Novel antibacterial agents

Abstract

This invention relates to novel macrolides, to the preparation of novel macrolides, to the use of such novel macrolides preventing, treating, or ameliorating various conditions, and to the use of such novel macrolides as antibacterial agents.

1 . A compound according to Formula 1 and Formula 2, and its pharmaceutically acceptable salts, hydrates, solvates and esters thereof, wherein: 
       
         
           
           
               
               
           
         
         R 1  is selected from H, cyclic and acyclic alkyl, cyclic and acyclic alkyl-hydroxyamine, aryl, aryl-hydroxyamine, cyclic and acyclic acyl, cyclic and acyclic acyl-hydroxyamine, heteroalkyl, heteroalkyl-hydroxyamine, heteroaryl, heteroaryl-hydroxyamine, acylaryl, acylaryl-hydroxyamine, acylheteroaryl, acylheteroaryl-hydroxyamine, alkylaryl, alkylaryl-hydroxyamine, alkylheteroaryl, alkylheteroaryl-hydroxyamine, sulfonylalkyl, sulfonylalkyl-hydroxyamine, acylalkoxylsulfonylalkyl, acylalkoxylsulfonylalkyl-hydroxyamine; 
         or R 1  can be —C(O)—NR 4 R 5 , where R 4  and R 5  can be independently or taken together as hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, urea or carbamate and acceptable salts thereof; 
         or R 1  can also be a monosaccharide (including amino sugars and their derivatives, particularly, a mycaminose derivatized at the C-4′ position or a 4-deoxy-3-amino-glucose derivatized at the C-6′ position), a disaccharide (including, a mycaminose derivatized at the C-4′ position with another sugar or a 4-deoxy-3-amino-glucose derivatized at the C-6′ position with another sugar), a trisaccharide (including aminosugars and halosugars), chloramphenicol, clindamycin or their analogs; provided that R 1  can not be desosamine; 
         R 2  and R 3  are each independently OH, or R 2  and R 3  are taken together as follows: 
       
       
         
           
           
               
               
           
         
       
       where Z is O, or —N(R 6 ); where R 6  is hydrogen, hydroxy, alkyl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, or sulfonyl, and pharmaceutically acceptable salts thereof;
 X is H; 
 Y is OR 7 ; where R 7  is a monosaccharide or disaccharide (including aminosugars or halosugars), alkyl, aryl, heteroaryl, acyl (particularly, 4-nitro-phenylacetyl and 2-pyridylacetyl), or —C(O)—NR 8 R 9 , where R 8  and R 9  can be independently or taken together as hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureyl or carbamyl and pharmaceutically acceptable salts thereof, 
 or X and Y taken together are O; 
 V is —C(O)—, —C(═NR 11 )—, —C(NR 12 ,R 13 )—, or —N(R 14 )CH 2 —, wherein the first dash of each of the foregoing V groups is attached to the C-10 carbon of the compounds of Formulae 1 and 2 and the last dash of each group is attached to the C-8 carbon of the compounds of Formulae 1 and 2 and R 11  is hydroxy or alkoxy, R 12  and R 13  can be independently or taken together as hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureyl or carbamoyl and pharmaceutically acceptable salts thereof and R 14  is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureyl or carbamoyl and pharmaceutically acceptable salts thereof; 
 W is H, F, Cl, Br, I, or OH; 
 A is —CH 2 —, —C(O)—, —C(O)O—, —C(O)NH—, —S(O) 2 —, —S(O) 2 NH—, —C(O)NHS(O) 2 —; 
 B is —(CH 2 ) n — where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons, which may contain any alkenyl or alkynyl group; and 
 C is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, aminoaryl, alkylaminoaryl, acyl, acyloxy, sulfonyl, ureyl or carbamoyl and pharmaceutically acceptable salts thereof; wherein R 10  is hydrogen or acyl. 
 
     
     
         2 .- 17 . (canceled)