Febuxostat Case Study

In order to design a drug with a particular biological activity, the medicinal chemist requires a lead compound that will have a potent activity. The level of

It was found that BChE showed broader substrate specificity when compared to AChE, hydrolysing all substrates (at least to some extent), excluding Carbachol. AChE failed to hydrolyse suxamethonium or carbachol to any extent. It was also found that Atropine and Malathion failed to significantly inhibit either cholinesterase, whereas Edrophonium displayed short-acting inhibition. Physostigmine, Nestogmine and Carbachol displayed greater inhibition.

Uloric (Febuxostat) is a xanthine oxidase inhibitor used to control hyperuricemia in patients with gout. Xanthine oxidase inhibitors inhibit the activity of xanthine oxidase, an enzyme involved in the metabolism of purines. This medication should not be used for the treatment of asymptomatic hyperuricemia. Uloric was first FDA approved on February 13th, 2009 for chronic management of hyperuricemia. Given that this medication is fairly new to the market, it is more expensive then the other prescription medication in the same pharmaceutical categories, allopurinol. Uloric comes in two strengths, 40 mg, and 100 mg tablets. Bothe the 40 mg and the 80 mg tablets costs $310.39 for a 30-day supply (quantity of 30). Allopurinol also comes in 2 strengths, 100 mg, and 300 mg tablets. The cost of 100 allopurinol 100 mg tablets is $37.69 and $76.14 for

This information is useful so that pharmaceutical researchers can understand the enzyme interactions between these drugs and the enzymes in the brain and know what to include in the new drugs they design and synthesize. Therefore, the ultimate goal of this study is to evaluate the 3D chemical structures of each of these drugs in comparison with the active sites of the enzymes they work on in order to determine what factors of the current drugs have that leads to the best enzyme interaction in order to prevent seizures in epilepsy patients in the

The condensation product of primary amines with active carbonyl compounds have resulted in the formation of Schiff base compound. This has been reported by Hugo Schiff in 1864. Schiff base compound contain azomethine -C≡N with a general formula RHC=N-R’ where R and R’ are alkyl, aryl, cyclo alkyl or heterocyclic groups which may be variously substituted. These compounds are also known as anils, imines or azomethines (Mishra N. et al, 2013). Structurally, a Schiff base is a nitrogen analogue of an aldehyde or ketone in which the carbonyl group (C=O) has been replaced by an imine or azomethine group (Figure 1.1) (Abu-Dief M.A et al, 2015).

This lab tested known substances against an unknown substance in order to determine the molecular makeup of the given unknown substance. The unknown substance benzaldehyde was determined by conducting six test followed by Proton NMR, C13 NMR and IR Spectroscopy reading. Test 52 D: 2,4-Dinitrophenylhydrazine, determined that the unknown product was a ketone and test 52 H: Acetyl Chloride indicates the presence of a secondary or primary amine.

In order to confirm the precise reaction on inhibition of our discovered drugs combination to

To analyze the product and confirm its molecular identity, infrared spectroscopy and proton NMR spectroscopy were conducted. The H1NMR produced a spectra (Figure 5) which was consistent with the predicted chemical shift from the hypothesized product. The presence of a multiplet centered on the 7 ppm region is indicative of the presence of protons bound to a benzene ring as would be expected in the desired product. This region also likely had some overlap of the hydrogen bound to the sp2 Carbon that occurred as a result of the aldol dehydration step. Furthermore, the fact that all remaining proton signals lie in the sp3 up-field region validates the probable formation of the desired product as no other functionality is present to cause a

The five active compounds were submitted to the evaluation of their in vitro potency against P. falciparum, and the standard drug mefloquine was used as reference parameter, as shown in Table 2. Mefloquine exhibited an IC50 value of 0.04±0.01 μM. In comparison to mefloquine, vanillinyl moiety-bearing derivatives of N-acylhydrazone-1,2,4-oxadiazole SintMed2 (4-mehylsubstituted), SintMed5 (4-bromosubstituted) and SintMed6 (4-nitrosubstituted) displayed potent anti-P. falciparum activities. While compound SintMed5 was found to be almost as potent as mefloquine with IC50 of 0.07±0.12 μM, the other two analogues SintMed2 and SintMed6 were less potent, but still exhibited expressive activities: 0.12±0.16 μM and 0.20±0.16 μM, respectively. Replacement

Substitution in the aromatic ring at the para position with chloro group or chlorine containg isopropyl group lead to production of drug with significant longer half life and hence prolong the duration of action such as: clofibrate.

Initial structure activity relationship studies were conducted in order to improve the activity against integrase, focusing in particular on the basic amine. “This effort led to compounds such as morpholine 5 and tetrahydropyran 6, both showing low nanomolar activity in the enzymatic assay (5 IC50 =0.003 μM; 6 IC50 = 0.002 μM) and good potency in the antiviral cell based assays in low serum condition (CIC95=0.250 μM 10% FBS). However, a large potency shift was observed in the presence of 50% NHS for both analogues, which led us to explore other modifications. The simple acetamide derivative 7 showed a good potency in all assays and limited shift in high serum conditions. Various acetamide replacements such as sulfonamide 8, urea 9, and sulfamide 10 were also prepared. While for all these analogues the potency in the enzyme assay was in the nanomolar range (IC50= 0.007-0.018 μM), in the antiviral cell based assays, the compounds showed a larger variability in the activity values, ranging from 0.062 to >1.0 μM in low serum conditions. Only 7 retained activity below 1 μM in high serum conditions (CIC95=0.4 and 0.5 μM 50% NHS for 7.” [17] The amide functionality offered the opportunity to explore very rapidly a large series of fragments by rapid analogue synthesis. It was discovered that the introduction of an oxalamide moiety on the scaffold resulted in a very potent compound both in the

In order to improve photolytic deprotection with enhanced efficeincy, several other photoremovable groups have been developed. Figure X.X.X shows o-nitrobenzyl protecting group together with other common photolabile protecting groups such as 1-(o-nitrophenyl)ethyl (NPE), 2-(o-nitrophenyl)-propyl (NPP), 6-nitroveratryloxycarbonyl (NVOC), 2,2-bis(2-nitrophenyl)ethoxycarbonyl (diNPEOC), 4-N-[2-(2-nitropehnyl)-propoxy]carbonyl (NPPOC), 1-(3-nitrodibenzofuran-1-yl)ethyl (NDBF), 6-nitropiperonyloxymethyl (NPOM), p-hydroxyphenacyl (pHP), 7-(diethylaminocoumarin-4-yl)methoxy carbonyl (DEACM), and 6-bromo-7-hydroxycoumarinyl-4-yl-methyl (Bhcmoc) and 6-bromo-7-methoxycoumarinyl-4-yl-methyl (Bmcmoc). A combination of NPOM and NDBF caging group

readily liquefied at 5170 Tarr or 6.8 atmospheres, at 20 C (68 F), and has a

An efficient method for the synthesis of fourteen novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in DMF/K2CO3. The structure of the newly synthesized compounds was determined by IR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. The in vitro antioxidant activity revealed that, among all the tested compounds 5n has exhibited maximum scavenging activity with ABTS. The compound 5b has showed good antiproliferative activity as good inhibitor of EGFR tyrosine

What allosteric enzyme inhibitors do is that they act as modulators, attaching themselves to a molecule that will alter the binding site for the enzyme and make it unusable and as a result the enzyme becomes inactive. Theophylline inhibits the activity of the enzyme phosphodiesterase, which forms part of a group of enzymes that degrade the phosphodiester bond (DrugBank, n.d.).