Multi-component reactions and evolutionary chemistry.

Fluorinated organic compounds have received considerable attention because they possess unique properties such as greater stability, higher electronegativity, and water and oil repellency, which are potentially beneficial in terms of the development of novel pharmaceutical agents and advanced materials. Such extreme behaviors of fluoro-organic compounds however, often make their syntheses all the more complicated, especially when the synthesis of target compounds requires an enantiocontrolled methodology. Many strategies can be employed for introducing chirality into organic molecules, but enantioselective fluorination and trifluoromethylation reactions are especially attractive because non-fluorinated prochiral substrates can be directly transformed to chiral fluoro-organic compounds with a control of absolute configuration. Significant progress has been made in the development of the asymmetric fluorination reaction in recent years; however, the direct enantioselective trifluoromethylation reaction remains a challenge. In this report, we discuss recent developments in the enantioselective trifluoromethylation reactions, including nucleophilic, electrophilic, and radical approaches. Although the emphasis of this report is on the enantioselective trifluoromethylation reaction, the less-studied enantioselective difluoromethylation and monofluoromethylation reactions are also covered.

Recent advances in enantioselective trifluoromethylation reactions

Compounds of structure (1) are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids such as lowering LDL cholesterol and/or increasing HDl cholesterol, and treating hyperlipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis and pharmaceutically acceptable salts thereof, wherein X is O or S; Z is (2) or (3); n is O or 1; R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; and R3 to R9 are as defined herein.

Hmg-coa reductase inhibitors and method

Progress in the synthesis and transformations of alkylidenecyclopropanes and alkylidenecyclobutanes.

Cholesteryl ester transfer protein (CETP), a plasma glycoprotein, mediates the transfer of neutral lipids in the blood among various lipoproteins.1,2 Because of their poor water solubility, neutral lipids such as triglycerides (TG), free cholesterol (FC), and cholesteryl esters (CE) generally are not freely circulating in plasma but instead are packaged together and transported through the body in larger lipoprotein particles that have amphipathic lipids and proteins as surface components. Low-density lipoprotein (LDL) and high-density lipoproteins (HDL) particles help move cholesterol to and from the periphery, respectively. The entire transport process is highly regulated in terms of lipoprotein production and the transfer of lipids to and from these particles. CETP facilitates the transfer of CE from HDL containing apolipoprotein-A (apo-A) to apo-B-containing lipoproteins such as very-low-density lipoprotein (VLDL) and LDL with a balanced exchange of TG. For every CE acquired from HDL and transferred to LDL or VLDL, CETP takes up one TG molecule from LDL or VLDL and transfers it to HDL. Thus, CETP plays a critical role in both CE and TG transfer among lipoproteins. A CETP inhibitor would thus be expected to raise plasma HDL cholesterol (HDLc) levels, lower LDL cholesterol (LDLc), and provide a potential therapeutic benefit for patients with coronary artery disease (CAD). As discussed in more detail below, whether CETP inhibition might induce an antiatherogenic response by raising HDLc or have proatherogenic effects by interfering with reverse cholesterol transport (RCT) has been the subject of considerable debate and controversy.2-5 Important insights from studies over the past several years have added to our understanding of the multiple mechanisms by which HDL achieves its atheroprotective effects6 and the complex physiological and pathophysiological roles CETP plays in lipoprotein metabolism. However, the field still remains controversial. Recently, a number of potent, selective, and orally active CETP inhibitors have also been identified that raise HDLc in animals and more clearly define the role of CETP in preclinical models of atherosclerosis.2 Several of these new CETP inhibitors have been brought forward and evaluated in clinical trials, and two have now independently demonstrated phase II proof of concept by dramatically increasing HDLc levels by 50% or more in healthy volunteers and patients with low HDLc.7,8 Thus, for the first time, pharmacological agents are available that have the potential to elevate HDLc in patients with low HDLc to about the same extent that the current standard of care drugs reduce LDLc in hyperlipidemic patients. These exciting clinical results have generated renewed interest in CETP inhibition as a potential new therapeutic strategy for treating CAD, and more than 750 related patents or publications have appeared in Chemical Abstracts since 2000. It remains to be seen whether prolonged treatment with these new agents leads to a profound reduction in secondary coronary events across a broader patient population without disrupting normal lipoprotein balance and function. This Perspective summarizes the current status of orally active CETP inhibitors as potential new treatments for CAD.

Oral cholesteryl ester transfer protein (CETP) inhibitors: a potential new approach for treating coronary artery disease.

Die Cycloalkano-pyridine werden hergestellt, indem man entsprechende Cycloalkano-pyridin-aldehyde
mit geeigneten metallorganischen Verbindungen oder
Wittig- oder Grignard-Reagenzien umsetzt oder Verbindungen vom Typ Cycloalkano-pyridinalkohole
mit geeigneten Bromverbindungen umsetzt, und gegebenenfalls
die funktionellen Gruppen entsprechend variiert. Die Cycloalkano-pyridine eignen sich als Wirkstoffe in Arzneimitteln, insbesondere
in Arzneimitteln zur Behandlung von Hyperlipoproteinaemia und
Arteriosklerose.

Cycloalkano-pyridine as CETP inhibitors

Seemingly heartbreaking for a stereochemist, the one-step selective construction of a stereopentad and its prompt destruction by aromatization has been proven to be an efficient strategy for the synthesis of fivefold substituted, pharmacologically highly active arenes (see scheme).

Stereoselective Mukaiyama-Michael/Michael/Aldol Domino Cyclization as the Key Step in the Synthesis of Pentasubstituted Arenes: An Efficient Access to Highly Active Inhibitors of Cholesteryl Ester Transfer Protein (CETP).

The invention relates to substituted chinolines of general formula (I) which are highly effective inhibitors of cholesterol ester transfer proteins (CTEP) and stimulate reverse cholesterol transfer. The inventive substances lower the LDL cholesterol level in the blood while at the same time increasing the HDL cholesterol level. Said substances can therefore be used in the treatment and prevention of hyperlipoproteinemia, hypolipoproteinimia, dyslipidiemia, hypertriglyceridemia, combined hyperlipidemia or arteriosclerosis.

5-oxysubstituted chinolines and their use as cholesterol ester transfer proteins inhibitors

According to the invention, the tetrahydrochinoline can be produced in which corresponding substituted tetrahydrochinoline-aldehyde is condensed with suitable substances and afterwards the existing substituents are varied according to usual methods. The tetrahydrochinoline is suited for additives in medicaments, especially in medicaments for treating arteriosclerosis and dyslipidaemia.

4-phenyltetrahydrochinoline utilized as an inhibitor of the cholesterol ester transfer protein

The present invention relates to a process for preparing 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxarnide, its salts and monohydrate.

Process for the preparation of 4- {4-[({[4 -chloro-3 -(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-n-methylpyridine-2-carboxamide, its salts and monohydrate

Michael Lögers

Papers

Cycloalkano-pyridine as CETP inhibitors

Stereoselective Mukaiyama-Michael/Michael/Aldol Domino Cyclization as the Key Step in the Synthesis of Pentasubstituted Arenes: An Efficient Access to Highly Active Inhibitors of Cholesteryl Ester Transfer Protein (CETP).

5-oxysubstituted chinolines and their use as cholesterol ester transfer proteins inhibitors

4-phenyltetrahydrochinoline utilized as an inhibitor of the cholesterol ester transfer protein

Process for the preparation of 4- {4-[({[4 -chloro-3 -(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-n-methylpyridine-2-carboxamide, its salts and monohydrate