine, and triethylenediamine. Third
and class amines. As the reaction solvent, alkanols such as methanol and ethanol, dichloromethane, non-rogenated hydrocarbons such as chloroform, ethers such as tetrahydrofura/dioxane, acetonitrile, dimethylformamide, dimethylsulfoxide, etc. are used.

The amount of the compound represented by the general formula (g) relative to acid chloride I is preferably 1 to 10 times the molar range, more preferably 1 to 3 times the molar range, when an acid acceptor is present. When it is not present, it is preferably 2 to 20 times the mole, particularly preferably 2 to 10 times the mole.

When using the M”II container, the amount used is determined by the formula (In)
The amount is preferably in the range of 1 to 6 ions, particularly preferably 1 to 6 equivalents, relative to the compound represented by. The reaction temperature was 0°C to 12°C.
A range of 0°C is preferred, and a range of 0°C to 80°C is particularly preferred.

Furthermore, when horse is a hydrogen atom, it can be synthesized according to the following formula.

(In the formula, R1, R3, m, nli have the same meanings as above, and X represents a protecting group.) Examples of the protecting group X include a formyl group, an acetyl group,
Examples include an acyl group such as a hendiyl group, a pair 7''yloxycarbonyl group, an amylmethyl-alkyl-oxycarbonyl group such as a t-butoxycarbonyl group, and a benzyl group.

Examples of the compound of formula (IV) include N'-7cetyl-1,2-diaminoethane, N'-acetyl-1,5-
Diaminopropane, shea-acetyl-1,4-diaminobutane, N'-acetyl-1,5-diaminopentane, N
'-7 cetyl-1,6-diamithexane, N'-7 cetyl-1,8-diaminooctane, N'-acetyl-1
, 10-diaminodecane, 2-pe/zyloxycarbonylamino-1-methylethylamine, 1-(benzyloxycarbonylaminomethyl)propylamine, '-(
benzyloxycarbonylaminomethyl)pentylamine, 2-(benzyloxycarbonylamino)propylamine, 2-benzyloxycarbonylamino-3-methylbutylamine, 2-7 cetamide globilamine, 2
-acetamido-3-methylbutylamine, 2-acetamido-2-phenylethylamine, 2-(N-benzyl-
N-methylamino)ethylamine, 2-(N-benzyl-N-ethylamino)ethylamine, 2-(N-benzyl-N-ingrobilamine)ethylamine, 2-benzyloxycarbonylamino-1-phenylethylamine, 2- Benzyloxycarbonylamino-2-phenylethylamine, N'-formyl-1,4-diaminobutane, etc. can be added.

(2) and (iv) The reaction conditions for obtaining YoshiM are the above-mentioned ■ and [
It can be carried out under the same reaction conditions as those for [Strain]. Myoshi■
The method for obtaining the target (V)t- is selected depending on the protecting group X, and all of them are commonly known methods.

That is, for example, in the case of an acyl group such as a formyl group or an acetyl group, hydrolysis with an acid or alkali, in the case of a benzyl group, hydrogenation, and in the case of a benzyloxycarbonyl group, hydrogenation or acid content IM, t-butyl In the case of an oxycarbonyl group, the purpose can be achieved by acid decomposition.

According to the research of the present inventors, the compound represented by the general formula (I) and its pharmaceutically acceptable acid addition salt provided by the present invention have a strong smooth muscle relaxing effect and a blood flow increasing effect. It is a substance that is useful as a vasodilator, a cerebral circulation improver, a therapeutic agent for angina pectoris, and a preventive and therapeutic agent for thrombosis in the cerebro-cardiovascular system.

The effect of this compound on phlegm was confirmed by the relaxing effect on the superior intestinal j≦1 membranous artery in domestic rabbits, and the vasodilatory effect was confirmed by increasing the blood flow in the femoral artery and vertebral artery in dogs.

The smooth muscle relaxing effect was demonstrated by suspending the superior zygomatic artery isolated from a rabbit in a spiral shape, contracting it with potassium chloride, and adding the compound of the present invention to the suspension, which caused relaxation.

For example, when N-(4-7minoptyl)-5-isoquinolinesulfonic acid amide (3) is added, the complete relaxation is taken as 100st, and the relaxation is 50St; 4t;bflllL
(EDs*) u 11 tt M f display.

The expansion effect of the colonic artery and vertebral artery is
~15 klil) tpe/tobarbital sodium 55
The patient was anesthetized by intravenous administration of 1/kg, and a non-invasive probe (manufactured by Nihon Kohden) was attached to the femoral and vertebral arteries.
Blood flow was measured using an electromagnetic blood flow needle (Nihon Kohden MP-27). Under these conditions, the compounds of the present invention, such as N-(
When 9 was administered intravenously to 4-7minobutyl)-5-isoquinolinesulfonic acid amide (3) 1/2, the femoral artery blood flow Fiss-1 and the vertebral artery blood flow #'i36 increased.

Furthermore, for the above-mentioned reasons, when the compounds of the present invention are administered intravenously or intraarterially, no serious toxicity is observed; Acute toxicity value LD of amide f31.

was 87~/boiled when administered intravenously to male mice.

Hereinafter, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited to this.

Example 1 8.82 1,4-diaminozutane was dissolved in chloroform 20
Dissolve 0 dK and add 100% chloroform to this solution under ice cooling.
A solution of 4,559 5-inquinolinsulfonic acid chloride dissolved in dK was added dropwise. After the dropwise addition, the mixture was stirred at 20 to 25°C for 2 hours, and the reaction solution was extracted with 10-hydrochloric acid water. The aqueous layer was adjusted to pH 16 with 10% caustic soda and extracted with chloroform. The chloroform layer was washed with water and dried over anhydrous potassium carbonate. Chloroform was concentrated, and the residue was subjected to column chromatography using silica gel 2, IjkH solvent 2% methanol/chloroform (volume ratio), and N
('-Aminobutyl)-5-isoquinolinesulfonic acid amide f315.469 was obtained as an oily substance.

Yield 62 Timas spectrum (m/e): 279 (%”) -22
'NMR spectrum (CDCI4): 1.5-2.0
(4H.

2×q-12,5~3.2 (4H, 2XNCH,),
2.4 (2H, Tomo), 7.5-7.7 (IH), 7.
9-8.7 (4H), 9.3 (III) IR spectrum (y"p, 3-'): f330,11
60ax Same method! 5N-(#-aminoalkyl)-5-
Isoquinoline sulfonic acid amide was obtained (Table 1-11Table 1
-2).

Table 1-1 Example 2 3-dimethylaminopropylamine 1,4? and 5-inquinolinsulfonic acid chloride 2,6 in a chloroform 50-solution containing triethylamine 1,49 under ice cooling.
A chloroform 30-solution containing f was added dropwise. After dripping 2
Stirred at ~10°C for 4 hours. The reaction mixture was washed with water and dried over anhydrous magnesium sulfate. Chloroform was distilled off under reduced pressure, and the residue was subjected to column chromatography (chloroform) on silica gel (709) to obtain 52.389 of N-(3-dimethylaminopropyl)-5-isoquinolinesulfonic acid 7mi). Yield 71911 Mass spectrum (m/e): 29!, 24?, 235.221
207 192 IRe collection)k (y"p#3-'): 2950
, ax 2860.2840.1460.1320.1150.
1130.850.76O NMR spectrum (CDC): 1.6 (2H, C, ), 2.0 to 2-6 (8H, 2xNe, +NC
quick), 5.1 (2H, NC le), 6-2 (Ndan), 7
．． 4-7.7 (IM), 8.0-8.6 (4H), 9.
3(1H) Similarly, N-(5-diethylaminopropyl)-5-
Isoquinoline sulfonic acid amide, N-(5-di-n-
(butylaminoglovir)-5-inoquinoline sulfonic acid, N-(5-biveridinoglovir)-5-
Isoquinoline sulfonamide, N-(3-morpholinopropyl)-5-inquinoline sulfonamide, N-(3-(N-methyl-N-cyclohexylamino)propyl)-S-isoquinoline sulfone Acid amide, N-tj-(N-methyl-N-phenylamino)propyl-5-isoquinolinesulfonic acid amide C
41), N-[3-(N-methylto-benzylamino)propyl-5-isoquinolinesulfonic acid amide (
) was obtained. The results are shown in Table 2-1 and Table 2-2.

Example 3 2-benzyloxycarbonylamino-1-methylethylamine 2,239. ) Dissolve 1.2 ml of ethylamine in 40 ml of chloroform, and add 2 ml of chloroform to this solution.
5-Inquinolinesulfonic acid chloride dissolved in 0-
, 289 was added dropwise over water cooling. 20-25℃ after dropping
The mixture was stirred for 2 hours.

The reaction solution was washed successively with saturated hydrogen carbonate solution and water, dried over magnesium sulfate, chloroform was distilled off under reduced pressure, and N-(2-benzyloxycarbonylamino-1-methylethyl)-5-ino Quinoline sulfonic acid amide 3,55f was obtained.

89%0 IR spectrum (Shin deafness, α-1): 3350.170
0.1530.116O NMR spectrum (CDC13): 0.95 (3
H, CH, ), 2.5-4.5 (3H), 5.0 (2H
, oc le φ), 4.4 (IH), 7.2 (5H), 7.
6(IH), 8.0-B, 6(43N), 9j(1)i
) N-(2-benzyloxycarbonylamino-1-methylethyl)-5-isoquinolinesulfonic acid amide2.
0fK25-Hydrobromic acid water monoacetic acid solution 5- was added, and 20
Stirred at ~25°C for 20 hours.

Ko-Teen 30- was added, and the precipitated crystals were collected.

Dissolve the crystals in water, wash with chloroform, and then
The mixture was made alkaline with -NaOH and extracted with chloroform. After washing the chloroform layer with water, it was dried over magnesium sulfate, and the chloroform was dried under reduced pressure to give N-(2-amino-1
-Methylethyl)-5-in 1.22 of quinolinesulfonic acid amide (7) was obtained. 90% yield mass spectrum (m
/e): 265.240.221.192 128 IR spectrum (y"p*cn4-"): 5400
．． 2900, ax 161tl, 1460.133G, 1160.114O
NMB spectrum (CDC): 1,1 (3H)
, 1.7 (2H), z, 6 (2B), 3.7 (111
), 6-5 (IH), 7,6 (11'l), 8.0-8
．． 7 (4H),? j(IH) By the same method as in Example 3, N-(1-aminomethylglobil)-5-inquinolinesulfonic acid amide (8j% N-(1-7minomethylbentyl)-5-isoquinolinesulfone Acid amide Q (
1,N-(2-amino-1-phenylethyl)-5-isoquinolinesulfonic acid amide Q51 was obtained as follows.

The results are shown in Table 3-1.3-2.3-5.

Coating 5-1 (In the formula, 2 represents -coocH, φ.) Table 3-2 Example 4 2-acetamidopropylamine 2. Of and triethylamine m, 6t were dissolved in 50-chloroform, and a solution of 5.289% of 5-isoquinolinesulfonic acid chloride dissolved in 50-chloroform was added dropwise to the solution while cooling with water. 15~
After stirring at 25° C. for 2 hours, the reaction solution was washed with water and dried over magnesium sulfate. Chloroform was distilled off under reduced pressure and N-(
5.67 f of 2-acetamidopropyl)-5-inquinolinsulfonic acid amide was obtained. Yield: 83 IR absorption scale (y, 5I-1): 53oo
, 1670ax 1365 1150 113O NMR spectrum (CDCt, ): 1.0 (5TI
, d, Cdan, ), 2.2 (3H, COCdanS
), 2.6-3.8 (5H), 5.5-7.0 (
2H) 7.6 (IH), 8.0-8.7 (4H), 9.
5(1111)N-(2-acetamidoglovir)-5-
Isoquinoline sulfonamide 3.02 and 10-hydrochloric acid 5
The reaction mixture of 〇- was stirred at 90-100°C for 56 hours. The reaction solution was washed with chloroform, made alkaline with 1N-NaOH, and extracted with chloroform.

The chloroform layer was washed with water, dried with magnesium sulfate,
Chloroform was distilled off under reduced pressure. The residue is alumina (70f
) to obtain N-(2-aminopropyl)-5-isoquinolinesulfonic acid amide aυ1,14S'. Yield 44 Timas spectrum (m/e): 265.222.193
．． 129.128 IR absorption spectrum (ν #m-'): 3400,
ax 1610.1460.1370.1150.115°N
MR spectrum (CDC): 1,0 (3H), 1
．． 7 (2H), 2.9-4.0 (3H),! , 8(1)
I), 7.5 (1) 1), 8.1-8.4 (4H), ?
,! (111) N-(2-amino-3-methylbutyl)-5-isoquinolinesulfonamide α3% N(2-amino-2-phenylethyl)-5
- Isoquinoline sulfonamide aQ was obtained. Table 4 shows the results.
-1.4-2.4-3.

Table 4-1 Table 4-2 Table 4-3 □□-] Example 5 2-(N-methyl-N-benzylamino)ethylamine 3,249 and triethylamine y2. IIIF was dissolved in 70 ml of methylene chloride, and a solution of 5.02 ml of 5-inquinoline sulfonic acid chloride dissolved in 50 ml of methylene chloride was added dropwise to this solution under ice-cooling.

After dropping, the mixture was stirred at 15 to 25°C for 1 hour. The reaction solution was washed with water and then extracted with 10-hydrochloric acid water. The aqueous layer was washed with fl roform, then alkalized with 1N-NaOH and extracted with chloroform. The chloroform layer was poured into water, dried over magociram sulfate, and then evaporated under reduced pressure.

The residue was subjected to column chromatography on silica gel 1002 to obtain 3,849 N-(2-(N-methyl-N-pen-dylamino)ethyl-5-isoquinoline/1-phonic acid amide QI). Yield 84 tima spectrum (
m/e): 355.340.264.221.128 IR absorption spectrum (5-voice, 5M-1): 3050
．． 2950.1620.1450.1330.1155
．． 1135 Abuse spectrum (CDCt,): 1,9(
3H, NC Dan, ), 263-2.7 (21(), 3.0
~3.3 (2H), 3. j5 (2H, Cdan, φ), 6.
8 (IH), 7.2 (5) 1), 7.6 (IH), 8.
0 to 8.5 (4H1,9,3(IH) In the same manner as in Example 5, N-(2-(N-improvil-N-be/dylamino)ethyl-5-isoquinolinesulfonic acid amide [with] The results are shown in Table 5-1 and Table 5-
Shown in 2.

Table 5-2 Example 6 N-(:2-(N-methyl-N-benzylamino)ethyl]-5-isoquinolinesulfonic acid amide υ2.0?
was dissolved in 100 d of ethanol, 0.2 f of 10-chipalladium-carbon was added, and the mixture was heated under a hydrogen stream of 2.0 to 2.5 atm.
The mixture was stirred vigorously for 5 hours at 0-25°C. After passing off the palladium on carbon, it was concentrated to dryness and N-(2-methylamineethyl)-5-inquinolinsulfonic acid amide α7) was reduced to 0.
I got 951. Yield: 64 Mass spectrum (m/e): 2
65.250.221, 28 rR absorption spectrum (%H + +'): 5400,
161o.

1350.1530.1160,114ONMR spectrum (CDC4): 1.7 ('H, NH), 2
．． 9 (3H, CHm), 2.5-5.1 (2H), 5
．． 1-5.5 (2H), 7.0 (Ill), 7.6
(I H), 8.1-8.5 (4H), 9.3 (1) f
) N-(2-inpropylaminoethyl)-5-isoquinolinesulfonamide α1 gold was obtained in the same manner as in Example 6.

The results are shown in Table 6-1 and Table 6-2.

Table 6-1 Table 6-2 Test Example 1 Relaxation effect on mesenteric artery A domestic rabbit (Japanese native species, weighing approximately 3 kg) was exsanguinated to death, then the abdomen was opened and the superior mesenteric artery was removed. According to the conventional method of blood vessels,
Cut into a spiral into 2 rich lx25+u, 95qAo:
Suspended in a 20D organ bath filled with Kreps-Hensneut nutrient solution passed through a mixed gas of ssco. Connect one side of the blood vessel to an isometric transducer and
When a load of 9 is applied, the contraction and relaxation reactions of the blood vessels occur using a transducer (Nihon Kohden, FD pickup TB-q).
12T). 15-20
The compound of the present invention was added under conditions of contraction of approximately 1/2 of the maximum contraction of KCl using mM KCL, and its relaxing effect was observed. The complete relaxation is defined as 100 inches, and Table 7 shows the concentration (E Ds e value) that causes 50 degrees of relaxation.

Table 7 Test Example 2 Effect on femoral artery and vertebral artery blood flow in dogs The experiment was conducted using the constant force method described in the text. The results are shown in Table 8.

Table 8 Test Example 3 Table 9 shows the LDso values when administered intravenously to ddY male mice.

Table 9

Claims (1)

[Claims] il+ General formula CI+ R1 (wherein m and n are integers from FiO to 9, R1 represents a hydrogen atom, an alkyl group or an aryl group having 1 to 10 carbon atoms, and R,, R, are hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an aryl group, an aralkyl group, or -1R5 represents a group bonded directly or through an oxygen atom to form a heterocycle with the adjacent N;
) Isoquinoline sulfonic acid amide derivatives and acid addition salts thereof. 121 In the general formula (I), m and n are integers from 0 to 9, where m+1 does not exceed 9, R1 is a hydrogen atom, an alkyl group having 1 to 1 carbon atoms, or a phenyl group, and R
t, R3Fi hydrogen atom, C1-C8 alkyl group, phenyl group, benzyl group, or -s R1
are bonded to each other directly or through oxygen atoms, and the complex l
The compound according to claim 1, which is a group forming N. 3. The compound according to claim 2, wherein f31 g, , and Rs are all hydrogen atoms. (Claim 41R1 is a hydrogen atom, the compound described in the third tomb. Compound. (6) A compound according to claim 5, wherein the alkyl group is a methyl group, ethyl group, propyl group, or butyl group. (A claim in which η m 1 n is 1 and R1 is a phenyl group The compound according to item 3, where m+n is 1 or 2, R8 is a hydrogen atom, 7'c is an alkyl group having 1 to 4 carbon atoms, R1
is an alkyl group having 1 to 6 carbon atoms, a phenyl group, a benzyl group, or a group in which -1R1 is bonded directly or through an oxygen atom to form a complex m together with the adjacent N. Compound according to item 2. (9) Claim 8 in which m+rl is 1, R1 is a hydrogen atom, and R1 is a methyl group, an ethyl group, or a propyl group.
Compounds described in Section. 8. The compound according to claim 8, wherein m-+-11 is 1, R3 is a methyl group, ethyl group, or propyl group, and R1 is a benzyl group. Q1im+n is 2, - is an alkyl group having 1 to 4 carbon atoms, R3 is an alkyl group having 1 to 6 carbon atoms, or the phenyl group is a benzyl group.Special i! F'l - Compound according to claim 8. 9. The compound according to claim 8, which is an N-group, a diptylamino group, or an N-methyl-N-cyclohexylamino group. (I4) The compound according to claim 13, wherein the heterocycle is amperidine or morpholine.