Mehrnoosh Hashemzadeh

Reductive cleavage of 2-methyleneoxetanes with lithium and 4,4′-di-tert-butylbiphenyl

Abstract 3,3-Dimethyl-2-methylene-4-phenyloxetane ( 5 ) undergoes reductive cleavage with lithium and 4,4′-di- tert -butylbiphenyl (DTBB) to give an intermediate dianion, which reacts regioselectively with aldehydes and ketones to give aldol adducts in modest yields. Alternatively, the enolate can be trapped with TMSCl to give the corresponding silyl enol ether.

Perioperative Management of Patients on Adenosine Diphosphate Inhibitors in the Era of Drug-Eluting Stents : Review of the Literature and Clinical Implications

The current adenosine diphosphate inhibitors, ticlopidine and clopidogrel, are thienopyridine compounds that inhibit adenosine diphosphate mediated platelet aggregation. They interfere with platelet activation by selectively and irreversibly blocking P2Y12 sub-unit of the adenosine diphosphate receptor on the surface of platelets. This provides an antiplatelet effect that is additive to the inhibition of the thromboxane A2 pathway by aspirin. Dual antiplatelet therapy is extensively used in cardiovascular medicine. Randomized controlled trials have substantiated the fact that thrombotic complications after percutaneous coronary intervention procedures can be decreased by using dual antiplatelet therapy. However, there is a concern of bleeding due to enhanced and irreversible platelet inhibition in patients who will require any operation including coronary artery bypass grafting while on adenosine diphosphate inhibitors. This applies to a large population of patients requiring either coronary artery bypass grafting after angiographic definition of their coronary anatomy, or patients requiring semi-elective or urgent operation while under dual antiplatelet therapy. This concern is more present in era of drug-eluting stents, where long-term use of dual antiplatelet therapy is encouraged, and the incidence of late thrombosis after late cessation of adenosine diphosphate inhibitors is increasingly surfacing in the literature. The goal this review is to provide the medical chemistry of most commonly used adenosine diphosphate inhibitors, examine the literature on the effect of adenosine diphosphate inhibitors in hemorrhagic-related complications after surgical intervention, and provide the ramifications and alternatives in modern clinical practice.

An unusual and efficient reaction of 2-methylene-3-phenyloxetane in the presence of lithium and 4,4′-di-tert-butylbiphenyl in THF

Abstract When 2-methylene-3-phenyloxetane ( 4 ) was treated with excess lithium and DTBB (cat.), lactone 6 was isolated as an unexpected product in high yield. It is postulated that 6 arises from a coupling of a radical enolate derived from 4 and the enolate of acetaldehyde, a product of THF decomposition under the reaction conditions.

A Novel Design of Combining the Angiotensin Converting Enzyme (ACE) Inhibitor Captopril with the Angiotensin Receptor Blocker (ARB) Losartan Using Homo Coupling via PEG Diacid Linker

Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.

Vorapaxar: A New Antiplatelet Therapy

Antiplatelet therapy plays an integral role in the treatment of ischemic heart disease, the leading cause of death in most Western Countries. Previously, the classes of antiplatelet drugs that proved effective included aspirin, thienopyridines (e.g.ticlopidine, clopidogrel, prasugrel), a non-thienopyridine (ticagrelor), and glycoprotein (GP) IIb/IIIa receptor antagonists (e.g. abciximab, eptifibatide, tirofiban). Administration of antiplatelet therapy typically included dosages of acetylsalicylic acid alongside either a thienopyridine or non-thienopyridine ADP receptor inhibitor. Particular combinations within this dual antiplatelet therapy were contingent on specific needs and occurrences of patients. Inherent limitations of these antiplatelet drugs, however, lead inevitably to the development of new agents that not only conquer said limitations but also possess new, more efficient mechanistic modes of action. Vorapaxar functions as a thrombin receptor antagonist, working against the protease activated receptor PAR-1 to inhibit platelet aggregation without affecting hemostasis.

TCT-177 Obesity is independently associated with occurrence of ST elevation myocardial infarction with steady decline of this association over the recent years.

Obesity is associated with many cardiovascular risk factors. The goal of this study was to evaluate any association between obesity and ST elevation myocardial infarction (STEMI) after multivariate adjustment. We used ICD-9 Codes for obesity and ST elevation myocardial infarction from the

Utilization of serial intravascular ultrasound in the evaluation of cardiac transplant vasculopathy

Introduction: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in diabetic patients. It is unclear whether the coronary atherosclerotic plaque burden is similar in diabetics as in the general population. The aim of the study was to assess the differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by multislice computed tomography coronary angiography (MSCTA) in diabetic patients as compared to those with no diabetes. Methods: A total of 150 consecutive patients of whom 69 (46%) were diabetics underwent MSCTA. Study patients were classified as having no CAD, mild-moderate CAD (b50% stenosis), or moderate-severe CAD (N50% stenosis). Plaques were classified as calcific, noncalcific (mixed), or soft. Finally, patients were classified as having no CAD, having singlevessel CAD, and having more than one vessel CAD. Results: Diabetics less frequently had a normal MSCTA (36.2% vs. 59.3%, P=.008) and more frequently had obstructive plaques (43.5% vs. 18.5, P=.002). They had more calcific (0.83±1.2 vs. 0.28±0.71, P=.004) and noncalcific plaques (0.55±0.88 vs. 0.29±0.52, P=.048) and had more coronary arteries diseased (1.9±1.8 vs. 0.99±1.6, P=.001). Diabetes correlated with number of obstructive plaques (CI=1.6–7.1, P=.001), number of calcified plaques (CI=0.87–0.54, P=.001), and presence of multivessel disease (CI=2.41–10.27, P=.001). Conclusion: Diabetics have an overall increased coronary atherosclerotic plaque burden with approximately fourfold higher risk of coronary stenosis independent of other cardiovascular risk factors and a ninefold higher risk of multivessel CAD independent of other cardiovascular risk factors. Thus, MSCTmay be used to identify differences in coronary plaque burden, which may be useful for risk stratification. Abstracts / Cardiovascular Revascu