Rifamycin analogs and uses thereof
View Patent ↗The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3′-hydroxy analogs, 4′- and/or 6′ halo and/or alkoxy analogs, and various 5′ substituents that incorporate a cyclic amine moiety.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof; wherein
A is H, OH, or O—(C 1-6 alkyl);
W is O, S, or NR 1 , wherein R 1 is H, or C 1-6 alkyl;
X is H or COR 2 , wherein R 2 is C 1-6 alkyl or O—(C 3-7 alkyl);
Y is H, Hal, or OR Y3 , wherein R Y3 is H or C 1-6 alkyl;
Z is H, Hal, or OR Z3 , wherein R Z3 is H or C 1-6 alkyl; and
R 4 is
wherein R 22 is H, C 1-6 alkyl, C 6-12 aryl, COR 24 , CO 2 R 24 , CONHR 24 , CSR 24 , COSR 24 , CSOR 24 , CSNHR 24 , SO 2 R 24 , or SO 2 NHR 24 , wherein R 24 is C 1-6 alkyl or C 6-12 aryl, and r is 1 or 2.
2. The compound of claim 1 , wherein A is H or OH; and X is H or COCH 3 .
3. The compound of claim 1 , wherein R 4 is
4. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
5. 3′-hydroxy-5′-(3,8-diazabicyclo[3.2.1]octan-3-yl)benzoxazinorifamycin or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising 3′-hydroxy-5′-(3,8-diazabicyclo[3.2.1]octan-3-yl)benzoxazinorifamycin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.