Patent EA-003776-B1 (EA)
Title: Novel 6-deoxy erythromycin derivatives, method for preparing same and use as medicines
Inventor: AUGER JEAN MICHEL
IPC: A61P31/00
Filed: 1999-07-20
Abstract: 1. The compounds of formula (I) in which - X represents an (NH)a, CH2, or SO2 radical or an oxygen atom, a represents the number 0 or 1, - Y represents a (CH2)m-(CH=CH)n-(CH2)o radical with m+n+o <8, n = 0 or 1, - Ar represents penyl or naphtyl radical, or heteroaryl radical which can be the thienyl, furyl, pyrolyl, thiazolyl, oxazolyl, imidazolyl radical, for example the 4-(3-pyridinyl) 1H-imidazolyl, thiadiazolyl, pyrazolyl or isopyrazolyl radical, a pyridyl, pyrimidyl, pyridazinyl or pyrazinyl radical, or also an indolyl, benzofurannyl, benzothiazyl or quinolinyl radical, unsubstituted or substituted by one or more groups chosen from the group constituted by the hydroxyl radicals, the halogen atoms, the NO2 radicals, the C [triple bond] N radicals, the alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl or O-alkynyl, S-alkyl, S-alkenyl or S-alkynyl and N-alkyl, N-alkenyl or N-alkynyl radicals, containing up to 12 carbon atoms optionally substituted by one or more halogen atoms, the radical where Ra and Rb identical or different representing a hydrogen atom or an alkyl radical containing up to 12 carbon atoms, the radical where R3 representing an alkylradical containing up to 12 carbon atoms, or a phenyl or naphtyl radical, or heteroaryl radical mentioned above optionally substituted by one or more of the substituents mentioned above. - W represents a hydrogen atom or a halogen atom, - Z represents a hydrogen atom or the remainder of an acid as well as their addition salts with acids. 2. The compounds of formula (I) defined in claim 1, in which Z represents a hydrogen atom. 3. The compounds of formula (I) defined in any one of claims 1 and 2, in which W represents a hydrogen atom. 4. The compounds of formula (I) defined in any one of claims 1, 2 and 3, in which X represents a CH2 radical. 5. The compounds of formula (I) defined in any one of claims 1 to 4, in which Y represents a (CH2)3 or (CH2)4 radical. 6. The compounds of formula (I) defined in any one of claims 1 to 5, characterized in that Ar represents the radical. 7. As a new chemical product defined in claim 1 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy]-3-oxo-12,11-[oxycarbonyl[[4-(4-(3-pyridinyl)-1H-imidazol-l-yl]butyl]imino]]-6,11,12-trideoxy-erythromycin. 8. As medicaments, the compounds according to any one of claims 1 to 6, as well as their pharmaceutically acceptable salts. 9. As a medicaments, the compound according to claim 7, as well as its pharmaceutically acceptable salts. 10. The pharmaceutical compositions containing at least one medicament according to claim 8 or 9 as medicaments. 11. Process for the preparation of compounds of formula (I) defined in any one of claims 1 to 7, characterized in that a compound of formula (II): is subjected to the action of a cladinose hydrolysis agent in aqueous medium in order to obtain the compound of formula (III): which is subjected to the action of a blocking agent of the hydroxyl function in position 2' in order to obtain a compound of formula (IV): in which OM represents a blocked hydroxyl group which is subjected to the action of an oxidizing agent of the hydroxyl group in position 3 in order to obtain the compound of formula (V): then if desired the hydroxyl in position 2' is released in order to obtain the compound of formula (VI): then if desired any one of products (V) or (VI) is subjected to the action of an agent capable of creating a double bond in position 11, 12 in order to obtain the compound of formula (VII): in which OM' represents a free or blocked hydroxyl radical which is subjected to the action of carbonyldiimidazole in order to obtain the compound of formula (VIII): which is subjected to the action of a compound of formula ArYXNH2 in which Y, X, and Ar have the meaning indicated in claim 1, in order to obtain the corresponding compound of formula (IA) in which W represents a hydrogen atom which is subjected if desire to the action of a halogenation agent in order to obtain the compound of formula (IB) in which W represents a halogen atom, then if desired the hydroxyl in position 2' is released and/or if appropriate subjected to the action of an acid in order to form the salt. 12. As new chemical products, the compounds of formula (V), (VI) defined in claim 11. 13. As new chemical products, the compounds of formula (VII) defined in claim 11. 14. As new chemical products, the compounds of formula (VIII) defined in claim 11.