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 (I):
or a pharmaceutically acceptable salt thereof, wherein
A is H, OH, O—(C 1 -C 6 alkyl), or O—(C 1 -C 4 alkaryl);
W is O, S, or NR 1 , wherein R 1 is H or C 1 -C 6 alkyl;
X is H or COR 2 , wherein R 2 is C 1 -C 6 alkyl, which can be substituted with from 1 to 5 hydroxyl groups, or O—(C 3 -C 7 alkyl), which can be substituted with from 1 to 4 hydroxyl groups, wherein each alkyl carbon is bound to no more than one oxygen;
Y is H, OR 3 , or Hal;
Z is H, OR 3 , or Hal;
R 3 is C 1 -C 6 alkyl; and
R 4 has the formula:
wherein,
each of m and n is independently an integer selected from 0 and 1, wherein,
when each of m and n is 1,
each of R 5 and R 6 is H, or R 5 and R 6 together are ═O;
R 7 and R 10 together form a single bond or a C 1 -C 3 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), R 7 and R 12 together form a single bond or a C 1 -C 2 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 7 and R 14 together form a single bond or a C 1 linkage, wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl,
R 8 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 8 and R 12 together form a single bond, or R 8 and R 9 together are ═N—O R 18 , wherein R 18 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl;
R 9 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 9 and R 8 together are ═N—OR 18 ;
R 10 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 10 and R 7 together form a single bond or a C 1 -C 3 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 10 and R 16 together form a C 1 -C 2 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 10 and R 17 together form a C 1 -C 3 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 10 and R 11 together are ═O, wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
R 11 is H, or R 11 and R 10 together are ═O;
R 12 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 12 and R 7 together form a single bond or a C 1 -C 2 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 12 and R 8 together form a single bond, or R 12 and R 16 together form a C 2 -C 4 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, C 1 -C 4 alkaryl;
each of R 13 and R 15 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl;
R 14 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 14 and R 7 together form a single bond or a C 1 linkage;
R 16 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, or R 16 and R 12 together form a C 2 -C 4 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 16 and R 10 together form a C 1 -C 2 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl; and
R 17 is H, C 1 -C 6 alkyl, COR 19 , CO 2 R 19 , or CONHR 19 , CSR 19 , COSR 19 , CSOR 19 , CSNHR 19 , SO 2 R 19 , or SO 2 NHR 19 , wherein R 19 is C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, or R 17 and R 10 together form a C 1 -C 3 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
or
when m is 0 and n is 1,
R 7 and R 10 together form a single bond or a C 1 -C 4 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), R 7 and R 12 together form a single bond or a C 1 -C 3 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), or R 7 and R 14 together form a single bond or a C 1 -C 2 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
each of R 8 , R 9 , and R 11 is H;
R 15 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl;
R 10 is H or R 10 and R 7 together form a single bond or a C 1 -C 4 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
R 12 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 12 and R 7 together form a single bond or a C 1 -C 3 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), R 12 and R 13 together form a —CH 2 CH 2 — linkage, or R 12 and R 16 together form a C 2 -C 4 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
R 13 is H, C 1 -C 6 alkyl, C 1 -C 4 alkaryl, or R 13 and R 12 together form a
—CH 2 CH 2 — linkage;
R 14 is H, C 1 -C 6 alkyl, or C 1 -C 4 alkaryl, or R 14 and R 7 together form a single bond or a C 1 -C 2 linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or 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 -C 6 alkyl, C 6 -C 12 aryl, C 1 -C 4 alkaryl;
R 16 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 6 -C 12 aryl, or C 1 -C 4 alkaryl; together form a C 2 -C 4 alkyl linkage, which optionally contains a non-vicinal O, S, or N(R 23 ), wherein R 23 is H, C 1 -C 6 alkyl, COR 24 , CO 2 R 24 , or CONHR 24 , CSR 24 , COSR 24 , CSOR 24 , CSNHR 24 , SO 2 R 24 , SO 2 NHR 24 , wherein R 24 is C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl; and
R 17 is H, C 1 -C 6 alkyl, COR 19 , CO 2 R 19 , or CONHR 19 , CSR 19 , COSR 19 , CSOR 19 , CSNHR 19 , SO 2 R 19 , or SO 2 NHR 19 , wherein R 19 is C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
or
A is OH;
X is H;
W, Y, and Z are defined as above; and
R 4 is selected from the group consisting of:
wherein R 21 is H, C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, R 20 is H, C 1 -C 6 alkyl, COR 19 , CO 2 19 , or CONHR 19 , CSR 19 , COSR 19 , CSOR 19 , CSNHR 19 , SO 2 R 19 , or SO 2 NHR 19 , wherein R 19 is C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
or
A is OH;
X is COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is selected from the group consisting of:
wherein R 21 is H, C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, R 20 is H, C 1 -C 6 alkyl, COR 19 , CO 2 R 19 , or CONHR 19 , CSR 19 , COSR 19 , CSOR 19 , CSNHR 19 , SO 2 R 19 , or SO 2 NHR 19 , wherein R 19 is C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
or
A is H or OH;
X is H or COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is
with the proviso that one or both of Y and Z are Hal;
or
A is H or OH;
X is H or COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is
wherein R 22 is H, C 1 -C 6 alkyl, C 6 -C 12 aryl, C 1 -C 4 alkaryl, 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, and r is 1-2;
or
A is H or OH;
X is H or COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is
wherein R 21 is H, C 1 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl;
or
A is H or OH;
X is H or COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is
wherein ═E is ═O or (H,H), R 22 is H, C 1 -C 6 alkyl, C 6 -C 12 aryl, C 1 -C 4 alkaryl, 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 -C 6 alkyl, C 6 -C 12 aryl, or C 1 -C 4 alkaryl, r is 1-2, and s is 0-1;
or
A is H or OH;
X is H or COCH 3 ;
W, Y, and Z are defined as above; and
R 4 is
2. The compound of claim 1 , wherein W is O.
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of claim 1 .
4. The composition of claim 3 , wherein said composition is (i) a compound of claim 1 in an amount between 0.00 1% and 5% weight/volume (w/v) and (ii) a pharmaceutically acceptable carrier suitable for topical administration to a patient.
5. A method of treating a Gram-positive bacterial infection in an animal, said method comprising administering to said animal a pharmaceutical composition of claim 3 in an amount sufficient to treat said bacterial infection.
6. The method of claim 5 , wherein said pharmaceutical composition is administered orally, topically, intravenously, intramusculary, or subcutaneously.
7. The method of claim 5 , wherein said animal is a human patient.
8. The method of claim 5 , wherein said bacterial infection is Clostridium difficile.
9. The method of claim 5 , wherein said infection is Chlamydia trachomatis or N. gonorrhoeae.
10. The method of claim 5 , wherein said bacterial infection is H. pylori.
11. The compound of claim 1 , wherein said compound is selected from:
3′-hydroxy-5′-(4-ethylcarbamyl-1-piperdinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-(4-ethylcarbamyl-1-piperidinyl)benzoxazinorifamycin,
3′-hydroxy-5′-[6-amino-(1R,5S)-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
3′-hydroxy-5′-(1-piperidinyl-4-(N-phenyl)propanamide)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-(1-piperidinyl-4-(N-phenyl)propanamide)benzoxazinorifamycin,
3′-hydroxy-5′-(3,8-diazabicyclo[3.2.1]octan-3-yl)benzoxazinorifamycin,
3′-hydroxy-5′-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
3′-hydroxy-5′-(4-(2-methylpropyl)carbamyl-1-piperidinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-(4-(2-methylpropyl)carbamyl-1-piperidinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-(3,8-diazabicylo[3.2.1]octan-3-yl)benzoxazinorifamycin,
3′-hydroxy-5′-(4-N,N-dimethylamino-1-piperidinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-(4-N,N dimethylamino-1-piperidinyl)benzoxazinorifamycin,
5′-(4-ethylcarbamyl-1-piperidinyl)-N′-methylbenzodiazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[6-amino-(1R,5S)-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[6-ethylcarbamyl-(1R,5S)-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-isopropylcarbamyl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-trifluoromethylsulfonyl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-butanamide-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-methylsulfonyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-propyluryl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-methylsulfonyl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-propyluryl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-isopropylcarbamyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-methylcarbamyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-5′-(4-ethylcarbamyl-1-piperidinyl)-N′-methylbenzdiazinorifamycin,
3′-hydroxy-5′-[4-methylcarbamyl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-amino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-ethyluryl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-propylsulfonyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-butanamide-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-ethyluryl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-amino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[1-ethylcarbamyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl ]benzoxazinorifamycin,
3′-hydroxy-5′-[1-ethylcarbamyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl ]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-ethylcarbamyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-ethylcarbamyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-acetamide-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-acetylamino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-S-methylthiocarbamyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-acetyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-acetyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-benzoxazinorifamycin,
3′-hydroxy-5′-[1-acetyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[1-acetyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-(2,2-dimethylethyl)carbamyl-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-(4S-methylthiocarbamyl)-1-pipercarbonyl)amino-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-(2,2-dimethylethyl)carbamyl-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[6-N,N-dimethylamino-(1R,5S)-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[1-methyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
3′-hydroxy-5′-[1-methyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-methyl-(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[1-methyl-(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-[4-ethylcarbamylmethyl-1- piperidinyl]benzoxazinorifamycin,
25-O-deacetyl3′-hydroxy-5′-[4-propylsulfonyl-1-piperidinyl]benzoxazinorifamycin,
5′-[4-N,N-dimethylamino-1-piperidinyl]benzthiazinorifamycin,
3′-hydroxy-5′-[4-methyl-4-N,N-dimethylamino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[4-acetylamino-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl3′-hydroxy-5′-[4-methyl-4-N,N-dimethylamino-1-piperidinyl]benzoxazinorifamycin,
25-O-deacetyl3′-hydroxy-5′-[4-methyl-4-acetylamino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[(3R)-N,N-dimethylamino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[(3S)-N,N-dimethylamino-1-piperidinyl]benzoxazinorifamycin,
3′-hydroxy-5′-[3-hydroxy-1-azetidinyl]benzthiazinorifamycin,
and
25-O-deacetyl3′-hydroxy-5′-[3-hydroxy-1-azetidinyl-]benzoxazinorifamycin.
12. The compound of claim 1 , wherein said compound is selected from:
4′-fluoro-5′-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin,
4′-fluoro-6′-methoxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
4′-fluoro-5′-[6-amino-3-azabicyclo[3.1.0]benzoxazinorifamycin,
25-O-deacetyl-4′-fluoro-5′-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin,
25-O-deacetyl-4′-fluoro-6′methoxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-4′-fluoro-5′-[6-amino-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
25-O-deacetyl-25-(2″,3″-dihydroxypropylcarbonoxy)-4′-fluoro-6′-methoxy-5′-[(4aS,7aS)-octahydro-6H-pyrrlo[3,4-b]pyridin-6-yl]benzoxazinorifamycin,
25-O-deacetyl-25-(2″,3″-dihydroxypropylcarbonoxy)-4′-fluoro-5′-[6-amino-3-azabicyclo[3.1.0]hex-3-yl]benzoxazinorifamycin,
4′-fluoro-5′-(4-isobutyl-1-piperazinyl)benzthiazinorifamycin,
4′-fluoro-6′methoxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6yl]benzthiazinorifamycin,
4′-fluoro-5′-[6-amino-3-azabicyclo[3.1.0]hex-3-yl]benzthiazinorifamycin,
25-O-deacetyl4′-fluoro-5′-(4-isobutyl-1-piperazinyl)benzthiazinorifamycin,
25-O-deacetyl-4′-fluoro-6′-methoxy-5′-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]benzthiazinorifamycin,
25-O-deacetyl-4′-fluoro-5′-[6-amino-3-azabicyclo[3.1.0]hex-3-yl]benzthiazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-((3R,5S)-3,5-dimethylpiperazinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-((3R,5S)-3-ethyl-5-methylpiperazinyl)benzoxazinorifamycin,
25-O-deacetyl-3′-hydroxy-5′-((3R,5S)-3,5-diethylpiperazinyl)benzoxazinorifamycin,
3′-hydroxy-5′-((3Z)-4-(aminomethyl)-pyrrolidinyl-3-one O-methyloxime) benzoxazinorifamycin, and
3′-hydroxy-5′-(5-azaspiro[2.4]heptan-7-amino-5-yl) benzoxazinorifamycin.