10-SUBSTITUTED 1,8-DIHYDROXY-9-ANTHRONES AND THEIR USE AS THERAPEUTIC AGENTS IN HUMAN AND VETERINARY MEDICINES AND AS COSMETIC AGENTS

31-12-1985 дата публикации

Номер:

CA0001198732A1

Автор: SHROOT BRAHAM, MAIGNAN JEAN, LANG GERARD

Принадлежит:

Контакты:

Номер заявки: 388367

Дата заявки: 20-10-1981

[1]

The present invention relates to novel chemical compounds from the group consisting of dihydroxy -1,8 - 9-substituted anthrones 10 and their use in human or veterinary medicine in particular in the treatment of psoriasis and warts, and cosmetics. The dihydroxy -1,8 - 9-substituted anthrones of the invention can be represented by the following general formula: wherein: is a radical selected from the group consisting of: CH. CON, r_3.r_3.' R, ΦΦand (e)-CH-CH-R R2 representing hydrogêne, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical, , R ^ and R [-representing a hydrogen atom, an alkyl radical having from 1 _AOUNI167AO> 8 carbon atoms, a mono-or polyhydroxyalkyl radical, optionally interrupted by an oxygen atom, having 1 _AOUNI167AO> 8 carbon atoms (e. g. 2 has 8 carbon atoms), or a cycloalkyl radical having 3 to 6 carbon atoms, or R ^ ^ and R taken together form a radical divalent selected from the group consisting of:^{n ^-ant 4®} or 5, - (CH2) 2^-0 "(CH2) 2" " and-(CH₂₎_2- N-(CH₂₎_2-.^{R 8}Rg is hydrogêne, a methyl radical or 2-hydroxy ethyl, Rg representing-CC ^ Rg, -CN, -CHO, -CONH_{2 or}conh -ch_2-oh,_{7 and R and} R ' η representing a hydrogen atom or a methyl radical and when suitable salts thereof. The compounds of the invention, with the exception of the compounds in which R = 7 R ' = 7 H, may be in the form of their optical isomers. The compounds of 1' present invention can also be provided in the form of salts, when the radical R ^ is the radical (b) and/or the radical (c) in which Rg is hydrogêne. In this case these salts have the following formulae: Zr ^ and have the same meanings as given above for formula (1). The present invention also provides a process for the preparation of novel chemical compounds from the group consisting of dihydroxy -1,8-substituted 9-anthrone and having a general formula selected from the group consisting of (A) the general formula (I) (B) the general formula (Ilb) (I) (Ilb)

O OH OH

[2]

(Ile)) wherein: is a radical selected from the group consisting of: and (e)-CH-CH-R, I i⁶R_? R '_vR2 representing hydrogêne, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical, R ^, R4 and R ^ same or different represents a hydrogen atom, a linear or branched alkyl radical having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical linear or branched, optionally interrupted by one of oxygêne atom, having 1 to 8 carbon atoms (e. g. 2 to 8 carbon atoms), or a cycloalkyl radical having 3 to 6 carbon atoms, or R ^ ^ and R taken together form a divalent radical selected from the group consisting of: - {CH₂₎-, n is 4 or 5, -(CH_{2 2} >_" ~ 0-2' and- (Ch₂₎_2- n-(ch₂₎_2-,^{: eroism 8}r_{d is} a hydrogen atom, a methyl radical O or 2-hydroxy ethyl, Rg representing-CC ^ R, ., -CN, -CHO, -CONH_{2 or}conh -ch_2-oh,_{7 and R and} R '_{7 same or different} representing a hydrogen atom or a methyl radical, characterized in that or for the preparation of a compound of general formula (I) as defined previously, is reacted under an inert atmosphere in an organic solvent the dihydroxy -1,8-anthrone 9 with an unsaturated compound selected from the group consisting of: O in which R, , R_3" R^, R,-, R_g, R_? and R '_{7 have the same meanings} as above, to obtain a compound of general formula (I) as defined previously, or for the preparation of a compound of general formula (I) as defined hereinbefore wherein R ^ is either the radical (b) as defined hereinbefore or the radical (σ) as defined previously, a compound of formula with an amine of formula , R-. H-N \ R, wherein R and R ^ ^ have the same meanings as above, to obtain a compound of general formula (I) as defined previously, where R ^ is either the radical (b) as previously defined and/or (c) the radical as defined above, R ^ representing a hydrogen atom and optionally 1 ' said compound obtained is subjected to the action of an esterifying agent to obtain a compound of general formula (I) in which R, .has different meanings from those of an oxygen atom hydrogêneor for the preparation of a compound of general formula (Ilb) or (Ile) as defined previously, a compound of general formula where R ^ is a radical selected from the group consisting of R ^ ^ R and having the same meanings as above, with an amine of formula wherein R and R ^ ^ have the same meanings as above to obtain a compound of general formula (Ilb) or (Ile) such as defined above. Among the alkyl radicals, linear or branched, having 1 to 8 carbon atoms entering the meaning of the radicals R_2, R ^,^{and R 4 R 5}^{is P}^{may in particular} include the radicals: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl and octyl. Among the mono or polyhydroxyalkyleε radicals, linear or branched, having 1 to 3 carbon atoms, can be include the radicals: hydroxymethyl, 2-hydroxy ethyl, 2-hydroxy propyl and dihydroxy -2, propyl 3. Among the cycloalkyl radicals defined entering of the radical R or R ^ ^ can be include the radicals: cyclopropylε, cyclobutylε, cyclopentyl and cyclohexyl. For lower alkyl radical according to the invention refer to linear or branched radicals having from 1 to 4 carbon atoms, such as methyl, ethyl, propyl... Among the compounds of formula (I) in which the radical represents the radical (a) can be combined include those the after in Table I. - 3f-

TABLE I

[3]

1	( άihydroxy -1,8	anthrone-9)	yl -10	succinimide	H
2	(dihydroxy -1,8	anthrone-9)	yl -10	N-methyl succinimide	^{H 3}-c
3	(dihydroxy -1,8	anthrone-9)	yl -10	N-succ imide (hydroxymethyl) in	Ch_2-oh
4	(dihydroxy -1,8	anthrone-9)	yl -10	N-(2-hydroxy ethyl) succinimide	_2- ch_{2-ch oh}
5	(dihydroxy -1,8	anthrone-9)	yl -10	N-ethyl succinimide	Ch_2-ch₃
6	(dihydroxy -1,8	anthrone-9)	yi-io	N-(dihydroxy -2,3 propyl) succinimide	_2-ch- choh R-ch_{2 oh}
7	(dihydroxy -1,8	anthrone-9)	yl -10	N-(2-hydroxy propyl) succinimide	_2-ch- choh R-ch₃
8	(dihydroxy -1,8	anthrone-9)	yl -10	N-(carbamoyl) succinimide	Conh_2-
9	(dihydroxy -1,8	anthrone-9)	yl -10	N-phenyl succinimide

nc ( άihydroxy -1,8-anthrone 9) succinimide yl -10 H Among the compounds of formula (I) in which the radical is the radical (e) can be include those collected, the after in the table (II). TABLE II

Compounds No.		^{R 7}	^{R, 7}	^{R 6}
10	£" (dihydroxy-l, anthrone 8-9)/ - 3 yl-lθ propanoate	H	H	H_{c0 2-c} 2
11	^ Acid (dihydroxy -1,8-anthrone 9) yl-lθ / 3-propanoic acid	H	H	h 2-co
12	^ (dihydroxy -1,8-anthrone 9) yl- lC ) 7-3 propanai	H	H	-CHO
13	/ " (dihydroxy-l, anthrone 8-9)/ 10-3 yl-propionitrile	H	H	-CN
14	[( dihydroxy -1,8-anthrone 9) yl-lθ / 3-propionamide	H	H	conh_2-
15	^ f (dihydroxy-l, anthrone 8-9) 3-yl- ioj methyl butanoate	_3-ch	H	co_2-ch₃
16	^ (dihydroxy -1,8-anthrone 9) yl -10 ^ - 3 methyl 2-propanoate
	methyl	H	_3-ch	co_2-ch₃
17	ZT acid (dihydroxy-l, anthrone 8-9) yl -10 ^ / 3-butanoic acid	_3-ch	H	- COOH
18	^ Acid " (dihydroxy -1,8-anthrone 9) yl-lθ 7 ~ 3 methyl 2-propanoic acid	H	_3-ch	- COOH

R. =-CH-CH-R, Among the compounds of formula (I) represents 1st adical (b) and/or particular include those collected the after, (III). in which the (c) may be in the table

19	Acid	(dihydroxy -1,8	anthrone-9)
20	Acid	(dihydroxy -1,8	anthrone-9)
21	Acid	(dihydroxy -1,8	anthrone-9)
22	Acid	(dihydroxy -1,8	anthrone-9)
23	Acid (dihydroxy -1,8 succinamic	arithrone-9)
24	Acid	(dihydroxy -1,8	anthrone-9)
25	Acid (dihydroxy -1,8 succinamic	anthrone-9)
26	Acid	(dihydroxy -1,8	anthrone-9)
27	Acid (dihydroxy -1,8 succinamic	anthrone-9)
28	Acid (dihydroxy -1,8 propyl) succinamic	anthrone-9)
29	Acid	(dihydroxy -1,8	anthrone-9)

	_r-'^{C 2 R 5 °}
	L
	CON
	^{R 4}
	(c)
^{R 3}	^{R 4}	R
H	H	H
H	_3-ch	H
H	^{H 5 c 2}-	H
H	nC H_{<sup>7</sup>-} 3	H
H	^- isoC H-,	H
H	^{nC 4}-^{H 9}	H
H	cyclohexyl	H
H	^{H 17} 8^- c	H
H	_2- ch_{2-ch oh}	H
H	_2-ch- choh R-ch_{2 oh}	H
<ch-₂₎	^{1 2}_"^{(ch 2}₎ ° ~ 2 ~	H

n acid (dihydroxy -1,8-anthrone 9) TABLE III CON ^ "^{3 and}/or succinamic yl -10 yl -10 N-methyl succinamic yl -10 N-ethyl succinamic yl -10 N-propyl succinamic yl -10 N-isopropyl yl -10 N-butyl succinamic yl -10 N-cyclohexyl yl -10 N-octyl succinamic N yl -10 - (hydroxy -2 ëthyl ) n yl -10 - (dihydroxy -2,3 morpholino succinamic yl -10 TABLE III ( result)

Compounds	no.			^{R 3}	⁴ e	^{R 5}
30	Acid (dihydroxy -1,8-anthrone 9) succinamic	yl -10	pyrrolidino		-^<CH2>4-	H
31	Acid (dihydroxy -1,8-anthrone 9) succinamic	yl -10	piperidino		- (^{℮ h}₂₎- 5	H
32	Acid (dihydroxy -1,8-anthrone 9) piperazino ") succinamic	yl -10	(methyl 4-	-	(ch₂₎_2- n-(ch₂₎- 2
33	Acid (dihydroxy -1,8-anthrone 9) piperazino) succinamic	yl -10	(hydroxyethyl -4	-	_{3 ch (}^{ch 2})_2- n-(^{ch 2}^{) - 2}	H
34	Acid (dihydroxy -1,8-anthrone 9) succinamic	yl -10	N, N- dimëthyl	3^- ch	(Ch)_{2 oh-}^{ch 3}	H
35	Acid (dihydroxy -1,8-anthrone 9) succinamic	yl -10	N, N-Diethyl	^{H 5 c 2}-	^{H 5 c 2}-	H
36	Acid (dihydroxy -1,8-anthrone 9) succinamic	yl -10	N, N-Dipropyl	nC H ^ -^	nC H_{<sup>7</sup>-} 3	H
37	Acid (dihydroxy -1,8-anthrone 9) succinamic	yi-io	N, N Dibutyl	"^{n C}_{4 H}₉	^{nC 4}-^{H 9}	H
38	Acid (dihydroxy -1,8-anthrone 9) xy -2 ethyl) succinamic	yl -10	N, N-Di (Hydro-	Ch_{2-ch 2 ~2 ~ oh}-ch ch_{2 0:00}	H
39	Acid (dihydroxy -1,8-anthrone 9) ethyl oxyethyl) succinamic	yl -10	N, N-( hvdroxy -2	H	"^{(Ch 2}^{) 2} '"^0"^{0:00 2 (ch 2)}	H
40	Carbamoyl -3 (dihydroxy -1,8-anthrone 9) methyl	- 10 yl propanoate	H	H	"^{Ch 3}
41	(dihydroxy -1,8-anthrone 9) - 10 yl propanoate	(N-Methylcarbamoyl) -3	H	_3-ch	_3-ch

TABLE III (result)

Compounds	no.	^{R r 4 3}	^{R 5}
42	(dihydroxy -1 , 8-anthrone 9) yl -10 (N- ëthylcarbamoyl ) -3 propanoate	^H-^{c Λ}	_3-ch
43	(dihydroxy -1,8-anthrone 9) - 10 (N-propylcarbamoyl)-3 yl propanoate	^{H 7 3 hr-} c	_3-ch
44	(dihydroxy -1,8-anthrone 9) - 10 (N-butylcarbamoyl)-3 yl propanoate	^{H '}^{h 9 c 4}	_3-ch
45	( dihÿdroxy -1,8-anthrone 9) - 10 (N-cyclohexylcarbamoyl)-3 yl propanoate	H cyclohexyl	3^- ch
46	(dihydroxy -1,8-anthrone 9) yl -10 N, N di (2-hydroxy ethyl) carbamoyl -3 propanoate	ch_2-ch oh_-ch 2_{2 2 ~ ch oh}	_3-ch
47	(dihydroxy -1,8-anthrone 9) N yl -10 - (2-hydroxy ethyl) carbamoyl -3 propanoate	H-ch_{2 ch 2 ~ oh}	_3-ch
48	(dihydroxy -1,8-anthrone 9) yl -10 (N-dihydroxy -2,3			H"

	propylcarbamoyl) -3 propanoate	h-ch_{2 2 ~ choh R-ch oh}	_3-ch
49	(dihydroxy -1,8-anthrone 9) N yl -10 - (2-hydroxy ethyl
	oxyethyl) carbamoyl -3 propanoate	H-(ch₂₎_2- 0-0:00 2 (ch₂₎	_3-ch	^5
50	(dihydroxy -1,8-anthrone 9) yl -10 N-morpholino carbamoyl -3 propanoate	- (ch₂₎_2-O-(ch₂₎- 2	3^- ch
51	(dihydroxy -1,8-anthrone 9) yl -10 N-pyrrolidino carbamoyl -3 propanoate	- (ch₂₎- 4	_3-ch
52	(dihydroxy -1,8-anthrone 9) 10 N-piperidino-yl carbamoyl -3 propanoate	-^{(Ch 2}-> 5	3^- ch

TABLE III (result)

Compounds	no.	^{R r 4 3}	^{R 5}
53	(dihydroxy -1,8-anthrone 9) yl -10 N, N-dimethyl carbamoyl -3 propanoate	Ch ch-_3-₃	_3-ch
54	(dihydroxy -1,8-anthrone 9) yl -10 N, N-di (2-hydroxy ethyl) carbamoyl -3 propanoate	_2- ch_{2-ch oh}-ch_2-ch oh 2	-Gens
55	(dihydroxy -1,8-anthrone 9) N yl -10 - (2-hydroxy ethyl) carbamoyl -3 propanoate	H-ch_2-ch oh 2	h_{5 c 2-}
56	(dihydroxy -1,8-anthrone 9) yl -10 N, N-di (dihydroxy -2,3 propyl) carbamoyl -3 propanoate	_2-ch- choh R-ch_{2 oh-} ch_2- ch0 0:00 h_{-ch 2}	^{H 5 c 2}-
57	(dihydroxy -1,8-anthrone 9) N yl -10 - (hydroxy -2 ethyl oxy ℮ methyl) carbamoyl -3 propanoate	h-{ CH₂₎_2- 0-0:00_{(CH 2)} 2	^{H 5 c 2}-
58	(of ihydroxy -1,8-anthrone 9) yl -10 (πi ℮ tetramethyl -4
	piperazino) carbamoyl -3 propanoate	- (ch₂₎_2- n-(ch₂₎- 2		tύ φ
59	(dihydroxy -1,8-anthrone 9) yl -10 (hydroxy ℮ tetramethyl -4	Ch₃	^{H 5 c 2}-	<1 02? 0
	piperazino) carbamoyl -3 propanoate	- (ch₂₎_2- n-(ch₂₎- 2
		oh 2 (ch₂₎	^{H 5 c 2}-

Salts of primary or secondary amine of the formula (Ilb) or (Ile) can be combined include the after the compounds in the table (IV): TABLE IV

Compounds	no.	^{R 3}	^{R 4}
60	carbamoγl -3 ^ " ( dϋiydroxy -1,8-anthrone 9)-ammonium 10_7 yl propanoate	H	H
61	(dihydroxy -1,8-anthrone 9) yl -10 N-methyl carbamoyl -3 methyl propanoate	H	_3-ch
62	(dihydroxy -1,8-anthrone 9) yl -10 N-ethyl carbamoyl -3 d^{1 ethylammonium} propanoate	H	H_{<sup>5</sup> c} 2-
63	(dihydroxy -1,8-anthrone 9) yl -10 N-propyl carbamoyl -3 propanoate propylammonium	H	nC_3-H_?
64	(dihydroxy -1,8-anthrone 9) N yl -10 - (2-hydroxy methyl ℮ ) carbamoyl-3-hydroxy 2 ethylammonium propanoate	H	_2- ch_{2-ch oh}
65	(dihydroxy -1,8-anthrone 9) yl -10 N, N-di (hydroxy -2 ℮ methyl) carbamoyl -3 propanoate di (hydroxy -2 ℮ methyl) ammonium	CH-CH-OH	CH-CH-OH

TABLE IV (following) Compounds No. 66 (dihydroxy -1,8-anthrone 9) N yl -10 - (dihydroxy -2,3 propyl) carbamoyl -3 propanoate dihydroxy -2,3 propylammonium 67 (dihydroxy -1,8-anthrone 9) N yl -10 - (hydroxy -2 ëthyloxyëthyl ) carbamoyl-3-propanoate hydroxy ethyl oxyëthylammonium 2 68 (dihydroxy -1,8-anthrone 9) 10-morpholino yl carbamoyl-propanoate morpholinium 3 69 (dihydroxy -1,8-anthrone 9) 10 pyrrolidino-yl carbamoyl-propanoate Pyrrolidinium 3. R, R 4 H_2-ch- choh R-ch oh H - (ch₂₎_{2 ~} o-(ch₂₎ oh 2 - (ch₂₎_2-O-(ch₂₎_{2 (}^{CH 2}⁾Among the compounds of formula (I) in which the radical is the radical (d) can be combined include the after those in the table (V). TABLE V Compounds No. R R ^^

70	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' Dimethyl	H	_3-ch
71	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' Diethyl	H	^{H 5 c 2}-
72	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' Diisopropyl	H	c iso H_{7- 3}
73	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' Dibutyl	H	^{nC 4}-^{H 9}
74	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' tétramëthy1	~^{Ch 3}	3^- ch
75	(dihydroxy -1,8 disuccinamide	anthrone-9)	yl -10	N, N ' tetraethyl	^C-jH--	-C, H,

R 1 3 4 3 R 4 The compounds of the invention are prepared by reacting Michael according to the technique described by 0. E. Schultz and g. Frey, Archi, Pharrα. 310, 781-787 (1977), comprising reacting to under inert atmosphere in an organic solvent, the dihydroxy -1,8-anthrone 9 (or anthralin) optionally in the presence of a basic catalyst with an unsaturated compound wherein the double bond is conjugated, activated by an electronegative unsaturated group. The reaction is generally carried out at boiling temperature of the organic solvent for at least 8 hours and is preferably used as the basic catalyst dimëthylamino 4-pyridine or the lithium or sodium methoxide. When the product crystallizes within the reaction mixture during the formation thereof or by cooling it is dewatered, washed then dried under reduced pressure. Otherwise the reaction medium is concentrated under reduced pressure and the residue is either crystallized in a suitable solvent is purified by silica gel chromatography. The synthesis of the compounds of the invention may be represented by the reaction scheme (A) according to: The compounds of formula P) are obtained by reacting a molar equivalent of maleimide P) or a R2=H malëimide N-substituted P) H ^ R2^{on the} anthralin (1). The compounds of formula (j > b or J3c) are obtained by reacting the maleamic acid P) X = OH and Y =-NH ^ or a derivative of maleamic N-substituted (4) and X = OH Y = NR R with R ^ ^ ^ H and H ≈ R^ / or a derivative of maleamic N, N disubstituê (4) X = OH with R and Y = NR ^^³ R 4^R = ^ H^{on the} anthralin P) ·The compounds of formula (2) are obtained by reacting preferably an excess of the unsaturated compound of formula (6) on the anthralin (1). Finally the compounds of formula (£) are obtained by reacting an dimalëamide (8) on the anthralin (1). The compounds of formula (5b or 5c) can also be obtained according to another method of after the reaction schéam (B) according to: The method comprises preparing in a first step to the anhydride (dihydroxy -1,8-anthrone 9) yl succinic -10 of formula (11.) according to the method described by O. E Schultz and g. Frey Arch Pharm. 310, 776-780 (1977) by reacting Michael between anthralin (1) and maleic anhydride (10). From the intermediate compound (13J it is possible to obtain the compounds of formula (5b or 5c) in series, reacted in inert organic solvent medium at a temperature of between and 50 °C ° -10 one molar equivalent of a primary or secondary amine. The salts of formula (Ilb) or (Ile) S may also be obtained from the intermediate compound (11J by reacting under the same conditions two equivalents of primary amine or secondary to the anhydride. These salts of formula (Ilb) and (Ile) may further yield the compounds of formula (5b or 5c) by washing to using hydrochloric acid. The compounds of formula (J5) obtained by reacting michael according to the reaction scheme (A) or according to the reaction scheme (B) may be in the form of a mixture of isomers i.e. compounds of formula 5b and 5c by cannot always orient clearly the reaction. Also, note that the compounds according to the invention, with the exception of the compounds in which R ^ ≈ R ' ^ ≈ H, all have at least one asymmetric carbon so that they may also be in the form of their optical isomers (d and 1) or a mixture of these isomers. The starting unsaturated compounds for the preparation of the compounds according to the invention are mostly commercially available or can be obtained by known methods described in the literature. Thus n-hydroxymethyl maléirnide may be prepared by action formalin on the maléirnide according to the method described by: P. Tawney O and al. JOC, p. 15 (1961). N- carbamoylmaléimide can be prepared according to the method described by:O and P. Tawney Al. JOC, p56 Vol 25 (1960); the dimaléimides are prepared using the method described by Roth m.. Helv. Chem. Act. P6_2 1966 (1979). Maléamiquas N-substituted acids are also prepared by opening the maleic anhydride by a primary or secondary amine using the method described by Y. LIWSHITZ and al, JACS, 78,3069 (1956). The present invention also relates to the use of compounds of the present invention in human medicine or veterinary particular in the treatment of psoriasis and warts, and cosmetics. Psoriasis skin is manifested essentially by the occurrence of dry dander, whitish or pearlescent. Psoriasis manifested preferably the knee and the elbow, to the sacrum, to the soles of the feet, to the palm of the hand, to the chest, S the face and also on the leather scalp. Tests show that these compounds have good activity when they were within various pharmaceutical vehicles for use in particular systemically and percutaneously. Maintaining One will provide illustrative but not limited to several examples for preparing the compounds of the invention. Example 1Preparation of the (dihydroxy -1,8-anthrone 9) yl -10 succinimide (No. l). A an agitated solution of 1,12g anthralin (5rn Mole) in 40 cm3 of chloroform, is added once 0,48g maleimide (eq 1.) to the exclusion of light and under an inert atmosphere as well as a few crystals of dimêthylamino -4 pyridine (DMAP). The reaction mixture is then heated to a boiling temperature chloroform for about 7 hours. A yellow solid crystallizes in the course of the reaction. After the end of the reaction followed by thin layer chromatography silica gel, leaving the reaction medium to the ordinary temperature. The then the solid, are dried under reduced pressure and thus 1,3g of (dihydroxy -1,8-anthrone 9) succinimide yl -10 light yellow in colour point to 220 °C decomposition. The Assay: ^ ^ ^ NO GH C Calc. H C: 66.87: 4.05 N: 4.33 0:24,74 Tr. 66,85 4.15 4.43 24.65 Example 2Preparation of the (dihydroxy -1,8-anthrone 9) yl -10 N-hydroxymethyl succinimide (no.3). According to the same procedure as described example 1 to the above is reacted in chloroform 1,12g anthralin medium in the presence of maleimide 0,63g N-hydroxymethyl (eq 1.) in the presence of a few crystals of ( DMAP ). After the end of the reaction is isolated from the reaction mixture a solid yellow decomposes at: 200 °C. The Assay: ^ ^ gNOg GH C Chock. H C: 64.58: 4.28 N: 3.96 Tr. 65,01 4.32 4.00 EXAMPLE 3 Preparation of the (dihydroxy -1,8-anthrone 9) yl -10 N-ethyl succinimide (no.5). A solution placed under a nitrogen atmosphere the absence of atmospheric humidity and light 4,5g anthralin with 1.1 equivalent of N-ethyl maleimide and 20 mg of 4-dimethylamino pyridine 100cm3 in chloroform is heated to the boiling point of the chloroform for fifteen hours. The reaction mixture after cooling is directly deposited on a silica gel column. The desired product is eluted with ethyl acetate. After evaporation phases is obtained elution 6,5g bright yellow crystal having a melting point of 200 °C. The assay: io^{H 17N0 5} C Calc. H C: 68.3 7: 4.88 N: 3.99 0:22,77 Tr. 68,49 4.94 4.03 22.87 Example 4Preparation of the (dihydroxy -1,8-anthrone 9) y .1-10 N-carbamoyl succinimide (no.8). A mixture agitated 1,1g anthralin, an equivalent N-carbamoyl maleimide in 20cm3 of anhydrous acêtonitrile placed under inert atmosphere S the absence of atmospheric humidity and light is refluxed 1 of ' acêtonitrile during 8 hours. After cooling, the solid is dried, washed S acetonitrile then dried under reduced pressure and phosphoric anhydride. Thus 1,45g yellow crystal having a melting point of 200 °C snapshot is. The assay:^{c i9} i4^{N 2} H ° 6 Chock. H C: 62.29: 3.85 N: 7.65 0:26,21 Tr. 62,17 3.93 7.70 26.22 EXAMPLE 5 Preparation of the (dihydroxy -1,8-anthrone 9) yl -10 N-phenyl succinimide (no.9). A mixture agitated 4,5g anthralin, an equivalent N-phenyl maleimide in anhydrous acetonitrile^{100cm3 d} 1 placed under an inert atmosphere to the absence of atmospheric humidity and light is refluxed 1 of ' acetonitrile during 17 hours. After cooling, the solid is dried, washed with chloroform, and benzene. To 120 °C After drying under reduced pressure is obtained 7g of a bright yellow solid having a melting point of 260 °C snapshot is. The assay:^{N C 24H 17 °} 5 Calc. H C: 72.17: 4.29 N: 3.51 0:20,03 Tr 72.03 4.25 3.47 20.00 Example 6Preparation of (dihydroxy -1,8-anthrone 9) - 10 yl propanoate (no.10). A mixture of 4,52g anthralin (0.02 mole), of 6cm3 ethyl acrylate and lithium mêthylate to 0.5% ( lcm3 ) in anhydrous chloroform 35cm3 is heated to a boiling temperature of the solvent during 5 hours S the shade under an inert atmosphere. After the mixture dropped to the ordinary temperature for about 48 hours then to gel chromatography silica. The (dihydroxy -1,8-anthrone 9) - 10 yl propanoate is then eluted by benzene-chloroform mixture (50-50) then recrystallized in 1' hexane. The compound is in the form of a yellow solid having a melting point of 90 °C. Acid preparation (dihydroxy -1,8-anthrone 9) 10-yl propanoic acid (No. ll). A 6g solution of ( dlhydroxy -1,8-anthrone 9) propanoate yl -10 d '. ethyl in a mixture of dioxane and 150cm3 150cm3 5N hydrochloric acid under inert atmosphere to the exclusion of light during 2 hours to 100 °C. The reaction mixture is then concentrated under reduced pressure. The residue is deposited on a silica gel chromatography column and the expected acid is eluted to the mixture benzene-ethyl acetate (1-1), and recristallisë in toluene, lg Therefore, yellow powder melting point 191 °C. The mass spectra has the parent peak expected to m/e: 298 ·Example 8Acid preparation (dihydroxy -1,8-anthrone 9) yl -10 succinamic (no.19). -3 a) A a solution of 0,678g anthralin (3.10 mole) in anhydrous acetonitrile 25cm3, placed under an inert atmosphere of the shelter of the light and the humidity of the air, is added at once 0,345g malêamique acid (eg. 1). The reaction mixture is then heated to a boiling temperature of the solvent during 6 hours. The acid ( dihydroxy1, anthrone 8-9) yl -10 succinamic crystallizes within of the reaction mixture as it forms. After the end of the reaction followed by thin layer chromatography, the mixture is dropped to the ordinary temperature and is filtered light yellow and the solid is dried under reduced pressure. Thus 0,85g of desired product having a decomposition at 220 °C. The Assay: C._{0 h.},_{c n0}, 18 15,6 Chock. C:6,3.34 H: 4.43 N: 4.10 0:28,13 Tr. 63,46 4.44 4.09 28.12 b) A a solution of 0,972g (^ 3.10 mole) anhydride (dihydroxy -1, anthrone 8 ~ 9) yl -10 succinimique (O.E. and g. Schultz prepared according to Frey Arch. Pharm 310, 776-780, 1977) in 80 cm3 of acetonitrile, to 5 °C stirred under inert atmosphere and protected from the light, 3 drop drop is added a solution of ammonia (eq 1.) diluted by 20cm3 of acetonitrile. The acid (dihydroxy -1,8-anthrone 9) yl -10 succinamic precipitates during formation. It is dewatered and washed by a hydrochloric acid solution in ether and finally dried under reduced pressure. Obteint 0,9g The and of a yellow product decomposes at 220 °C. Example 9Acid preparation (dihydroxy -1,8-anthrone 9) yl -10 N-methyl succinamic (no.20). A mixture agitated .4,5g d ' anthralin, one equivalent of N-methyl maleamic, die 20 mg of 4-dimethylamino pyridine in chloroform 50cm3 chloroform is refluxed for 24 hours under an inert atmosphere protected from the light and humidity of the air. After cooling the yellow solid formed is dewatered, washed with chloroform and then with a diluted aqueous solution of acetic acid and long stirred in water. The solid is dewatered again and dried in phosphoric anhydride under reduced pressure. Thus 1,5g yellow crystal having a melting point (decomposition) is 260 °C. The Assay: Calc. H C: 64.22: 4.82 N: 3.94 0:27,02 Tr. 64,07 4.79 3.85 26.93 Example 10Acid preparation (dihydroxy -1,8-anthrone 9) yl -10 N-ethyl succinamic (no.21). A mixture agitated 4,5g anthralin with one equivalent of N-ethyl maleamic acid and of a few crystals of D.M. A.P 50cm3 in chloroform is heated to a boiling temperature of the solvent with stirring to the shelter air humidity light for 8 hours. Then the mixture is dropped to the ordinary temperature. The crystals are then squeezed, deposited in chloroform solution on a silica gel column. The product expected soiled an impurity is éluêwith ethyl acetate. Elution After concentration of the phases of the mixture is resumed to the acetone, the impurity is removed by filtration. Concentration of the filtrate is obtained After acid (dihydroxy -1,8-anthrone 9) yl -10 N-ethyl succinamic yellow color S 190 °C flux. The assay:^{H 19}^{N C 20 °} 6 _AOE296A0AO> Calc. H C: 65.03: 5.18 N: 3.79 0:25,99 Tr. 65,13 5.12 3.78 25.91 Example 11Acid preparation (dihydroxy -1,8-anthrone 9) yl -10 N-isopropyl succinamic (no.23). A mixture agitated 4,5g anthralin, one equivalent of N-isopropyl succinamic, of 20 mg of 4-dimethylamino pyridine 50cm3 in chloroform is refluxed chloroform under inert atmosphere for 24 hours. The reaction mixture is placed in the absence of moisture of air and light. After cooling the precipitate formed is dried, washed with chloroform washed with a dilute solution of acetic acid and finally dried under reduced pressure to 120 °C and phosphoric anhydride. 3,2g of yellow crystals are obtained having a melting point of snapshot is 220 °C. The assay: ^ ^ 21 21^{N °} 6 Calc. C:65,78 H: 5.52 N: 3.65 0:25,04 Tr. 65,77 5.55 3.54 24.86 Example 12Acid preparation (dihydroxy -1,8-anthrone 9) yl N-hydroxy -10-2 ethyl) succinamic (no.27). Are has the ordinary temperature, and under inert atmosphere to the exclusion of light a mixture of 0,486g (1,5m Mole) anhydride (dihydroxy -1,8-anthrone 9) yl succinic -10 and an equivalent of êthanolamine 50cm3 in anhydrous chloroform. After stirring for 48 hours is drained a yellow powder are dried and which is then treated with a solution of hydrochloric acid (0, lN) to 0 °C. The acid (dihydroxy -1,8- anthron℮ 9) N yl -10 - (2-hydroxy ethyl) succinamic is then dewatered and dried under reduced pressure. II is in the form of a yellow powder from 120 °C 3 decomposes. The assay:^{NO C 20 19 7} H Chock. C: 62.33 11:4,97 N: 3.63 0:29,06 Tr. 62,45 5.00 3.72 29.04 Example 13Acid preparation (dihydroxy -1,8-anthrone 9) yl-morpholino (no.29) succinamic 10. A suspension of 600 mg of the salt of the below in example 23 10cm3 5N hydrochloric acid is stirred about half an hour. The solid is dewatered, rapidly and washed with acetone. Therefore, 300 mg of yellow powder after drying having a melting point of 150 °C snapshot is. The assay: ^^{N0 C 22 21 7}Calc. C: 64.23 H: 5.14 N: 3.40 0:27,22 Tr. 64,14 5.20 3.34 27.34 Example 14Preparation acid (dihydroxy -1,8-anthrone 9) pyrrolidino succinamic yl -10 (no.30). Lg A suspension of the salt of the example 24 below is agitated in 10cm3 5N hydrochloric acid to 0 °C under an inert atmosphere for approximately half an hour. The solid is then dewatered, washed rapidly to the acetone and then dried. Thus 0,5g yellow powder melting point 215 °C instantaneous. Example 15Acid preparation (dihydroxy -1,8-anthrone 9) 10-4-yl methyl pipêrazino succinamic (no.32). A a solution of 1,35g anthralin (6m economic role) is added to the exclusion of light acid 1,2g pipêrazino maleamic methyl -4. The mixture is stirred and heated to the boiling temperature of the solvent for 18 hours. The expected product crystallizes within the solution during formation. under reduced pressure at 120 °C. Thus 1,32g acid (dihydroxy -1,8-anthrone 9) 10-4-yl methyl pipêrazino succinamic form of a yellow powder The assay:^{C 22}^{H 21}^{N0 6}Chock. H C: 55.83: 5.35 N: 3.54 0:24,28 Tr 66,87 5.34 3.49 24.48 in 180 cm3 chloroform placed under inert atmosphere After cooling, it is dewatered and dried pale decomposes at 210 °C. The assay: Calc. C:65,08 H: 5.70 N: 6.60 0:22,62 Tr 5,79 6.54 64,35 23,09 Example 16Acid preparation (dihydroxy -1,8-anthrone 9) yl-£ 10" (2-hydroxy ethyl) piperazino -4/succinamic (no.33). A a solution of anhydride (dihydroxy -1,8-anthrone 9) yl succinic 0,972g -10 (3m economic role) in 50cm3 of chloroform, stirred to ordinary temperature under an inert atmosphere and S the exclusion of light, is added in small fractions -3 an equivalent d ' (hydroxy -2 ëthyl ) -4 piperazine (0,390g: 10 mole). The reaction medium is then idled a night to ordinary temperature. The wrings and then the solid is dried under reduced pressure to 120 °C. The resulting product is in the form of a solid yellow-beige decomposes to 190 °C. The assay:^{C 24}^{H 26} °^{N 2} 7 (monohydrate) Calc. H C: 61.01: 5.97 N: 5.93 0:27,09 Tr. 61,41 5.83 6.24 28.69 Example 17Acid preparation ( d.ihydroxy -1,8-anthrone 9) yl -10 N, N-di (2-hydroxy ethyl) Succinamique (no.38). A a solution of 0,972g (3m economic role) anhydride (dihydroxy -1,8-anthrone 9) yl succinic -10 in anhydrous acetonitrile 60cm3 agitated to ordinary temperature and under nitrogen atmosphere is added slowly in the shade one equivalent of diethanolamine diluted in 20cm3 of acetonitrile. The then relinquishes reaction mixture for a night S room temperature. After removed by filtration the insoluble, the filtrate is concentrated under reduced pressure. After being washed with ether, dewatering and drying under reduced pressure, a product is obtained which decomposes to 100 °C. The assay:^{C 22} 23⁸^H N0 (^{my °} hydrate) Chock. C:59,05 H: 5.63 N: 3.13 - 5.47- Tr. 59,05 3,20 Example 18Preparation of Carbamoyl -3 (dihydroxy -1,8-anthrone 9) - 10 yl propanoate (no.40). Lg A an agitated solution of acid (dihydroxy -1,8-anthrone 9) succinamic 150cm3 yl -10 in methanol cooled to 0 °C is added an excess of diazomethane solubilized in 1' ether. The mixture is then idled a night to room temperature. The following day after adding 2cm3 acetic acid to destroy the excess diazomethane, the reaction medium is concentrated under reduced pressure. The residue obtained is dissolved in the minimum of chloroform and deposited on a silica gel column. The expected ester is eluted with acetone. After concentration of the acetone powder is obtained yellow melting point 250 °C. The assay:^< " 19 17^{N0 6} H Calc. H C: 64.22: 4.82 N: 3.94 0:27,01 Tr. 64,18 4, .84 3,84 26.87 Example 19Preparation of (dihydroxy -1,8-anthrone 9) yl -10 N-morpholino carbamoyl -3 propanoate (no.50). 0,5g A solution of acid (dihydroxy -1,8- anthrohe 9) 10 yl-morpholino succinamic in 30cm3 of anhydrous methanol, two drops of sulfuric acid and lcm3 of diméthoxy2, 2 propane is refluxed methanol for 10 hours under an argon atmosphere in the absence of moisture of air and light. The reaction mixture is dewatered, the filtrate concentrated under reduced pressure and the residue directly resumed by the minimum of benzene. The benzene phase is deposited on a silica gel chromatography column. The desired product is eluted by benzene-acetone mixture (1-1). Phases After concentration of the elution is obtained and drying 0,30g yellow powder having a melting point of 158 °C. The assay: C_{23 H}_{23 > 7 NC}Calc. H C:6,4.93: 5.45 N: 3.29 0:26,32 Tr. 64,94 5.46 3.28 26.28 Example 20Preparation of the (dihydroxy -1,8-anthrone 9) N yl -10 - (2-hydroxy ethyl) carbamoyl-3-propanoate (no.64) ethylammonium hydroxy 2. A a solution of 0,366g of ëthanolamine (6m economic role) in chloroform 50cm3 stirred at ordinary temperature is added in small fractions 0,972g (3m economic role) anhydride (dihydroxy -1,8-anthrone 9) yl succinic -10. The reaction medium after being homogenized gives rise to the formation of crystals form light yellow. After a night the crystals are squeezed and dried. The salt thus isolated (1,25g) is in the form of a light yellow powder is decomposing to 170 °C. The assay:^{C 22}^{H 26} ° 8 ·^{N 2}Chock. H C: 59.18: 5.87 N: 6.27 0:28,67 Tr. 59,31 5.77 6.20 28.67 Example 21Preparation of (dihydroxy -1,8-anthrone 9) yl -10 N, N-di (2-hydroxy ethyl) carbamoyl -3 propanoate di (2-hydroxy ethyl) ammonium (no.65). The anhydride (dihydroxy -1,8-anthrone 9) yl succinic -10 (0,972g) is solubilized in 120cm3 to hot anhydrous acetonitrile, obtained after filtration The solution is cooled to 0 °C are added, with stirring, then the drop to drop two equivalents of diethanolamine diluted in 80cm3 of acetonitrile. The salt expected gradually crystallizes and maintained but the stirring for 2 hours after the completion of the addition. The solid After dewatered and dried under reduced pressure is obtained 1,5g of a product in the form of light yellow crystals, with green reflections degrading to 150 °C. The assay: Calc. H C: 58.41: 6.41 N: 5.24 0:29,93 Tr. 58,52 6.38 5.23 29.92 Example 22Preparation of (dihydroxy -1,8-anthrone 9) yl -10 N-(hydroxy -2 éthyloxyéthyl ) propanoate carbamoyl-3-hydroxy 2 ëthyloxyëthylammonium (no.67). Are S the exclusion of light under a nitrogen atmosphere to room temperature a mixture of 0,972g (3m economic role) anhydride (dihydroxy -1,8-anthrone 9) yl -10 succinigue and 0,631g (6m economic role) hydroxy éthyloxyéthylamine 50cm3-2 in chloroform. The medium becomes progressively homogeneous and then the amine salt crystallizes slowly. After a night the solid is dried, then dried under reduced pressure. Thus 1,1g of the product in the form of a beige powder decomposes to 150 °C. Preparation of (dihydroxy -1,8-anthrone 9) 10-morpholino yl carbamoyl -3 (no.68) propanoate morpholinium. A a stirred suspension of 1g anhydride ( dihydroxy1, anthrone 8-9) yl -10 succiniqlie 100cm3 in chloroform, cooled to 0 °C and placed under an inert atmosphere and with the exclusion of light is added dropwise to two equivalents of morpholine. At the end of the addition, the solution obtained is filtered. The filtrate is concentrated under reduced pressure. The solid obtained is resumed S ether, dewatered and dried under reduced pressure. Thus 1,1g beige powder with a melting point of 130 °C snapshot is, the product hygroscopiquc is analyzed into half hydrate. The assay: ^ C^H^Î Og, 1/2 H_{2 0}. Calc. C: 61.54 H:6, ll N: 5.52 0:26,82 Tr. 61,79 5.90 4.93 26.98 Example 24Preparation of (dihydroxy -1,8-anthrone 9) 10 pyrrolidino yl carbamoyl-3-propanoate (no.69) pyrrolidinium. A a stirred suspension of 3,24g to 0 °C anhydride (dihydroxy -1,8-anthrone 9) yl succinic 150σm3 -10 in chloroform, placed in the shade and humidity of the air under an inert atmosphere is added slowly two equivalents of pyrrolidine. After two hours stirring the chloroform solution is concentrated under reduced pressure and the residue concrêtê in anhydrous ether. The brown solid thus obtained is dried, washed ύne again to the ether, then dried under reduced pressure. The brown powder melts at 120 °C, it is very hygroscopic and parsed into monohydrate. The assay:^{C 26}^{N 2 H 30} ° 6 '2^{' 0^} H Chock. H C: 64.45: 6.65 N: 5.78 0:23,11 Tr. 63,93 6.70 5.83 23.40 Example 25Preparation of (dihydroxy -1,8-anthrone 9) yl -10 N, N^{1-diisopropyl}disuccinamide (no.72). A mixture agitated lg anthralin, lg of of N, N '-diisopropyl dimaleimide in 50 cm3 of anhydrous acetonitrile is refluxed 1 of' acetonitrile S the shelter air humidity and light for 5 hours. After cooling the solid is dried, washed to 1' acetonitrile then dried under reduced pressure. Thus 1,72g pale yellow crystal decomposes to 280 °C. The assay:^{C 24}^{H 28} °^{N 2} 5

Chock.	C:6,7.9 0	H: 6.65 N: 6.60	0:18	, 85
Tr.	67,87	6,58 6.45	18	, 68

[4]

The invention relates to the dihydroxy-1,8 anthrones-9 substituted in position 10 of formula: < IMG > (I) in which: R1 represents a radical taken in the group consisted: (A) < IMG > (b) < IMG > (c) < IMG > (d) < IMG > and (E) < IMG > R2 representing H, alkyl of 1 - 8C, mono or polyhydroxyalkyle of 1 - 3C, carbamoyle or phenyl, R 3, R 4 and R5 representing H, alkyl of 1 - 8C, mono or polyhydroxyalkyle of 3 - 8C possibly stopped by an oxygen, cycloalkyle of 3 - 6C, or R3 and R4 form a divalent radical: < IMG >, - (CH2) 2-O- (CH2) 2 - or - (CH2) 2N (R8) - (CH2) 2, R8 being H, - CH3 or - CH2-CH2OH, R6 representing - CO 2R 5, - CN, - CHO, - CONH2 or - CONH-CH2OH, and R7 and R' 7 being H or - CH3, and their isomers optical. Use of made up (I) in medicine human or veterinary, in particular in the treatment of the psoriasis and the warts, and in cosmetic.

1. Process for the preparation of novel chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10, according to the general formula

(I)

[I)

wherein

R₂represents a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical,

characterized in that the is reacted under an inert atmosphere in an organic solvent the dihydroxy -1, 8-antrone insaturë 9 with a compound of formula

r wherein₂is as defined above to obtain a compound of general formula (I) as defined above.

2. Chemical compounds belonging to the group consisting of dihydroxy -1, 8-substituted antrone 9 and 10 having the general formula (I)

r wherein₂represents a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical, when prepared by a process according to claim 1 or a chemical equivalent manifest,

3. The method of claim 1, characterized in that the reaction is carried out in the presence of a basic catalyst selected from the group consisting of dimethylamino -4 pyridine and the lithium or sodium methoxide.

4, a method according to claim 1, characterized in that the reaction is carried out for at least 8 hours at boiling temperature of the organic solvent.

5. Compounds corresponding to general formula (I) as defined in claim 2 when prepared by a process according to claim 3 or a chemical equivalent manifest.

6. Compounds having the general formula (I) as defined in claim 2, when prepared by a process according to claim 4 or a chemical equivalent manifest.

7. The method of claim 1, characterized in that:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

and-the mono-or polyhydroxyalkyl radical, linear or branched having 1 to 3 carbon atoms is selected from the group consisting of the: hydroxymethyl, 2-hydroxy ethyl, 2-hydroxy propyl and dihydroxy -2, propyl 3.

8. Compounds of the general formula (I) as defined in claim 2 wherein:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

linear or branched having 1 to 3 carbon atoms is selected from the group consisting of the: hydroxymethyl, 2-hydroxy ethyl, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

when prepared by a process according to claim 7 or a chemical equivalent manifest.

and-the mono-or polyhydroxyalkyl,

9. The method of claim 1, characterized in that the radical P ·₂represents a hydrogen atom or a radical B selected from the group consisting of-CH₃,-THIS ^ OH,

-cH₂-cH₂oH, -CH₂cH₃,-cH₂-cHOH-CH₂oH, -CH₂-cHOH-CH₃,-cONH₂and-CGH ^.

10. Compounds of the general formula (I) as defined in claim 2, wherein the radical represents a hydrogen atom or a radical chosen from the group consisting of-CH₃, ^ OH-CH, -CH₂~ CH₂OH,

-cH₂cH₃,-cH₂~ ~ cHOH CH₂oH, -CH₂-cHOH ~ ch₃, ~ conh₂and-C_℮H₅, when prepared by a process according to claim 9 or the like chemical manifest.

11. The method of claim 3, characterized in that the radical R₂hydrogêne or is a radical selected from the group consisting of CH~₂OH,

-CH₂CH₃,-C0NH₂and- CgHj., The dimêthylamino the basic catalyst is 4-pyridine.

12. Compounds of the general formula (I) as defined in claim 2, wherein the ' R₂represents a hydrogen atom or a radical chosen from the group consisting of-CH₂OH, ~ CH₂CH₃, ~ CONH₂-and- CgHj , when prepared by a process according to claim 11 or a chemical equivalent manifest.

13. Process for the preparation of novel chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10, according to the general formula

(I)

wherein

R rg and ^, identical or different, represent a hydrogen atom, an alkyl radical, linear or branched having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r R ^ ^ and or taken together form a divalent radical selected from the group consisting of:

-(^ CH)_n", n is 4 or 5, -(^ ch)₂-0 ~(^CH2^ 2 ~' ^{T ℮}

-(CH₂)₂-N-(CH₂)₂-,

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

characterized in that the is reacted under an inert atmosphere in an organic solvent the dihydroxy -1, 8-antrone irtsaturé 9 with a compound of formula:

? Ï L wherein and have the same meanings as defined above, to obtain a compound of general formula (I) as defined above.

14. Chemical compounds belonging to the group consisting of dihydroxy ~ l, antrone 8-9 10-substituted represented by the general formula (I)

wherein

R R ^ ^ and, same or different, represent a hydrogen atom, an alkyl radical, linear or branched having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r Rj and ^ or taken together form a divalent radical selected from the group consisting of:

-(CH₂)-, n is 4 or 5, -(CH₂)₂' ° " (CH₂~ ^ 2'^and

-(CH₂)₂-N-(CH₂)₂-,

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2, when prepared by a process according to claim 13 or a chemical equivalent manifest.

15. Method according to claim 13, characterized in that the reaction is carried out in the presence of a basic catalyst selected from the group consisting of dimethylamino -4 pyridine and the lithium or sodium methoxide.

16. Method according to claim 13, characterized in that the reaction is carried out for at least 8 hours at boiling temperature of the organic solvent.

17. Compounds having the general formula (I) as defined in claim 14, when prepared by a process according to claim 15 or a chemical equivalent manifest.

18. Compounds having the general formula (I) as defined in claim 14, when prepared by a process according to claim 16 or a chemical equivalent manifest.

19. A method according to claim 13, characterized in that:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of :-2 ethyl hvdroxy , and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

20. Compounds of TO general Formula (I) as defined in claim 14, wherein

-alkyl radicals, linear or branched,

having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyie , isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, hydroxy-2-2 and dihydroxy propyie , propyie 3,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl,

when prepared by a process according to claim 19 or a chemical equivalent manifest.

21. Method according to claim 13, characterized in that:

or R₃is hydrogêne and represents a radical selected from the group consisting of-ch · ^, -C₂H, -, -ISO CGH · y and~^nC4^H9

or R ^ ^ represents-CH, and

R ^ ^ is-CH

or R Δc represents-C₂H ^, and

R Δc represents-C₂H, -.

22. Compounds of the general formula (I) as defined in claim 14, wherein:

or is and r hydrogêne Δc represents a radical selected from the group consisting of-ch ^ >"^C2^H5' c ^ ~ ISO H., and

^-n^ ' 4® 9

or R ^ ^ represents-CH, and

R₄^ is-CH

or R Δc represents-C₂H₅, and

R Δc represents-C₂H, _

when prepared by a process according to claim 21 or a chemical equivalent manifest.

23. Process for the preparation of novel chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10, according to the general formula

(I)

wherein

Rg represents-C 0₂R, -, -CN, -CHO, -CONH₂or

-cONH-CH₂oH,

Rg representing a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r and ^ and r ' ^, identical or different, represent a hydrogen atom or a methyl radical,

characterized in that the is reacted under an inert atmosphere in an organic solvent the dihydroxy -1, 8-9 antrone with an unsaturated compound of formula

CH = C-R_c

I I < IV)

R? R · ,

wherein Rg, r ^ and r'₇have the same meanings as above, to obtain a compound of general formula

(I) as defined above.

24. Chemical compounds from the group consisting of dihydroxy -1, 8-9-substituted antrone 10 and corresponding to the general formula (I)

wherein

Rg is-CC ^ RG, -CH, -CHO, -CONH₂or

-cONH-CH₂oH,

r and_?r ' and₇, identical or different, represent a hydrogen atom or a methyl radical,

when prepared by a process according to claim 23 or a chemical equivalent manifest.

25. Method according to claim 23, characterized in that the reaction is carried out in the presence of a basic catalyst selected from the group consisting of the 4-pyridine dimëthylamino and the lithium or sodium methoxide.

26. Method according to claim 23, characterized in that the reaction is carried out for at least 8 hours at boiling temperature of the organic solvent.

27. Compounds of the general formula S (i) as defined in claim 24, when prepared by a process according to claim 25 or a chemical equivalent manifest.

28. Compounds of the general formula (I) as defined in claim 24, when prepared by a process according to claim 26 or a chemical equivalent manifest.

29. A method according to claim 23, characterized in that:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, 2-hydroxy propyl and dihydroxy -2, propyl 3, and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

30, compounds of the general formula S (i) as defined in claim 24, wherein:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl,

when prepared by a process according to claim 29 or a chemical equivalent manifest.

31. Method according to claim 23, characterized in that:

or r and ' ^ are hydro-

r and_℮represents a radical selected from the group consisting of"^C02^C2^H5'-CC ^ H, -CHO,

0NH CN and-c-₂,

or R Δc represents a hydrogen atom,

R ' η ^ is-CH,

and RG is-CC ^ ^ ch, or-C 00H

gene,

or ^ is-CH,

R ' η hydrogêne is,

r and, is-COOH _CH_ or-co,.

O O Z

32. Compounds of the general formula (I) as defined in claim 24, wherein:

or R ^ and r ' ^ represent

hydrogen,

and Rg represents a radical chosen from the group consisting of-C 0₂C₂H₅,-C0₂H, -CHO,

CN and-CONH-₂,

or R Δc represents a hydrogen atom,

R ' j ^ is-CH,

and Rg represents-C 0₂CH₂or-COOH

or R ^ ^ represents-ch,

R ' η represents a hydrogen atom,

and RG is-COOH · or-co ^ ^ ch

when prepared by a process according to claim 31 or a chemical equivalent manifest.

33. Method according to claim 23, characterized in -j is hydrogêne

R'_?is hydrogêne

and Rg represents a radical chosen from the group consisting of-C 0₂C₂H^0 and-C₂H.

34. Compounds of the general formula (I) as defined in claim 24, wherein:

represents a hydrogen atom

R ' η represents a hydrogen atom

Rç and represents a radical chosen from the group consisting of-CO 2C2HÇ and-CC ^ hr.

when prepared by a process according to claim 33 or manifest a chemical equivalent.

35. Process for the preparation of novel chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10 and corresponding to the general formula OH OH 0

(I)

wherein:

R Δc represents a radical selected from the group consisting of:

and/or

■Ch

R₃, and₃, identical or different, representing

a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r or₃r and ^ taken together form a divalent radical selected from the group consisting of:

-(CH2) n" ' ⁿbeing 4 or 5, -(CH₂) 2"^0-^^CIÎ2) 2 ~' ^{T ℮}

-(CH₂)₂-N-(CH₂)₂-,

hydrogêne RG is an atom, a methyl radical or ethyl hydroxy -2,

characterized in that:

or is reacted under an inert atmosphere in an organic solvent the dihydroxy -1, 8-9 antrone with an unsaturated compound of formula

wherein Rg, r ^ and RG have the same meanings as above, to obtain a compound of general formula (I) as defined hereinbefore,

or reacting a compound of the formula

with an amine of formula

H-N

r where R ^ ^ and have the same meanings as above, to obtain a compound of general formula (I) as defined above, wherein the radical R Δc represents a hydrogen atom, and optionally said compound obtained is subjected to the action of an esterifying agent to obtain a compound of general formula (I) wherein r^a corresponding meanings different from hydrogen atom.

36. Chemical compounds from the group consisting of dihydroxy -1, 8-substituted antrone 9 and 10 having the general formula (I)

(I)

wherein:

R Δc represents a radical selected from the group consisting of:

and/or

R rg/and, ., same or different, representing a hydrogëne atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r ^ or RG and taken together form a divalent radical chosen from the group consisting of pars

-(CH₂)_n-, n is 4 or 5, -(CH₂)₂~ 0-(CH₂) ₂~ , and

-^lch2 > 2-? -^ICH₂'2' -

* 8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

when prepared by a process according to claim 35 or a chemical equivalent manifest.

37. The method of claim 35, characterized in that:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

38. Compounds of the general formula (I) as defined in claim 36, wherein:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl,

when prepared by a process according to claim 37 or manifest a chemical equivalent.

39. The method of claim 35, characterized in that:

or R ^ and r, . represent a hydrogen atom,

r and ^ is hydrogêne or a radical selected from the group consisting of-ch ^, ~^C2^H5'^{-n c}3^H7' ~ i ·^soC^H^ ,

-n, cyclohexyl, -CGH^₇,-CH₂-CH₂OH,

-cH₂-cHOH-CH₂oH and-(CH₂)₂o--(CH₂)₂oH

or Rg is a hydrogen atom

r and RG and ^ taken together represent a radical selected from the group consisting of-(CH₂)₂~ 0-(CH₂)₂-, -(CH₂>₅

-(cH₂)₂-n-(CH₂)₂-and-(CH₂)₂-n-(CH₂)₂-

CH 3 (CK₂)₂-0:00

or R ^ = ^ hydrogêne is-CH

r and hydrogêne ^ is an atom or a radical chosen from the group consisting of

^-CH, C~₂Hg, -C₄H_g, cyclohexyl

-cH₂-cH₂oH-, -CH₂-cHOH-CH₂oh and

-(cH₂)₂o--(CH₂)₂oH

or ^ RG is-CH

r and ^ and taken together represent a radical selected from the group consisting of-(CH₂)₂" 0 ~ (CH₂)₂,-(CH₂)₄~ and-(CH₂)₅or R ^ ^ is-CH

R ^ is-CH

r and ^ ^ is-CH

or R ^ is hydrogêne

r and R ^ ^ being identical and are selected from the group consisting of-ch ^, -C₂H^,-n C-^H ^,

-n c₃H_gand-CH₂-CH₂OH

or R ^ is hydrogêne

R Δc represents-C₂H,-

r ^ and represents a radical chosen from the group consisting of-CH₂~ CH₂Oh and

-(cH₂)₂o--(CH₂)₂oH

or R Δc represents-C₂H^

r and₃and being identical, are selected from the group consisting of-CH₂~ CH₂OH and-CH₂-cHOH-CH₂oH

or R₅represents"^C2^H5

and and taken together represent a radical selected from the group consisting of-(CH₂)₂-N-(CH₂)₂-and-(CH₂)₂~ N-(CH ₂)₂~.

cH₃(cH₂)₂oH

40. Compounds of the general formula (I) as defined in claim 36, wherein:

or R₃Rjreprésentent and an atom

hydrogen

r ^ and represents a hydrogen atom or a radical chosen from the group consisting of " CH-j, -C₂H^,-n · h ^ ^ c, c ~ ^ ^ h ISO · ,

-n c₄H_g, cyclohexyl, -C_gH₁₇,-CH₂~ CH₂OH,

-cH₂~-cHOH · CH₂oH and-(CH₂)₂o--(CH₂)₂OH

or R_gis hydrogêne

r and_gr and₄taken together represent a radical selected from the group consisting of-(CH₂)₂-0-(CH₂)₂-, --(^ CH-,

-(cH₂)₂-n-(CH₂)₂-and-(CH₂)₂-n-(CH₂)₂-

CH.

(cH₂)₂-oH

or R_grepresents a hydrogen atom

R_gis-CH₃

r and₄hydrogêne or is a radical selected from the group consisting of-CH₃, C~₂H_g,-C₃H₇,-C₄H_g, cyclohexyl,

-CH "-CH-OH, -CH_OH-CH-CH0_O0:00 and

2 2,2 2

-(cH₂)₂o--(CH₂)₂oH

or R_gis-CH₃

r and₃r and₄taken together represent a radical selected from the group consisting of-(CH₂)₂~ 0-(CH₂)₂j

or Bi r₃is-CH₃

(cH₂)₄-and-(CH₂)₅R ^ ^ is-CH

^ and Rjreprésente -CH

or R ^ is hydrogêne

r and R ^ ^ being identical and are selected from the group consisting of-CH₃,--C₂H₃,

-n c₃H_?,-n c₄H_gand-CH₂~ CH₂OH

or R₃represents a hydrogen atom

R,-represents-C₂HJ-

r ^ and represents a radical chosen from the group consisting of-CH₂-CH₂Oh and ~ (CH₂)₂o--(CH₂)₂oH

or Rjreprésente -C₂HJ.

r and₃r ^ and being identical, are selected from the group consisting of-CH₂-CH₂Oh and

-cH₂-cHOH-CH₂oH

or Rj. is-C₂Hj_

r and₃r and ^ taken together represent a radical selected from the group consisting

by-(CH₂)₂-N-(CH₂)₂-and-(CH₂)₂~ N-(CH ₂)₂~

cH₃( c^h₂)₂oh when prepared by a process according to claim 39 or

manifest a chemical equivalent.

41. The method of claim 35, characterized in that:

or R₃and. are Rç

hydrogen

r and Δc represents a hydrogen atom or a radical selected from the group consisting of-CH₃,-C₂H₅,-iso C₃H₇and-CH₂~ CH₂OH or R₃represents a hydrogen atom

r and₃r and ^ taken together represent a radical selected from the group consisting of-(CH₂)₂-0-(CH₂)₂-, -(CH₂)₄~, <-CH₂)₅~ and

-(cH₂)₂-n-(CH₂)₂~

42. Compounds of the general formula (I) as defined in claim 36, wherein:

or R ^ Rβ and represent an atom

hydrogen

r and ^ is hydrogêne or a radical selected from the group consisting of-CH₃,-C₂H₅,-iso C₃H₇and-CH₂~ CH₂OH or R ^ is hydrogêne

r and₃and taken together represent a radical selected from the group consisting of-(CH₂)₂-0- ÎCH₂)₂-,

and-(CH₂)₂-n-(CH ₂)₂~

(cH₂)₂-oH

or R₃r and₄are

hydrogen,

Rj_ represents and^_CH₃

or R, reorésente -CH-₀

5 3

r and₃r and₄taken together represent

or R,. is hydrogen this is-C ^-^ OH

r and₄this is-the ^-^ OH

when prepared by a process according to claim 41 or manifest a chemical equivalent.

43. Process for the preparation of novel chemical compounds from the group consisting of dihydroxy -1, 8-9-substituted antrone 10 s and having a general formula selected from the group consisting of the general formula (Ilb)

and/or general formula (iie)

(Hb)

(Iie)

wherein

R R ^ ^ and, or diffêrents identical, represent a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

or RG and taken together form a divalent radical selected from the group consisting of:

-(CH₂)_n-, n is 4 or 5, -(CH₂)₂~ 0-(CH ₂)₂~' ^and

- <^CH2>2-^-<^CH₂)₂"

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

characterized in that a compound of general formula

wherein r-^ is a radical selected from the group consisting of

and/or

R ^ RG and having the same meanings as above, with an amine of formula

where R ^ and have the same meanings as above to obtain a compound of general formula (Ilb) or (lie) as defined above.

44. Chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10 and having a general formula selected from the group consisting of the general formula (Ilb)

and/or

(Ilb)

(Iie)

wherein

R R ^ ^ and the same or different represent a hydrogêne atom, an alkyl radical, linear or branched, having 1 S 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 2 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r ^ and or taken together form a divalent radical selected from the group consisting of:

-(^CH2^n^-'^{n atant}4 and 5,-(CH2) 2^-°-(^CH2 "" ^ 2^and

-(CH₂)₂" N-(CH₂)₂",

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

when prepared by a process according to claim 43 or manifest a chemical equivalent.

45.Un method according to claim 43, characterized in that:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting of:2-hydroxy ethyl, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

46. Compounds of the general formula (I) as defined in claim 44, wherein:

-alkyl radicals, linear or branched, having 1 to 8 carbon atoms is selected from the group consisting of the: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl or octyl,

the mono-or polyhydroxyalkyl radical, linear or branched are selected from the group consisting

radical: ëthyle hydroxy -2, and dihydroxy propyl 2-hydroxy -2, 3 propyl,

and-cycloalkyl radicals are selected from the group consisting of the: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl,

when prepared by a process according to claim 45 or manifest a chemical equivalent.

47. The method of claim 43, characterized in that:

or represents a hydrogen atom

r and₄d is¹hydrogen or a radical selected from the group consisting of-CH₃,-C₂H₅,-n, -CH₂" Ch₂OH,

-cH₂-cHOH " ch₂oH and-(CH₂)₂o--(CH₂)₂oH

or R₃is-CH₂CH₂OH

r and ^ is-CH₂CH₂OH

or R₃R^j and taken together represent a radical selected from the group consisting of-(CH₂)₂-0-(CH₂)₂-and-(CH₂)₄~.

48. Compound of general formula (I) as defined in claim 44, wherein:

or R Δc represents hydrogen

r and Δc represents a hydrogen atom or a radical selected from the group consisting of-CH₃,-C₂H₅,-n c₃H_?,-CH₂" Ch₂OH,

-cH₂-cHOH-CH₂oH and-(CH₂)₂o--(CH₂)₂oH

or R₃is-CH₂CH₂OH

r and ^ is-CH₂CH₂OH

or R₃r and ^ taken together represent a radical selected from the group consisting of-(CH₂>₂" 0-(CH₂)₂~ and-(^ ch-,

when prepared by a process according to claim 47 or a chemical equivalent manifest.

49. The method of claim 43, characterized in that:

radical selected from the group consisting of-(CH₂)₂-0-(CH₂)₂and " (^ ch-.

50. Compound of general formula (I) as defined in claim 44, wherein:

or hydrogen and r Δc represents a radical-{ €H₂)₂~ 0-(CH₂)₂OH

or R ^ is ~ ch₂CH₂OH

and is-CH₂CH₂OH

or r and ^ taken together represent a radical selected from the group consisting of-(CH₂)₂-0-(CH₂)₂and-(^-CH

when prepared by a process according to claim 49 or an equivalent chemical manifest.

51. Process for the preparation of novel chemical compounds belonging to the group consisting of dihydroxy -1, 10-substituted 8 anth.rone~9 and responsive to a general formula selected from the group consisting of

Ù > 3

(A) General Formula (I)

(B) General Formula (Ilb)

(I) (Ilb)

and/or general formula (iie)

0 OH OH

(Iie)

wherein:

represents a radical selected from the group consisting of:

(c)

(d)

and (e)-CH-CH-R

R2 representing a hydrogêne atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical,

R3, R ^ and r, -representing a same or different hydrogêne atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 1 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

r-j and r or ^ taken together form a divalent radical selected from the group consisting of:

-<^CH2 ~ ^ n'ⁿ®^{both 4}or 5, -(CH2) 2-0-(CH₂) 2-,^and

-(CH₂)₂-N-(CH₂)₂-,

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

Rg representing-C 0₂Rg, -CN, -CHO, -CONH₂or

-cONH-CH₂oH,

r and -j r and ' same or different, representing

hydrogêne atom or a methyl radical,

characterized in that

or for the preparation of a compound of general formula

(I) as defined above, is reacted under an inert atmosphere in an organic solvent the dihydroxy -1, 8-9 antrone with an unsaturated compound selected from the group consisting of:

(iV) and

where, R ^, r ^, , Rg, r ^, and R ^ have the same meanings as above, to obtain a compound of general formula (I) as defined above.

or for the preparation of a compound of general formula

(I) as defined hereinbefore wherein represents or the radical (B) as defined hereinbefore or the radical (C) as defined above which comprises reacting a compound of formula

with an amine of formula

r where R ^ ^ and have the same meanings as above, to obtain a compound of general formula (I) as defined above, where R ^ is or the radical (B) as previously defined and/or the radical (C) as defined hereinbefore, r ^ representing a hydrogen atom, optionally said compound obtained is subjected to the action of an esterifying agent to obtain a compound of general formula (I) in which a corresponding meanings different from hydrogen atom

well for the preparation of a compound of general formula (Ilb) or (lie) as defined above which comprises reacting a compound of general formula

r wherein ^ is a radical selected from the group consisting of

and/or

R R ^ ^ and having the same meanings as above, with an amine of formula

r where R ^ ^ and have the same meanings as above to obtain a compound of general formula (Ilb) or (lie) as defined above.

52. Chemical compounds belonging to the group consisting of dihydroxy -1, 8-9-substituted antrone 10 and having a general formula selected from the group consisting of

(A) General Formula (I)

(B) General Formula (Ilb)

(Hb) and/or general formula (iie)

R " (Lle)

wherein:

R Δc represents a radical selected from the group consisting of:

<d) ch, !

CON

•Ch

CH,

' R.

CON-

"' SR,

and (e)-CH-CH-R

R₂representing a hydrogen atom, an alkyl radical, linear or branched, having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, having 1 to 3 carbon atoms, a carbamoyl radical or a phenyl radical,

R₃, R₄r and₅the same or different hydrogêne representing a hydrogen, a linear or branched alkyl radical having 1 to 8 carbon atoms, a mono-or polyhydroxyalkyl radical, linear or branched, optionally interrupted by an oxygen atom, having 1 to 8 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms,

or taken together form a divalent radical selected from the group consisting of:

-(CH₂)_n~, n is 4 or 5, -(CH₂)₂~ 0-(CH₂)₂"/^and

-(CH₂)₂-N-(CH₂)₂-,

^R8

Rg is a hydrogen atom, a methyl radical or ethyl hydroxy -2,

Rg representing-CC ^ r, -, -CN, -CHO, ~ conh₂or

-cONH-CH₂oH,

r and ^ and r ', identical or different, representing

hydrogêne atom or a methyl radical,

when prepared by a process according to claim 51 or manifest a chemical equivalent.

CPC - классификация

A A6 A61 A61K A61K8 A61K8/A61K8/3 A61K8/35 A61K8/37 A61K8/4 A61K8/42 A61K8/44 A61K8/49 A61K8/491 A61K8/4913 A61Q A61Q1 A61Q19 A61Q19/A61Q19/0 A61Q19/00 C C0 C07 C07C C07C5 C07C59 C07C59/C07C59/8 C07C59/86 C07D C07D2 C07D20 C07D207 C07D207/C07D207/4 C07D207/40 C07D29 C07D295 C07D295/C07D295/1 C07D295/18 C07D295/185

IPC - классификация

A A6 A61 A61K A61K3 A61K31 A61K31/A61K31/1 A61K31/11 A61K31/12 A61K31/16 A61K31/165 A61K31/19 A61K31/2 A61K31/21 A61K31/215 A61K31/4 A61K31/40 A61K31/401 A61K31/4015 A61K31/44 A61K31/49 A61K31/495 A61K31/5 A61K31/53 A61K31/535 A61K31/537 A61K31/5375 A61K8 A61K8/A61K8/3 A61K8/35 A61K8/37 A61K8/4 A61K8/42 A61K8/44 A61K8/49 A61P A61P1 A61P17 A61P17/A61P17/0 A61P17/00 A61Q A61Q1 A61Q19 A61Q19/A61Q19/0 A61Q19/00 C C0 C07 C07C C07C2 C07C23 C07C231 C07C231/C07C231/0 C07C231/00 C07C233 C07C233/C07C233/0 C07C233/00 C07C233/1 C07C233/12 C07C235 C07C235/C07C235/3 C07C235/32 C07C235/7 C07C235/78 C07C25 C07C253 C07C253/C07C253/0 C07C253/00 C07C255 C07C255/C07C255/4 C07C255/40 C07C4 C07C45 C07C45/C07C45/0 C07C45/00 C07C49 C07C49/C07C49/7 C07C49/74 C07C49/747 C07C5 C07C51 C07C51/C07C51/0 C07C51/00 C07C59 C07C59/C07C59/8 C07C59/86 C07C6 C07C62 C07C62/C07C62/3 C07C62/38 C07C67 C07C67/C07C67/0 C07C67/00 C07C69 C07C69/C07C69/7 C07C69/73 C07C69/738 C07D C07D2 C07D20 C07D207 C07D207/C07D207/0 C07D207/04 C07D207/4 C07D207/40 C07D209 C07D209/C07D209/5 C07D209/56 C07D21 C07D211 C07D211/C07D211/0 C07D211/06 C07D24 C07D241 C07D241/C07D241/0 C07D241/04 C07D26 C07D265 C07D265/C07D265/3 C07D265/30 C07D29 C07D295 C07D295/C07D295/1 C07D295/16 C07D295/18 C07D295/185