Indazoles (azaindoles) are heterocyclic compounds structurally related to indoles and can be viewed as indole isosteres. The indazole moiety is a 10-π electron aromatic heterocyclic system. Like the pyrazole, indazole resembles both pyridine and pyrrole and its reactivity reflects this. In this...

Topical application of prostaglandin (PG) analogues are currently the most commonly used intraocular pressure lowering drugs in glaucoma. They have been available since the mid 1990’s, and are efficacious and generally well tolerated, the compliance rates are good due to the once a day applicat...

A2/J2-Isoprostanes (IsoPs) are prostaglandin (PG) A2/J2-like compounds that are produced in vivo as dehydration products of D2/E2-IsoPs. One A2-IsoP that should be formed is 15-A2t-IsoP (8-iso-PGA2). Analogous to cyclopentenone PGs, 15-A2t-IsoP readily undergoes nucleophilic addition to various ...

Better control of intraocular pressure (IOP) is the most effective way to preserve visual field function in glaucomatous patients. While prostaglandin FP analogs are leading the therapeutic intervention for glaucoma, new target classes also are being identified with new lead compounds being deve...

A decade has passed since the first topical prostaglandin analog was prescribed to reduce intraocular pressure (IOP) for the treatment of glaucoma. Now four prostaglandin analogs are available for clinical use around the world and more are in development. The three most efficacious of these drug...

Latanoprost is a practically insoluble prostaglandin F2α analog considered a first-line agent for glaucoma treatment. From a pharmaceutical point of view, latanoprost is challenging to be formulated as an eye drop due to its poor water solubility and the presence of an ester bond that needs to ...

Cultures of mouse peritoneal resident macrophages produced prostaglandin E2 when exposed to extracellular group II phospholipase A2. The response to group II phospholipase A2 was concentration dependent, and prostaglandin E2 production in response to 1 μg/ml purified group II enzyme was compara...

In a randomized, double-masked, placebo-controlled study, 0.25 μg (n = 11) or 0.5 μg (n = 13) of prostaglandin F2α-1-isopropyl ester (PGF2α-IE) was applied topically twice daily for 8 days to one eye of ocular hypertensive or chronic open-angle glaucoma patients. Compared with contralateral,...

Several prostaglandins (PGs), their prodrugs, and their analogues have been shown to reduce intraocular pressure (IOP) in normotensive volunteers and in patients with elevated IOP. Initial clinical trials demonstrated efficacy with most of these agents, but a PGE2 analogue, PGD2, and BW245C (an ...

It has been shown that prostaglandin A2 (PGA2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA2-1-isopropyl ester (PGA2-IE) than with PGA2, P...

SummaryBackgroundBisphosphonates are routinely used in the treatment of metastatic bone disease from breast cancer to reduce pain and bone destruction. Zoledronic acid given by intravenous infusion has been widely used, but places a substantial logistical burden on both patient and hospital. As ...

This manuscript describes the preparation of dabigatran derivatives and their inhibitory potentials toward human thrombin. Among the tested compounds, 7c, 7k, 7m and 7o, with IC50 values of 1.54, 0.84, 1.18 and 1.42 nM, exhibited comparable inhibitory activity to dabigatran (IC50 = 1.20 nM). The...

Diastereoisomeric 4-methyl-3-phenyl-3-piperidinols and related esters have been prepared by phenylation of 4-methyl-3-piperidones and subsequent acylation. The synthesis of the intermediate piperidones is also described. Configurational and conformational assignments are based on the IR and NMR ...

We describe the synthesis of a library of new pseudopeptides and their inhibitory activity of the rabbit 20S proteasome chymotrypsin-like (ChT-L) activity. We replaced a natural α-amino acid by an α- or a β-hydrazino acid and obtained inhibitors of proteasome up to a submicromolar range (0.7 ...

The 18F-labelled amino acid derivative 3-O-methyl-6-[18F]fluoro-l-DOPA ([18F]OMFD) is a potential radiotracer for imaging tumour tissue using positron emission tomography. The precursor N-formyl-3-O-methyl-4-O-boc-6-trimethyl-stannyl-l-DOPA-ethyl ester enables direct electrophilic radiofluorinat...

Two analogs of rat atrial natriuretic factor, rANF7–28-NH2 and [Mpr7, Ala2O,D-Arg27]rANF7–27-NH2 were prepared by the solid-phase method. These peptides had 2-fold and 7-fold less affinity, respectively, than rANF1–28 in binding to membranes prepared from cultured aortic smooth muscle cells, ...

Interest in accurate measurement of atrial natriuretic factor (ANF) in biological fluids and various tissues has been stimulated by recent data indicating the possible role of ANF in the homeostasis of salt and water. The presence of high-affinity binding sites for ANF in rat glomeruli has allow...

Atrial natriuretic peptide (ANP) is a peptide hormone that is synthesized and secreted by cardiac tissues and plays a pivotal role in maintaining cardiovascular homeostasis. Clinically, ANP is used as a marker of cardiovascular diseases, including heart failure. Although multiple ANP assays are ...

The natriuretic peptide family contains three members; A-type atrial natriuretic peptide (ANP), B-type or brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP are produced primarily in the heart whereas CNP originates more widely in the systemic vasculature as well ...

Atrial natriuretic factor (ANF), a 28-amino-acid peptide secreted from the mammalian heart, is known to be cleared rapidly from the circulation. In vitro and in vivo studies implicate the kidney as an important site for clearance and subsequent degradation of atrial natriuretic factor. We have o...