Antimicrobial and antiviral sulfur containing glycerol monoester derivatives
Inventors
Reardan, Dayton T. • Brennan, Paul • Schlievert, Patrick
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11572342-B2
Publication Date
2023-02-07
Expiration Date
Abstract
The disclosure relates generally novel sulfur containing glycerol mono-ester derivatives and methods useful for treating gram positive, gram negative, fungal and envelope viral infections in a patient.
Core Innovation
The invention relates to sulfur-containing glycerol monoester derivatives, including glycerol thionomonolaureate (SGML) and glycerol dithionomonolaureate (S2GML), as antimicrobial and antiviral agents. The disclosure presents a compound scaffold defined as a compound of Formula (I) with substituents R1, R2, R3, and R4 and a heteroatom X that is O or S, including pharmaceutically acceptable salts of the Formula (I) compounds.
The patent describes SGML and S2GML analogs derived from glycerol monolaurate (GML), including sulfur-containing variants formed by converting glycerol-containing intermediates into target thioesters and dithioesters. The examples include (R)- and (S)-stereoisomeric forms for both SGML and S2GML, and the compounds are characterized using reported 1H NMR data.
Biological results are reported for SGML and S2GML compared with GML, including antibacterial and antifungal activity measurements using MIC and MBC, along with qualitative comparisons. Activity is reported for microorganisms including Staphylococcus aureus, including a toxic shock syndrome strain MN8 with TSST-1, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Candida auris.
Claims Coverage
The document contains one independent compound claim covering a Formula (I) sulfur-containing glycerol monoester derivative scaffold, including pharmaceutically acceptable salts. The claim coverage also extends to pharmaceutical compositions and methods of treating infections by administering the Formula (I) compounds.
Formula (I) sulfur-containing glycerol monoester derivative scaffold
A compound of Formula (I) wherein R1 is selected from alkyl, alkenyl, and alkynyl; R2 and R3 are independently selected from hydrogen, COR4, —CON(H)R4, —CO2R4, or P(O)(OR4)2, or taken together with the carbon to which they are attached may form a 3- to 5-membered aliphatic carbocyclic ring; R4 is H, alkyl, alkenyl, aryl, cycloalkyl, heterocyclyl, or heteroaryl; X is O or S; or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition comprising Formula (I) compound
A pharmaceutical composition that includes a Formula (I) compound or a pharmaceutically acceptable salt thereof.
Method of treating infection by administering Formula (I) compound
A method of treating an infection comprising administering to a subject a Formula (I) compound or a pharmaceutically acceptable salt thereof.
Treatment of specific infection categories using Formula (I) compounds
The method coverage further specifies infections including viral infections, fungal infections, and bacterial infections.
Overall claim coverage centers on the Formula (I) compound scaffold with defined substituent selections for R1 through R4 and X = O or S, including pharmaceutically acceptable salts, and extends to pharmaceutical compositions and methods of treating infections by administering the Formula (I) compounds.
Stated Advantages
Antimicrobial and antiviral agents.
Intended to address infections involving viral, fungal, and bacterial pathogens.
Provides an alternative where prior glycerol monolaurate (GML) has limitations, such as not being effective versus E. coli.
Improves potency compared with GML.
Improves esterase resistance, including reduced lipase (glycerol ester hydrolase) hydrolysis.
Reduces TSST-1 in Staphylococcus aureus MN8.
Documented Applications
Treatment contexts involving infections.
Viral infections.
Fungal infections.
Bacterial infections.
Antibacterial and antifungal activity evaluations of SGML and S2GML versus GML, including effects on Staphylococcus aureus MN8, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Candida auris.
Interested in licensing this patent?