Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

A pleuromutilin derivative having a 2-amino phenyl mercaptan side chain as well as a preparation method and application thereof are provided. The derivative has a structure represented by formula 2 or formula 3, wherein, R1, R2 and R3 are each independently selected from a hydrogen atom, hydroxyl, amino, sulfydryl, hydroxymethyl, amine methyl, nitro, halogen, trihalogenated methyl, methyl, natural amino acid acylamino and C1-6 alkoxy. The plueuromutilin derivative in the disclosure has good activity of inhibiting drug-resistant Staphylococcus aureus and mycoplasma, and is especially suitable for preventing and treating infectious diseases caused by human or animal mycoplasma or drug-resistant Staphylococcus aureus or multidrug resistant bacteria as a novel antibacterial drug.

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

A pleuromutilin derivative having a 2-amino phenyl mercaptan side chain as well as a preparation method and application thereof are provided. The derivative has a structure represented by formula 2 or formula 3, wherein, R1, R2 and R3 are each independently selected from a hydrogen atom, hydroxyl, amino, sulfydryl, hydroxymethyl, amine methyl, nitro, halogen, trihalogenated methyl, methyl, natural amino acid acylamino and C1-6 alkoxy. The plueuromutilin derivative in the disclosure has good activity of inhibiting drug-resistant staphylococcus aureus and mycoplasma, and is especially suitable for preventing and treating infectious diseases caused by human or animal mycoplasma or drug-resistant staphylococcus aureus or multidrug resistant bacteria as a novel antibacterial drug.

The present disclosure provides processes for preparing (+)-pleuromutilin and synthetic (+)-pleuromutilin produced therefrom. Also provided are intermediates prepared thereby and processes for preparing these intermediates.

A compound selected from 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteoroaryl-, or aryl)-sulfanyl)-acetyl]-12-epi-mutilins, or 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteoroaryl-, or aryl)-oxy)-acetyl]-12-epi-mutilins, wherein 12-epi-mutilin is characterized in that the mutilin ring at position 12 is substituted by two substituents, the first substituent at position 12 of the mutilin ring is a methyl group which methyl group has the inverse stereochemistry compared with the stereochemistry of the methyl group at position 12 of the naturally occurring pleuromutilin ring, the second substituent at position 12 of the mutilin ring is a hydrocarbon group comprising at least one nitrogen atom and all other substituents of the mutilin ring having the same stereochemistry compared with the stereochemistry of the substituents at the corresponding positions in the naturally occurring pleuromutilin ring; optionally in the form of a salt and/or solvate, wherein the naturally occurring pleuromutilin is of formula ##STR00001##
processes for the preparation of such compounds and their use as pharmaceuticals.

Provided herein is a pleuromutilin derivative containing a cycloalkyl group and preparation method and application thereof. Specifically, the pleuromutilin is reacted with p-toluenesulfonyl chloride to obtain an intermediate I, and the intermediate I is reacted with 1-amino-2-methylpropane-2-thiol hydrochloride to obtain an intermediate II, and then the intermediate II is reacted with cycloalkylcarbonyl chloride to obtain a target derivative. The synthesis process of these derivatives is simple, with a high yield and simple purification. These derivatives can effectively inhibit activities of Staphylococcus aureus and Streptococcus, and have superior activities to the marketed Tiamulin, and they also have good antibacterial activities against drug-resistant bacteria. In particular, the treatment effect of the derivative 2 of the target derivative is significantly superior to the clinical drugs Tiamulin and Valnemulin. They are suitable as new antibacterial drugs for prevention and treatment of infectious diseases caused by bacteria in humans or animals.

A compound of formula I, a pharmaceutically acceptable salt thereof, or a solvent compound, an enantiomer, a diastereomer or a tautomer of the compound or a pharmaceutically acceptable salt thereof is disclosed, wherein R is a phenyl substituted with an electron withdrawing group or a phenyl substituted with an electron donating group. The pleuromutilin derivative containing a thiazolo[5,4-C]pyridine side chain in the present invention exhibits good in vitro antibacterial activity and improves the problem of poor solubility of pleuromutilin derivatives. ##STR00001##