Patent EA-002168-B1 (EA)
Title: Novel erythromycin derivatives, method for preparing same and use thereof as drugs
Inventor: AGOURIDAS CONSTANTIN
IPC: A61K31/7048
Filed: 1997-07-23
Abstract: 1. The erythromycin derivatives of formula (I):   in which R represents a hydrogen atom, an alkyl containing up to 12 carbon atoms, optionally substituted by a halogen atom or a (CH2)mAr or   in which m represents an integer comprised between 1 and 8, n and p, identical or different, represent an integer comprised between 0 and 6, A and B, identical or different, represent a hydrogen or a halogen atom or an alkyl radical containing up to 8 carbon atoms and Ar represents phenyl or naphthyl, or heteroaryl radical selected from thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl, isopyrazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, benzofuranyl, benzothiazyl, or quinolinyl, and the above-mentioned radicals can be substituted with one or more substituents, selected from the group comprising hydroxyl, halogen atoms, radicals NO2 and CN, alkyl, alkenyl, or alkynyl, O-alkyl, O-alkenyl, O-alkynyl, S-alkyl, S-alkenyl, S-alkynyl, N-alkyl, N-alkenyl, N-alkynyl, comprising up to 12 carbon atoms, which can be substituted with one or more halogen atoms, radical    wherein Ra and Rb  are identical or different - hydrogen atom or alkyl comprising up to 12 carbon atoms, radical   wherein R3 - alkyl comprising up to 12 carbon atoms, or aryl or heteroaryl radical with 5 or 6 members comprising one or more heteroatoms, which can be substituted with one or more above-mentioned substituents, and Z represents a hydrogen atom or the remainder of a carboxylic acid containing up to 18 carbon atoms. 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 R represents a hydrogen atom. 4. The compounds of formula I as defined in Claim 1, 2 or 3 in which R represents (CH2)mAr, wherein m and Ar retaining the same meaning as in Claim 1. 5. The compounds of formula I as defined in Claim 4, in which R represents a (CH2)m'Ar, wherein m' represents the integer of 3, 4, 5 or 6. 6. The compounds of formula I as defined in Claim 5, in which Ar represents a 4-quinolinyl radical optionally substituted on one and/or the other of the 2 quinoline rings. 7. The compounds of formula I as defined in Claim 6, in which Ar represents a non-substituted 4-quinolinyl radical. 8. The compounds of formula I as defined in Claim 5, in which Ar represents a radical:   optionally substituted on one and/or the other of the 2 rings. 9. The compounds of formula I as defined in Claim 8, in which the Ar radical is not substituted. 10. The compounds of formula I defined in Claim 1 the name of which follows: 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl)oxy]-6-O-methyl-3-oxo-12,11-{oxycarbonyl[3-(4-quinolinyl)propoxy]imino}erythromycin. 11. As medicaments, the compounds of formula I as defined in any one of Claims 1 to 10. 12. The pharmaceutical composition containing at least one medicament according to Claim 11 as active ingredient. 13. Preparation process for the compounds of formula I, as defined in any one of Claims 1 to 10, characterized in that a compound of formula (II):   in which Z retains its previous meanings described in Claim 1, is subjected to the action with hydroxylamine or its halohydrate, in order to obtain the compound of formula IA:   which, if desired, is subjected to the action of a methanolysis hydroxyl agent in position 2', in order to obtain the corresponding compound of formula IB in which Z represents a hydrogen atom   then the compound IA or IB is subjected to the action of a compound of formula (III): R'Hal                                              (III), in which R' has the same meaning as R with the exception of the hydrogen and Hal represents a halogen atom, in order to obtain the corresponding compound of formula IC , which is optionally subjected to the action of a hydrogenation agent of the optional double bond of the  radical and/or to the action of an agent which releases the hydroxyl function in position 2'. 14. As intermediaries, the compounds of formula (III) the names of which follow: 4-(3-iodopropyl)-quinoline, 3-[1-(3-bromopropyl)-IH-imidazol-4-yl]-pyridine.