Patent EA-002359-B1 (EA)
Title: Erythromycin derivatives, method of preparation and application as mrdicines
Inventor: AGOURIDAS CONSTANTIN
IPC: A61P31/04
Filed: 1998-02-26
Abstract: 1) The compounds of formula (I):   in which A and B form together with the atoms to which they are linked a group:   - R1 represents an NH2radical or an NH-alkyI, NH-alkenyl or NH-alkynyl radical containing up to 18 atoms of carbon or a NH (CH2)nAr radical or or N=CH(CH2)nAr radical in which n represents an integer comprised between 1 and 6, and Ar represents an optionally substituted aryl or heceroaryl radical, Z represents a hydrogen atom or the remainder of a carboxylic acid containing up to 18 carbon atoms, and R represents: - a hydrogen atom,  - a heterocyclic radical containing at least one nitrogen atom and optionally another heteroatom aromatic or non aromatic, saturated or unsaturated, mono or bicyclic, containing up to 12 members, optionally substituted on the nitrogen atom, - an alkyl radical, a linear, branched or cyclic alkyl, containing up to 18 carbon atoms optionally substituted by one or more group: hydroxyl, halogen, cyano, amidinyl, guanidinyl, heterocyclic, as defined previously, alkyloxy having at most 6 carbon atoms, alkylthio having at most 6 carbon atoms, the sulphur atom being optionally oxidized into the sulphoxide or into the sulphone, aryl, aryloxy, arylthio, the sulphur atom being optionally oxidized into the sulphoxide or into the sulphone, radical:   in which: either R'1 and R'2, identical or different, represent a hydrogen atom, a linear, branched or cyclic alkyl radical, containing up to 18 carbon atoms, an aryl radical or aralkyl, R'1 and R'2 form together with the nitrogen atom to which they are linked a mono or bicyclic heterocycle radical, optionally containing another aromatic or non aromatic, saturated or unsaturated heteroatom, containing up to 12 members; 1,2-epoxyethyl or 2,2-dimethyl 1,2-epoxyethyl or a radical resulting from the opening of this group by a nucleophilic reagent,   in which B1  represents either an alkyl or alkyloxy radical having at most 6 carbon atoms, or an aryl or aralkyl radical; free, esterified or salified carboxy or acyl, thiocyanate, acyi or carbamoyl, as well as the addition salts with acids. 2. The compounds of formula (I) as defined in claim 1, in which Z represents a hydrogen atom. 3. The compounds of formula (I) as defined in claim 1 or 2, in which Ri represents an NH(CH2)n, wherein n and Ar retaining their meaning indicated in claim 1. 4. The compounds of formula (I) as defined in any one of claims 1 to 4 in which Ar represents a radical:   and in which X represents a hydrogen atom, a CH3, OH, OMe radical, or a halogen atom. 5. The compounds of formula (I) as defined in claim 4 in which Ar represents a radical   6. The compounds of formula (I) as defined in claim 3, 4 or 5 in which n represents the number 3. 7. The compounds of formula (I) as defined in claim 1, in which R represents a hydrogen atom, a radical:   or a radical:   8. The compounds of formula (I) as defined in claim 1, the name of which follow: (9E) 9-[O-(3-piperidinyl) oxime] of 11,l2-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyi) oxy] 6-O-methyl-3-oxo-12,ll-[oxycarbonyl-[[3-(4-quinolinyl) propyi] hydrazono]] erythromycin. 9. As medicaments, the compounds of formula (I) as defined in any one of claims l to 7. 10. As medicaments, the compound of formula (I) as defined in claim 8. 11. The pharmaceutical compositions containing at least one medicament as defined in claims 1 to 8 as active ingredient. 12. Preparation process for the compound of formula (I) as defined in claim 1, characterized in that a compound of formula (II):   in which A, B and Z retain their previous meaning is subjected to the action of a compound of formula (III) : HN2OR in which R retains its previous meaning in order to obtain the corresponding compound of formula (I), then if desired, the hydroxyl in position 2' is released and/or subjected to the action of an acid in order to form the salt, and/or to the action of an agent which modifies the R radical.