Nigelladine A among Selected Compounds from Exhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study.

COVID-19 has been a threat to the entire world for more than two years since its outbreak in December 2019 in Wuhan city of China. SARS-CoV-2, the causative agent, had been reported to mutate over time exposing new variants. To date, no impeccable cure for the disease has been unveiled.

Estimating Catastrophic Costs due to Pulmonary Tuberculosis in Bangladesh.

To eliminate TB from the country by the year 2030, the Bangladesh National Tuberculosis (TB) Program is providing free treatment to the TB patients since 1993. However, the patients are still to make Out-of-their Pocket (OOP) payment, particularly before their enrollment Directly Observed Treatment Short-course (DOTS). This places a significant economic burden on poor-households.

What Constitutes Health Care Seeking Pathway of TB Patients: A Qualitative Study in Rural Bangladesh.

Given the targeted 4-5% annual reduction of tuberculosis (TB) cure cases to reach the "End TB Strategy" by 2020 milestone globally set by WHO, exploration of TB health seeking behavior is warranted for insightful understanding. This qualitative study aims to provide an account of the social, cultural, and socioeconomic breadth of TB cases in Bangladesh. We carried out a total of 32 In-depth Interviews (IDIs) and 16 Key Informant Interviews (KIIs) in both rural and urban areas of Bangladesh.

Informal allopathic provider knowledge and practice regarding control and prevention of TB in rural Bangladesh.

Background: BRAC (formerly Bangladesh Rural Advancement Committee), in collaboration with the National Tuberculosis Control Programme, provides one full-day training on TB to make informal allopathic providers knowledgeable for managing TB in rural Bangladesh. This study explored the knowledge and practices of the providers receiving the above training in the control and prevention of TB.

Methods: The study was conducted in 30 subdistricts, with 30 trained and 30 untrained providers randomly selected from each subdistrict.

A program impact pathway analysis identifies critical steps in the implementation and utilization of a behavior change communication intervention promoting infant and child feeding practices in Bangladesh.

Mapping pathways of how interventions are implemented and utilized enables contextually grounded interpretation of results, differentiates poor design from poor implementation, and identifies factors that might influence the utilization of interventions. Few studies in nutrition have comprehensively examined the steps of implementation and utilization in behavior change communication (BCC) interventions, thus limiting the interpretation of variable impacts of BCC interventions. A program impact pathway (PIP) analysis was used to study a BCC intervention implemented in Bangladesh to improve infant and young child feeding (IYCF) practices.

Tribal formulations for treatment of pain: a study of the Bede community traditional medicinal practitioners of Porabari Village in Dhaka District, Bangladesh.

The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long.

Discovery of a novel series of nonacidic benzofuran EP1 receptor antagonists.

We describe the discovery and optimization of a novel series of benzofuran EP(1) antagonists, leading to the identification of 26d, a novel nonacidic EP(1) antagonist which demonstrated efficacy in preclinical models of chronic inflammatory pain.

Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.

We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.

Discovery of brain penetrant, soluble, pyrazole amide EP1 receptor antagonists.

We describe the discovery of a series of pyrazole amide EP(1) receptor antagonists with good aqueous solubility and CNS penetration. In order to achieve solubility we investigated the incorporation of a basic group in the region of the molecule previously occupied by a carboxylic acid, which was known to be a key element of the pharmacophore. This study led to the identification of compounds such as 4h, 4j and 10b which demonstrated brain-to-blood ratios of 0.

Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.

Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP(1) receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.

Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping.

We describe the medicinal chemistry approach that generated a novel indole series of EP(1) receptor antagonists. The SAR of this new template was evaluated and culminated in the identification of compound 12g which demonstrated in vivo efficacy in a preclinical model of inflammatory pain.

Novel methylene-linked heterocyclic EP1 receptor antagonists.

We describe the SAR, in terms of heterocyclic replacements, for a series of pyrazole EP(1) receptor antagonists. This study led to the identification of several aromatic heterocyclic replacements for the pyrazole in the original compound. Investigation of replacements for the methylene linker uncovered disparate SAR in the thiazole and pyridine series.

Identification and optimization of novel 1,3,4-oxadiazole EP1 receptor antagonists.

A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with highest affinity displayed a binding IC50 of 2.

Discovery of novel, non-acidic 1,5-biaryl pyrrole EP1 receptor antagonists.

Replacement of the carboxylic acid group in a series of previously described 1,5-biaryl pyrrole EP1 receptor antagonists led to the discovery of various novel non-acidic antagonists. Several analogues displayed high binding affinity and high binding efficiency indices.

1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure-activity relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives.

Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP(1) receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP(1) receptor that displayed good efficacy in the established FCA model of inflammatory pain. Furthermore, several analogues were prepared which combined substitution at the 5- and 6-positions as well as derivatives with an aromatic ring fused to the 5- and 6-positions.

1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists: Structure-activity relationships of 4- and 5-substituted benzoic acid derivatives.

This paper details the SAR of 1,5-biaryl pyrrole derivatives with substituents in the 2-, 4-, and 5-positions of the benzoic acid group as EP1 receptor antagonists. Substitution at the 2-position was poorly tolerated, whereas only fluorine was tolerated at the 4-position. In contrast, a range of substituents at the 5-position were discovered which enhanced the in vitro affinity and led to compounds with promising oral exposure.

The discovery of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and selective prostaglandin EP1 receptor antagonist for the treatment of inflammatory pain.

The discovery of a series of selective EP1 receptor antagonists based on a 1,2-diarylcyclopentene template is described. After defining the structural requirements for EP1 potency and selectivity, heterocyclic rings were incorporated to reduce logD and improve in vitro pharmacokinetic properties. The 2,6-substituted pyridines and pyridazines gave an appropriate balance of potency, in vivo pharmacokinetic properties and a low potential for inhibiting a range of CYP450 enzymes.

Identification of novel pyrazole acid antagonists for the EP1 receptor.

The discovery, synthesis and structure-activity relationship (SAR) of a novel series of EP1 receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and cytochrome P450 (CYP450) profile and good exposure levels in blood. This compound had an ED50 of 1.

Structure-activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists.

The preliminary SAR of a series of novel 1,5-biaryl pyrrole EP1 receptor antagonists derived from compound 1 is described. Replacement of the benzyl group of 1 with isosteric groups was investigated. The most effective replacement was found to be the isobutyl group.

Adaptation of kangaroo mother care for community-based application.

Objective: Working with a multidisciplinary team of Ecuadorians, Bangladeshis and Americans, we developed a simple protocol for community-based implementation of kangaroo mother care (CKMC) that does not require birth weight or clinical judgment to identify which newborns should receive CKMC. CKMC could stabilize newborns and possibly reduce neonatal mortality where there is little medical care for newborns and low birth weight (LBW) is common.

Study Design: During their CKMC training, community-based workers identified 35 expectant or recently delivered women in the pilot study area and taught them about CKMC.