Macrolides with Anti-Inflammatory Activity

A compound of Formula (I)

• wherein:
• A is a bivalent radical selected from —C(O)—, —N(R7)CH2—, —CH2N(R7)—, —CH(OH)— and —C(═NOR7)—;
• R1 is —OC(O)(CH2)nNR8R9, —O—(CH2)nNR8R9, —OC(O)N(R7)(CH2)nNR8R9,
• —O(CH2)nCN , —OC(O)(CH2)n N (CH2)nNR8R9, or
• —OC(O)CH═CH2 with the proviso that if R1 is —OC(O)CH═CH2, R3 cannot be methyl;
• R2 is hydrogen or a hydroxyl protecting group;
• R3 is C1-4 alkyl substituted at terminal carbon atom with CN or NH2 group, or C1-5 alkanoyl;
• R4 is hydrogen, C1-4 alkyl, or C2-6 alkenyl;
• R5 is hydroxy, methoxy group, —OC(O)(CH2)nNR8R9, —O—(CH2)nNR8R9, or —O(CH2)nCN;
• R6 is hydroxy;
• or
• R5 and R6 taken together with the intervening atoms form a cyclic group having the following structure:
• wherein Y is a bivalent radical selected from —CH2—, —CH(CN)—, —O—, —N(R7)— and —CH(SR7)—;
• R7 is hydrogen or C1-6 olkyl;
• R8 and R9 are each independently hydrogen, C3-7 cycloalkyl, or C1-18 alkyl, wherein C1-18 alkyl is:
• (i) uninterrupted or interrupted by 1-3 bivalent radical groups selected from —O—, —S— and —N(R7)—;
• and/or
• (ii) unsubstituted or substituted by 1-3 groups selected from halogen, OH, NH2, N—(C1-C6)alkylamino, N,N-di(C1-C6-alkyl)amino, CN, NO2, OCH3, a C3-8 membered non-aromatic ring which is saturated or unsaturated, a non-aromatic heterocyclic ring containing 2-6 carbon atoms which is saturated or unsaturated containing from 1-2 heteroatoms selected from oxygen, sulphur and nitrogen, alkylcarbonylalkoxy and alkoxycarbonylamino;
• or
• R8 and R9 taken together with nitrogen to which they are attached form a non-aromatic heterocyclic ring containing 2-6 carbon atoms which is:
• (iii) saturated or unsaturated containing from 0 or 1 additional heteroatoms selected from oxygen, sulphur and nitrogen;
• and/or
• (iv) unsubstituted or substituted by 1-2 groups selected from C1-5alkanoyl and C1-8 alkyl, wherein C1-8 alkyl is uninterrupted or is interrupted by 1-3 bivalent radical groups selected from —O—, —S— and —N(R7)—, and/or being unsubstituted or substituted by 1-2 groups selected from OH, NH2, a non-aromatic heterocyclic ring containing 2-6 carbon atoms which is unsubstituted or is substituted by group selected from C1-4 alkyl, halo, NH2, OH, SH, C1-6 alkoxy and C1-4 hydroxyalkyl, a C3-7 cycloalkyl which is unsubstituted or is substituted by group selected from C1-4 alkyl, halo, NH2, OH, SH, C1-6 alkoxy and C1-4 hydroxyalkyl;
• n is an integer from 1 to 8;
• or a pharmaceutically acceptable salt thereof.