Aim: The objective of preformulation study is to develop the elegant, stable, effective and safe dosage form by establishing kinetic profile, compatibility with other formulation excipients and physico-chemical parameters of new drug substance. This could provide important information for formulation design or support the need for molecular modification. So, in the present study preformulation studies were performed on Glimepiride (GMP) to assess its suitability for parenteral formulation. Glimepiride is the first IIIrd generation sulphonyl urea used to treat type –II diabetes mellitus. Methods: The authenticity of GMP was established by DSC and FTIR spectra. A UV spectrophotometric method and HPLC method were employed for determination of GMP in bulk active pharmaceutical ingredient (API). Results: The UV method was linear in the range of 3-10 μg/ml. The low % CV values of intra-day and inter-day variations revealed that the proposed method is robust. The retention time of GMP in HPLC method was found to be 1.9 min. The method was proven robust by obtaining very high regression coefficient value (0.999). Conclusions: The results of the physicochemical study of drug revealed suitability of GMP for parenteral route. Moreover, the drug was found stable in both solid as well as liquid state at different conditions.

The histone acetyltransferases, CREB binding protein (CBP) and EP300, are master transcriptional co-regulators that have been implicated in numerous diseases, such as cancer, inflammatory disorders, and neurodegeneration. A novel, highly potent, orally bioavailable EP300/CBP histone acetyltransferase (HAT) inhibitor, CPI-1612 or 17, was developed from the lead compound 3. Replacement of the indole scaffold of 3 with the aminopyridine scaffold of 17 led to improvements in potency, solubility, and bioavailability. These characteristics resulted in a 20-fold lower efficacious dose for 17 relative to lead 3 in a JEKO-1 tumor mouse xenograft study.

EP300 and CBP (KAT3A/3B) are two highly homologous, multidomain, epigenetic coregulators that play central roles in transcription through the acetylation of lysine residues on histones and other proteins. Both enzymes have been implicated in human diseases, especially cancer. From a high‐throughput screen of 191 000 compounds searching for EP300/CBP histone acetyltransferase (HAT) inhibitors, 18 compounds were characterized by a suite of biochemical enzymatic assays and biophysical methods, including X‐ray crystallography and native mass spectrometry. This work resulted in the discovery of three distinct mechanistic classes of EP300/CBP HAT inhibitors, including two classes not previously described. The profiles of an example of each class of inhibitor are described in detail. A subsequent medicinal chemistry effort led to the development of a novel class of orally bioavailable AcCoA‐competitive EP300/CBP HAT inhibitors with in vivo activity. We believe that this work will prove to be a useful guide for other groups interested in the development of HAT inhibitors.

The synthesis and biochemical evaluation of a series of esters of 4- sulfamoylated cinnamic acid as potential inhibitors of the enzyme estrone sulfatase (ES) is reported. The results of the study show that the esters of trans 4-sulfamoylated cinnamic acid are weaker irreversible inhibitors of ES in comparison to 4- methylcoumarin-7-O-sulfamate (COUMATE) and its tricyclic derivatives such as 667- COUMATE, as well as the steroidal inhibitor estrone-3-O-sulfamate (EMATE). Structureactivity relationship determination indicates that the flexible nature of the cinnamic acid backbone results in these compounds possessing greatly reduced inhibitory activity compared to the corresponding coumarin derivative. Furthermore, from the superimpositioning of the synthesised compounds onto the substrate, we propose that steric hindrance is an important factor which results in a marked decrease in the inhibitory activity within the large alkyl chain containing compounds.