New Pleuromutilin Antibiotic Compounds, Compositions and Methods of Use and Synthesis

A compound according to the chemical structure:

• Where A is O, S, —N(RN)(C(RA)(RB))g— or —(C(RA)(RB))h—;
• RN is H or a C1-C3 alkyl group which is optionally substituted with from 1 to 3 hydroxyl groups or halogen groups (preferably fluoro groups);
• RA and RB are each independently H, a halogen group (often F), a C1-C3 alkyl which is optionally substituted with from 1-3 halogen groups (often 1-3 fluoro groups) or 1-3 hydroxyl groups (often a single hydroxyl group) or together RA and RB form a cyclopropyl or cyclobutyl group on a single carbon;
• R1 is H, an optionally substituted C1-C7 alkyl group (preferably C1-C3 alkyl, preferably methyl) which is preferably substituted with from 1-5 halogens (F, Cl, Br or I), often from 1-3 fluoro groups or from 1-3 hydroxyl groups, a Sugar group wherein said sugar group is a monosaccharide or disaccharide sugar as otherwise described herein which forms a glycosidic linkage with the oxygen (preferably at the 1 or 4 carbon position of the sugar moiety bonded to the oxygen), an optionally substituted —(CH2)i—C(O)—C0-C6 alkyl group (forming an ester) which is preferably substituted with from 1-5 halogens, often 1-3 fluoro groups and from 1-3 hydroxyl groups (preferably, R1 forms a methyl ester group substituted with a single hydroxyl group) or a —(CH2)i—C(O)—(CH2)i—O-Sugar group;
• R1A and R1B are each independently H, an optionally substituted C1-C6 alkyl or C2-C6 alkenyl group (preferably vinyl, often R1B is a vinyl group wherein said alkyl group or said alkenyl group is preferably substituted with from 1-5 halogen groups and/or from 1-3 hydroxyl groups), an optionally substituted —(CH2)iNRNARNB group, OH, an optionally substituted —(CH2)iO—C1-C6 alkyl group, an optionally substituted —(CH2)iC(O)—C0-C6 alkyl, an optionally substituted —(CH2)iC(O)O—C1-C6 alkyl or an optionally substituted —(CH2)iOC(O)—C1-C6 alkyl wherein each of the aforementioned alkyl groups is preferably substituted with from 1-5 halogen groups (often 1-3 fluoro groups) or from 1-3 hydroxyl groups, an optionally substituted —(CH2)iAryl, an optionally substituted —(CH2)iO-Aryl, an optionally substituted —(CH2)iHeteroaryl or an optionally substituted —(CH2)iO-Heteroaryl, an optionally substituted —(CH2)iSugar, an optionally substituted —(CH2)iO-Sugar, an optionally substituted —(CH2)i—C(O)—(CH2)i—O-Sugar group, or R1A or R1B together with the carbon atom to which R2 is attached form an optionally substituted 5-6 membered carbocyclic ring which link the carbon atoms which are bonded to R1A or R1B and R2, respectively, wherein the alkylene group extends above or below the plane of the molecule;
• RNA and RNB is each independently H, a C1-C6 alkyl which is optionally substituted with from 1-3 halo groups (preferably F) or 1-3 hydroxyl groups (often 1 hydroxyl group), an optionally substituted —(CH2)iO—C1-C6 alkyl, an optionally substituted —(CH2)iC(O)C0-C6 alkyl, an optionally substituted —(CH2)iC(O)OC1-C6 alkyl, an optionally substituted —(CH2)iOC(O)C1-C6 alkyl, an optionally substituted —(CH2)iAryl, an optionally substituted —(CH2)iO-Aryl, an optionally substituted —(CH2)iHeteroaryl or an optionally substituted —(CH2)iO-Heteroaryl, an optionally substituted —(CH2)iSugar, an optionally substituted —(CH2)iO-Sugar or an optionally substituted —(CH2)i—C(O)—(CH2)i—O-Sugar group;
• R2 is H, an optionally substituted C1-C8 alkyl group which is preferably substituted with from 1-5 halo groups, often 1-3 fluoro groups or from 1-3 hydroxyl groups, OH, SH, an optionally substituted —(CH2)iNRNARNB group, an optionally substituted —(CH2)iO—C1-C6 alkyl group, an optionally substituted —(CH2)iC(O)—C1-C6 alkyl, an optionally substituted —(CH2)iC(O)O—C1-C6 alkyl or an optionally substituted —(CH2)iOC(O)—C1-C6 alkyl wherein each of the aforementioned alkyl groups is preferably substituted with from 1-5 halogen groups (often 1-3 fluoro groups) or from 1-3 hydroxyl groups, an optionally substituted —(CH2)iAryl, an optionally substituted —(CH2)iO-Aryl, an optionally substituted —(CH2)iHeteroaryl or an optionally substituted —(CH2)iO-Heteroaryl, an optionally substituted —(CH2)iSugar, an optionally substituted —(CH2)iO-Sugar or an optionally substituted —(CH2)i—C(O)—(CH2)i—O-Sugar group, or R2 together with R1A or R1B forms a C2-C5 alkylene group optionally substituted with from 1 to 4 methyl groups which links the carbon atoms which are bonded to R2 and R1A or R1B, respectively, wherein the alkylene group extends above or below the plane of the molecule;
• R2A and R2B are each independently H, OH, an optionally substituted C1-C6 alkyl or C2-C6 alkenyl group (preferably vinyl) wherein said alkyl group or said alkenyl group is preferably substituted with from 1-5 halogen groups and from 1-3 hydroxyl groups), an optionally substituted —(CH2)iNRNARNB group, an optionally substituted —(CH2)iO—C1-C6 alkyl, an optionally substituted —(CH2)iC(O)—C0-C6 alkyl (often C1-C6 alkyl), an optionally substituted —(CH2)iC(O)O—C1-C6 alkyl or an optionally substituted —(CH2)iOC(O)—C1-C6 alkyl wherein each of the aforementioned alkyl groups is preferably substituted with from 1-5 halogen groups (often 1-3 fluoro groups) or from 1-3 hydroxyl groups, an optionally substituted —(CH2)iAryl, an optionally substituted —(CH2)iO-Aryl, an optionally substituted —(CH2)iHeteroaryl or an optionally substituted —(CH2)iO-Heteroaryl, an optionally substituted —(CH2)iSugar, an optionally substituted —(CH2)iO-Sugar or an optionally substituted —(CH2)i—C(O)—(CH2)i—O-Sugar group;
• R3A and R3B are each independently H, OH, a C1-C6 optionally substituted alkyl group, an optionally substituted —(CH2)iO—C1-C6 alkyl group, or R3A and R3B together with the carbon atom to which they are attached form a C2-C6 diether group, often a C3 or C4 diether group (each of the two oxygens of the diether group being bonded to the carbon to which R3A and R3B are bonded) or a keto group (═O) with the carbon to which they are bonded;
• R4 and R5 are each independently H or an optionally substituted C1-C8 alkyl group (preferably methyl) wherein said substitution is preferably from 1-5 halo groups (often F) or from 1-3 hydroxyl groups (often a single hydroxyl group);
• g is 0, 1, 2 or 3;
• h is 1, 2, 3 or 4;
• i is 0, 1, 2, 3, 4, 5 or 6;
• and
• the carbon atoms to which OR1 and R2 are attached optionally are bonded to each other;
• or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof.