A 2-pyridone amide inhibitor of transcriptional activity in .

is a strict intracellular bacterium that causes sexually transmitted infections and eye infections that can lead to life-long sequelae. Treatment options are limited to broad-spectrum antibiotics that disturb the commensal flora and contribute to selection of antibiotic-resistant bacteria. Hence, development of novel drugs that specifically target would be beneficial.

Methyl sulfonamide substituents improve the pharmacokinetic properties of bicyclic 2-pyridone based inhibitors.

infections are a global health problem and new approaches to treat with drugs of high specificity would be valuable. A library of substituted ring fused 2-pyridones has been synthesized and evaluated for their ability to attenuate infectivity. pharmacokinetic studies were performed, with the best candidates demonstrating that a C8-methylsulfonamide substituent improved pharmacokinetic properties important for oral administration.

Chlamydia trachomatis fails to protect its growth niche against pro-apoptotic insults.

Chlamydia trachomatis is an obligate intracellular bacterial agent responsible for ocular infections and sexually transmitted diseases. It has been postulated that Chlamydia inhibits apoptosis in host cells to maintain an intact replicative niche until sufficient infectious progeny can be generated. Here we report that, while cells infected with C.

Thiazolino 2-Pyridone Amide Isosteres As Inhibitors of Chlamydia trachomatis Infectivity.

Chlamydia trachomatis is a global health burden due to its prevalence as a sexually transmitted disease and as the causative agent of the eye infection trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated C. trachomatis infectivity without affecting host cell or commensal bacteria viability.

N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF.

The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that is capable of FASII and this pathway is indispensable for growth. Previously, a high-content screen with -infected cells was performed, and acylated sulfonamides were identified to be potent growth inhibitors of the bacteria.

Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity.

The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 ≤ 100 nM) in attenuating infectivity across multiple serovars of C.