Claims for Patent: 8,071,643

Summary for Patent: 8,071,643

Title:	Pleuromutilin derivatives for the treatment of diseases mediated by microbes
Abstract:	A pleuromutilin derivative compound of general formula (I)
Inventor(s):	Rosemarie Mang, Werner Heilmayer, Rudolf Badegruber, Dirk B. Strickmann, Rodger Novak, Mathias Ferencic, Atchyuta Rama Chandra Murty Bulusu
Assignee:	Hong Kong King Friend Industrial Co Ltd, Kreos Capital IV UK Ltd
Application Number:	US12/531,839
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,071,643
Patent Claims:	1. A compound of formula (I) wherein n is 0 to 4; m is 0 or 1 with the proviso that the sulphur atom and R3 are in vicinal position, if m =0 then R3 is in position 2′, and if m =1 then R3 is on position 1′; R is ethyl or vinyl; R1 is hydrogen or (C1-6)alkyl, R2 is hydrogen or (C3-6)cycloalkyl, or unsubstituted (C1-6)alkyl, or (C1-6)alkyl substituted by one or more of hydroxy, methoxy, halogen, or (C3-6)cycloalkyl, or R1 and R2 together with the nitrogen atom to which they are attached form a 5 to 7 membered heterocyclic ring containing at least 1 nitrogen atom or 1 nitrogen and 1 additional heteroatom selected from N or O, or R1 is hydroxy and R2 is formyl; R3 is OH, OR4, or a halogen atom, or R3 is bound to 2′ and R3 represents —O—(CH2)p—O— with p being 2 or 3; and R4 is unsubstituted (C1-6)alkyl or (C3-6)cycloalkyl. 2. A compound of formula (II) wherein n, R, R1, R2 and R3 are as defined in claim 1. 3. A compound of formula (III) wherein n, R, R1 and R2 are as defined in claim 1. 4. A compound of formula (IV) wherein n, R1 and R2 are as defined in claim 1. 5. A compound of formula (V) wherein n, R1 and R2 are as defined in claim 1. 6. A compound of formula (VI) wherein n, R1 and R2 are as defined in claim 1. 7. A compound according to claim 1, selected from the group consisting of: 14-O-{[(1R, 2R, 4R)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1S, 2S, 4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1R, 2R, 5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1S, 2S, 5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1R, 2R, 4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof; 14-O-{[(1R, 2R, 5R)-5-Amino-2-hydroxy cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1S, 2S, 5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[(1R, 2R, 3R)-3-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof; 14-O-{[(1R, 2R, 4R)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S) diastereomer thereof; 14-O-{[(1R, 2R, 4R)-4-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 4S)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof; 14-O-{[(1R, 2R, 5R)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5S) diastereomer thereof; 14-O-{[(1R, 2R, 3R)-3-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof; 14-O-{[(1R, 2R, 3R)-3-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof; 14-O-{[(1R, 2R, 4S)-4-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 3R/S)-3-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3R/S) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-2-Hydroxy-5-methylamino-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-Allylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-2-Hydroxy-5-(2-methoxy-ethylamino)-cyclohexylsulfanyl]acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 4R*)-2-Hydroxy-4-(2-hydroxy-ethylamino)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S*) diastereomer thereof; 14-O-{[(1R, 2R, 4R*)-4-Cyclohexylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S*) diastereomer thereof; 14-O-{[(1R, 2R, 4R*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S*) diastereomer thereof; 14-O-{[(1R, 2R, 5S*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R*) diastereomer thereof; 14-O-{[(1R, 2R, 4S*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R*) diastereomer thereof; 14-O-{[(1R, 2R, 5R*)-2-Hydroxy-5-morpholin-4-yl-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5S*) diastereomer thereof; 14-O-{[(1R, 2R, 5S *)-2-Hydroxy-5-morpholin-4-yl-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R*) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 5S)-5-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S, 2S, 5R) diastereomer thereof; 14-O-{[(1R, 2R, 5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S, 2S, 5S) diastereomer thereof; 14-O-{[(1R, 2R)-4-Aminomethyl-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomers thereof; 14-O-{[5-Amino-2-chloro-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-{[4-Amino-2-chloro-cyclohexylsulfanyl]-acetyl}-mutilin; 14-O-[(4-Amino-1-hydroxy-cyclohexylmethylsulfanyl)-acetyl]-mutilin; 14-O-{[(1R, 2R)-2-Hydroxy-5-(3 -methylamino-propyl)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomers thereof; 14-O-{[(1R, 2R)-2-Hydroxy-4-(3 -methylamino-propyl)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomers thereof; 14-O-{[(1R, 2R)-5-(3-Amino-propyl)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomers thereof; 14-O-{[(1R, 2R)-4-(3-Amino-propyl)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomer thereof; 14-O-{[(6R, 8R)-8-Amino-1,4-dioxa-spiro[4.5]dec-6-ylsulfanyl]-acetyl}-mutilin and the (6S, 8S) diastereomer thereof; 14-O-{[4-Amino-2-methoxy-cyclohexylsulfanyl]-acetyl}-mutilin; and 14-O-{[5-Amino-2-methoxy-cyclohexylsulfanyl]-acetyl}-mutilin. 8. The compound according to claim 1 in the form of a salt. 9. A compound according to claim 1 in the form of a pharmaceutical drug substance. 10. A pharmaceutical drug composition comprising a compound of claim 1 in association with at least one pharmaceutical excipient. 11. A pharmaceutical drug composition according to claim 10, further comprising another pharmaceutically active agent.