Amphiphilic compounds with neuroprotective properties

An amphiphilic compound with tetradecahydrophenanthrene skeleton of general formula I,

• wherein
• R1 is selected from the group comprising (—OSO3pyH), (—OSO3Na), (—OSO3H), NaOOC—R6—C(R7)—R8—, HOOC—R6—C(R7)—R8—, HOOC—C(R7)—R8—, or R9—R10—C(R)—R12—, where
• R6 represents straight or branched C1 to C6 alkylene or C2 to C6 alkenylene chain, unsubstituted or substituted with one or more halogen atoms or amino group or amino group protected by protecting groups,
• or R6 means trivalent —CH(CH2-)2 alkylene that forms with the carbon carrying R7 and with R8 being nitrogen a five-membered ring;
• R7 represents atom of oxygen, nitrogen or sulphur bound by double bond, or two atoms of hydrogen,
• R8 represents an at least divalent atom,
• R9 represents a cationic group selected from guanidinyl derivatives of formula (a),
• and quaternary ammonium groups of formula (b)
• wherein R13 to R20 are selected from hydrogen atoms, linear or branched C1 to C6 alkyl, linear or branched C2 to C6 alkenyl,
• R10 represents straight or branched C1 to C6 alkylene or C2 to C6 alkenylene, wherein the alkylene and alkenylene are unsubstituted or substituted by 1 to 10 halogen atoms or by amino group which is primary or substituted by linear or branched C1 to C4 alkyl;
• R11 represents atom of oxygen, nitrogen or sulphur bound by double bond, or two atoms of
• hydrogen, and
• R12 is selected from the group comprising oxygen, nitrogen and carbon atoms, and when R12 is carbon or nitrogen, its further valences are occupied by hydrogen or hydrogens, while any of hydrogen is optionally replaced by C1 to C4 alkyl or C2 to C4 alkenyl;
• R2 represents hydrogen atom or methyl;
• R3 represents a) hydrogen atom, and then
• i) R4 and R5 are hydrogen atoms, or
• ii) one of R4 and R5 represents hydrogen atom and the other one represents a straight or branched C1 to C6 alkyl or C2 to C6 alkenyl chain, optionally substituted by 1 to 13 halogen atoms in case of said alkyl and by 1 to 9 halogen atoms in case of said alkenyl, or by atom of oxygen or sulphur bound by a double bond, while one of the methylene groups in the chain is optionally replaced by oxygen or sulphur atom;
• or
• b) straight or branched C1 to C6 alkyl or C2 to C6 alkenyl, optionally substituted by 1 to 13 halogen atoms in case of alkyl or by 1 to 9 halogen atoms in case of alkenyl, or by atom of oxygen or sulphur bound by a double bond, while one of the methylene groups in the chain is optionally replaced by oxygen or sulphur atom, and then R4 and R5 are hydrogen atoms, or
• c) C5 or C6 alicyclic or aromatic ring, while carbon atoms are optionally substituted by 1 to 8 atoms of halogen in case of C5 alicyclic ring, or 1 to 10 halogen atoms in case of C6 alicyclic ring or by 1 to 4 halogen atoms in case of C5 aromatic ring or 1 to 5 halogen atoms in case of C6 aromatic ring;
• and then
• i) R5 is selected from the group comprising hydrogen atom, linear or branched C1 to C6 alkyl, linear or branched C2 to C6 alkenyl, wherein said alkyl or alkenyl is optionally substituted by 1 to 13 halogen atoms in case of said alkyl and by 1 to 9 halogen atoms in case of said alkenyl, or by double-bond-bound atom of oxygen or sulphur, while one of the methylene groups in the chain is optionally replaced by oxygen or sulphur atom, or
• ii) R4 and R5 represent alkylene or alkenylene substituent —(CHm)n—, where n=3-4, m=1-2, forming with the parent carbon atoms of the skeleton at position 7 and 8 a saturated or unsaturated 5- or 6-membered cycle, wherein the hydrogen atoms of the alkylene or alkenylene substituent are optionally substituted at least by one halogen atom or linear or branched C1 to C4 alkyl or C2 to C4 alkenyl chain, wherein optionally one methylene group of the alkylene substituent forming the cycle is replaced by carbonyl group and the carbon atom at the adjoining position is optionally substituted by another methylene group, or one methylene group of the alkylene substituent forming the cycle is optionally replaced by oxygen or sulphur atom, while the sulphur atom is optionally functionalized by oxygen atom;
• or the hydrogens of one methylene group of the alkylene substituent are optionally replaced by —O—CH2—, thereby forming oxirane ring,
• d) substituent —CH2—O—CH(CH3)— bound to the first carbon of an alkylene group —(CH2)3— which is formed by R4 and R5;
• and enantiomers of compounds of general formula I,
• with the proviso that compounds wherein R1 represents HO2C—R6CR7—R8—, R6 is —(CH2)2—, R7 is oxygen atom bound by double bond and R8 is oxygen atom, while R2 and R3 are methyl groups, R4 and R5 together form group-(CH2)3— forming with parent carbon atoms of tetradecahydrophenanthrene skeleton at position 7 and 8 a saturated five-membered ring;
• with absolute configuration 3R,5S,8S,9S,10S,13S,14S are excluded from formula I.