2-{N-[(2,4,5-trichlorophenoxy) acetyl]-N-methylamino}-3-pyrrolidinepropanamide analogs as potential antagonists of Urotensin II receptor.

The Purpose Of The Article: To identify novel small molecule antagonists of Urotensin II receptor with acceptable pharmacological profile.

Materials And Methods: Structure-activity-relationship (SAR) studies on 2-{-[(2,4,5-trichlorophenoxy) acetyl]--methylamino}-3-pyrrolidinepropanamide series were conducted and shortlisted compounds were synthesized and evaluated in cell-based assays. Human and mouse Urotensin II receptor overexpressing CHO cells were used for calcium release and radioligand binding assays.

Identification of novel Urotensin-II receptor antagonists with potent inhibition of U-II induced pressor response in mice.

Urotensin II (U-II) has been found to be one of the most potent vasoconstrictor (Ames et al., 1999; Bohm et al., 2002) reported till date.

Encapsulating Rifampicin into SLNs: A Viable Option for Managing its Bioavailability Issues Upon Co-Delivery with Isoniazid.

Background: Rifampicin is known to degrade at the acidic pH of the stomach, especially in the presence of isoniazid. Although isoniazid also degrades partially, its degradation is reversible.

Objective: Presently, we provide a proof of the fact that the simultaneous oral administration of rifampicin (RIF), upon incorporation into solid lipid nanoparticles (RIF-SLNs), with isoniazid (INH) overcomes its INH-induced degradation and improves its oral bioavailability in rats.

Identification and synthesis of novel inhibitors of mycobacterium ATP synthase.

A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.

A review on leukotrienes and their receptors with reference to asthma.

Objective And Methods: Leukotrienes (LTs) including cysteinyl leukotrienes (CysLTs) and LTB4 are the most potent inflammatory lipid mediators and play a central role in the pathophysiology of asthma and other inflammatory diseases. These biological molecules mediate a plethora of contractile and inflammatory responses through specific interaction with distinct G protein-coupled receptors (GPCRs). The main objective of this review is to present an overview of the biological effects of CysLTs and their receptors, along with the current knowledge of mechanisms and role of LTs in the pathogenesis of asthma.

Hepatocyte growth factor is an attractive target for the treatment of pulmonary fibrosis.

Introduction: Pulmonary fibrosis (PF) is a progressive fatal disorder and is characterized by alveolar epithelial injury, myofibroblast proliferation, and extracellular matrix remodeling, resulting in irreversible distortion of lung's architecture. Available therapies are associated with side effects and show restricted efficacy. Therefore, there is an urgent need to find a therapeutic solution to PF.

Treating inflammation with the Janus kinase inhibitor CP-690,550.

Commonly used immunosuppressants possess several significant dose-limiting toxicities, prompting the search for agents whose mechanisms of action are limited to immune cells. Inhibition of Janus Kinase 3 (JAK3), a hematopoetic cell-restricted tyrosine kinase, represents an attractive target for immunosuppression owing to its limited distribution in tissue and specific role in lymphoid homeostasis. CP-690,550, a JAK3 inhibitor undergoing clinical trials for the treatment of transplant rejection and autoimmune disorders, has shown efficacy similar to comparator immunosuppressants.