The solubility data of 5-amino salicylic acid in methanol, ethanol, carbon tetrachloride, and tetrahydrofuran (THF) at various temperatures were measured by gravimetrical method from (293.15 to 313.15) K under atmospheric pressure, and the solubility data were correlated as a function of temperature. The order of solubility is THF > carbon tetrachloride > ethanol > methanol. Further, some thermodynamic parameters such as enthalpy, Gibb’s energy, and entropy have also been evaluated for the dissolution process. It is observed that enthalpy and entropy are positive, whereas the Gibb’s energy of activation is negative for all of the four solvents. The negative Gibb’s energy suggests the spontaneous nature of dissolution process, whereas positive enthalpy indicates endothermic dissolution of compounds. The positive entropy is due to favorable dissolution in the studied solvents.

BackgroundThe inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent.MethodsWe performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn’s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn’s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007), but not for the smaller number of UC cases.ConclusionsThe allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD.

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Objective Nevirapine is an important component of highly active antiretroviral therapy used in the treatment of human immunodeficiency virus infection. There is considerable variation in the pharmacokinetics of nevirapine and this variation can impact the efficacy and toxicity of nevirapine. While some of this variation can be attributed to environmental factors, the degree to which heritability influences nevirapine pharmacokinetics is unknown. This study aims to estimate how much variation in nevirapine pharmacokinetics is due to genetic factors and to investigate the contribution of selected polymorphisms to this variability. Methods Two doses of immediate-release nevirapine were administered to European (n=11) and African American (n=6) subjects recruited from the Research in Access to Care in the Homeless (REACH) cohort. A repeated drug administration (RDA) method was then used to determine the relative genetic contribution (rGC) to variability in nevirapine AUC0–6h. Nevirapine plasma levels were quantified using LC-MS/MS. Patients were also genotyped for selected polymorphisms in candidate genes that may influence nevirapine pharmacokinetics. Results A significant rGC for nevirapine AUC0–6h was found in Europeans (p = 0.02) and African Americans (p = 0.01). A trend towards higher nevirapine AUC0–6h for the CYP2B6 516TT (rs3745274; Q172H) genotype was observed in European Americans (p = 0.19). Conclusions This study demonstrates that there is a significant genetic component to variability in nevirapine pharmacokinetics. While genetic variants such as CYP2B6 polymorphisms attributed to some of this variation, these data suggest that there may be additional genetic factors that influence nevirapine pharmacokinetics.

Protein tyrosine phosphatase 1B (PTP1B) is an important target for the treatment of diabetes. A series of thiazolidin‐4‐one derivatives 8–22 was designed, synthesized and investigated as PTP1B inhibitors. The new molecules inhibited PTP1B with IC50 values in the micromolar range. 5‐(Furan‐2‐ylmethylene)‐2‐(4‐nitrophenylimino)thiazolidin‐4‐one (17) exhibited potency with a competitive type of enzyme inhibition. structure–activity relationship studies revealed various structural facets important for the potency of these analogues. The findings revealed a requirement for a nitro group‐including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation with experimental results. H‐bonding and π–π interactions were responsible for optimal binding and effective stabilization of virtual protein‐ligand complexes. Furthermore, in‐silico pharmacokinetic properties of test compounds predicted their drug‐like characteristics for potential oral use as antidiabetic agents.Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which can be employed in the design of future potential PTP1B inhibitors.