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Synthesis and antibacterial activity of pentacyclines: a novel class of tetracycline analogs.

Sun C, Hunt DK, Clark RB, Lofland D, O'Brien WJ, Plamondon L, Xiao XY - J. Med. Chem. (2011)

Bottom Line: Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10.Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity.A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms.

View Article: PubMed Central - PubMed

Affiliation: Tetraphase Pharmaceuticals, Watertown, MA 02472, USA.

ABSTRACT
Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.

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Structures of known tetracyclines.
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fig1: Structures of known tetracyclines.

Mentions: Tetracyclines are a class of antibiotics with broad spectrum antibacterial activity.(1) Since the isolation of its first member, chlorotetracycline (1, Figure 1), from the culture broth of Streptomyces,(2) several generations of tetracycline analogs have been discovered and used to treat infections caused by a wide range of pathogens. These tetracyclines include oxytetracycline (2),(3) tetracycline (3),(4) doxycycline (4),(5) and minocycline (5),(6) all discovered before the early 1970s, as well as the recently approved analog tigecycline (6).(7)


Synthesis and antibacterial activity of pentacyclines: a novel class of tetracycline analogs.

Sun C, Hunt DK, Clark RB, Lofland D, O'Brien WJ, Plamondon L, Xiao XY - J. Med. Chem. (2011)

Structures of known tetracyclines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108469&req=5

fig1: Structures of known tetracyclines.
Mentions: Tetracyclines are a class of antibiotics with broad spectrum antibacterial activity.(1) Since the isolation of its first member, chlorotetracycline (1, Figure 1), from the culture broth of Streptomyces,(2) several generations of tetracycline analogs have been discovered and used to treat infections caused by a wide range of pathogens. These tetracyclines include oxytetracycline (2),(3) tetracycline (3),(4) doxycycline (4),(5) and minocycline (5),(6) all discovered before the early 1970s, as well as the recently approved analog tigecycline (6).(7)

Bottom Line: Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10.Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity.A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms.

View Article: PubMed Central - PubMed

Affiliation: Tetraphase Pharmaceuticals, Watertown, MA 02472, USA.

ABSTRACT
Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.

Show MeSH